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SummaryThe goals of a cardiac surgical procedure are both technical excellence and complete protection of cardiac function. Cardioplegia is used almost universally to protect the heart and provide a quiet bloodless field for surgical accuracy. Yet, despite the importance of myocardial protection in cardiac surgery, manuscripts or dedicated sessions at major meetings on this subject have become relatively rare, as though contemporary techniques now make them unnecessary. Nevertheless, septal dysfunction and haemodynamic support (inotropes, intra-aortic balloon pump, assist devices) are common in postoperative patients, indicating that myocardial damage following cardiac surgery is still prevalent with current cardioplegic techniques and solutions. This article first describes why cardiac enzymes and septal function are the ideal markers for determining the adequacy of myocardial protection. It also describes the underappreciated consequences of postoperative cardiac enzyme release or septal dysfunction (which currently occurs in 40–80% of patients) from inadequate protection, and how they directly correlate with early and especially late mortality. Finally, it reviews the various myocardial protection techniques available to provide a detailed understanding of the cardioplegic methods that can be utilized to protect the heart. This will allow surgeons to critically assess their current method of protection and, if needed, make necessary changes to provide their patients with optimal protection.

Pulmonary artery catheters can be valuable in directing therapy in select patients. These specialized catheters are placed through introducer sheaths in the internal jugular or subclavian veins, and obtain direct measurements of central venous pressure, right-sided intracardiac pressures, pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac output, and mixed venous oxyhemoglobin saturation. The most common indications for their placement are the evaluation and/or management of patients with complicated myocardial infarction, unexplained or unknown volume status in shock, severe cardiogenic shock, and suspected or known pulmonary arterial hypertension.

OBJECTIVES: Neurological injury after global brain ischaemia (i.e. sudden death) remains problematic, despite improving cardiac survival. Unfortunately, sudden death models introduce unwanted variables for studying the brain because of multiple organ injury. To circumvent this, a new minimally invasive large animal model of isolated global brain ischaemia, together with baseline perfusion studies is described. METHODS: The model employs neck and small (3–4 inches) supra-sternal incisions to block inflow from carotid and vertebral arteries for 30 min of normothermic ischaemia. Neurological changes after 24 h in six pigs was compared with six Sham pigs assessing neurological deficit score (NDS, 0 =normal, 500=brain death), brain oedema and cerebral infarction by 2,3,5-triphenyltetrazolium chloride (TTC) stain. Six other pigs had baseline perfusion characteristics in this new model evaluated at carotid flows of 750, 550 and 450 cc/min, with cerebral perfusion pressure, cerebral oximeter saturation [IN Vivo Optical Spectroscopy (INVOS)] and transcranial O2 uptake measurements. RESULTS: The model never altered cardiac or pulmonary function, and six Sham pigs had normal (NDS=0) neurological recovery without brain injury. Conversely, 24 h analysis showed that 30 min of global normothermic brain ischaemia caused multiple postreperfusion seizures (P

OBJECTIVEBrain damage is universal in the rare survivor of unwitnessed cardiac arrest. Non-pulsatile-controlled cerebral reperfusion offsets this damage, but may simultaneously cause brain oedema when delivered at the required the high mean perfusion pressure. This study analyses pulsatile p

OBJECTIVES: Neurologic injury after sudden death is likely due to a reperfusion injury following prolonged brain ischaemia, and remains problematic, especially if the cardiac arrest is unwitnessed. This study applies a newly developed isolated model of global brain ischaemia (simulating unwitnessed sudden death) for 30 min to determine if controlled reperfusion permits neurologic recovery. METHODS: Among the 17 pigs undergoing 30 min of normothermic global brain ischaemia, 6 received uncontrolled reperfusion with regular blood (n = 6), and 11 were reperfused for 20 min with a warm controlled blood reperfusate containing hypocalcaemia, hypermagnesemia, alkalosis, hyperosmolarty and other constituents that were passed through a white blood cell filter and delivered at flow rates of 350 cc/min (n = 3), 550 cc/min (n = 2) or 750 cc/min (n = 6). Neurologic deficit score (NDS) evaluated brain function (score 0 = normal, 500 = brain death) 24 h post-reperfusion and 2,3,5-triphenyltetrazolium chloride (TTC) staining determined brain infarction. RESULTS: Regular blood (uncontrolled) reperfusion caused negligible brain O2 uptake by IN Vivo Optical Spectroscopy (INVOS) ( 50 mmHg, but the lower pressure (

The purpose of this study was to determine (1) the role of emergency cardiopulmonary bypass (CPB) after prolonged cardiac arrest and failed cardiopulmonary resuscitation, and (2) the use of systemic hyperkalemia during CPB to convert intractable ventricular fibrillation (VF).Thirty-one pigs (34 +/- 2 kg) underwent 15 minutes of cardiac arrest after induced VF, followed by 10 minutes of cardiopulmonary resuscitation-advanced life support. Peripheral CPB was used if cardiopulmonary resuscitation failed to restore stable circulation. Damage was assessed by evaluating hemodynamics, biochemical variables (creatine kinase-MB, neuron-specific enolase), neurologic deficit score, and brain magnetic resonance imaging.Cardiopulmonary resuscitation alone was successful in only 19% (6 of 31 pigs). Cardiopulmonary bypass was initiated in 81% of animals (25 of 31 pigs) either for hypotension (5 of 25 pigs) or intractable VF (20 of 25 pigs). Defibrillation was successful in 7 of 20 animals during the first 10 minutes after initiating CPB. Ventricular fibrillation persisted more than 10 minutes in 13 of 20 pigs, and animals were treated either with repeated defibrillation (6 of 13 pigs) or with a potassium bolus (7 of 13 pigs) to induce transient cardiac arrest. Overall survival at 24 hours was 84% with cardiopulmonary resuscitation (100% of pigs with hypotension; 71% in CPB-VF10 minutes). Despite CPB, fatal myocardial failure occurred after VF duration of more than 10 minutes in all pigs treated with electrical defibrillation, whereas hyperkalemia allowed 100% cardioversion and 86% survival. Biochemical variables remained elevated in all groups. Similarly, severe brain injury was present in all animals as confirmed by neurologic deficit score (197 +/- 10) and magnetic resonance imaging.Emergency CPB after prolonged cardiac arrest improves survival and allows systemic hyperkalemia to convert intractable VF, but fails to reduce neurologic damage.

Summary Background The fundamental goal of cardiopulmonary resuscitation (CPR) is recovery of the heart and the brain. This is best achieved by (1) immediate CPR for coronary and cerebral perfusion, (2) correction of the cause of cardiac arrest, and (3) controlled cardioplegic cardiac reperfusion. Failure of such an integrated therapy may cause permanent brain damage despite cardiac resuscitation. Methods This strategy was applied at four centers to 34 sudden cardiac death patients (a) after acute myocardial infarction ( n =20), (b) "intraoperatively" following successful discontinuation of cardiopulmonary bypass ( n =4), and (c) "postoperatively" in the surgical ICU ( n =10). In each witnessed arrest the patient failed to respond to conventional CPR with ACLS interventions, including defibrillation. The cardiac arrest interval was 72±43min (20–150min). Compression and drugs maintained a BP>60mmHg to avoid cerebral hypoperfusion. Operating room (OR) transfer was delayed until the blood pressure was monitored. In four patients femoral bypass maintained perfusion while an angiographic diagnosis was made. Results Management principles included no repeat defibrillation attempts after 10min of unsuccessful CPR, catheter-monitored peak BP>60mmHg during diagnosis and transit to the operating room, left ventricular venting during cardiopulmonary bypass and 20min global and graft substrate enriched blood cardioplegic reperfusion. Survival was 79.4% with two neurological complications (5.8%). Conclusions Recovery without adverse neurological outcomes is possible in a large number of cardiac arrest victims following prolonged manual CPR. Therapy is directed toward maintaining a monitored peak BP above 60mmHg, determining the nature of the cardiac cause, and correcting it with controlled reperfusion to preserve function.

Significant advances have been made in the technical performance of operations for infants and neonates with congenital heart disease. However, postoperative organ dysfunction is a frequent problem, particularly in hypoxic (cyanotic) infants. We review both our experimental and subsequent clinical experience with the injury caused by abrupt reoxygenation of the hypoxic patient and examine the modalities of gradual reoxygenation and leukodepletion in limiting this injury, thereby improving operative outcomes for cyanotic lesions. As a result of our experimental and clinical experience we conclude that: (1). reoxygenation injury is a real source of postoperative cardiac and pulmonary dysfunction; (2). white blood cells play an integral role in the production of oxygen-free radicals that are responsible for the damage; and (3). this injury can be modified and possibly ameliorated by changes in the intraoperative management of cardiopulmonary bypass.

