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Objective Systemic effects of carbon dioxide (CO 2 ) insufflation during left-sided cardiac surgery were evaluated in a prospective randomized study, with regard to acid–base status, gas exchange, cerebral hemodynamics, and red blood cell morphology. Methods Twenty patients undergoing elective left-sided cardiac surgery were randomized to de-airing procedure either by CO 2 insufflation technique (CO 2 group, n = 10) or by Lund technique without CO 2 insufflation (Lund group, n = 10). Groups underwent assessment of acid–base status by intermittent arterial blood gases and in-line blood gas monitoring. Capnography was used to determine volume of CO 2 produced. Cerebral hemodynamics was measured by transcranial Doppler sonography and near-infrared spectroscopy. Red cell morphology from cardiotomy suction and vent tubing was studied by scanning electron microscopy. Results Patients in the CO 2 group consequently developed significantly higher levels of hypercapnia with a concomitant increase in the volume of CO 2 produced despite significantly higher oxygenator gas flows compared with the Lund group. Effects on cerebral hemodynamics were observed in the CO 2 group with significantly higher blood flow velocities in the middle cerebral artery and higher regional cerebral saturation. Red blood cell damage was observed in the CO 2 group by scanning electron microscopy (97% in CO 2 group vs 18% in Lund group). Conclusions Insufflation of CO 2 into the cardiothoracic wound cavity during left-sided cardiac surgery can induce hypercapnic acidosis and increased cerebral blood flow and local blood cell damage. These systemic effects should be monitored by in-line capnography and acid–base measurements for early and effective correction by increase in gas flows to the oxygenator.

Post-operative renal dysfunction after cardiac surgery is not uncommon and can lead to adverse outcome. The ability to accurately monitor renal function is therefore important. Cystatin C is known to be a sensitive marker of the glomerular filtration rate (GFR), but it has not been fully evaluated in cardiac surgery. Iohexol clearance is considered a reliable reference method for the determination of GFR. The aim of this study is to, for the first time, evaluate the diagnostic accuracy of plasma cystatin C compared with iohexol clearance in cardiac surgery.

BACKGROUND: We compared the association of levosimendan or dobutamine with norepinephrine for the maintenance of systemic and hepatosplanchnic perfusion during early endotoxemic shock. METHODS: Twenty anesthetized pigs (26.8 +/- 0.5 kg) were instrumented with flow probes and catheters to monitor systemic and regional perfusion as described in our companion article in this issue of the journal. Two animals were excluded because of surgical complications. Oxygen consumption (VO2) was measured by indirect calorimetry. Starting 1 h after instrumentation, an endotoxin infusion (Escherichia coli lipopolysaccharide, 2 mu g . kg(-1) . h(-1)) was administered for 300 min. Sixty minutes after the start of endotoxin, the animals were fluid resuscitated (20 mL/kg dextran 70); at 120 min, they were randomized into three groups of six animals each: levosimendan (25-50 mu g . kg(-1) . h(-1)), dobutamine (10-20 mu g . kg(-1) . min(-1)), and control. In the first two groups, norepinephrine (0.5-2 mu g . kg(-1) . min(-1)) was added when mean arterial blood pressure (MAP) = baseline. The data were divided into two subsets: before (0-120 min, all animals) and after (120-300 min, three groups) randomization, and analyzed by analysis of variance. P < 0.05 was considered significant. RESULTS: At 120 min, cardiac output was 15% higher (P < 0.001), systemic vascular resistance was 30% lower (P < 0.001), and MAP decreased 12.5% (P = 0.004); blood flow in the hepatic artery, superior mesenteric artery, and portal vein had increased by 100% (P = 0.004), 60% (P < 0.001), and 20% (P < 0.001), respectively. Between 120 and 300 min, cardiac output and systemic oxygen delivery decreased 50% in control animals (P < 0.05), remained unchanged in the levosimendan group, and increased 60% with dobutamine (P = 0.05). MAP (P = 0.043) and VO2 (P = 0.001) decreased 20% in the control group. Portal vein flow decreased in the control (50%) and levosimendan (30%) groups (P < 0.001) and was therefore higher in the dobutamine group (P = 0.003) at 300 min. Hepatic and gut oxygen deliveries decreased in the levosimendan (50%,, and 30%, respectively, P < 0.001) and control groups (70% and 45%, respectively, P < 0.05); thus, regional oxygen deliveries were greater in the dobutamine group (P < 0.05). In this group, mixed venous and hepatic vein oxygen saturation were maintained; the latter variable was higher than in the other groups (P < 0.05). Although unchanged with dobutamine, arterial (P = 0.020), portal (P = 0.020), and hepatic vein (P = 0.034) lactate concentrations increased twofold with levosimendan. CONCLUSION: In volume-resuscitated endotoxemic pigs, the association of either levosimendan or dobutamine with norepinephrine preserved systemic blood flow, oxygen delivery, and VO2. However, only dobutamine-norepinephrine maintained portal blood flow, which was associated with preservation of splanchnic and hepatic oxygen homeostasis and stable lactate concentrations. (Anesth Analg 2009;109:1576-83) (Less)

