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Study Objective: This study was designed to evaluate the use of retrograde cerebral perfusion (RCP) combined with deep hypothermic circulatory arrest (DHCA) in the treatment of complex congenital and adult cardiac disease., Design: Retrospective chart review of 52 cardiac surgery patients (34 male and 18 female; age range, 3 weeks to 89 years old; mean age, 60 years old) who received RCP in conjunction with DHCA from July 1991 through August 1998., Results: Surgical procedures consisted of the following: (1) repair of ascending aortic aneurysms (n = 16); (2) repair of type A aortic dissection (n = 16); (3) repair of arch aneurysms (n = 10); (4) renal cell carcinoma with tumor extension to the inferior vena cava (IVC) and right atrium (n = 5); (6) coronary artery bypass grafting and concomitant aortic valve replacement with calcified aorta (n = 2); (7) Norwood procedure and take down of a Pott's shunt (n = 2); and (8) massive air embolism treatment (n = 1). Mean RCP time was 39 min (range, 3 to 88 min). Thirteen patients had RCP times > 60 min. Mean core temperature (rectal or bladder) was 19 degrees C (range, 15 degrees to 28 degrees C). There were six early deaths, four of which were related to persistent low-output cardiac failure, and two resulted from perioperative stroke. All remaining patients recovered fully without neurologic deficits., Conclusion: RCP is a reliable and technically appealing tool that does the following: (1) it improves DHCA safety and is applicable in a variety of clinical settings with relative ease; (2) it potentially provides oxygen and nutritional support to the brain during DHCA; (3) it helps remove air and other debris from the cerebral vessels; and (4) it is useful in dealing with congenital heart disease and tumor extension into the IVC.

Background: The maximum degree of microvascular distribution of cardioplegic solution is considered important to achieve optimum myocardial protection. This study attempts to demonstrate that the addition of retrograde cardioplegia to antegrade cardioplegia improves overall microvascular perfusion., Methods: Explanted human hearts (n = 6) were treated with cold cardioplegic arrest and bicaval cardiectomy. Blood cardioplegia (37 degrees C) containing colored microspheres (color A for antegrade, color B for retrograde) was simultaneously infused antegrade at a pressure of 80 mm Hg and retrograde at a pressure of 40 mm Hg for 2 minutes. The ventricular myocardium was then sampled at three sites to determine absolute and relative cardioplegic microvascular flow., Results: Of the total microvascular capillary flow, 27% to 32% was found to be the contribution of retrogradely delivered cardioplegia., Conclusions: Despite being delivered simultaneously and at a lower pressure, retrograde cardioplegia contributed substantially to overall microvascular perfusion. This suggests that antegrade cardioplegia alone does not perfuse all available myocardial capillaries and that the addition of retrograde cardioplegia enhances overall microvascular distribution and perfusion.

Unlabelled: Commercially available cardioplegia delivery systems now allow for antegrade (aortic root, coronary ostia, saphenous vein graft) perfusion to occur either sequentially or simultaneous with retrograde (coronary sinus) perfusion. This study was designed to compare the total flow and local distribution of sequential versus simultaneous antegrade/retrograde cardioplegia delivery., Methods: Explanted human hearts diagnosed with idiopathic cardiomyopathy underwent a cold cardioplegic arrest and bicaval cardiectomy. Thirty-seven degree centigrade blood cardioplegia containing colored microspheres was then delivered antegrade (red color) at a pressure of 80 mmHg or retrograde (blue color) at a pressure of 40 mmHg. In the sequential group (n = 6), cardioplegia was delivered antegrade and then retrograde for 2 minutes, respectively. For the simultaneous group (n = 6), cardioplegia was delivered both antegrade and retrograde for 2 minutes. The ventricular myocardium was then sampled at 12 representative sites to determine regional cardioplegic flow., Results: Mean total cardioplegia delivery/minute was 0.69 +/- 0.62 mL/g per minute for sequential cardioplegia, and 0.46 +/- 0.19 mL/g per minute for simultaneous cardioplegia (p > 0.05, NS). At the 12 ventricular sites sampled, mean regional cardioplegic flow (mL/g per min) was in general slightly greater for sequential delivery. However, this was not statistically significant (p > 0.05, NS)., Conclusion: The data suggest that there may be a slight advantage in total cardioplegia delivery and regional cardioplegia delivery when using sequential rather than simultaneous cardioplegia delivery. However, this difference was not statistically significant and is likely not of clinical significance. Therefore, we would recommend using either sequential or simultaneous antegrade/retrograde cardioplegia based upon whichever technique facilitates the conduct of the individual operation.

Background: The complete and uniform distribution of cardioplegia to the microvasculature of the heart is considered critical for myocardial protection. This study explores the hypothesis that enhanced microvascular perfusion can be achieved by using both antegrade and retrograde cardioplegia., Methods: Infant piglet hearts (n = 15) were arrested with antegrade blood cardioplegia, excised, and fixed with 2.5% glutaraldehyde by retrograde perfusion. Hearts were then perfused retrograde with an inert intracapillary marker (NTB-2). Six of these hearts served as controls (group 1) to anatomically demonstrate the degree of capillary perfusion achieved by the retrograde delivery route. Nine experimental hearts (group 2) underwent a subsequent infusion of antegrade blood cardioplegia to wash out NTB-2 capillaries coperfused by both the antegrade and retrograde delivery techniques. Sections of the left ventricular free wall and anterior-mid interventricular septum were taken and examined by light microscopy at four separate sites (average, 126 capillaries per section)., Results: In control hearts, 91.9% +/- 0.9% of ventricular capillaries and 91.4% +/- 5.8% of septal capillaries were perfused by retrograde cardioplegia. After antegrade blood cardioplegia washed out group 2 hearts, 14.0% +/- 4.1% of capillaries in the ventricle still contained NTB-2, as did 12.5% +/- 5.4% of capillaries in the septum., Conclusions: In this experimental model, antegrade blood cardioplegia did not coperfuse (and therefore washout) 12.5% to 14% (p < 0.05) of capillaries perfused by retrograde cardioplegia. This suggests that an additional 12.5% to 14% of capillaries within the myocardium may receive cardioplegia if retrograde cardioplegia is used in addition to antegrade cardioplegia. We conclude that by combining both antegrade and retrograde cardioplegia, there is a potential for enhanced overall microvascular perfusion.