J Thorac Cardiovasc Surg 2002;124:16-9

Objectives: This study was undertaken to compare conventional cardioplegic strategies with a new approach that uses a modified nonpotassium maintenance solution between cardioplegia doses in stressed neonatal hearts. Methods: Thirty-five neonatal piglets underwent 60 minutes of ventilator hypoxia (inspired oxygen fraction 8%-10%) followed by 20 minutes of ischemia on cardiopulmonary bypass. In 10 animals bypass was discontinued without further ischemia (stress control group). The other 25 received a warm blood cardioplegic induction and were separated into 5 groups. In 5 animals cardiopulmonary bypass was discontinued without further ischemia (cardioplegia control group); the remaining 20 underwent an additional 70 minutes of cold blood cardioplegic arrest. Five received only intermittent cardioplegia every 20 minutes, whereas 15 also received cold blood maintenance infusions between cardioplegic doses (integrated strategy). In 5 of these animals the blood was unmodified, whereas in 10 a modified nonpotassium “cardioplegia-like” solution was delivered either antegradely (n = 5) or retrogradely (n = 5). Myocardial function was assessed by pressure-volume loops (expressed as percentage of control); vascular function was assessed by coronary vascular resistance. Results: All piglets that underwent hypoxic ischemic stress alone (controls) died. Warm induction alone (cardioplegic controls) partially repaired the stress injury. Intermittent cardioplegia preserved the depressed systolic function (end-systolic elastance 40% vs 39%), increased diastolic stiffness (255% vs 239%), reduced adenosine triphosphate (10.6 vs 12.2 μg/g tissue), and elevated coronary vascular resistance at levels identical to warm induction alone; infusing unmodified blood between cardioplegia doses (standard integrated) improved results slightly. In contrast, infusion of a cold modified solution (antegrade or retrograde) between cardioplegia doses (modified integrated) completely restored systolic function (end-systolic elastance 100% and 97%, P

As cardiopulmonary bypass (CPB) in infants and neonates is becoming more frequent, the technical performance of these operations for congenital heart disease has made significant progress. However, little research has been carried out into the conduct of CBP in producing myocardial and pulmonary dysfunction. Postoperative organ dysfunction is a problem, particularly for cyanotic infants. This paper examines the experimental and clinical experience of injury brought about by abrupt reoxygenation of the hypoxic, or cyanotic, heart. The modalities of gradual reoxygenation and leukodepletion in limiting this injury are examined, leading to the conclusion that injury can be reduced and possibly ameliorated by changes in intraoperative management during CBP in children with cyanotic disease.

Warm cardioplegic induction improves the ischemically "stressed" adult heart. However, it is rarely used in infants, despite the fact that many newborn hearts are stressed by other factors such as hypoxia. The need for amino acids as well as their mechanism of action has also not been studied.We first assessed the role of cardioplegic induction temperature in 10 nonhypoxic neonatal piglets undergoing 70 minutes of multidose blood cardioplegic arrest. Five piglets (group 1) received a cold (4 degrees C) induction, and 5 (group 2) a warm (37 degrees C) induction. Twenty-six other piglets underwent ventilator hypoxia (fraction of inspired oxygen, 8% to 10%) for 60 minutes before cardiopulmonary bypass (stress). Six piglets (group 3) then underwent 70 minutes of cardiopulmonary bypass without ischemia (hypoxia controls), and 20 underwent 70 minutes of cardioplegic arrest. Five of these (group 4) received cold cardioplegic induction, and 15 received warm induction; in 5 of these (group 5), the warm cardioplegic solution contained amino acids, in 5 others (group 6), it was unsupplemented, and in the remaining 5 (group 7), nitroglycerin was added to determine the role of vasodilation. Myocardial function was assessed by pressure-volume loops (expressed as a percent of control), and coronary vascular resistance was measured with cardioplegic infusions.In nonhypoxic (normal) piglets, cold (group 1) and warm (group 2) induction completely preserved systolic function (end-systolic elastance, 100% versus 104%) and preload recruitable stroke work (100% versus 102%), with minimal increase in diastolic compliance (162% versus 156%). Hypoxia-reoxygenation alone (group 3) depressed systolic function (end-systolic elastance, 51%+/-2%) and preload recruitable stroke work (54%+/-3%), and raised diastolic stiffness (260%+/-15%). The detrimental effects of reoxygenation persisted (unchanged from reoxygenation alone) with cold induction (group 4) or warm induction without amino acids (groups 6 and 7). In contrast, warm induction with amino acids (group 5) restored systolic function (end-systolic elastance, 105%+/-3%; p0.001 versus groups 3, 4, 6, and 7) and preload recruitable stroke work (103%+/-2%; p0.001 versus groups 3, 4, 6, and 7), and decreased diastolic stiffness (154%+/-7%; p0.001 versus groups 3, 4, 6, and 7). However, there was no difference in myocardial oxygen consumption in hypoxic hearts receiving a warm induction (6.9 versus 6.5 versus 7.3 mL/g per 5 minutes) (groups 5, 6, 7), and coronary vascular resistance was lowest with nitroglycerin (group 7).Cardioplegic induction can be given either warm or cold in nonhypoxic neonatal hearts. In contrast, only warm induction with amino acids repairs the hypoxic injury, but the primary mechanism of action is not related to increased metabolic activity or vasodilation.

The in vitro activity of LY333328 was evaluated for 1,479 nosocomial gram-positive pathogens isolated in 12 countries during 1997. LY333328 MICs at which 90% of the isolates tested were inhibited for Enterococcus faecalis ( n = 351), Enterococcus faecium ( n = 100), Staphylococcus aureus ( n = 593), coagulase-negative Staphylococcus species ( n = 325), and Streptococcus pneumoniae ( n = 110) were 1, 1, 2, 2, and 0.015 μg/ml, respectively. LY333328 demonstrated potent activity against isolates of vancomycin-resistant enterococci, oxacillin-resistant staphylococci, and penicillin-resistant pneumococci.

Background . Coarctation repair in neonates or small infants, using a subclavian patch, has a relatively high risk of restenosis, especially if complicated by the presence of a short subclavian artery or long coarctation segment. We introduce a technical modification that facilitates the use of a subclavian flap, and decreases the restenosis rate in this subgroup of patients. It consists of a side-to-side transverse aortic anastomosis at the level of the coarctation, which widens the coarctation segment, shortens the isthmus, and pulls the distal end of the aortotomy proximally, allowing a tension-free subclavian flap aortoplasty. Methods . Fifty-three consecutive neonates or infants less than 18 weeks old, with complex coarctation, underwent repair using this technique. Mean age was 26 ± 3 days and 36 patients (68%) were less than 28 days old. Weights ranged from 1.4 to 6.4 kg (mean 3.4 ± 0.2 kg), and 26 patients had other cardiac anomalies. Preoperative gradient by Doppler measurement ranged from 25 to 90 mm Hg (mean 49 ± 2 mm Hg). Results . Mean aortic cross-clamp time was 27 ± 1 minutes (range 19 to 34 minutes). There were no deaths or surgical complications. Follow-up echocardiogram 4 to 52 months postoperatively (mean 25 ± 2 months) demonstrated no significant pressure gradient (less than 20 mm Hg) in 51 of 53 patients (96%), and a significant gradient in 2 patients (4%), which was subsequently corrected with balloon angioplasty. Conclusions . The technical modification described shortens the isthmus, and thus allows for a longer aortotomy distal to the area of coarctation resulting in a tension-free repair especially in patients with a short subclavian artery. It also widens the area of coarctation, and as a result leads to a lower early recoarctation rate in this high-risk group. With increasing emphasis on the need for a longer aortotomy to prevent restenosis, this modification will have increasing application, especially in the neonatal population.

Controlled reperfusion with a modified solution limits pulmonary injury following ischemia. Our initial studies infused this modified reperfusate at a pressure of 40 to 50 mm Hg to insure distribution. However, perhaps a lower pressure, which is closer to the normal physiologic pressure in the lung, would improve results by decreasing sheer stress.Fifteen adult pigs underwent 2 hours of lung ischemia by clamping the left bronchus and pulmonary artery. Five (group 1) then underwent uncontrolled reperfusion by removing the vascular clamps and allowing unmodified blood to reperfuse the lung at a pulmonary artery pressure of 20 to 30 mm Hg. The other 10 pigs underwent controlled reperfusion by mixing blood from the femoral artery with a crystalloid solution, and infusing this modified reperfusate into the ischemic lung through the pulmonary artery for 10 minutes before removing the arterial clamp. In 5 (group 2), the modified solution was infused at a pressure of 40 to 50 mm Hg, and in 5 (group 3) 20 to 30 mm Hg. Lung function was assessed 60 minutes after reperfusion and expressed as percentage of control.Compared to uncontrolled reperfusion (group 1), controlled reperfusion at a pressure of 40 to 50 mm Hg (group 2) significantly improved postreperfusion pulmonary compliance (77% versus 86%; p0.001 versus group 1), and arterial/alveolar ratio (a/A) ratio (27% versus 52%; p0.001 versus group 1); as well as decreased pulmonary vascular resistance (PVR) (198% versus 154%; p0.001 versus group 1), lung water (84.3% versus 83.5%; p0.001 versus group 1), and myeloperoxidase (0.35 versus 0.23 optical density/min/mg protein). Reducing the pressure of the modified reperfusate to 20 to 30 mm Hg further improved postreperfusion compliance (92%+/-1%; p0.001 versus groups 1 and 2) and a/A ratio (76%+/-1%; p0.001 versus groups 1 and 2); and lowered PVR (133%+/-2%; p0.001 versus groups 1 and 2), lung water (82.7%+/-0.1%; p0.001 versus groups 1 and 2), and myeloperoxidase (0.16%+/-0.01%; p0.001 versus groups 1 and 2).After 2 hours of pulmonary ischemia, a severe lung injury occurs following uncontrolled reperfusion, controlled reperfusion with a modified solution reduces this reperfusion injury, and lowering the pressure of the modified reperfusate to more physiologic levels (20 to 30 mm Hg) further reduces the reperfusion injury improving pulmonary function.