BACKGROUND: Septic shock may cause splanchnic hypoperfusion. We hypothesized that levosimendan would improve systemic and hepatosplanchnic perfusion during endotoxemic shock. METHODS: In 16 anesthetized pigs (31.4 +/- 3.4 kg), a jugular vein, a carotid artery, the Pulmonary artery (thermodilution), the portal vein, and a hepatic vein were cannulated for hemodynamic monitoring and blood sampling. Ultrasonic flow-probes were placed around the portal vein, the hepatic artery, and the superior mesenteric artery (SMA). In addition to 30 mL/kg of dextran 70 given before baseline, all animals received 1.0 mL . kg(-1) . h(-1) of IV fluids throughout the experiment. An endotoxin infusion (2 mu g . kg(-1) . h(-1)) was given for 300 min; 100 min after the start of endotoxin, the pigs were randomized to receive levosimendan (50 mu g . kg(-1) . h(-1), n = 8) or placebo (n = 8). To evaluate the isolated effects of endotoxemia, all data before randomization were pooled into one group. Data were analyzed by analysis of variance and presented as mean +/- SEM. RESULTS: Endotoxemia (t = 90 min, pooled data) decreased systemic vascular resistance (SVR, 2526 +/- 203 to 1946 +/- 122 dyn . s . cm(-5), P = 0.003) and mean arterial blood pressure (MAP, 109 +/- 6 to 84 +/- 3 mm Hg, P < 0.05), whereas heart rate (66 +/- 4 to 98 +/- 8 bpm), and mean pulmonary arterial pressure (MPAP, 20 +/- 1 to 38 +/- 2 mm Hg) increased (P < 0.001). Cardiac output (CO, 3.4 +/- 0.2 L/min) and systemic oxygen delivery (414 +/- 33 mL/min) were unchanged, but blood flows in the SMA (575 +/- 34 to 392 +/- 38 mL/min) and the portal vein (881 +/- 62 to 568 +/- 39 mL/min) decreased (P < 0.001). Although hepatic arterial blood flows increased (36 +/- 8 to 219 +/- 38 mL/min), gut (114 +/- 11 to 84 +/- 7 mL/min) and hepatic (94 +/- 11 to 67 +/- 8 mL/min) oxygen deliveries decreased (P < 0.05). At t = 300 min, the levosimendan group showed lower MPAP (39 +/- 3 vs 49 +/- 2 mm Hg, P = 0.025), lower SVR (2158 +/- 186 vs 3069 +/- 370 dyn . s . cm(-5), P = 0.052), and lower MAP (55 +/- 9 vs 87 +/- 9 mm Hg, P < 0.001) than the control group. In both groups, CO, portal vein, and hepatic arterial blood flows decreased (P < 0.001); the mean values for the levosimendan group at t = 300 min were 2.0 +/- 0.4 L/min, 390 +/- 83 mL/min, and 36 +/- 12 mL/min, respectively. SMA blood flow decreased only in the levosimendan group (432 +/- 40 to 320 +/- 78 mL/min, P < 0.001), whereas gut oxygen delivery decreased in the levosimendan (85 +/- 12 to 63 +/- 12 mL/min, P < 0.001) and in the control (83 +/- 6 to 59 +/- 3 mL/min, P = 0.03) groups. CONCLUSION: Levosimendan administered after the establishment of endotoxemic shock to pigs receiving moderate fluid resuscitation prevented further increases in MPAP and maintained a low SVR. There were, however, no improvements in CO, MAP decreased, and levosimendan neither prevented the development of circulatory shock nor improved hepatosplanchnic perfusion. (Anesth Analg 2009:109:1568-75) (Less)

OBJECTIVE: We have evaluated a new technique of cardiac de-airing that is aimed at a) minimizing air from entering into the pulmonary veins by opening both pleurae and allowing lungs to collapse and b) flushing out residual air from the lungs by staged cardiac filling and lung ventilation. These air emboli are usually trapped in the pulmonary veins and may lead to ventricular dysfunction, life-threatening arrhythmias, and transient or permanent neurologic deficits. METHODS: Twenty patients undergoing elective true left open surgery were prospectively and alternately enrolled in the study to the conventional de-airing technique (pleural cavities unopened, dead space ventilation during cardiopulmonary bypass [control group]) and the new de-airing technique (pleural cavities open, ventilator disconnected during cardiopulmonary bypass, staged perfusion, and ventilation of lungs during de-airing [study group]). Transesophageal echocardiography and transcranial Doppler continually monitored the air emboli during the de-airing period and for 10 minutes after termination of the cardiopulmonary bypass. RESULTS: The amount of air embolism as observed on echocardiography and the number of microembolic signals as recorded by transcranial Doppler were significantly less in the study group during the de-airing time (P < .001) and the first 10 minutes after termination of cardiopulmonary bypass (P < .001). Further, the de-airing time was significantly shorter in the study group (10 vs 17 minutes, P < .001). CONCLUSION: The de-airing technique evaluated in this study is simple, reproducible, controlled, safe, and effective. Moreover, it is cost-effective because the de-airing time is short and no extra expenses are involved. (Less)

Sequestration of 111In–labeled neutrophils (polymorphonuclear leukocytes–PMNs) in the lungs during sham dialysis was studied dynamically using a gamma camera. Five animals were pretreated with cobra venom factor, naja naja (CVF), to achieve depletion of the complement system, mainly C5a. Seven animals were studied without pretreatment with CVF. Central hemodynamics and gas exchange were studied as well as neutrophil function using luminescence and aggregation. In the control group there was a significant sequestration of neutrophils in the lungs, which reached a maximum between 15 and 17 min after the start of hemodialysis. The peripheral neutrophil count decreased concomitantly. These changes were virtually absent in the CVF–treated group. PMN aggregation and luminescence were abolished in CVF–treated animals. Both pulmonary artery pressure and pulmonary vascular resistance increased significantly in the control group, whereas in the CVF group these parameters remained unchanged. There were no differences in blood gases, platelet count, or hematocrit between the groups. The results clearly indicate that the activation of neutrophils within minutes after the start of hemodialysis is greatly dependent on C5a activation because it can be abolished by C5a depletion. This activation is accompanied by changes in the pulmonary circulation with increases in pressure and resistance.

To study the kinetics of lipid micro-emboli during cardiac surgery.Eleven pigs were studied. Seven of these were put on extracorporeal circulation. A shed blood phantom consisted of blood, saline and radioactive triolein was added to the circuit. Both venous and arterial blood samples were taken at short intervals. Four animals were used to study renal kinetics without extracorporeal circulation. The same kind of shed blood phantom was infused into the ascending aorta. Samples were taken from the renal artery and vein. All samples were analyzed for radioactivity by scintillation counting.A median 130-fold increase in radioactivity was seen in the blood and was quickly eliminated. Systemic first-pass wedging was found to be 62%. The first-pass elimination in the kidney was 77%. No radioactivity was found in urine.This study shows that the turnover of lipid micro-emboli is fast, and that the majority of the emboli are trapped on their first passage through the capillary system. No evidence was found of a renal excretion of these lipid emboli.

Sepsis-associated myocardial depression is associated with calcium desensitization and adrenergic uncoupling. We conducted a prospective randomized investigation on the effects of the calcium sensitizer, levosimendan, on hemodynamics, myocardial blood flow, and myocardial lactate metabolism during porcine endotoxemia. Twelve pigs were studied. Oxygen consumption was measured by indirect calorimetry, and myocardial blood flow was measured by retrograde thermodilution. Pulmonary, arterial, and venous indwelling catheters allowed measurements of cardiac output, vascular pressures, and blood sampling. Fluids were given at an average of 15 mL . kg . h. After baseline measurements (0 min), an infusion of Escherichia coli LPS (2 microg . kg . min) was started in all animals. Beginning at 100 min, six animals received levosimendan (50 microg . kg . h), whereas six control animals received placebo. The study lasted for 300 min. All animals responded to endotoxin with pulmonary hypertension, a transient decrease in cardiac output, tachycardia, and systemic hypotension. Levosimendan infusion decreased systemic vascular resistance (P = 0.001), coronary vascular resistance (P = 0.004), and mean arterial (P < 0.001) and coronary perfusion pressures (P < 0.001), whereas pulmonary hypertension was unaffected. Heart rate progressively increased in both groups and was significantly higher in the levosimendan group (P = 0.048). Myocardial blood flow remained unchanged in both groups; however, 80 min after the start of levosimendan infusion, left ventricular myocardial hypoxia ensued, as evidenced by a negative myocardial lactate gradient (P = 0.01). Two control and five levosimendan animals died before the end of the study. Early administration of levosimendan during porcine endotoxemia increased heart rate, caused arterial vasodilation, and decreased coronary perfusion pressure, resulting in myocardial hypoxia.