Background: In human hearts, as much as two thirds of retrograde cardioplegia is shunted through thebesian and arteriosinusoidal channels into the ventricular cavities. This ventricular effluent is believed to have bypassed the myocardial capillary beds and is therefore considered nonnutritive., Methods: To test this hypothesis, we studied the explanted hearts from 9 cardiac transplant recipients with the diagnosis of idiopathic cardiomyopathy. These hearts were arrested in situ with cold blood cardioplegia and excised with the coronary sinus intact. The left and right coronary ostia and the coronary sinus then were cannulated. Colored microspheres (15 +/- 5 microns) mixed in 37 degrees C blood cardioplegia were administered through the coronary sinus at a pressure of 30 to 40 mm Hg. Effluents from the coronary arteries and ventricular chambers were collected and analyzed for microsphere concentration., Results: Approximately 80% of retrograde cardioplegia solution was recovered in the ventricular chambers. Nearly 40% of this ventricular chambers effluent had traversed capillary beds and, thus, we believe has nutritive properties. Almost all of the coronary artery effluent of retrograde cardioplegia solution had traversed capillary beds. The total nutritive fraction of retrograde warm blood cardioplegia in this explanted human heart model was approximately 55%., Conclusions: These findings suggest that the ventricular chamber effluent of retrograde blood cardioplegia contributes to the metabolic homeostasis of the arrested human heart.

Warm retrograde blood cardioplegia is frequently used for myocardial protection, despite experimental studies questioning the adequacy of capillary flow to the right ventricle and septum. The capillary distribution of retrograde blood cardioplegia in the human heart is unknown. Hearts from eight transplant recipients with the diagnosis of idiopathic or dilated cardiomyopathy were arrested in situ with cold blood cardioplegia and excised with the coronary sinus intact. Within 20 minutes of explanation, colored microspheres mixed in 37 degrees C blood cardioplegia were administered through the coronary sinus at a pressure of 30 to 40 mm Hg for 2 minutes. Twelve transmural myocardial samples were taken horizontally at the level of midventricle and apex to determine regional capillary flow rates. When retrograde warm blood cardioplegia was administered at a rate of 0.42 +/- 0.06 ml/gm/min, the left ventricle, the septum, the posterior wall of the right ventricle, and the apex consistently received capillary flow rates in excess of their metabolic requirements. The capillary perfusion of anterior and lateral walls of the right ventricle was marginally adequate to sustain aerobic metabolism. In explanted human hearts, retrograde blood cardioplegia provides adequate capillary flow to the left ventricle, the septum, the posterior wall of the right ventricle, and the apex; however, capillary flow to the anterior and lateral walls of the right ventricle is marginal. This study delineates the tenuous balance between supply and demand for right ventricular protection with warm continuous retrograde blood cardioplegia.

Unlabelled: This study documents the gross flow characteristics and capillary distribution of cardioplegic solution delivered retrogradely with the coronary sinus open versus closed., Methods: Five explanted human hearts from transplant recipients were used as experimental models. Hearts served as their own controls and received two doses of warm blood cardioplegic solution, each containing colored microspheres. The first dose was delivered through a retroperfusion catheter with the coronary sinus open and the second dose was delivered with the sinus occluded. Capillary flow was measured at twelve ventricular sites and gross flow was measured by examining coronary sinus regurgitation, thebesian vein drainage, and aortic effluent (nutrient flow)., Results: Coronary sinus ostial occlusion allowed for a significant decrease in total cardioplegic flow (1.74 +/- 0.40 ml/gm versus 1.06 +/- 0.32 ml/gm; p < 0.05) to occur while maintaining an identical intracoronary sinus pressure. Ostial occlusion also resulted in an increase in the ratio of nutrient flow/total cardioplegic flow from 32.3% +/- 15.1% to 61.3% +/- 7.9% (p < 0.05). A statistically significant improvement in capillary flow was found at the midventricular level in the posterior intraventricular septum and posterolateral right ventricular free wall. This improvement was also documented for the intraventricular septum and right ventricle at the level of the apex., Conclusion: Coronary sinus occlusion during retrograde cardioplegia significantly improves cardioplegic delivery to the right ventricle and posterior intraventricular septum. Furthermore, the technique affords a significant improvement in nutrient cardioplegic flow while reducing the overall volume of cardioplegic solution administered.