Background . Posttransplantation lung reperfusion injury continues to be a major problem. We have shown that controlling the initial period of reperfusion limits this injury after 2 hours of warm lung ischemia. The effectiveness of this modality, however, is unknown after longer periods of cold ischemia, which more closely mimics the clinical situation. Methods . After baseline measurements, 10 pigs had the left lung flushed with a modified Euro-Collins solution, explanted, stored at 4°C for 24 hours, and transplanted into 10 other pigs. Five (group 1) underwent uncontrolled reperfusion created by removal of the vascular clamps after implantation of the new left lung, mimicking the clinical situation. The other five (group 2) underwent controlled reperfusion, which we performed by taking blood from the femoral artery, mixing it with a crystalloid solution (using a mixer heater) to make the blood hyperosmolar, alkalotic, and substrate-enriched, and pumping it through a leukocyte-depleting filter into the transplanted lung for 10 minutes at a pressure of 20 to 30 mm Hg before removing the pulmonary artery clamp. The right pulmonary artery and bronchus were then ligated, and left lung function was assessed each hour for 4 hours and compared with baseline. Results . Controlled reperfusion (group 2) minimized the reperfusion injury, preserving posttransplant pulmonary compliance (92% ± 1% versus 68% ± 1%; p p 2 , 425 ± 14 versus 82 ± 11 mm Hg; p p p Conclusions . After 24 hours of cold ischemia uncontrolled reperfusion results in a severe pulmonary reperfusion injury. This injury is almost completely avoided by controlling the composition (modified solution and white blood cell filter) and conditions (pressure) of the reperfusion. Because this experiment mimics the clinical situation, it suggests surgeons should begin to use this modality to limit reperfusion injury after lung transplantation.

Objectives: Recent studies have shown that an injury occurs when the hypoxic heart is suddenly reoxygenated (as occurs with cardiopulmonary bypass), resulting in myocardial depression, impaired oxygenation, and increased pulmonary vascular resistance. We hypothesize that this injury is, in part, due to oxygen-derived radicals produced by activated white cells and may therefore be ameliorated by limiting leukocytes in the bypass circuit. Methods: Fifteen neonatal piglets underwent 60 minutes of ventilator hypoxia (inspired oxygen fraction 8% to 10%), followed by reoxygenation with cardiopulmonary bypass at an inspired oxygen fraction of 100% for 90 minutes. In nine piglets (group 1) our routine bypass circuit was used with no modifications, and in six piglets (group 2) a leukocyte-depleting filter (Pall BC-1; Pall Biomedical Products Corporation, Glencoe, N.Y.) was inserted in the arterial line to lower the neutrophil count. Six additional piglets underwent 90 minutes of bypass without hypoxia (cardiopulmonary bypass controls). Postbypass myocardial and pulmonary function was assessed by pressure volume loops, arterial/alveolar ratio, and pulmonary vascular resistance index. Results are expressed as a percentage of control. Results: By comparison with group 1 piglets (reoxygenation without a filter), hypoxic piglets undergoing reoxygenation with a leukocyte-depleting filter (group 2) had improved myocardial systolic function (88% vs 52%; p < 0.05), diastolic compliance (175% vs 275%; p < 0.05), and preload recruitable stroke work (91% vs 54%; p < 0.05); had better preservation of the arterial/alveolar ratio (97% vs 74%; p < 0.05); and had less increase in pulmonary vascular resistance (229% vs 391%; p < 0.05). Furthermore, leukocyte filtration prevented adenosine triphosphate depletion or a change in tissue antioxidants. Conversely, unprotected piglets (group 1) exhibited lower levels of adenosine triphosphate and significant loss of tissue antioxidants. Indeed, the results in the leukocyte-filtered piglets (group 2) were nearly identical to those of piglets subjected to bypass without hypoxia (controls). Conclusions: (1) This study demonstrates that a major component of the injury that occurs when the hypoxic heart is abruptly reoxygenated is caused by oxygen radicals produced by white blood cells; (2) this injury can be prevented by a leukocyte-depleting filter; and (3) avoidance of this injury improves postbypass myocardial and pulmonary function. These data suggest that leukocyte depletion should be used routinely in all children undergoing operations for cyanotic heart disease or extracorporeal membrane oxygenation. (J Thorac Cardiovasc Surg 1997;113:1081-90)

Objectives: The ideal cardioplegic calcium (Ca +2 ) concentration in newborns continues to be debated. Most studies examining cardioplegia calcium concentrations have been done with a nonclinical model (i.e., isolated heart preparation), the results of which may not be clinically applicable, and they have not examined the effect of calcium concentration in a clinically relevant stressed (hypoxic) heart. Methods: Twenty neonatal piglets 5 to 18 days old were placed on cardiopulmonary bypass, and their aortas were crossclamped for 70 minutes with hypocalcemic or normocalcemic multidose blood cardioplegic infusions. Group 1 (n = 5; low Ca+2, 0.2 to 0.4 mmol/L) and group 2 (n = 5; normal Ca+2, 1.0 to 1.3 mmol/L) were nonhypoxic (uninjured) hearts. Ten other piglets were first ventilated at an Fio2 of 8% to 10% (O2 saturation 65% to 70%) for 60 minutes (i.e., causing hypoxia) and then reoxygenated at an Fio2 of 100% with cardiopulmonary bypass, which produces a clinically relevant stress injury. They then underwent cardioplegic arrest (as described above) with a hypocalcemic (n = 5, group 3) or normocalcemic (n = 5, group 4) blood cardioplegic solution. Myocardial function was assessed with pressure volume loops and expressed as a percentage of control values. Coronary vascular resistance was measured during each cardioplegic infusion. All values were reported as the mean ± standard error. Results: In nonhypoxic hearts (groups 1 and 2), good myocardial protection was achieved at either concentration of cardioplegia calcium, as demonstrated by preservation of postbypass systolic function (104% vs 99% end-systolic elastance), minimally increased diastolic stiffness (152% vs 162%), no difference in myocardial water (78.9% vs 78.9%), and no change in adenosine triphosphate levels or coronary vascular resistance. Low-calcium blood cardioplegia solution repaired the hypoxic reoxygenation injury in stressed hearts (group 3), resulting in no statistical difference in myocardial function, coronary vascular resistance, or adenosine triphosphate levels compared with nonhypoxic hearts (groups 1 and 2). Conversely, when a normocalcemic cardioplegia solution was used in hypoxic hearts (group 4), there was marked reduction in postbypass systolic function (49% ± 4% end-systolic elastance; p < 0.05), increased diastolic stiffness (276% ± 9%; p < 0.05), increased myocardial water (80.1% ± 0.2%; p < 0.05), rise in coronary vascular resistance (p < 0.05), and lower adenosine triphosphate levels compared with groups 1, 2, and 3. Conclusions: This study demonstrates that, in the clinically relevant, intact animal model, good myocardial protection is independent of cardioplegia calcium concentration in nonhypoxic (noninjured) hearts; hypoxic (stressed) hearts are extremely sensitive to the cardioplegic calcium concentration; and normocalcemic cardioplegia is detrimental to neonatal myocardium subjected to a preoperative hypoxic stress. (J THORAC CARDIOVASC SURG 1996;112:1193-201)