BACKGROUND: Stroke after cardiac surgery is a clinical problem with often fatal or disabling outcome. To assess severity and probable outcome in affected patients only from clinical and radiological examinations is difficult. The glial-derived protein S100B has been suggested to be a marker of cerebral ischemia, and increased blood concentrations of S100B have been shown to correlate with size of lesion and prognosis after stroke. We studied the validity of S100B as a predictor of size of brain lesion and median term outcome in a consecutive group of patients suffering from stroke after cardiac surgery. METHODS: During a period of 17 months, 20 patients with clinical signs of postoperative stroke were investigated with S100B measurement, sampled at 5, 15 and 48 hours after surgery. All patients were examined with computed tomography or magnetic resonance imaging to confirm the diagnosis, and the size of cerebral infarction was estimated from the radiological examinations. The patients were followed up for survival 24 to 39 months after surgery. RESULTS: S100B concentration in blood 48 hours after surgery correlated with the size of infarcted brain tissue (r = 0.68, p < 0.001). Nine patients had S100B levels exceeding 0.5 microg/L and a 2-year mortality of 78%, whereas the 11 patients with S100B below 0.5 microg/L had a mortality of 18%. CONCLUSIONS: Increased S100B in patients with a stroke following cardiac surgery correlate with the size of infarcted brain tissue. High S100B levels 48 hours after surgery have a negative predictive value for median term survival. (Less)

OBJECTIVES: To determine the biologic half-life of the S100B protein and to investigate if the elimination of S100B depends on glomerular filtration rate (GFR). DESIGN: Prospective human study. SETTING: University hospital. PARTICIPANTS: Sixteen patients who underwent cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Shed mediastinal blood (autotransfusion) was returned to the patients postoperatively and used to study the kinetics of S100B. Iohexol was infused simultaneously to estimate GFR. S100B was measured at 0, 20, 40, 60, and 180 minutes after infusion. Iohexol was measured at 180 and 240 minutes after infusion. MEASUREMENTS AND MAIN RESULTS: S100B followed first-order kinetics, and the biologic half-life for S100B was determined to be 25.3 +/- 5.1 minutes. GFR was determined to be 63.8 +/- 34.4 mL/min. No correlation was found between GFR and S100B half-life. CONCLUSIONS: The elimination of S100B after cardiac surgery is faster than reported earlier and not affected by a moderate decrease in GFR. This finding is important when evaluating S100B levels after cardiac surgery.

BACKGROUND: S100beta has been suggested as a marker of brain damage after cardiac operation. The aim of this study was to characterize the early S100beta release in detail and relate it to neuropsychological outcome. METHODS: Three groups of patients were investigated. All patients underwent coronary artery bypass surgery (CABG) with extracorporeal circulation. In group A, 110 patients had sampling of S100beta for the first 10 postoperative hours and also underwent neuropsychological testing. In group B, 14 patients were examined for the effect of autotransfusion on S100beta levels. Eight patients in group C had their intraoperative bleeding processed with a cell-saving device. RESULTS: Group A had a heterogeneous release pattern with several rapid elevations in S100beta concentration. In group B, high concentrations of S100beta were found in the autotransfusion blood (range 0.2 to 210 microg/L) with a concurrent elevation of serum S100beta levels after transfusion of shed blood. In group C, high levels of S100beta were found in the blood from the surgical field (12.0+/-6.0 microg/L) and decreased (1.1+/-0.64 microg/L) after wash. Group C had significantly lower S100beta values at the end of cardiopulmonary bypass compared to group A (0.53+/-0.35 microg/L versus 2.40+/-1.5 microg/L). S100beta values were corrected for extracerebral contamination with a kinetic model. With this correction, an association was found between adverse neuropsychological outcome and S100beta release in group A (r = 0.39, p < 0.02). CONCLUSIONS: A significant amount of S100beta is found both in the blood from the surgical field and in the shed mediastinal blood postoperatively. Infusion of this blood will result in infusion of S100beta into the blood and interfere in the interpretation of early systemic S100beta values.

Objective: To study pressure-volume (P/V) curves over a wide pressure and volume range in pigs.¶Design: Dynamic and static P/V curves (Pdyn/V and Pst/V) and compliance of the respiratory system were studied. The effects of recruitment, positive end-expiratory pressure (PEEP) and body position were analysed.¶Setting: Research animal laboratory.¶Materials: Seven anaesthetised, paralysed and ventilated healthy pigs of 21 kg.¶Measurements: P/V curves up to a pressure of about 40 cmH2O were recorded with a computer-controlled ventilator. Pst/V curves were obtained with the static occlusion method and Pdyn/V curves during an insufflation at a low, constant flow rate.¶Results: Pdyn/V recording showed a complex pattern. During the insufflation compliance increased, fell, increased and fell again. A 2nd ¶Pdyn/V recording immediately following the 1st one was displaced towards higher volumes and showed only one maximum of compliance. The difference between the two curves reflected: (1) lung collapse during a period of 5 min of ventilation at zero end-expiratory pressure (ZEEP) following a recruitment manoeuvre, (2) recruitment during the measurement of the 1st Pdyn/V curve. These observations were similar in the supine and in the left lateral position. After ventilation at PEEP, 4 cmH2O, the signs of collapse and recruitment were reduced. It was confirmed that PEEP offers a partial protection against collapse. Pst/V curves showed higher volumes and higher compliance values compared to Pdyn/V curves. This reflects the influence of viscoelastance on Pdyn/V curves.¶Conclusion: The study demonstrates a particularly strong tendency to lung collapse in pigs.

Background: Inhibition of nitric oxide synthase (NOS) has been claimed to be beneficial in septic shock. We investigated the overall and regional effects of a NOS-inhibitor on perfusion and metabolism during severe endotoxic shock. Methods: Nineteen anaesthetised pigs were catheterised and ultrasonic flow-probes were placed around the portal vein, the hepatic artery, and the superior mesenteric artery. Thirteen animals were given a 3-h infusion of endotoxin; in 6 of these an infusion of NG-nitro-L-arginine-methyl-ester (L-NAME) was started an hour after the start of endotoxin while 7 animals served as controls and received endotoxin only. Six animals were sham operated with no further intervention. Results: Endotoxin produced a hypodynamic shock with pulmonary hypertension. L-NAME did not increase arterial blood pressure, but deepened the fall in cardiac output and enhanced the increase in systemic and pulmonary vascular resistance. The infusion of endotoxin caused a decrease in flows in all regions. The addition of L-NAME induced a further decrease in the mesenteric artery flow only. L-NAME had no additional effect on hepatic artery flow ratio, while a transient decrease was seen in mesenteric flow ratio. Portal flow ratio decreased in the control group only. Global as well as regional oxygen extraction increased in both groups, more so in the L-NAME group. Lactate levels increased with no differences between the groups. Conclusion: In hypodynamic endotoxic shock, L-NAME infusion enhanced pulmonary vasoconstriction and increased left ventricular afterload. The resulting hypoperfusion caused an increase in mortality. The effects of L-NAME on global and mesenteric blood flow and metabolism were similar, while L-NAME had no additional effects on hepatic hypoperfusion or oxygen extraction. Thus, nitric oxide does not seem to be a major factor in the preservation of hepatic perfusion during unresuscitated endotoxic shock.