Amino acid enrichment of cardioplegic solutions has been shown to improve both the metabolic and functional recovery of ischemic myocardium. However, because of the marked systemic vasodilatation involved, use of amino acid enrichment is limited to the periods of induction and reperfusion. Fumarate is a Krebs' cycle intermediate whose conversion to succinate is responsible for the generation of adenosone triphosphate and the oxidation of the reduced form of nicotinamide-adenine nucleotide which is the pathway by which aspartate exerts its effect. Fumarate may also function as a free-radical scavenger and is involved in calcium transport. To determine if fumarate-enriched blood cardioplegia would improve the functional recovery of the neonatal heart, 14 neonatal piglet hearts were isolated and placed on a blood-perfused working heart circuit. After the baseline functional and metabolic assessment was done, cold ischemic arrest was initiated with either standard blood cardioplegic solution (group I; N = 7) or fumarate-enriched (13 mmol/L) blood cardioplegic solution (group II; N = 7). Cardioplegic solution was given at a pressure of 40 mm Hg every 20 minutes for 2 hours, and topical hypothermia was used. Sixty minutes after warm whole blood reperfusion, the functional recovery at left atrial pressures of 3, 6, 9, and 12 mm Hg was 70%, 66%, 66%, and 65%, respectively, in group I, versus 102%, 106%, 105%, and 109%, respectively, in group II (p < 0.05). The tissue creatinine phosphate levels after reperfusion were significantly higher in group II hearts (15.0 +/- 1.2 mumol/g dry heart tissue) than in group I hearts (9.2 +/- 1.9 mumol/g dry heart tissue), although the adenosine triphosphate levels were not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

Unlabelled: The existence of inhomogeneous distribution of coronary flow with antegrade or retrograde perfusion alone has led to alternating between these delivery routes to maximize their individual benefits. Concern over myocardial damage prevented the simultaneous application of antegrade and retrograde cardioplegic blood delivery. Based upon the predominance of retrograde drainage via Thebesian veins, and evidence that pressure-controlled intermittent coronary sinus occlusion during antegrade cardioplegic delivery enhances its distribution and protective properties, this study tests (a) the hypothesis that simultaneous aortic and coronary sinus perfusion is safe during aortic clamping, and (b) reports initial clinical application of this combined strategy in 174 patients. Five minipigs (25-30 kg) underwent 1 hr of aortic clamping with simultaneous aortic (antegrade) and coronary sinus (retrograde) perfusion at 200 ml/min with normal blood (37 degrees C) before and after 30 minutes of perfusion with either warm (37 degrees C) or cold (4 degrees C) blood cardioplegia (BCP). Furthermore, the combined strategy was used in 174 high-risk patients (NYHA class III-IV) at 3 university hospitals to perform myocardial protection during CABG or valve replacement, or a combination of both. Included were 16 patients in cardiogenic shock and 24 undergoing reoperation. In both the clinical and the experimental studies the coronary sinus pressure was always < 40 mmHg in beating or arrested hearts., Experimental: Compared to control values (81.4 +/- 0.4% tissue water content), no right-ventricular (80.8 +/- 0.8%) or left-ventricular (79.5 +/- 0.3%) edema developed, no lactate was produced (control: -1.0 +/- 0.5 mg/100 g/min, empty beating: -0.64 +/- 5, and BCP arrest: -8.6 +/- 6.6).(ABSTRACT TRUNCATED AT 250 WORDS)

University of Wisconsin solution has proved to be a superior form of cardioplegia for cardiac transplantation, demonstrating better functional recovery than that provided by extracellular crystalloid solutions. Furthermore, experimental data have suggested a role for University of Wisconsin solution in protection of the neonatal heart during operations for congenital heart defects. However, significant concerns have been raised regarding potential endothelial injury from the high potassium concentration contained in University of Wisconsin solution that could affect its safety and thus its clinical application. Fourteen neonatal (aged 1 to 3 days) piglet hearts were harvested and supported on an isolated, blood-perfused circuit. Endothelium-dependent vasodilatation was measured by bradykinin (10(-6) mol/L) infusion and nitric oxide release was determined. Endothelium-independent vasodilatation was then induced by sodium nitroprusside (10(-6) mol/L) infusion. A 2-hour period of cold cardioplegic arrest was instituted with multidose University of Wisconsin solution (group 1, n = 7) or blood cardioplegia (group 2, n = 7). After reperfusion and stabilization, another stimulation with bradykinin and nitroprusside was carried out and nitric oxide was again measured. After 2 hours of arrest with University of Wisconsin solution, there was a near-complete loss of vasodilatation in response to bradykinin infusion; coronary blood flow reached 245% of baseline before arrest versus only 117% of baseline after arrest (p = 0.0011). This correlated with an inability of the endothelium to release nitric oxide (96 +/- 30 nmol/min before arrest versus -32 +/- 9 nmol/min after arrest, p = 0.0039. In group 2, the vasodilatory response to bradykinin was preserved after arrest and reperfusion; 265% of baseline before arrest versus 222% of baseline after arrest. These results demonstrate a loss of endothelium-dependent vasodilatation after multidose University of Wisconsin cardioplegia caused by the inability of the endothelium to release nitric oxide. In contrast, blood cardioplegia does not result in impaired endothelial function.