This study tested the hypothesis that the developing heart is susceptible to oxygen-mediated damage after reintroduction of molecular oxygen and that this "unintended" reoxygenation injury causes lipid peroxidation and functional depression that may contribute to perioperative cardiac dysfunction. Among 49 Duroc-Yorkshire piglets (2 to 3 weeks old, 3 to 5 kg) 15 control studies were done without hypoxemia to test the effects of the surgical preparation ( n = 10) and 60 minutes of cardiopulmonary bypass ( n = 5). Twenty-nine piglets underwent up to 2 hours of ventilator hypoxemia (with inspired oxygen fraction reduced to 6% to 7%) to lower arterial oxygen tension to approximately 25 mm Hg. Five piglets did not undergo reoxygenation to determine alterations caused by hypoxemia alone. Twenty-four others received reoxygenation by either raising ventilator inspired oxygen fraction to 1.0 ( n = 12) or instituting cardiopulmonary bypass at oxygen tension 400 mm Hg ( n = 12). Ventilator hypoxemia produced sufficient hemodynamic compromise and metabolic acidosis that 18 piglets required premature reoxygenation (78 ± 12 minutes). To avoid the influence of acidosis and hemodynamic deterioration during ventilator hypoxemia, five others underwent 30 minutes of hypoxemia during cardiopulmonary bypass (circuit primed with blood at oxygen tension 25 mm Hg) and 30 minutes of reoxygenation (oxygen tension 400 mm Hg) during cardiopulmonary bypass. Biochemical markers of oxidant damage included measurement of coronary sinus and myocardial conjugated dienes to determine lipid peroxidation and antioxidant reserve capacity assessed by incubating myocardial tissue in the oxidant t -butylhydroperoxide. Functional recovery was determined by inscribing pressure volume loops to determine end-systolic elastance and Starling curves by volume infusion. No biochemical or functional changes occurred in control piglets. Hypoxemia without reoxygenation did not change plasma levels of conjugated dienes, but lowered antioxidant reserve capacity 24%. Reoxygenation by ventilator caused refractory ventricular arrhythmias in two piglets (17% mortality), raised levels of conjugated dienes 45%, and reduced antioxidant reserve capacity 40% with recovery of 39% of mechanical function in the survivors. Comparable biochemical and functional changes occurred in piglets undergoing ventilator hypoxemia and/or cardiopulmonary bypass hypoxemia and reoxygenation on cardiopulmonary bypass. We conclude that hypoxemia increases vulnerability to reoxygenation damage by reducing antioxidant reserve capacity and that reoxygenation by either ventilator or cardiopulmonary bypass produces oxidant damage with resultant functional depression that is not a result of cardiopulmonary bypass. These findings suggest that initiation of cardiopulmonary bypass in cyanotic immature subjects causes an unintended reoxygenation injury, which may increase vulnerability to subsequent ischemia during surgical repair. (J THORAC CARDIOVASC SURG 1995; 110:1171-81)

Surgeons often rely primarily on retrograde cardioplegia for myocardial protection, because it provides adequate left ventricular perfusion even in the presence of coronary artery disease. Clinically, however, adequate right ventricular perfusion by retrograde delivery has not been demonstrated. Using intraoperative transesophageal echocardiography, we examined retrograde delivery of cardioplegic solutions by contrast echocardiography, which directly assesses myocardial perfusion. In 15 patients (seven having coronary bypass and eight having valve operations), 4 ml of sonicated Isovue medium was injected retrograde via a coronary sinus catheter. Myocardial perfusion was assessed quantitatively by visual inspection and background-subtracted videodensitometric analysis. In five patients undergoing aortic valve replacement, right and left coronary ostial drainage was estimated during retrograde infusion. Before the aortic crossclamp was removed, myocardial oxygen extraction was calculated in all 15 patients by first delivering warm blood cardioplegic solution for 2 minutes in a retrograde fashion and then taking samples from the cardioplegia line and aortic root. This determined the oxygen extraction ratio across the myocardium at the end of retrograde delivery. Warm blood cardioplegic solution was next given antegrade, and 15 seconds later samples were taken from the cardioplegia line and a right ventricular (acute marginal) vein to determine the oxygen extraction ratio across the right ventricle. As assessed by contrast echocardiography, retrograde infusion resulted in almost four times more perfusion to the left ventricular free wall and septum than to the right ventricular free wall (74 ± 2 versus 69 ± 2 versus 20 ± 2, p < 0.05). In those five patients with an aortotomy the right ostial drainage was less than 5 ml/min whereas left ostial drainage was estimated at 80 ml/min during retrograde administration. Oxygen extraction across the myocardium supplied by retrograde infusion was low after 2 minutes. Conversely, when antegrade cardioplegia was started, right ventricular oxygen extraction rose fourfold (42% ± 5% versus 11% ± 1%, p < 0.05), demonstrating that retrograde cardioplegia had not adequately perfused the right ventricular myocardium. Conclusions: 1. Retrograde cardioplegia provides poor right ventricular myocardial perfusion as assessed by contrast echocardiography and coronary ostial drainage. 2. This poor perfusion is inadequate to meet myocardial demands as demonstrated by the high right ventricular oxygen extraction after a prolonged retrograde infusion. 3. Therefore surgeons must not rely solely on retrograde cardioplegia for right ventricular myocardial protection. This concept is especially important if continuous warm blood cardioplegia is used, because myocardial requirements are then higher. (J T HORAC CARDIOVASC SURG 1995;109:1116-26)

This report describes the technique of integrated myocardial management, which combines the advantages of various cardioprotective strategies to compensate for their individual shortcomings. This approach coordinates the myocardial protective techniques with the continuity of the operation so that the surgical procedure is never interrupted. This method (1) provides unimpaired vision, (2) avoids unnecessary ischemia and cardioplegic overdose, (3) allows aortic clamping as soon as cardiopulmonary bypass is started, (4) permits aortic unclamping and discontinuation of bypass shortly after the technical procedure is completed, (5) minimizes the duration of ischemia and cardiopulmonary bypass, and (6) maximizes the positive attributes of the strategies available currently. The background for this myocardial management method, which combines antegrade/retrograde delivery, warm/cold blood cardioplegia, intermittent/continuous perfusion, blood/blood cardioplegia, and avoidance of cardioplegic overdose, hemodilution, and tangential aortic clamping, is discussed. The preliminary results in 1474 patients from four centers where surgeons participated in the infrastructure of this method are presented. This has led to our adoption of this approach in all adult cardiac operations.

Summary Despite advanced cardiac life support (ACLS), the mortality from sudden death after cardiac arrest is 85–95%, and becomes nearly 100% if ischaemia is prolonged, as occurs following unwitnessed arrest. Moreover, 33–50% of survivors following ACLS after witnessed arrest develop significant neurological dysfunction, and this rises to nearly 100% in the rare survivors of unwitnessed arrest. Although, whole body (cardiac) survival improves to 30% following recent use of emergency cardiopulmonary bypass, sustained neurological dysfunction remains a devastating and unresolved problem. Our studies suggest that both brain and whole body damage reflect an ischaemic/reperfusion injury that follows the present reperfusion methods that use normal blood, which we term ‘uncontrolled reperfusion’. In contrast, we have previously introduced the term ‘controlled reperfusion’, which denotes controlling both the conditions (pressure, flow and temperature) as well as the composition (solution) of the reperfusate. Following prolonged ischaemia of the heart, lung and lower extremity, controlled reperfusion resulted in tissue recovery after ischaemic intervals previously thought to produce irreversible cellular injury. These observations underlie the current hypothesis that controlled reperfusion will become an effective treatment of the otherwise lethal injury of prolonged brain ischaemia, such as with unwitnessed arrest, and we tested this after 30 min of normothermic global brain ischaemia. This review, and the subsequent three studies will describe the evolution of the concept that controlled reperfusion will restore neurological function to the brain following prolonged (30 min) ischaemia. To provide a familiarity and rationale for these studies, this overview reviews the background and current treatment of sudden death, the concepts of controlled reperfusion, recent studies in the brain during whole body ischaemia, and then summarizes the three papers in this series on a new brain ischaemia model that endorses our hypothesis that controlled reperfusion allows complete neurological recovery following 30 min of normothermic global brain ischaemia. These findings may introduce innovative management approaches for sudden death, and perhaps stroke, because the brain is completely salvageable following ischaemic times thought previously to produce infarction.

Warm blood cardioplegic induction (WBCI) improves recovery of cardiogenic shock hearts by repaying their energy debt before cold ischemic arrest. This study tests the hypothesis that despite the absence of shock, many hearts are energy depleted and would benefit from WBCI. Twenty-five consecutive (nonshock) patients undergoing open heart operations received antegrade WBCI. Simultaneous samples were drawn from the aortic root and coronary sinus 15 seconds and 2 minutes after cardiac arrest. Samples were analyzed and compared to determine the oxygen consumption, oxygen extraction ratio, and glucose uptake across the left ventricular myocardium. There was a positive linear correlation between oxygen and glucose uptake (p < 0.001). By univariate analysis, severe multivessel disease and high Parsonnet (severity) score were predictors (p < 0.05) of increased metabolic uptake during warm induction. In addition, patients requiring urgent operations (unstable angina, left main disease, or congestive heart failure) and those with a history of hypertension (coronary artery bypass grafting) or left ventricular overload (valve patients) had higher consumption of oxygen and glucose (p < 0.05) compared with patients undergoing elective operations or those without a history of hypertension. In conclusion, warm cardioplegic induction in nonshocked hearts results in increased metabolic uptake indicating energy repayment and correlates with severity of underlying myocardial disease. The need for WBCI is especially great in patients with a history of hypertension or left ventricular overload and those requiring an urgent operation, where increased metabolic extraction was still present after 2 minutes. In addition, even for completely elective patients, WBCI may be useful if the patient has severe multivessel disease or a high Parsonnet score.