Background. S100 protein has been suggested to be a serum marker for cerebral complications after cardiac operation and extracorporeal circulation. The aim of this study was to characterize the S100 release pattern after extracorporeal circulation in 515 consecutive patients undergoing coronary artery bypass grafting. Methods. Clinical variables and outcome were prospectively registered. The cerebral outcome was determined by clinical examination. S100 was measured at the end of extracorporeal circulation, and after 5, 15, and 48 hours. Results. After operation, 13 patients had stroke, 12 had delayed awakening, and 17 had encephalopathy. Early S100 release, immediately after extracorporeal circulation, was associated with age and perfusion time, but not with cerebral outcome. However, S100 release after 5 to 48 hours was associated with cerebral complications and risk factors for such outcome. Patients with stroke had higher S100 levels after 15 to 48 hours. A subset of patients with renal failure had overall higher S100 levels at 5 hours. Conclusions. Early and late S100 release indicate different mechanisms for release and emphasizes the potential power of this new biochemical marker for cerebral damage.

Objective: To investigate the appearance and elimination of brain-specific S-100 protein in serum during and immediately after cardiopulmonary bypass. Design: Prospective study. Participants: Twenty-nine patients undergoing elective cardiac surgery. Interventions: Twenty-seven patients were operated on for coronary artery disease; two patients had valve replacement. Serial measurements of S-100 in arterial blood during and up to 48 hours after cardiopulmonary bypass were made. Measurements and Main Results: The perioperative and postoperative course was uneventful in 25 patients, with no clinical signs of neurologic complications. S-100 was not detected before extracorporeal circulation was started. Detectable concentrations (detection limit, 0.2 μg/L) appeared in serum after 10 minutes of perfusion and reached maximum levels, 2.43 ± 0.3 μg/L, at the end of bypass. The levels then declined with elimination t12 of 2.2 hours. Only two patients had detectable concentrations of S-100 48 hours after the end of bypass. In four patients who developed clinical signs of cerebral injury, levels of S-100 were significantly higher at the end of bypass and 24 hours after the end of bypass. Conclusions: Cardiopulmonary bypass initiates a release of brain-specific S-100 to the systemic circulation. The release and elimination of S-100 seem to follow a reproducible pattern in patients with no signs of cerebral injury. In patients who developed cerebral injury, the concentrations of S-100 in blood were increased, thus suggesting that S-100 may be a usable marker for cerebral injury after extracorporeal circulation.

Objective To study and compare the effects of inhibiting endothelial nitric oxide synthase on systemic and pulmonary circulation in an in vivo model. Design Prospective, randomized, controlled study. Setting Laboratory for experimental surgery at a university medical center. Subjects Seventeen anesthetized, mechanically ventilated pigs. Interventions To produce a stable and continuous stimulation of endothelial nitric oxide synthase, an infusion of acetylcholine was given to one group of animals (n = 5) in a dose that decreased mean arterial pressure by 15%. After 45 mins, N sup G-monomethyl-L-arginine (L-NMMA) was given in a dose of 3 mg/kg for 5 mins in order to inhibit the enzyme. A second dose of 10 mg/kg was given 30 mins later. L-arginine was then given in a dose of 100 mg/kg to reverse the inhibition. One group of animals (n = 6) received a single dose of indomethacin (2.5 mg/kg) 15 mins after the start of acetylcholine infusion. L-NMMA and L-arginine were then given. In a control group (n = 5), the effects of L-NMMA and L-arginine were studied without acetylcholine. Circulatory parameters were monitored and resistance indices were calculated via arterial, central venous, and pulmonary artery catheters. Measurements and Main Results In control animals, 3 and 10 mg/kg of L-NMMA induced an increase in mean arterial pressure of 14% and 25%, respectively, with similar increases in systemic vascular resistance. Mean pulmonary arterial pressure increased by 22% and 48%, respectively. Acetylcholine lowered mean arterial pressure by 15% and did not affect the relative changes induced by L-NMMA. Acetylcholine had no effect on pulmonary resting tone but enhanced the pulmonary hypertension and increase in resistance induced by L-NMMA. This enhancement was abolished by indomethacin, which produced systemic hypertension while no effect on pulmonary pressure was seen. Conclusions A basal release of nitric oxide contributes to the maintenance of normal vascular tone in the anesthetized pig. Stimulation of endothelial nitric oxide synthase by acetylcholine did not result in any further pulmonary vasodilation as was seen in the systemic circulation. Inhibition of nitric oxide synthase had a greater effect on pulmonary pressure than on systemic pressure. However, this difference was abolished by the administration of indomethacin. Increased nitric oxide release or acetylcholine itself seems to stimulate the production of a vasoconstricting prostanoid in the pulmonary circulation. (Crit Care Med 1997; 25:280-285)

The objective of the present study was to validate the presence and explore the characteristics of mitochondrial permeability transition (mPT) in isolated mitochondria from human heart tissue in order to investigate if previous findings in animal models of cardiac disorders are translatable to human disease. Mitochondria were rapidly isolated from fresh atrial tissue samples obtained from 14 patients undergoing Maze surgery due to atrial fibrillation. Human heart mitochondria exhibited typical mPT characteristics upon calcium overload such as swelling, evaluated by changes in light scattering, inhibition of respiration and loss of respiratory coupling. Swelling was a morphologically reversible event following transient calcium challenge. Calcium retention capacity (CRC), a quantitative measure of mPT sensitivity assayed by following extramitochondrial [Ca(2+)] and changes in respiration during a continuous calcium infusion, was significantly increased by cyclophilin D (CypD) inhibitors. The thiol-reactive oxidant phenylarsine oxide sensitized mitochondria to calcium-induced mPT. Release of the pro-apoptotic intermembrane protein cytochrome c was increased after, but not before, calcium discharge and respiratory inhibition in the CRC assay. From the present study, we conclude that adult viable heart mitochondria have a CypD- and oxidant-regulated mPT. The findings support that inhibition of mPT may be a relevant pharmacological target in human cardiac disease and may underlie the beneficial effect of cyclosporin A in reperfusion injury.