Unlabelled: Concern over myocardial damage from simultaneous arterial (antegrade) and coronary sinus (retrograde) perfusion has led to alternating between these delivery routes to maximize their individual benefits. Based upon predominant retrograde drainage via Thebesian veins, this study: (1) confirms experimentally the safety of simultaneous arterial and coronary sinus perfusion; and (2) reports initial clinical application of this combined strategy in 155 consecutive patients., Experimental: Five mini-pigs (25 to 30 kg) underwent 1 hour of aortic clamping with simultaneous aortic and coronary sinus perfusion at 200 mL/min with normal blood (37 degrees C) before and after 30 minutes of perfusion with either warm (37 degrees C) or cold (4 degrees C) blood cardioplegia. Coronary sinus pressure was always less than 30 mmHg. There was no right or left ventricular edema, lactate production, or lipid peroxidation as transmyocardial and myocardial conjugated dienes were unaltered, and postbypass recovered left ventricular end-systolic elastance (conductance catheter) and preload recruitable stroke work index 101% +/- 3% and 109% +/- 90%, respectively. CLINICAL: Simultaneous arterial/coronary sinus perfusion was used in 155 consecutive high risk patients (New York Heart Association Class III to IV) undergoing isolated coronary artery bypass grafting (CABG) (n = 109) and CABG+valve replacement/repair or aneurysm (n = 46). Included were 16 patients in cardiogenic shock and 24 undergoing reoperation. Mean aortic clamping time averaged 90 +/- 4 minutes (range 30 to 207), with 3.5 +/- 0.1 grafts per patient; all anastomoses were performed with the aorta clamped. Cold intermittent blood cardioplegia was used for distal anastomoses and valve implantation/repair in 123 patients, and warm continuous blood cardioplegia was used in 32 patients. Following a warm cardioplegic reperfusate, all patients received warm noncardioplegic blood perfusion simultaneously via grafts and coronary sinus. Coronary sinus pressure was always less than 40 mmHg. Of 18 patients requiring postoperative mechanical circulatory support (IABP), 16 had IABP placed preoperatively for cardiogenic shock. There were three postoperative myocardial infarctions (2%), and six patients died (3.9% mortality)., Conclusion: These experimental and clinical findings overcome perceived concerns about myocardial damage from simultaneous arterial and coronary sinus perfusion, and suggest this approach may add to the armamentarium of cardioprotective strategies.

In this report, explanted hearts from transplant recipients with the diagnosis of idiopathic cardiomyopathy underwent a blood cardioplegia arrest and extended subatrial resection to preserve their coronary sinus venous system. The coronary sinus and left and right coronary arteries were then cannulated and warm blood cardioplegia retrograde infused at a pressure of 30 to 40 mm Hg. Effluent from the coronary arteries and thebesian veins was then collected. Hearts were subsequently fixed with retrograde glutaraldehyde perfusion and perfused retrograde with NTB-2 (an inert intracapillary marker). Histologic sections were examined from 12 separate sites. There was no significant difference in the percentage of capillaries perfused by retrograde-delivered cardioplegia between corresponding regions of the left and right ventricles. However, effluent analysis indicated that 67.2% +/- 6.4% of retrograde-delivered blood cardioplegia was shunted through thebesian veins, thereby bypassing the microvasculature, whereas 29.3% +/- 6.3% and 3.5% +/- 3.1% traversed the myocardium supplied by the left and right coronary arteries, respectively. The results indicate that all regions of both ventricles are perfused by retrograde blood cardioplegia. However, they also suggest that nutrient flow to the microvasculature of the right ventricle is minimal during retrograde cardioplegia.

The uniform distribution of cardioplegic solution to all areas of the microvasculature is considered critical for myocardial protection. Despite this, little information exists regarding the ability of retrogradely infused cardioplegic solution to perfuse the microvasculature of the heart. In this report, the microvascular distribution of retrogradely delivered cardioplegic solution was studied by means of a technique to quantitatively demonstrate capillary perfusion. Duroc piglet hearts were subjected to either antegrade (n = 4) or retrograde (n = 8) perfusion fixation with 2.5% glutaraldehyde and subsequently perfused with NTB-2 (an intracapillary marker). The results indicate that retrogradely delivered NTB-2 consistently perfused the anterior half of the intraventricular septum and the anterior and lateral free walls of the left ventricle but inconsistently perfused the posterior half of the intraventricular septum, the posterior wall of the left ventricle, and a small paraseptal region of the right ventricle. The remainder of the right ventricle was not perfused. In contradistinction, all regions of the heart were consistently perfused by the antegrade technique. In regions of the heart in which retrograde microvascular perfusion occurred, no statistical difference was found in the quantitative degree of capillary perfusion achieved by either the antegrade or retrograde technique. These results have important implications for planning strategies of myocardial protection and suggest that further investigation concerning the microvascular distribution of retrogradely delivered cardioplegic solution in human beings is merited.

We use warm induction and reperfusion with amino acid enhancement on all neonates and preoperatively stressed patients to induce arrest without contracture and to replete high-energy substrates. Blood cardioplegia is used in all age groups. We then employ hypothermia in the majority of patients (all neonates), ranging from deep (18 degrees C), to moderate (26 degrees to 28 degrees C), with warm or near normothermia used in only simpler anatomic repairs. The clear benefits of hypothermia in conferring additional cardiac and systemic ischemic protection along with the relatively greater ease of cooling and rewarming in the pediatric patient warrant its continued use in the majority of open-heart cases. Calcium levels are maintained in the 0.3 to 0.5 mM/L range during the conduct of the operation and reperfusion phase. Before removal from bypass, calcium is administered through either bolus or continuous drip technique to provide a normocalcemic level of 1 to 1.2 mM/L. This close attention is particularly important in the neonate to avoid contracture injuries and to maximize cardiac function, and is warranted if citrate-phosphate-dextrose (CPD)-containing transfusion or prime components are used. Preoperative evaluation for aortopulmonary collaterals with coil embolization is routinely performed, and is particularly important in single ventricle physiology where preserved myocardial function is so vital to a favorable outcome. The opportunity to perform some surgeries off bypass, such as on the RV outflow tract, may be used whenever it represents a viable alternative in very young or ill patients. Similarly, the majority of Glenn shunts, for example, are performed using a caval-RA shunt without formal cardiopulmonary bypass.(ABSTRACT TRUNCATED AT 250 WORDS)