Objective: To determine if cardiopulmonary bypass (CPB), together with inhibition of the sodium—hydrogen exchanger (NHE), limits myocardial and neurological injury and improves recovery after prolonged (unwitnessed) cardiac arrest (CA), as NHE inhibition improved recovery after deep hypothermic circulatory arrest. Methods: Twenty-seven pigs (31—39 kg) underwent 15 min of prolonged (no-flow) CA followed by 10 min of cardiopulmonary resuscitation-advanced life support (CPR-ALS). Subjects with restoration of spontaneous circulation (ROSC) during CPR-ALS received either no drug (n = 6) or an inhibitor of the NHE (HOE-642; n = 5). In the 16 unsuccessfully resuscitated animals, peripheral normothermic CPB was instituted, and either no drug (n = 9) or similar HOE-642 (n = 7) therapy started. Hemodynamic data, a speciesspecific neurological deficit score (0 = normal to 500 = brain death), and mortality were recorded at 24 h, and biochemical variables of organ injury measured. Results:CPR-ALS restored ROSC in 41% (11/27) of animals, but was unsuccessful in 59% (16/27) that required CPB. Without CPB, HOE-642 increased cardiac index and decreased vascular resistance; with CPB, HOE-642 caused higher pump flows (3.4 0.6 l min 1 m 2 vs 2.5 0.7 l min 1 m 2 ; p < 0.001) and higher post-arrest cardiac index; but animals required more vasopressors (p = 0.019) from drug-induced vasodilation. No differences between biochemical markers of oxidative and organ injury and overall 24-h mortality (20%) were found between groups. Neurological score was improved at 24 h compared with 4 h only after HOE-642 treatment with (150 34 vs 220 43; p = 0.003) or without CPB (162 39 vs 238 48; p 0.001), but failed to reach statistical difference with respect to the untreated group. Conclusions:CPB is an effective resuscitative tool to treat prolonged CA but there is limited improvement of neurological function. NHE inhibition augments cardiac and neurological function, but its effect was less pronounced than in other studies. # 2011 Published by Elsevier B.V. on behalf of European Association for Cardio-Thoracic Surgery.

Although percutaneous transluminal coronary angioplasty is successful in more than 90% of patients after acute coronary occlusion, overall mortality remains approximately 10% with higher subgroup mortality (i.e., occlusion of the left anterior descending coronary artery, multivessel disease, age older than 70 years, cardiogenic shock) and early recovery of regional wall motion is marginal. This multicenter report shows that controlled surgical reperfusion in patients with acute coronary occlusion reduces overall and subgroup mortality and restores substantial early contractility. In a survey from six institutions, 156 consecutive patients with acute coronary occlusion documented by angiography underwent surgical revascularization with controlled reperfusion using amino acid-enriched blood cardioplegic solution on total vented bypass. Ventricular wall motion was studied by echocardiography or multiple gated acquisition scan on postoperative days 5 to 7 and scored independently (0 = normal, 1 = mild hypokinesia, 2 = severe hypokinesia, 3 = akinesia, 4 = dyskinesia). Results are compared with results in 1203 patients with acute coronary occlusion treated by angioplasty in five reported medical series. Surgically treated patients were revascularized at longer ischemic intervals (6.3 versus 3.9 hours, p < 0.05) and had a greater incidence of left anterior descending occlusion (61% versus 43%, p < 0.05), multivessel disease (42% versus 22%, p < 0.05), and cardiogenic shock (41% versus 10%, p < 0.05), with 12 patients undergoing cardiopulmonary resuscitation en route to the operating room. Surgical results were superior in all categories, with overall mortality reduced from 8.7% after angioplasty to 3.9% after coronary bypass (p < 0.05). All surgical deaths occurred in patients with preoperative cardiogenic shock. Regional wall motion recovered significantly (score < 2) in 131 of 150 (87%) surgically treated patients with an average score of 0.9 +/- 0.8 (normal to mild hypokinesia) despite longer ischemic times.

This report describes an initial experience applying warm glutamate/aspartate substrate-enriched blood cardioplegic solution to resuscitate hearts in 14 patients with witnessed perioperative arrest. Ten patients were in stable hemodynamic condition in the catheterization laboratory (n = 3) or intensive care unit when sudden irreversible fibrillation developed. It progressed to electromechanical arrest in six patients. In patients with preoperative or postoperative arrest, conventional cardiopulmonary resuscitation and defibrillation were unsuccessful and extracorporeal circulation was started 22 to 150 minutes after arrest The left ventricle was vented, the aorta clamped, and warm (37° C) aspartate/glutamate blood cardioplegic solution was given at a rate of 150 ml/min for 20 minutes. All bypass grafts were open with good flows in patients who had had coronary bypass, and coronary bypass was done in the three patients who had preoperative arrest Eleven of 14 hearts resumed normal sinus rhythm after aortic unclamping, only two electrocardiographically proved infarctions occurred, and 13 patients had complete hemodynamic recovery with improved ejection fraction. Three patients died: one of progressive cardiogenic shock, another of mediastinitis, and the third of irreversible neurologic damage. Eleven patients were discharged from the hospital and are well after a follow-up period between 3 and 9 months. We conclude that witnessed perioperative arrest with intractable ventricular fibrillation should be treated aggressively by administering cardiopulmonary resuscitation during prompt transfer to the operating room for total vented bypass and delivery of warm substrate-enriched blood cardioplegic solution. This treatment may salvage hearts thought to be damaged irreversibly and may be a feasible approach to intractable witnessed cardiac arrest, provided cardiopulmonary resuscitation maintains satisfactory cerebral perfusion pressure. (J T horac C ardiovasc S urg 1992;104:1141-7)

This retrospective analysis tests the hypothesis that topical cardiac hypothermia is an unnecessary adjunct to intraoperative myocardial protection and an avoidable cause of pulmonary morbidity in patients with coronary disease receiving blood cardioplegia. The hospital records of 150 nonrandomized consecutive patients undergoing elective and emergency isolated coronary revascularization were reviewed. All patients received multidose cold blood cardioplegia followed by warm blood cardioplegic reperfusion distributed through grafts. Fifty patients received iced slush, 50 received topical 4 degrees C saline, and no topical cooling was used in 50 others. Patients groups were comparable in number of grafts (3.7 versus 3.5 versus 3.5) and crossclamp time (61 versus 62 versus 61 minutes). More emergency operations were performed in the patients receiving no topical hypothermia (12/50 versus 8/50 versus 7/50). Postoperative x-ray films were reviewed by a radiologist who did not know of patient grouping. Postoperative results were comparable in hemodynamics, inotropic requirements (10/50 ice versus 8/50 saline versus 5/50 no cooling), myocardial infarction (1/50 versus 2/50 versus 2/50), and enzymes (aspartate aminotransferase myocardial band creatine kinase). No patient died. Ice topical hypothermia (versus no topical cooling) was associated with more left pleural effusions (25/50 versus 9/50; p less than 0.05), atelectasis (33/50 versus 18/50; p less than 0.05), elevated left hemidiaphragms (13/50 versus 0/50; p less than 0.05), and longer postoperative hospitalization (11.2 versus 8.5 days; p less than 0.05). Topical 4 degrees C saline reduced diaphragmatic elevation and pleural effusion (versus topical ice) but was associated with more atelectasis (34/50 versus 18/50; p less than 0.05) than no topical cooling. These data suggest that routine topical hypothermia is an unnecessary adjunct to blood cardioplegic protection in patients with coronary disease, since supplemental topical cooling does not improve postoperative hemodynamics or reduce inotropic requirements, enzyme release, or prevalence of postoperative myocardial infarction, and it increases pulmonary morbidity, which can be reduced by its avoidance.

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Combined coronary artery bypass grafting and orthotopic liver transplantation was carried out successfully in a 58-year-old man with angina pectoris and end-stage liver disease. To date, only 2 similar cases have been documented worldwide whereby the transplantation was performed either during cardiopulmonary bypass or with femoral-to-axillary venovenous bypass initiated at the termination of cardiopulmonary bypass. In this report we describe our experience with a simplified one-exposure approach for the combined operation using cardiopulmonary bypass in tandem with percutaneous femoral-to-right atrial venovenous bypass.

J Thorac Cardiovasc Surg 1997;114:278-80

Objective: This paper reports our experience of a large series of elephant trunk patients accumulated over 12 years. Background Data: Extensive aneurysms of the ascending/arch and descending thoracic or thoracoabdominal aorta are significant surgical problems that have potential for great morbidity. We adopted a staged approach known as the elephant trunk procedure in 1991, and we have used it with some modifications since that time. Methods: Between February 1991 and December 2003, we performed 1660 operations for ascending/arch or descending thoracic/ thoracoabdominal aortic aneurysms. Of these, 321 operations were performed in 218 patients for extensive aneurysms with the elephant trunk technique. We performed 218 ascending/arch repairs and 103 descending thoracic or thoracoabdominal aortic replacements. Results: In 218 ascending/arch repairs, strokes occurred in 3 of 218 (2.7%) patients, with 1 of 187 (0.5%) in the retrograde cerebral perfusion group and 2 of 31 (6.5%) in the no-retrograde cerebral perfusion group (odds ratio 0.08, P < 0.009). Thirty-day mortality for this group was 19 of 218 (8.7%). Among 199 recovering patients after stage 1 repair, 4 of 199 (2%) died during the 30-day to 6-week interval between stages. After stage 2 repair, 0 of 103 patients experienced immediate neurologic deficit, and 10 of 103 (9.7%) died within 30 days of surgery. Actuarial survival after completed stage 2 was 71% at 5 years. Conclusion: Despite extreme underlying disease, long-term survival is excellent in patients with extensive aneurysms when both stages of repair are completed. To prevent rupture, the second stage should be completed as soon as the patient's condition permits, preferably within 6 weeks.