Background: Increased levels of cardio-enriched microRNAs (miRNAs) have been described in patients with myocardial infarction (MI). We wanted to evaluate the diagnostic and prognostic potential of cardio-enriched miRNAs in patients presenting with a suspected acute coronary syndrome (ACS). Methods: Cardio-enriched miRNAs (miR-1, miR-208b and miR-499-5p) were measured using real time PCR in plasma samples from 424 patients with suspected ACS treated in a coronary care unit. miRNAs were assessed for discrimination of a clinical diagnosis of myocardial infarction and for association with 30-day mortality and diagnosis of heart failure. Correlation with left ventricular systolic dysfunction as measured by the ejection fraction (LVEF) was also assessed. To confirm myocardial origin miRNA was measured during coronary artery bypass surgery. Results: miRNAs were higher in MI patients and correlated with LVEF (p < 0.001). Discrimination of MI was accurate for miR-208b (AUC = 0.82) and miR-499-5p (AUC = 0.79) but considerable lower than for Troponin T (AUC = 0.95). Increased miRNA levels were strongly associated with increased risk of mortality or heart failure within 30 days for miR-208b (OR 1.79, 95% CI = 1.38-2.23, p = 1 × 10 -5 ) and miR-499-5p (OR 1.70, 95% CI = 1.31-2.20, p = 5 × 10 -5 ) but the association was lost when adjusting for Troponin T. During surgery miR-208b and miR-499-5p was released in the coronary sinus after cardioplegia-reperfusion to markedly higher levels than in a peripheral vein. Conclusions: Our findings confirm increased levels of cardio-enriched miRNAs in the blood of MI patients and establish association of increased miRNA levels with reduced systolic function after MI and risk of death or heart failure.

The purpose of this study was to investigate the effects of iloprost, a synthetic prostacyclin analogue, on the pulmonary cellular trapping after a standardized soft tissue trauma. In two groups 1 and 2 iloprost was given in doses of 100 ng/kg/min commencing 30 and 20 min respectively prior to trauma and ceasing 10 min after trauma. 111Indium-oxine was used to label neutrophils in 6 animals from each group. Platelets were labelled in 6 and 7 animals respectively. A third group of 11 pigs served as a control and did not receive iloprost. The pulmonary sequestration of platelets and neutrophils was studied dynamically with a gamma camera and directly after trauma was significantly less in group 1 when compared to the control group. A rise in pulmonary vascular resistance and pulmonary arterial pressure was seen in the control group immediately after trauma but this was not evident in the iloprost groups. PaO2 decreased significantly in group 1 and 2 during the iloprost infusion. The results indicate that iloprost attenuates the pulmonary cellular sequestration and changes in central hemodynamics during trauma in this model.

Standardized intra-abdominal hemorrhage was induced in 7 anesthetized pigs. The resulting hypovolemic shock was treated with pneumatic anti-shock garment (PASG) followed by intra-aortic balloon occlusion. The effects of this treatment on circulation, lung mechanics and gas exchange were studied. Hemorrhage was induced by pulling out sutures introduced in the inferior caval vein. We found that the use of PASG partially restored mean arterial blood pressure from 44 +/- 6 to 66 +/- 6 mm Hg. When intraaortic balloon occlusion was added, the arterial pressure returned to basal levels. Cardiac output fell severely due to the hemorrhage from 3.7 +/- 0.2 to 1.3 +/- 0.2 liters/min and could not be restored during the treatment. A severe fall in total lung compliance was recorded after inflation of the PASG from 18.6 +/- 0.9 to 10 +/- 0.7 ml/cm H2O, this was accompanied by a fall in alveolar ventilation. These findings emphasize the severe restriction in lung function that occurred during treatment with PASG. Both parameters returned to near normal values when the PASG was deflated and the intra-aortic balloon was inflated. Pulmonary vascular resistance increased by more than 400% and remained high during the study period. There was no change in arterial PO2, however the fall in mixed venous PO2 caused by hemorrhage was reversed at the end of the treatment. Indirect monitoring of cerebral function by continuous EEG showed a decreased voltage during the hemorrhage, this was reversed by the combined treatment. We conclude that the outlined treatment makes it possible to restore central hemodynamics and preserve cerebral function at least for a short period of time until definite surgical treatment can be performed. However, severe restriction on lung mechanics, especially when PASG was inflated, makes it probable that ventilatory support can be necessary in such cases.

OBJECTIVE: We have compared the effectiveness, time required for de-airing, and safety of a newly developed de-airing technique for open left heart surgery (Lund technique) with a standardized carbon dioxide insufflation technique. METHODS: Twenty patients undergoing elective open aortic valve surgery were randomized prospectively to the Lund technique (Lund group, n = 10) or the carbon dioxide insufflation technique (carbon dioxide group, n = 10). Both groups were monitored intraoperatively during de-airing and for 10 minutes after weaning from cardiopulmonary bypass by transesophageal echocardiography and online transcranial Doppler for the severity and the number of gas emboli, respectively. The systemic arterial partial pressure of carbon dioxide and pH were also monitored in both groups before, during, and after cardiopulmonary bypass. RESULTS: The severity of gas emboli observed on transesophageal echocardiography and the number of microembolic signals recorded by transcranial Doppler were significantly lower in the Lund group during the de-airing procedure (P = .00634) and in the first 10 minutes after weaning from cardiopulmonary bypass (P = .000377). Furthermore, the de-airing time was significantly shorter in the Lund group (9 vs 15 minutes, P = .001). The arterial pH during the cooling phase of cardiopulmonary bypass was significantly lower in the carbon dioxide group (P = .00351), corresponding to significantly higher arterial partial pressure of carbon dioxide (P = .005196) despite significantly higher gas flows (P = .0398) in the oxygenator throughout the entire period of cardiopulmonary bypass. CONCLUSIONS: The Lund de-airing technique is safer, simpler, and more effective compared with the carbon dioxide insufflation technique. The technique is also more cost-effective because the de-airing time is shorter and no extra expenses are incurred. (Less)

Endotoxaemia is thought to occur in cardiac surgery using extracorporeal circulation (ECC) and a positive correlation has been proposed between the magnitude of endotoxaemia and risk for postoperative complications. We studied the effects of a new endotoxin adsorber device (Alteco® LPS adsorber) in patients undergoing cardiac surgery with ECC, with special reference to safety and ease of use. Fifteen patients undergoing coronary artery bypass and/or valvular surgery were studied. In 9 patients, the LPS Adsorber was included in the bypass circuit between the arterial filter and the venous reservoir. Flow through the adsorber was started when the aorta was clamped and stopped at the end of perfusion. Flow rate was kept at 150 ml/min. Six patients served as controls with no adsorber in the circuit. Samples were taken for analysis of endotoxin, TNFα, IL-1ß and IL-6 as well as complement factors C3, C4 and C1q. Whole blood coagulation status was evaluated using thromboelastograpy (TEG) and platelet count. No adverse events were encountered when the adsorber was used in the circuit. Blood flow through the device was easily monitored and kept at the desired level. Platelet count decreased in both groups during surgery. TEG data revealed a decrease in whole blood clot strength in the control group while it was preserved in the adsorber group. Endotoxin was detected in only 2 patients and IL-1ß in 4 patients. IL-6 decreased in both groups whereas no change in TNF concentrations was found. C3 fell in both groups, but no changes wer found in C4 and C1q. The Alteco® LPS adsorber can be used safely and is easy to handle in the bypass circuit. No complications related to the use of the adsorber were noted. The intended effects of the adsorber, i.e. removal of endotoxin from the blood stream could not be evaluated in this study, presumably due to the small number of patients and the relatively short perfusion times.