Reperfusion injury remains a limiting factor in extending ischemic storage time for human heart transplantation. In this study, initial myocardial reperfusion with an oxygenated perfluorochemical (Fluosol) was investigated as a means of limiting such injury. Neonatal piglet hearts were arrested with crystalloid cardioplegia, excised, and stored for 12 hours in saline solution at 0 degrees C. Initial reperfusion (10 minutes) was either with whole blood (n = 6), unmodified perfluorochemical (n = 8), or aspartate/glutamate-enriched perfluorochemical cardioplegia (n = 6), and was followed by an additional 40 minutes of whole blood perfusion. Functional evaluation was then completed, and left ventricular biopsy specimens were taken. A control group (n = 7) was evaluated without an intervening period of ischemia. At a left ventricular end-diastolic pressure of 9 mm Hg, hearts stored in whole blood cardioplegia developed a left-ventricular stroke work index of 3.8 +/- 2.3 x 10(3) erg/g (mean +/- standard error of the mean). Under the same conditions, perfluorochemical-reperfused hearts achieved a stroke work index of 14.6 +/- 1.3 x 10(3) erg/g, significantly greater than that of the whole blood group (p < 0.001). Stroke work index for hearts reperfused with aspartate/glutamate-enriched perfluorochemical cardioplegia was 19.8 +/- 1.6 x 10(3) erg/g, significantly increased over that of the nonenriched perfluorochemical group (p < 0.01) and not different from values obtained in controls (19.2 +/- 0.8 x 10(3) erg/g).(ABSTRACT TRUNCATED AT 250 WORDS)

Although standard blood cardioplegia provides good myocardial protection for cardiac operations in adults, protection of the cyanotic, immature myocardium remains suboptimal. Calcium, which has been implicated in reperfusion injury and in the development of "stone heart" in mature myocardium, is routinely lowered in standard cardioplegic solutions. Immature, neonatal myocardium has lower intracellular calcium stores and is more reliant on extracellular calcium for contraction. To determine if normocalcemic cardioplegia would result in improved cardiac function in the neonatal heart, we conducted a series of experiments using an isolated, blood-perfused working heart model. Thirty-two neonatal piglet hearts (24 to 48 hours) were excised without intervening ischemia and were placed directly on a blood-perfused circuit. Baseline stroke work index was assessed. Hearts were then arrested with cold cardioplegic solution delivered at 45 mm Hg for 2 minutes: group I, low-calcium blood cardioplegic solution (Ca = 0.6 mmol/L); group II, normal-calcium blood cardioplegic solution (Ca = 1.1 mmol/L); group III, University of Wisconsin solution; and group IV, University of Wisconsin solution with added calcium (Ca = 1.0 mmol/L). Cardioplegic solution was administered every 20 minutes for 2 hours and topical hypothermia was used. Hearts were then reperfused with warm whole blood. Functional recovery, expressed as a percentage of control stroke work index, was determined minutes after reperfusion. Hearts preserved with normocalcemic cardioplegic solution (groups II and IV) had complete functional recovery at 60 minutes, whereas hearts preserved with low-calcium cardioplegic solution (groups I and III) achieved functional recoveries of only 80% and 65%, respectively, at a left atrial pressure of 9 mm Hg. Electron micrographs taken 1 hour after reperfusion showed minimal edema and only mild myofibrillar changes. They were identical in both the low-calcium and normocalcemic groups. Complete functional recovery is possible in immature myocardium when calcium is added to either blood or an intracellular crystalloid cardioplegic solution. The addition of calcium does not result in ultrastructural damage and does result in good functional recovery.

Blood cardioplegia is considered by many to be the preferred solution for myocardial protection. Proposed benefits include the ability to deliver oxygen and the ability to maintain metabolic substrate stores. However, the decreased capacity of blood to release oxygen at hypothermic conditions as well as the presence of deleterious leukocytes, platelets, and complement may limit complete functional recovery. Fluosol is an asanguineous solution with the ability to bind and release oxygen linearly at low temperatures. Neonatal piglet hearts (24 to 48 hours old) were excised and supported on an isolated, blood-perfused working heart model. After baseline stroke-work index was determined, hearts were arrested with either normocalcemic blood cardioplegia (group 1, n = 8) or normocalcemic Fluosol cardioplegia (group 2, n = 8). Cold cardioplegia was administered at 45 mm Hg every 20 minutes for 2 hours. Hearts were then reperfused with whole blood. Functional recovery, expressed as percent of control stroke-work index, was determined 60 minutes after reperfusion at left atrial pressures of 3, 6, 9, and 12 mm Hg. Functional recovery at 60 minutes was similar between group 1 (95%, 93%, 93%, 88%) and group 2 (100%, 94%, 94%, 95%) at left atrial pressures of 3, 6, 9, and 12 mm Hg, respectively. Mean lactate consumption 5 minutes after reperfusion was significantly greater (p = 0.0001) in group 1 (31.8 +/- 6.3 micrograms.min-1 x g-1) than in group 2 (-0.59 +/- 0.1 microgram.min-1 x g-1), indicating superior metabolic recovery in the blood cardioplegia hearts. Edema formation, as determined both by water content (group 1, 81.10%; group 2, 81.63%) and by electron microscopy, was not significantly different between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