This article describes the experimental infrastructure and subsequent successful clinical application of a comprehensive cardioplegic strategy that limits intraoperative injury and improves postoperative outcomes in pediatric patients. The infant heart is at high risk of damage from poor protection as a result of preoperative hypertrophy, cyanosis, and ischemia. These factors may also make the immature (pediatric) heart more sensitive to cardioplegic arrest compared with the mature (adult) heart. The preoperative factors of cyanosis and pressure volume overload are discussed, followed by the infrastructure of the strategies of warm induction and reperfusion with substrate enhancements, multidose cardioplegia, and a "modified" integrated approach to allow ischemia only when visualization is needed in pediatric surgeries. The importance of using a blood cardioplegia solution, with reduced calcium, increased magnesium, and low perfusion pressure are also shown. A practical clinical framework based on these experimentally proven principles is then presented to allow the surgeon to apply these strategies clinically. The results of using these principles are depicted in a series of 567 patients, including 93 patients with hypoplastic left heart syndrome. Applications of these concepts should improve the safety of protection of the infant heart and reduce postoperative morbidity and mortality.

ObjectivesTo determine whether controlled reperfusion using conditioned leukodepleted blood can substantially limit cerebral reperfusion injury following prolonged ischemia.MethodsEighteen pigs (25-35 kg) underwent 90 minutes of hypothermic circulatory arrest (19°C) to produce brain ischemia. At the start of rewarming, 10 pigs received uncontrolled reperfusion with unmodified (normal) blood. The other 8 pigs underwent 10 minutes of controlled reperfusion by selectively perfusing both common carotid arteries with blood passed through a CoBRA filter. This filter conditions the blood by removing white blood cells, platelets, and attenuating complement. Two other pigs underwent cooling and rewarming only (controls) without ischemia. Neurologic assessment was done using neurologic deficit scoring (0 = normal, 500 = brain death), and jugular venous samples were obtained for biochemical analysis postreperfusion.ResultsThere were no statistical differences in hemodynamics between groups. At 6 hours postanesthesia, all animals receiving normal blood were substantially neurologically impaired. At 24 hours, they all had abnormal positioning and all but 1 were unable to sit or stand (neurologic score 124 ± 19). In contrast, nonischemic controls and pigs receiving conditioned blood reperfusion showed only minor neurologic deficits at 6 hours, and at 24 hours all were considered normal (neurologic scores 0 and 6 ± 5; P < .005 vs uncontrolled reperfusion). Compared with pigs receiving normal blood reperfusion, oxygen free radical formation (conjugated dienes 1.70 ± 0.03 vs 1.60 ± 0.02 Abs 240 nm; P < .05 vs uncontrolled reperfusion), and endothelin-1 release (2.12 ± 0.09 vs 1.84 ± 0.06 pg/mL; P < .05 vs uncontrolled reperfusion) were also significantly lower in animals receiving conditioned blood.ConclusionsFollowing prolonged cerebral ischemia, reperfusion injury is avoided by delivering conditioned blood, which is devoid of white cells, platelets, and membrane attack complex. These results suggest that this modality is clinically useful in situations where the brain is subjected to prolonged ischemia.

Background Several operative approaches are utilized for the management of anomalous origin of the left coronary artery from the pulmonary artery, each with some limitation. The long-term results of a technique that facilitates direct and tension-free implantation of the anomalous artery to the aorta in all patients are described. Methods From January 1, 1992 through August 30, 2000, 10 consecutive patients with anomalous left coronary artery underwent operation using this technique. It consists of isolating an anterior and posterior transverse segment of pulmonary artery in continuity with the origin of the anomalous coronary artery. The two segments are folded with the orifice of the coronary as its fulcrum, and the edges sutured together to form an extension tube of pulmonary artery tissue. This lengthens the coronary artery and allows direct aortic implantation (posterior to the pulmonary artery) without tension. The pulmonary artery is reconstructed with autologous pericardium, Results Patient age ranged from 3 weeks to 3 years old (median 8 weeks), with 80% of patients less than 11 weeks old. Median weight was 4.6 kg (3.7 to 23 kg). The left ventricle was dilated with an end-diastolic diameter z-value of +1 to +3, and the shortening fraction was markedly reduced to 16% ± 6% (7% to 28%), with 8 of 10 patients having a shortening fraction less than 20%. Mitral regurgitation was severe in 5 patients, moderate in 2 patients, and all patients were in congestive heart failure. After repair there were no hospital deaths. Inotropic support was needed in all patients, but none required mechanical assistance. At a follow-up of 4.3 ± 2.5 years (0.5 to 8.5 years), 9 patients are asymptomatic and 1 patient has intermittent chest pain. All patients (10/10) have echocardiographic documented patency of the reimplanted coronary artery, as well as marked improvement in the left ventricular shortening fraction (37% ± 5%; p > 0.05 versus preoperative) and decrease in the end-diastolic diameter z-value (−1 to +1; p > 0.05 versus preoperative). Mitral regurgitation was absent in 4 patients, mild in 4 patients, and moderate in 2 patients. severe in 1 patient. Four patients have evidence of mild supravalvar pulmonary stenosis (15 to 32 mm Hg), 1992 Conclusions This technique allows a tension-free direct aortic connection in all cases, has a low rate of coronary artery occlusion, and avoids significant pulmonary artery distortion or stenosis, making it an excellent alternative for the surgical management of anomalous origin of the coronary artery.

Thoracoabdominal aortic graft replacement has been plagued with the risk of postoperative neurologic deficits (paraplegia and paraparesis) since its inception. Before the early 1980s, the introduction of many surgical adjuncts aimed at spinal cord protection produced confusing results due to the lack of standardization in reporting criteria. The development of a meaningful system of aneurysm classification1 revealed that aneurysm extent has a significant influence in neurologic outcome (Fig. 1). Aneurysm classification also helped us to better analyze the success or failure of adjuncts. The simple cross-clamp technique was the mainstay of descending and thoracoabdominal aortic repair well into the 1980s, and the immediate survival rates and long-term results of that era were impressive. However, during that time, the rate of neurologic deficits, especially for extent II thoracoabdominal aortic aneurysm (TAAA), was persistently high. Neurologic deficits were clearly related to the duration of clamp time, aneurysm extent, rupture, patient age, proximal aortic aneurysm, and renal failure. FIGURE 1. Normal thoracoabdominal aorta and aneurysm classification. Extent I, distal to the left subclavian artery to above the renal arteries. Extent II, distal to the left subclavian artery to below the renal arteries. Extent III, from the sixth intercostal ... In the last decade an abundance of adjuncts—regional or systemic cooling, cerebrospinal fluid (CSF) drainage delivered independently, intraoperatively or postoperatively, distal aortic perfusion, also delivered independently, medications, spinal cooling, and monitoring somatosensory-evoked potentials—have met with varying degrees of success.2-9 Among this array of adjuncts, following the results of both animal and clinical studies, we became particularly interested in the use of combined CSF drainage and distal aortic perfusion. We have successfully used perioperative CSF drainage with distal aortic perfusion for the past 10 years. We have found that moderate passive hypothermia, active visceral cooling with blood or crystalloid solution, and aggressive intercostal artery reattachment further augment the success of these adjuncts. This report describes the progress of our experience with adjuncts and the way that preoperative and postoperative factors influence their success in descending thoracic and thoracoabdominal aortic repair.

Objective: We sought to determine whether damage after deep hypothermic circulatory arrest can be diminished by changing pump prime components when reinstituting cardiopulmonary bypass. Methods: Fifteen piglets (2-3 months old) were cooled to 19°C by using the alpha-stat pH strategy. Five were cooled and rewarmed without ischemia (control animals), and the other 10 piglets underwent 90 minutes of deep hypothermic circulatory arrest. Of these, 5 were rewarmed and reperfused without altering the cardiopulmonary bypass circuit blood prime. In the other 5 animals, the bypass blood prime was modified (leukocyte depleted, hypocalcemic, hypermagnesemic, pH-stat, normoxic, mannitol, and an Na+/H+ exchange inhibitor) during circulatory arrest before starting warm reperfusion. Oxidant injury was assessed on the basis of conjugated dienes, vascular changes on the basis of endothelin levels, myocardial function on the basis of cardiac output and dopamine need, lung injury on the basis of pulmonary vascular resistance and oxygenation, and cellular damage on the basis of release of creatine kinase and aspartate aminotransferase. Neurologic assessment (score 0, normal; score 500, brain death) was done 6 hours after discontinuing cardiopulmonary bypass. Results: Compared with animals undergoing cardiopulmonary bypass without ischemia (control animals), deep hypothermic circulatory arrest without modification of the reperfusate produced an oxidant injury (conjugated dienes increased 0.78 vs 1.71 absorbance (Abs) 240 nmol/L per 0.5 mL, P