Background The brain-derived protein S100B has been shown to be a useful marker of brain injury of different etiologies. Cognitive dysfunction after cardiac surgery using cardiopulmonary bypass has been reported to occur in up to 70% of patients. In this study we tried to evaluate S100B as a marker for cognitive dysfunction after coronary bypass surgery with cardiopulmonary bypass in a model where the inflow of S100B from shed mediastinal blood was corrected for. Methods 56 patients scheduled for coronary artery bypass grafting underwent prospective neuropsychological testing. The test scores were standardized and an impairment index was constructed. S100B was sampled at the end of surgery, hourly for the first 6 hours, and then 8, 10, 15, 24 and 48 hours after surgery. None of the patients received autotransfusion. Results In simple linear analysis, no significant relation was found between S100B levels and neuropsychological outcome. In a backwards stepwise regression analysis the three variables, S100B levels at the end of cardiopulmonary bypass, S100B levels 1 hour later and the age of the patients were found to explain part of the neuropsychological deterioration (r = 0.49, p < 0.005). Conclusions In this study we found that S100B levels 1 hour after surgery seem to be the most informative. Our attempt to control the increased levels of S100B caused by contamination from the surgical field did not yield different results. We conclude that the clinical value of S100B as a predictive measurement of postoperative cognitive dysfunction after cardiac surgery is limited.

Background: Deep sternal wound infection is a serious and potentially lethal complication of cardiac surgery when performed through a median sternotomy. We describe the outcome of a new treatment strategy with C-reactive protein level-guided vacuum-assisted closure used at our department. Methods: Data from 16 consecutive adult patients who had deep sternal wound infections after cardiac surgery were reviewed. Patients with superficial infection or sterile dehiscence were not included. All patients with postoperative deep sternal wound infections were treated with first-line vacuum-assisted closure therapy, followed by direct surgical closure. A purpose-built vacuum-assisted closure system consisting of polyurethane foam pieces and a special pump unit was used. The foam was placed in the wound after debridement of foreign material and necrotic tissue. The wound was covered with adhesive drape and connected to the pump unit, which was programmed to create a continuous negative pressure of 125 mm Hg in the wound cavity. Intravenous antibiotics were given according to tissue-culture results. The patients were immediately extubated after the operation. When ingrowth of granulation tissue was observed in all parts of the wound and the plasma C-reactive protein level showed a steady decline to 30 to 70 mg/L or less without confounding factors, such as tissue injuries or concomitant infections, the sternotomy was rewired, and the wound was closed. Results: All patients were alive and free from deep sternal wound infection 3 months after the operation. The median vacuum-assisted closure treatment time until surgical closure was 9 days (range, 3-34 days), and the median C-reactive protein level at closure was 45 mg/L (range, 20-173 mg/L). The median hospital stay was 22 days (range, 12-120 days). Conclusions: Early vacuum-assisted closure treatment, followed by surgical closure guided by the plasma C-reactive protein level, is a reliable and easily applied new strategy in patients with postoperative deep sternal wound infection.J Thorac Cardiovasc Surg 2002;123:895-900

Understanding of the elastic pressure/volume (Pel/V) curve is still limited in health and disease. The aim of the present study was to elucidate thePel/Vcurve and elastance of the respiratory system (ERS) lung (EL) and chest wall (ECW) in healthy pigs.Six young (20.8 kg) and seven adult (58.9 kg), anaesthetized, paralysed and ventilated pigs were studied.Pel/Vcurves were recorded at zero end-expiratory pressure (ZEEP) and at positive end-expiratory pressure (PEEP) up to 40 cmH2O with a computer controlled ventilator during an insufflation at a low, constant flow.Pel/Vcurves of the respiratory system showed a complex pattern in both young and adult pigs. During the insufflation,ERSdecreased, increased, fell, and increased again. A secondPel/Vcurve recorded immediately after the first one showed lower elastance and only one early fall inERS.ECWfell over the initial segment and was then nearly stable. Difference between 1st and 2nd curves reflected changes in ELcaused by recruitment during the 1st insufflation. At PEEP, such signs of collapse and recruitment were reduced.A strong tendency to lung collapse contributes to a complex pattern of elastic pressure/volume curves. At low volumes and distending pressures the chest wall contributes significantly to changes in respiratory system elastance.

Objective: Sequestration and migration of activated neutrophils plays a major role in the pulmonary injury typical of septic shock and the adult respiratory distress syndrome. Inhaled NO may counteract alveolar-capillary damage attributed to activated neutrophils. The present study describes a method to directly demonstrate the effects of NO inhalation on endotoxin-induced sequestration of 99 mTc-labelled leukocytes [As(t)] in the lungs of pigs.¶Design: Prospective controlled study.¶Setting: Laboratory for experimental surgery at a university medical centre.¶Subjects: Anaesthetised and ventilated pigs.¶Interventions: To induce inflammatory shock 26 animals received a continuous endotoxin infusion. Thirteen animals inhaled NO from the start of the experiments, while 13 served as controls. In 13 animals from both groups, leukocytes were labelled in vitro and reinjected, while in the 13 others erythrocytes were labelled in vivo to provide corrections for changes in blood volume.¶Measurements and results: The pulmonary distribution of 99 mTc-labelled leukocytes or erythrocytes was studied dynamically for 180 min. After correction for changes in pulmonary and heart blood volume (PBV, HBV), leukocyte sequestration curves were generated. Endotoxin induced pulmonary vasoconstriction, reduced PBV, impaired oxygenation, and caused a maximum increase in As(t) of 30 % in the lungs. NO inhalation attenuated pulmonary vasoconstriction and the reduction in PBV. The maximum increase in As(t) was reduced to 15 % of baseline.¶Conclusions: Inhaled NO exerts its main vascular effects in the pulmonary microvasculature, the primary site of physiological neutrophil margination and pathological adhesion of activated leukocytes. Early use of NO inhalation may offer protection against the development of more lasting pulmonary failure in septic shock by reducing leukocyte sequestration in the lungs.