The benefits of combined antegrade-retrograde infusion of blood cardioplegic solution are becoming well known in adult coronary and valvular heart operations. Many of these advantages relate directly to the pediatric patient. They include prompt arrest and even distribution, particularly with aortic insufficiency or open aortic root, avoiding or limiting ostial cannulation, allowing uninterrupted surgical procedures, and flushing air/debris from the coronary arteries. We therefore report on the first 123 pediatric patients at the University of California, Los Angeles, to receive myocardial protection with antegrade (aortic) infusion in conjunction with retrograde (coronary sinus) infusion of blood cardioplegic solution. We employed a retroplegia catheter with a self-inflating and deflating occlusion balloon on the tip of a pressure-monitored infusion cannula that remains in the coronary sinus during the operation. Induction blood cardioplegic solution, 30 ml/kg in equally divided doses, is administered in the coronary sinus first antegrade at an aortic pressure less than 80 mm Hg, followed by retrograde infusion at less than 40 mm Hg. Maintenance cardioplegic solution (15 ml/kg) is administered every 20 minutes through one or both of the infusion cannulas, depending on the surgical procedure. Patients' ages ranged from 1 week to 16 years with a mean of 4.6 years. The following procedures were included in descending order: Fontan 20, atrioventricular valve repair/replacement (and complete atrioventricular canal) 16, aortic root/Konno/Ross 16, Rastelli 13, aortic valve repair/replacement 13, ventricular septal defect (and double-outlet right ventricle) 13, tetralogy of Fallot 10, coronary artery reimplantation/fistula repair 6, truncus arteriosus 4, arterial switch 3, bidirectional Glenn 2, sinus venosus 2, and aortopulmonary window, Senning, Stansel, interrupted aortic arch, and Ebstein's, 1 each. Aortic crossclamp times ranged from 6 to 219 minutes with a mean of 87 minutes. Myocardial oxygen consumption data for a series of six patients indicated the supplemental benefit for retrograde infusion of cardioplegic solution along with antegrade infusion, particularly in hypertrophied myocardium. Three deaths occurred (2.4% 30-day mortality), in the following patients: the first with truncus arteriosus and interrupted aortic arch, the second with complete atrioventricular canal and pulmonary hypertension, and the third with truncal valve regurgitation and replacement. There were no complications related to the retroplegia catheter. From this initial positive experience, we conclude that (1) combined antegrade-retrograde infusion of blood cardioplegic solution can be safely used in an expanding number of pediatric heart operations in all age groups, and (2) combined antegrade-retrograde infusion of blood cardioplegic solution may provide additional myocardial protection, with excellent surgical outcome, in complex congenital heart repairs.

The effect of pH regulation on the function of the isolated neonatal heart during continuous hypothermic perfusion and arrest was tested in 3- to 6-day-old piglet hearts. Three groups of hearts were perfused from an adult support pig, with pH varied by a carbon dioxide/oxygen gas exchanger and temperature controlled by a heat exchanger. After control function studies were obtained at normothermia with a pH of 7.4, the hearts were cooled over 15 minutes to 10 degrees C. Hypothermic perfusion was maintained for 1 hour, followed by rewarming to 37 degrees C. In group 1 (n = 5), the alpha stat (neutral) model, the blood perfusate was maintained at a pH of 7.4 (calculated at 37 degrees C). In group 2, the alkaline model, the pH was maintained at 7.9, and in group 3, the pH-stat (acid) model, the pH was maintained at 7.0. In addition, the effect of 1 hour of hypothermic ischemia after hypothermic perfusion at a pH of 7.0 was evaluated in five hearts (group 4). After rewarming no significant difference was noted in functional recovery (group 1 = 93% +/- 5%, group 2 = 92% +/- 6%, group 3 = 96% +/- 5%, and group 4 = 95% +/- 2%), oxygen consumption, coronary resistance, lactate extraction, and myocardial extravascular water content. We conclude that neonatal heart function is resistant within the range of this study to changes in pH caused by changes in carbon dioxide tension during hypothermic perfusion and ischemia.

We report our initial experience with antegrade/retrograde cardioplegia using a self-inflating/deflating balloon cannula that allows rapid transatrial retrograde cannulation of the coronary sinus (10 to 15 seconds) without right heart isolation and permits routine single venous cannulation. We subjected 141 consecutive adult patients and nine children to antegrade/retrograde cardioplegia using rapid transatrial insertion of the Retroplegia cannula (Research Medical, Inc., Salt Lake City, Utah). Single venous cannulation was used in 116 patients having coronary artery bypass grafting or aortic valve replacement, or both. Initial antegrade blood cardioplegia caused immediate arrest (less than 1 minute) and the cardioplegic dose was divided equally between antegrade and retrograde delivery. Included are 95 patients having isolated bypass grafting (34 with extending infarction, cardiogenic shock, or ejection fraction less than 20%); 19 having coronary reoperations, 42 with aortic or mitral valve procedures, or both; and nine children having repair of congenital defects (e.g., repair of ventricular septal defect, Rastelli operation, Konno operation). Septal temperature in patients with occlusion of the left anterior descending coronary artery fell to 11.5 degrees +/- 0.5 degrees C after retrograde cardioplegia versus only 16 degrees +/- 3 degrees C after antegrade cardioplegia (p less than 0.05). The overall hospital mortality rate was 2% and no complications followed transatrial retrograde cannulation of the coronary sinus.

We report our updated experience with combined antegrade/retrograde cardioplegia using a self-inflating/deflating balloon cannula that allows rapid transatrial retrograde coronary sinus cannulation (10-15 s) without right heart isolation. This permits routine single venous cannulation and optimizes myocardial protection when combined with antegrade cardioplegia. Two hundred fifty-five consecutive patients underwent antegrade/retrograde cardioplegia. Initial antegrade blood cardioplegia caused immediate arrest (less than 1 min), and the cardioplegic dose was divided equally between antegrade and retrograde delivery. Included are 173 isolated CABG patients (39 with either extending infarction, cardiogenic shock, or ejection fraction less than 20%), and 37 coronary reoperations, 67 with aortic and/or mitral valve procedures, 3 with arrhythmia surgery, and 7 children (VSD, Rastelli, Konno, etc). Septal temperature in patients with LAD occlusion fell to 11.6 degrees C +/- 0.5 after retrograde vs only 16.1 degrees C +/- 3 after antegrade cardioplegia (p less than 0.05). Overall hospital mortality was 2.8% and no complications followed transatrial retrograde coronary sinus cannulation. Antegrade/retrograde cardioplegia allowed retrograde flushing of debris in redo coronary operations, produced immediate arrest with low cardioplegic volumes, improved cardioplegic distribution during IMA grafting, allowed aortic and mitral valve procedures to proceed uninterrupted, and ensured distribution in unforeseen aortic insufficiency. Antegrade/retrograde cardioplegia is now used routinely in all adult and in many pediatric operations because of its speed, safety, and simplicity.