Background . There is still no perfect conduit for reconstruction of the right ventricular outflow tract (RVOT) in children. Homografts are not always available in the appropriate size, and degenerate in a few years. This study evaluates the pericardial valve with Gore-Tex conduit as an alternative for RVOT construction. Methods . From January 1, 1993, to September 30, 1999, a pericardial tissue valve was inserted in all patients undergoing RVOT reconstruction or pulmonary valve replacement (PVR) who were large enough to accommodate a tissue valve. In patients without a native main pulmonary artery, a new technique was used to construct an RV-PA conduit out of a flat sheet of Gore-Tex, as Dacron frequently leads to stenosis. Data were collected by retrospective review, follow-up echocardiograms, and assessment by a single cardiologist. Results . There were 48 patients, 22 undergoing a PVR alone and 26 a RV-PA valved Gore-Tex conduit. Diagnosis included tetralogy of Fallot (n = 25); truncus arteriosis (n = 9); ventricular septal defect with PA (n = 5); DORV (n = 4); D-TGA with PS (n = 2); and 1 each IAA with sub AS, VSD with PI, and PS s/p Ross procedure. Patient age ranged from 3 to 33 years and 98% were reoperations. The valve sizes ranged from 19 to 33 mm and the median hospital length of stay was 4 days. There were 2 (4.2%) perioperative and 1 (2.1%) late deaths, none related to the valve or Gore-Tex conduit. At a follow-up of 15 to 86 months (mean 43 ± 16 months), all remaining 45 patients are New York Heart Association class I, all valves are functional, and no patient has required valve or conduit replacement or revision; more importantly, echocardiogram revealed no significant valve or conduit stenosis (mean gradient 16 ± 8 mm Hg) and no evidence of regurgitation or structural degeneration. Conclusions . A pericardial tissue valve and Gore-Tex conduit provides a reliable alternative for RVOT reconstruction in pediatric patients. It is readily available, molds in the limited retrosternal space, and has outstanding intermediate results with no evidence of failure or deterioration up to 7 years after insertion.

Background . Anatomic repair of congenitally corrected transposition of the great arteries has several advantages over the traditional approach but lacks long-term evaluation. Methods . The data on 12 patients who had the procedure between January 1989 and June 2000 were retrospectively reviewed. Associated lesions included ventricular septal defect in 12 patients, pulmonary stenosis in 10 patients, and moderate to severe tricuspid valve regurgitation in 4 patients. Mean age at operation was 9 ± 3.6 months. All patients had venous switch Mustard procedure. Tunneling of the morphologic left ventricle through the ventricular septal defect to the aorta with insertion of right ventricular to pulmonary artery conduit was performed in 10 patients, and arterial switch operation in 2. Concomitant tricuspid valvuloplasty was done in 2 patients and ventricular septal defect enlargement in 1. Results . There was one hospital death (9%) in the patient who needed ventricular septal defect enlargement. Complications included atrioventricular block requiring pacemaker insertion in 1 patient (9%) and superior vena caval obstruction in 1 patient (9%). Follow-up is available on all patients 0.5 to 10 years (mean, 7.6 ± 3.1 years). All patients are asymptomatic. Exercise test results on the three oldest patients were normal. Bradytachyarrhythmias developed in 4 patients (36%). Right ventricular to pulmonary artery conduit replacement was needed in 5 patients 2.2 to 7.1 years (mean 5.2 ± 3.6 years) postoperatively. Mild to moderate tricuspid valve regurgitation persisted in 2 patients. Systemic left ventricular fractional shortening was 36% to 47% (mean, 39% ± 4.6%), and ejection fraction was 49% to 70% (mean, 60.8% ± 7.9%). Conclusions . The double switch operation can be performed safely with minimal intermediate and long-term complications.

This study was undertaken to compare conventional cardioplegic strategies with a new approach that uses a modified non-potassium maintenance solution between cardioplegia doses in stressed neonatal hearts.Thirty-five neonatal piglets underwent 60 minutes of ventilator hypoxia (inspired oxygen fraction 8%-10%) followed by 20 minutes of ischemia on cardiopulmonary bypass. In 10 animals bypass was discontinued without further ischemia (stress control group). The other 25 received a warm blood cardioplegic induction and were separated into 5 groups. In 5 animals cardiopulmonary bypass was discontinued without further ischemia (cardioplegia control group); the remaining 20 underwent an additional 70 minutes of cold blood cardioplegic arrest. Five received only intermittent cardioplegia every 20 minutes, whereas 15 also received cold blood maintenance infusions between cardioplegic doses (integrated strategy). In 5 of these animals the blood was unmodified, whereas in 10 a modified non-potassium "cardioplegia-like" solution was delivered either antegradely (n = 5) or retrogradely (n = 5). Myocardial function was assessed by pressure-volume loops (expressed as percentage of control); vascular function was assessed by coronary vascular resistance.All piglets that underwent hypoxic ischemic stress alone (controls) died. Warm induction alone (cardioplegic controls) partially repaired the stress injury. Intermittent cardioplegia preserved the depressed systolic function (end-systolic elastance 40% vs 39%), increased diastolic stiffness (255% vs 239%), reduced adenosine triphosphate (10.6 vs 12.2 microg/g tissue), and elevated coronary vascular resistance at levels identical to warm induction alone; infusing unmodified blood between cardioplegia doses (standard integrated) improved results slightly. In contrast, infusion of a cold modified solution (antegrade or retrograde) between cardioplegia doses (modified integrated) completely restored systolic function (end-systolic elastance 100% and 97%, P.001 vs intermittent and standard integrated), only minimally increased diastolic stiffness (159% and 156%, P.001 vs intermittent and standard integrated), restored adenosine triphosphate (18.8 and 16.6 microg/g, P.001 vs intermittent and standard integrated), and normalized coronary vascular resistance (P.001 vs intermittent and standard integrated). This strategy was used in 72 consecutive hypoxic patients (21 arterial switch operations, retrograde; 51 Fontan procedures, antegrade) with a 2.8% mortality.Infusion of a cold modified solution between cardioplegic doses (modified integrated protection) significantly improved myocardial protection in the stressed neonatal heart, was effective delivered either antegradely or retrogradely, and was used successfully for hypoxic (stressed) pediatric patients.

This article describes the experimental infrastructure and subsequent successful clinical application of a comprehensive bypass and cardioplegic strategy that limits intraoperative injury and improves postoperative outcomes in pediatric patients. The infant heart is at high risk of damage from poor protection because of preoperative hypertrophy, cyanosis, and ischemia. The background factors of vulnerability to damage caused by cyanosis and ischemia are discussed, together with studies of the infrastructure of strategies to use normoxia versus hyperoxia as bypass starts, white blood cell filtration, warm induction and reperfusion with substrate enhancements, multidose blood cardioplegia, and an integrated approach to allow ischemia only when vision is needed in pediatric surgeries. Data on cardioplegic management, including reducing calcium, increasing magnesium, and reducing perfusion pressure are shown, as used during this technique. These principles were applied to a consecutive series of 567 patients at the Heart Institute for Children and University of Illinois hospital over a 2-year period. Included also were 72 patients with hypoplastic left heart over a 4-year period with this myocardial management strategy. Application of these concepts may improve the safety of protection in infant hearts.

In adult cardiac operations, a warm cardioplegic reperfusate ("hot shot") before removing the aortic cross-clamp improves postbypass myocardial function and metabolic recovery. This modality, however, is rarely used in infants, despite the fact that postbypass cardiac dysfunction remains problematic, especially in cyanotic ("stressed") patients.To produce stress, 15 neonatal piglets underwent 60 minutes of ventilator hypoxia (fraction of inspired oxygen, 8% to 10%). All piglets then received similar protection with multidose cold blood cardioplegic solution during 70 minutes of arrest and were separated into three groups to examine the role of a warm reperfusate as well as possible augmentation by aspartate and glutamate enrichment. In 5 piglets (group 1), the cross-clamp was simply removed; in 5 (group 2), an unsupplemented warm blood cardioplegic reperfusate was given; and in 5 (group 3), the warm reperfusate was enriched with aspartate and glutamate. Myocardial function was assessed using pressure-volume loops and expressed as a percentage of control.Compared with hearts receiving reperfusion with unmodified blood (group 1), a warm unsupplemented cardioplegic reperfusate (group 2) slightly improved systolic contractility (end-systolic elastance, 41% versus 50%; p0.05 versus group 1) and preload recruitable stroke work (41% versus 52%; p0.05 versus group 1), reduced diastolic stiffness (263% versus 245%; p0.05 versus group 1), and increased adenosine triphosphate (10.7 versus 11.9 microg/g tissue, p0.05 versus group 1). However, if aspartate and glutamate was included in the warm reperfusate (group 3), there was complete recovery of systolic function (end-systolic elastance, 105%+/-3%; p0.001 versus all groups) and preload recruitable stroke work (103%+/-2%; p0.001 versus all groups), a minimal rise in diastolic stiffness (154%+/-7%; p0.001 versus all groups), and preservation of adenosine triphosphate (15.5+/-0.5 microg/g; p0.001 versus all groups).A warm cardioplegic reperfusate helps reduce the reperfusion injury, resulting in improved myocardial function and metabolic recovery in hypoxic (stressed) neonatal hearts, and this effect is maximized if the reperfusate is enriched with aspartate and glutamate, which completely preserves myocardial function.