Background . Minor cerebral complications are common after cardiac surgery. Several biochemical markers for brain injury are under research; one of these is neuron-specific enolase (NSE). The purpose of this study was to investigate the release of this enzyme into the blood during and immediately after extracorporeal circulation and to evaluate the effect of hemolysis on this release. Methods . Sixteen patients scheduled for elective heart surgery were included in the study. Blood samples for analysis of NSE and free hemoglobin in plasma were drawn before, during, and up to 48 hours after the end of extracorporeal circulation. The release of NSE from erythrocytes and its correlation to the release of free hemoglobin was studied by serial dilution and hemolysis in vitro. Results . The peri- and postoperative course was uneventful in all patients. Extracorporeal circulation initiated a release of NSE that reached a maximum 6 hours after the end of perfusion. Thereafter, the levels declined with an estimated t 1/2 of 30 hours. The concentration of free hemoglobin increased during the perfusion, with maximum levels at the end of perfusion, after which they fell rapidly to normal values. The in vitro study showed a strong linearity between the release of NSE and free hemoglobin after induced hemolysis. Conclusions . The increased levels of enolase at the end of cardiopulmonary bypass can, to a major part, be explained by the release from hemolysed erythrocytes. The value of NSE as a marker for brain injury in these situations is therefore doubtful.

Background: Substance P is present in bronchial nerve fibres. The physiological actions of substance P are mediated via tachykinin NK1 receptors. Immunochemical studies have demonstrated tachykinin NK1 receptors in the rat airway epithelium. Objective: To elucidate how epithelial tachykinin NK1 receptors affect smooth muscle response to substance P. Methods: Contractile response of isolated rat bronchial trunk with or without epithelium was recorded. Results: In intact segments precontracted by 5-hydroxytryptamine, relaxation was induced by substance P and the nitric oxide donor, sodium nitroprusside. Removal of the epithelium abolished relaxation induced by substance P but did not affect relaxation induced by sodium nitroprusside. The cyclo-oxygenase inhibitor, indomethacin, but not the nitric oxide synthase inhibitor, L-NG-monomethylarginine, reduced the relaxation in response to substance P. Conclusions: Epithelial tachykinin NK1 receptors mediate substance-P-induced relaxation of rat bronchial smooth muscle via release of prostanoids but not nitric oxide.

Background: In the adult respiratory distress syndrome, nitric oxide (NO) inhalation improves oxygenation through reducing ventilation-perfusion mismatching, but detailed information on the pulmonary effects of NO inhalation in septic shock is scarce. The present study investigated the effects of inhaled NO on alveolar dead space (Vdalv) and venous admixture as well as on respiratory system compliance (Crs) and respiratory system resistance (Rrs) in a porcine model of septic shock. Protective effects of NO are discussed. Methods: Thirteen anaesthetised and ventilated pigs were given an infusion of endotoxin for an observation time of 220 min to induce acute lung injury (ALI). In the NO-early group (n=6), an inhalation of 60 ppm NO was started simultaneously with the endotoxin infusion and continued for 190 min. In 7 control/NO-late animals, 60 ppm NO was administered for 30 min following 190 min of endotoxin infusion. Haemodynamics, single-breath CO 2 -, pressure-, and flow signals were recorded. Results: Endotoxin induced haemoconcentration, pulmonary vasoconstriction, and a decrease in Crs, while venous admixture, Vdalv, and Rrs increased. In the NO-early group, the pulmonary vasoconstriction was attenuated, no increase in pulmonary venous admixture or in Vdalv was seen before cessation of NO, and the improvements in oxygenation outlasted the NO inhalation. In the control/NO-late group, the NO inhalation reversed the changes in dead space and venous admixture. NO had no effect on the changes in respiratory mechanics. Conclusion: In porcine ALI, 60 ppm NO diminishes pulmonary vasoconstriction and improves gas exchange by reducing pulmonary venous admixture and alveolar dead space, but does not prevent a fall in Crs. NO inhalation may help prevent long-lasting pulmonary failure.

Objective The inhibiting effect of nitric oxide on the aggregation and adhesion of neutrophils and platelets has been well documented in vitro. In vivo evidence, however, is more scant. In this study, we studied the effects of inhaled nitric oxide on pulmonary cellular sequestration in our sham hemodialysis model. Accumulation of neutrophils and platelets in the lungs has been shown to be an early event in this model. Design Prospective, randomized, controlled study. Setting Animal laboratory at a university medical center. Subjects Twenty-six anesthetized, mechanically ventilated pigs. Interventions 111 Indium-oxine was used to selectively label neutrophils or platelets and the activity over the lungs was followed dynamically with a gamma camera. Sham hemodialysis, using a cuprophan hollow-fiber dialyzer, was instituted via catheters in the femoral vessels. The animals were divided into two main groups: a) the nitric oxide recipient group (n equals 12, with platelets labeled in seven animals and neutrophils labeled in five animals); and b) the control group (n equals 14, with platelets labeled in seven animals and neutrophils labeled in seven animals). The animals in the former group were given 50 parts per million of nitric oxide in the inspiratory gas from the beginning of dialysis and for 30 mins onward. Measurements and Main Results Inhalation of nitric oxide attenuated the increase in activity over the lungs in both the neutrophil and platelet groups during sham hemodialysis. In addition, an inhibiting effect on the increase in pulmonary pressure was noted. Conclusion Apart from the effects of nitric oxide on central hemodynamics in this model, the scintigraphic findings indicate an in vivo effect of nitric oxide on the accumulation of platelets and neutrophils in the lungs, probably due to inhibition of the adhesion and/or aggregation of these cells.

The effects of intermittent inhalation of 57 ppm nitric oxide (NO) were studied in eight anesthetized, ventilated pigs given a continuous infusion of Escherichia coli endotoxin. Seven animals served as controls. By administering NO synchronized with inspiration and close to the orotracheal tube, measurable amounts of the toxic metabolite, NO2, in the inspiratory gas mixture were avoided. No direct systemic effects of NO inhalation were seen, but through counteracting pulmonary vasoconstriction, a fall in cardiac output was delayed. Nitric oxide effectively attenuated the initial peak rise in mean pulmonary artery pressure and resistance, both returning to control levels after cessation of NO. These effects were reproduced during later phases of endotoxemia, giving further proof to the role of gaseous NO as a selective pulmonary vasodilator. Nitric oxide diminished pulmonary shunting, but unimpaired oxygenation was preserved only during the first inhalation period. Leukocyte counts decreased drastically and platelet aggregation was enhanced, but after 1.5 hours of endotoxin infusion, platelet hyperaggregation was maintained in the NO group while it decreased in the control group.