The effect of cold blood cardioplegia in preventing microvascular injury owing to myocardial ischemia and reperfusion was studied. Two groups of eight dogs each were placed on cardiopulmonary bypass with separate coronary perfusion at 80 mm Hg. Microcirculatory function was assessed by measuring the extraction and permeability surface area product (PS) for inulin and albumin. These changes were correlated with the transport and extraction of oxygen, coronary blood flow, and morphologic studies of the microvasculature. In Group I, ischemic hearts were kept normothermic for 45 minutes. In Group II, 250 ml of cold (4 degrees C) blood cardioplegic solution (potassium chloride 30 mEq/L) was infused and the infusion repeated at 15 and 30 minutes. Reperfusion resulted in marked reactive hyperemia for Group I (p less than 0.05) but no hyperemic response in Group II. In Group I, but not II, ischemia-reperfusion caused a significant decrease in PS inulin (0.47 +/- 0.10 ml/min/gm) compared to the preischemic value (1.04 +/- 0.23) (p less than 0.05). There was a threefold decrease in the PS inulin/PS albumin ratio with reperfusion in Group I, indicating increased vascular permeability to albumin. There was also a significant decrease in myocardial oxygen consumption (from 5.1 +/- 0.7 to 3.4 +/- 0.5 ml/min/100 gm, p less than 0.05) for Group I. These did not decrease for Group II. Histologic studies showed diffused areas of no reflow in the unprotected hearts. The wet/dry weight ratio for Group I (4.97 +/- 0.09) was significantly greater than for Group II (4.49 +/- 0.07) (p less than 0.001). The results indicate that in the unprotected heart, ischemia-reperfusion caused microcirculatory injury resulting in increased permeability to albumin, edema, a reduction in surface area, and areas of no reflow. In contrast, in the hearts protected with cold blood cardioplegia, no evidence of microcirculatory injury occurred.

This report reviews the initial clinical application of our experimental studies inducing cardioplegia with a warm (37 degrees C) glutamate-enriched blood solution in ischemically damaged hearts. Over 15 months, 23 consecutive coronary patients requiring preoperative intra-aortic balloon and inotropic drug support for cardiogenic shock underwent operation for left ventricular power failure. Twelve patients were given a warm glutamate-enriched blood cardioplegic solution during the first 5 minutes of aortic clamping before multidose cold (4 degrees C) glutamate blood cardioplegia was begun; 11 patients received standard multidose cold blood cardioplegia without glutamate. All patients had comparably depressed left ventricular performance preoperatively despite maximal inotropic and balloon support and showed evidence of extending myocardial infarction. They did not differ in the number of grafts placed (3.7 +/- 0.2), associated valve and aneurysm procedures (seven patients) or cross-clamp time (89 +/- 6 minutes). All patients received warm blood cardioplegic reperfusion before aortic unclamping. The perioperative mortality was 9% (2/23); both patients who died received cold blood cardioplegia without glutamate. In addition to lower mortality, patients receiving warm glutamate blood cardioplegia exhibited better hemodynamics, allowing earlier discontinuation of inotropic drug infusion (1.3 +/- 0.5 versus 2.7 +/- 0.8 days, p less than 0.05) and intraaortic balloon support (1.2 +/- 0.2 versus 3.6 +/- 0.5 days, p less than 0.05). Late mortality was 30%, resulting in a 65% overall survival rate (2 to 15 months) for the entire series of patients. The operative principles evolving from this early experience include (1) warm blood cardioplegic induction, (2) glutamate enrichment, (3) meticulous attention to cardioplegic distribution and grafting sequence, (4) warm cardioplegic reperfusion before unclamping, and (5) graft perfusion during construction of proximal anastomoses. Hopefully, further application of these techniques will improve results in these extremely high risk coronary patients requiring operation.

Cold blood with potassium, 34 mEq/L, was compared with cold blood and with a cardioplegic solution. Three groups of 6 dogs had 2 hours of aortic cross-clamp while on total bypass at 28 degrees C with the left ventricle vented. An initial 5-minute coronary perfusion was followed by 2 minutes of perfusion every 15 minutes for the cardioplegic solution (8 degrees C) and every 30 minutes for 3 minutes with cold blood or cold blood with potassium (8 degrees C). Hearts receiving cold blood or cold blood with potassium had topical cardiac hypothermia with crushed ice. Peak systolic pressure, rate of rise of left ventricular pressure, maximum velocity of the contractile element, pressure volume curves, coronary flow, coronary flow distribution, and myocardial uptake of oxygen, lactate, and pyruvate were measured prior to ischemia and 30 minutes after restoration of coronary flow. Myocardial creatine phosphate (CP), adenosine triphosphate (ATP), and adenosine diphosphate (ADP) were determined at the end of ischemia and after recovery. Changes in coronary flow, coronary flow distribution, and myocardial uptake of oxygen and pyruvate were not significant. Peak systolic pressure and lactate uptake declined significantly for hearts perfused with cold blood but not those with cold blood with potassium. ATP and ADP were lowest in hearts perfused with cardioplegic solution, and CP and ATP did not return to control in any group. Heart water increased with the use of cold blood and cardioplegic solution. Myocardial protection with cold blood with potassium and topical hypothermia has some advantages over cold blood and cardioplegic solution.