We have shown that magnesium can offset the detrimental effects of normocalcemic cardioplegia in hypoxic neonatal hearts. It is not known, however, whether magnesium offers any additional benefit when used in conjunction with hypocalcemic cardioplegia.Twenty neonatal piglets underwent 60 minutes of ventilator hypoxia (FiO2 8% to 10%) followed by 20 minutes of normothermic ischemia on cardiopulmonary bypass (hypoxic-ischemic stress). They then underwent 70 minutes of multidose blood cardioplegic arrest. Five (Group 1), received a hypocalcemic (Ca+2 0.2 to 0.4 mM/L) cardiologic solution without magnesium, whereas in 10, magnesium was added at either a low dose (5 to 6 mEq/L, Group 2) or high dose (10 to 12 mEq/L, Group 3). In the last 5 (Group 4), magnesium (10 to 12 mEq/L) was added to a normocalcemic cardioplegic solution. Function was assessed using pressure volume loops and expressed as percentage of control.Compared to hypocalcemia cardioplegic solution without magnesium (Group 1), both high- and low-dose magnesium enrichment (Groups 2 and 3) improved myocardial protection resulting in complete return of systolic (40% vs 101% vs 102%) (p0.001 vs Groups 2 and 3) and global myocardial function (39% vs 102% vs 101%) (p0.001 vs Groups 2 and 3), and reduced diastolic stiffness (267% vs 158% vs 154%) (p0.001 vs Groups 2 and 3). Conversely, even high-dose magnesium supplementation could not offset the detrimental effects of normocalcemic cardioplegia resulting in depressed systolic (End Systolic Elastance [EES] 41%+/-1%) (p0.001 vs Groups 2 and 3) and global myocardial function (40%+/-1%) (p0.001 vs Groups 2 and 3), and a marked rise in diastolic stiffness (258%+/-5%) (p0.001 vs Groups 2 and 3). Hypocalcemic magnesium cardioplegia has now been used successfully in 247 adult and pediatric patients.Magnesium enrichment of hypocalcemic cardioplegic solutions improves myocardial protection resulting in complete functional preservation. However, magnesium cannot prevent the detrimental effects of normocalcemic cardioplegia when the heart is severely stressed. This study, therefore, strongly supports using both a hypocalcemic cardioplegic solution and magnesium supplementation as their benefits are additive.

Cardioplegia infusion pressure is usually not directly monitored during neonatal heart operations. We hypothesize that the immature newborn heart may be damaged by even moderate elevation of cardioplegic infusion pressure, which in the absence of direct aortic monitoring may occur without the surgeon's knowledge.Twenty neonatal piglets received cardiopulmonary bypass and the heart was protected for 70 minutes with multidose blood cardioplegia infused at an aortic root pressure of 30 to 50 mm Hg (low pressure) or 80 to 100 mm Hg (high pressure). Group 1 (n = 5, low pressure), and group 2 (n = 5, high pressure) were uninjured (nonhypoxic) hearts. Group 3 (n = 5, low pressure) and group 4 (n = 5, high pressure) first underwent 60 minutes of ventilator hypoxia (FiO2 8% to 10%) before initiating cardiopulmonary bypass to produce a clinically relevant hypoxic stress before cardiac arrest. Function was assessed using pressure volume loops (expressed as a percentage of control), and coronary vascular resistance was measured with each cardioplegic infusion.In nonhypoxic (uninjured) hearts (groups 1 and 2) cardioplegic infusion pressure did not significantly affect systolic function (end systolic elastance, 104% versus 96%), preload recruitable stroke work (102% versus 96%) diastolic compliance (152% versus 156%), or coronary vascular resistance but did raise myocardial water (78.9% versus 80.1%; p0.01). Conversely, if the cardioplegic solution was infused at even a slightly higher pressure in hypoxic hearts (group 4), there was deterioration of systolic function (end systolic elastance, 28% versus 106%) (p0.001) and preload recruitable stroke work (31% versus 103%; p0.001), rise in diastolic stiffness (274% versus 153%; p0.001), greater myocardial edema (80.5% versus 79.6%), and marked increase in coronary vascular resistance (p0.001) compared to hypoxic hearts given cardioplegia at low infusion pressures (group 3), which preserved function.Hypoxic neonatal hearts are very sensitive to cardioplegic infusion pressures, such that even moderate elevations cause significant damage resulting in myocardial depression and vascular dysfunction. This damage is avoided by using low infusion pressures. Because small differences in infusion pressure may be difficult to determine without a direct aortic measurement, we believe it is imperative that surgeons directly monitor cardioplegia infusion pressure, especially in cyanotic patients.

Objectives: Blood cardioplegia predominates in the adult because it provides superior myocardial protection, especially in the ischemically stressed heart. However, the superiority of blood over crystalloid cardioplegia in the pediatric population is unproved. Furthermore, because many pediatric hearts undergo a preoperative stress such as hypoxia, it is important to compare the different methods of protection in both normal and hypoxic hearts. Methods: Twenty neonatal piglets were supported by cardiopulmonary bypass and subjected to 70 minutes of cardioplegic arrest. Of 10 nonhypoxic hearts, five (group 1) were protected with blood cardioplegia and five (group 2) with crystalloid cardioplegia (St. Thomas' Hospital solution). Ten other piglets underwent 60 minutes of ventilator hypoxia (inspired oxygen concentration 8% to 10%) before cardioplegic arrest. Five (group 3) were then protected with blood cardioplegia and the other five (group 4) with crystalloid cardioplegia. Myocardial function was assessed by means of pressure volume loops and expressed as a percentage of control. Coronary vascular resistance was measured with each infusion of cardioplegic solution. Results: No difference waas noted between blood (group 1) or crystalloid cardioplegia (group 2) in nonhypoxic hearts regarding systolic function (end-systolic elastance 104% vs 103%), diastolic stiffness (156% vs 159%), preload recruitable stroke work (102% vs 101%), or myocardial tissue edema (78.9% vs 78.9%). Conversely, in hearts subjected to a hypoxic stress, blood cardioplegia (group 3) provided better protection than crystalloid cardioplegia (group 4) by preserving systolic function (end-systolic elastance 106% vs 40%; p < 0.05) and preload recruitable stroke work (103% vs 40%; p < 0.05); reducing diastolic stiffness (153% vs 240%; p < 0.05) and myocardial tissue edema (79.6% vs 80.1%); and preserving vascular function, as evidenced by unaltered coronary vascular resistance (p < 0.05). Conclusion: This study demonstrates that (1) blood or crystalloid cardioplegia is cardioprotective in hearts not compromised by preoperative hypoxia and (2) blood cardioplegia is superior to crystalloid cardioplegia in hearts subjected to the preoperative stress of acute hypoxia. (J Thorac Cardiovasc Surg 1997;113:994-1005)

Background. Traditionally, most surgeons have taken adversarial positions with respect to whether cardioplegia should be given warm or cold, antegrade or retrograde, continuous or intermittent. Because each method has weaknesses, myocardial protection is compromised when only one method is employed. It is our contention that an "integrated" approach that combines all of the aforementioned principles will improve myocardial protection, allowing the time needed for complex valve repairs. Methods. Thirty-four patients (25 undergoing complex mitral valve repairs and 9 undergoing Ross procedures) have undergone complex valve repair since we began using an integrated cardioplegic strategy that incorporates all of the techniques mentioned above and is based on the following principles: (1) Cardioplegia is infused antegrade and retrograde, warm and cold. (2) Surgical precision is optimized by a dry, bloodless field using cold intermittent arrest to limit ischemia when visualization is needed. (3) Continuous blood cardioplegia is used when visualization is not problematic, thereby avoiding unnecessary ischemia. Results. Average age was 46 ± 4 years (range, 9 to 79 years), and 9 patients (26%) were having reoperations. All mitral patients had severe mitral regurgitation, 52% (13/25) had a preoperative ejection fraction less than 0.40, and 40% (10/25) had pulmonary artery pressures greater than 60 mm Hg. In the Ross patients 33% (3/9) had an ejection fraction less than 0.40, including 2 patients who concomitantly underwent complex mitral valve repair. Despite cross-clamp times of 187 ± 12 minutes (range, 138 to 267 minutes) in the Ross group and 139 ± 8 minutes (range, 92 to 218 minutes) in the complex mitral valve repair group with a predicted mortality (Parsonnet) of approximately 10%, no patients died, only 5 (15%) required inotropes, none required intraaortic balloon pumping, only 1 (3%) required antiarrhythmics, and the average postoperative hospital stay was 8 days in the mitral repair group and 5 days in the Ross group. Conclusions. We believe an integrated approach incorporating the strategies of warm and cold blood cardioplegia, antegrade and retrograde delivery, and continuous and intermittent infusion affords better myocardial protection, avoids unnecessary ischemia, facilitates technical ease of operation, and results in a more stable postoperative course. Integrating these modalities into a comprehensive strategy (instead of relying on one) maximizes each method's strength while minimizing weaknesses, thereby allowing surgeons to perform complex valve repairs safely in all patients.