The technique of myocardial protection by means of a cardioplegic solution consisting of cold blood (10 degrees C) with potassium (30 mEq. per liter) is described. A disposable cooling coil is used and a separate pump head for coronary perfusion is avoided. The aortic perfusion cannula can be used for venting of the left ventricle and subsequently for venting of air. This method was used in 125 consecutive patients undergoing coronary revascularization and in 73 consecutive pediatric cardiac surgical procedures with excellent results.

Intermittent cold ischemic arrest was compared with hypothermic potassium cardioplegia using cold blood as the vehicle in two consecutive series of patients having isolated coronary bypass grafting. Between January 1, 1977, and June 30, 1977, 196 patients were operated on using cold ischemic arrest. The incidence of perioperative infarction was 14.3%, and mean total myocardial ischemia time was 42 +/- 1.2 minutes. From July 1, 1977, to June 30, 1978, there were 428 operations done using cold blood with potassium. The incidence of perioperative infarction was 5.6% (p less than 0.005), and the mean total myocardial ischemic time was 80 +/- 2.1 minutes. In the five years prior to this study, the incidence of perioperative infarction was constant at 13% while operative mortality was declining from 5 to 1% and the need for postoperative myocardial support was declining also. Use of cold blood potassium cardioplegia compared with cold ischemic arrest for myocardial protection during coronary artery operations has significantly reduced the incidence of perioperative infarction while doubling cross-clamp time.

To determine the importance of different methods of myocardial protection for combined aortic valve replacement and coronary revascularization, we analyzed the records of 82 consecutive patients who underwent the combined procedure between 1973 and 1978. Sixty-three (77%) had angina and 63 (77%) were in New York Heart Association Functional Class III or IV. Moderate to severe left ventricular impairment was present in 59%, and the mean number of diseased vessels was 1.9 per patient. Group I consisted of 18 patients with intermittent ischemia, almost all of whom had operation between 1973 and 1976. Group IIa consisted of 24 patients operated on between 1973 and December, 1976, with coronary perfusion, and Group IIb had 18 patients in whom a similar technique was used in 1977 and 1978. Group III consisted of 22 patients operated on in 1977 and 1978 in whom cold chemical cardioplegia was used. The early mortality (less than 30 days) for Group I was 50% and for Group IIa 29%. There were no deaths in Group IIb and Group III. The incidence of perioperative myocardial infarction was 21% in Group I, 6% in Group IIa, 11% in Group IIb, and zero in Group III. The incidence of cardiogenic shock requiring prolonged inotropic support and intraaortic balloon counterpulsation was significantly less in Group III (9%) than in Group IIb (50%) (p less than 0.05). If other manifestations of myocardial injury, such as perioperative infarction and cardiogenic shock requiring intraaortic balloon counterpulsation or inotropic support, are taken into consideration, cold chemical cardioplegia appears to provide better myocardial protection than coronary perfusion of the fibrillating heart.

Hypothermic coronary perfusion lengthens the safe duration of anoxic arrest. Intermittent selective hypothermic coronary perfusion provides extended myocardial protection. We describe a method of achieving profound myocardial hypothermia by selective deep hypothermic coronary perfusion using a cooling coil without a separate pump head.

Unlabelled: Myocardial protection achieved during 2 hours of ischemic arrest was evaluated in 45 isolated, blood perfused, neonatal (1 to 5 days) piglet hearts. Comparisons were made among five methods of myocardial protection: Group I, topical cooling; Group II, hyperosmolar (450 mOsm) low-calcium (0.5 mmol/L) crystalloid cardioplegia; Group III, St. Thomas' Hospital cardioplegia; Group IV, cold blood cardioplegia with potassium (21 mmol/L), citrate-phosphate-dextrose (calcium level 0.6 mmol/L), and tromethamine; and Group V, cold blood cardioplegia with potassium alone (16 mmol/L) (calcium level 1.2 mmol/L). Hemodynamic recovery (percent of the preischemic stroke work) after 30 and 60 minutes of reperfusion was 82.9% and 86.7% in Group I, 35.7% (p less than 0.0001) and 43.7% (p less than 0.0001) in Group II, 76.1% and 77.7% in Group III, 67.4% (p less than 0.05) and 60.6% (p less than 0.05) in Group IV, and 110.7% and 100.6% in Group V., Conclusions: Topical cooling is an effective method of myocardial protection in the neonate. Cold blood cardioplegia with potassium alone and a normal calcium level provides optimal functional recovery. The improved protection obtained with both crystalloid and blood cardioplegia with normal calcium levels suggests an increased sensitivity of the neonatal heart to the calcium level of the cardioplegic solution.

Eighty-eight operations for correction of intracardiac congenital heart defects were performed using local cardiac hypothermia for protection of the ischemic myocardium. Twenty-six patients underwent repair of tetralogy of Fallot, 23 had patch closure of ventricular septal defect, 24 had correction of various types of congenital aortic stenosis, and 15 were operated upon for other complex lesions. The overall operative mortality was 5.6%. Ischemia times ranged from 9 to 119 minutes (mean, 48 minutes). Ischemic arrest protected by local cardiac hypothermia provides an optimal operative field, permitting repair of uncomplicated intracardiac defects in a precise, unhurried manner. No hemodynamic abnormalities attributable to the technique were encountered.