We have previously documented that neutrophils (polymorphonuclear leukocytes) aggregate in the lungs 10-15 min after the start of dialysis. The aim of the present study was to investigate the corresponding platelet reaction and evaluate the effect of prewarmed priming solution on this reaction. The animals were divided into two groups, each consisting of 6 pigs. In group 1 the priming solution was prewarmed to 36-38 degrees C whereas it was maintained at room temperature in group 2. Platelets were selectively labelled with 111In-oxine. The activity over the lung was followed dynamically with a gamma camera and already after 2 min a significant difference in platelet sequestration showed between the groups. A significant increase in pulmonary vascular resistance was noted in group 2, but not in group 1. In conclusion, platelet aggregation occurs early on during dialysis in this model. The results also indicate that prewarming the priming solution attenuates the pulmonary platelet sequestration and also seems to decrease the changes in central hemodynamics.

Standardized intra-abdominal hemorrhage was induced in 7 anesthetized pigs. The resulting hypovolemic shock was treated with pneumatic anti-shock garment (PASG) followed by intra-aortic balloon occlusion. The effects of this treatment on circulation, lung mechanics and gas exchange were studied. Hemorrhage was induced by pulling out sutures introduced in the inferior caval vein. We found that the use of PASG partially restored mean arterial blood pressure from 44 +/- 6 to 66 +/- 6 mm Hg. When intraaortic balloon occlusion was added, the arterial pressure returned to basal levels. Cardiac output fell severely due to the hemorrhage from 3.7 +/- 0.2 to 1.3 +/- 0.2 liters/min and could not be restored during the treatment. A severe fall in total lung compliance was recorded after inflation of the PASG from 18.6 +/- 0.9 to 10 +/- 0.7 ml/cm H2O, this was accompanied by a fall in alveolar ventilation. These findings emphasize the severe restriction in lung function that occurred during treatment with PASG. Both parameters returned to near normal values when the PASG was deflated and the intra-aortic balloon was inflated. Pulmonary vascular resistance increased by more than 400% and remained high during the study period. There was no change in arterial PO2, however the fall in mixed venous PO2 caused by hemorrhage was reversed at the end of the treatment. Indirect monitoring of cerebral function by continuous EEG showed a decreased voltage during the hemorrhage, this was reversed by the combined treatment. We conclude that the outlined treatment makes it possible to restore central hemodynamics and preserve cerebral function at least for a short period of time until definite surgical treatment can be performed. However, severe restriction on lung mechanics, especially when PASG was inflated, makes it probable that ventilatory support can be necessary in such cases.

Significant soft-tissue trauma induces platelet activation, aggregation, and sequestration in the lungs. This pulmonary trapping is due either to the size of the platelet aggregates or to changes in the pulmonary microvasculature. To evaluate which one of these mechanisms is responsible for the trapping, we performed portacaval transposition in one group of pigs, making the liver the first receiving capillary bed for blood from the trauma sites in the lower extremities. One week after the operation, the platelets were labeled with indium oxine and reinfused, and the operated animals and a group of six control animals were subjected to standardized soft-tissue trauma to the lower extremities. Sequestration of platelets in the lungs and in the liver was registered dynamically before and for 90 minutes after the trauma. Soft-tissue trauma induced platelet sequestration in the liver in the operated group (p less than 0.01) and in the lungs in the control group (p less than 0.01). Trapping was paralleled by a decrease in the number of circulating platelets. This study has indicated that posttraumatic pulmonary platelet trapping is caused by platelet activation at the trauma sites and not by changes in the pulmonary microvasculature.

Soft tissue trauma is associated with platelet aggregation and sequestration in the lungs. This is believed to be an early step in the later development of adult respiratory distress syndrome. In the present experiment using a new method for in vivo dynamic studies of platelet sequestration, we wanted to evaluate the effect of soft tissue trauma on pulmonary platelet trapping in pigs and the influence of acute alcohol intoxication. The results show that significant pulmonary platelet trapping is registered within minutes of trauma and that alcohol significantly increases platelet sequestration in the lungs. This indicates an increased risk for posttraumatic pulmonary problems in alcohol-intoxicated trauma victims.

Neutrophils are thought to sequestrate in the lungs and the liver in association with shock. Indications for this have previously been demonstrated in different in vitro studies. In this experiment an in vivo technique for dynamic studies of pulmonary and liver neutrophil sequestration (PNT and LNT, respectively) is described. Autologous neutrophils from ten pigs were labelled with indium-111 oxine. The pigs were placed under a scintillation camera for continuous recording of the activity distribution in the pigs during 105 minutes. Following a steady-state period of 15 minutes seven pigs were subjected to a standardized soft-tissue trauma. Three pigs were used as controls and not traumatized. Within 1-3 minutes after trauma the radioactivity over the lungs increased dramatically, indicating PNT. This was followed by a fast decrease but 90 minutes after trauma PNT levels were still significantly elevated. LNT showed a similar pattern, although the immediate increase was less dramatic. This study shows that PNT and LNT occur immediately after soft-tissue trauma and can be studied dynamically in vivo.

Immediate reactions to different types of trauma have been the object of several studies recently. It has been shown that pulmonary platelet trapping (PPT) occurs within minutes after both septic shock and soft-tissue trauma. The purpose of this study was to investigate whether hypovolemia induced by hypoperfusion might trigger platelet trapping in the lungs in the same way as soft-tissue trauma. Platelets labelled with indium-oxine were reinfused in anesthetized and mechanically ventilated pigs 4 hours before either induction of standardized hypovolemia caused by bleeding to the amount of 20% of the estimated blood volume (n = 6) or a standardized soft-tissue trauma to the hind limbs (n = 7). Platelet sequestration in the lungs was recorded dynamically by means of scintigraphy for 15 minutes before and 90 min after the start of the trauma and bleeding episodes. Central hemodynamics were recorded using a Swan-Ganz catheter. Soft-tissue trauma induced a marked PPT; in the animals subjected to bleeding alone there was no such effect despite a hemodynamic deterioration of greater magnitude than in the trauma group. The PPT was accompanied by a reduction in the number of platelets and leukocytes in peripheral blood. Our results indicate that immediate trapping of plateletsmore » in the lungs after trauma occurs as a response to factors other than those related to simple hypovolemic hypoperfusion.« less

Immediate reactions to different types of trauma have been the object of several studies recently. Thus, it has been shown that pulmonary platelet trapping (PPT) occurs within minutes after both septic and traumatic shock following soft tissue trauma. To study whether block of the nervous supply to the traumatized tissue had any effect on PPT, 40 mg of mepivacaine was injected through an epidural catheter inserted between the second and third lumbar vertebrae in pigs. After a period of stabilization the animals were subjected to a standardized soft tissue trauma to the hind limbs. A group of animals without an epidural catheter served as control. The trauma induced a profound decrease in cardiac output and mean arterial pressure. Pulmonary platelet trapping was recorded dynamically by labelling platelets with radioactive indium. Trapping of platelets in the lungs occurred immediately after the trauma, and there was no difference in animals pretreated with epidural block compared with the control animals. Our findings indicate that the trapping of platelets after soft tissue trauma is triggered at the trauma site and not affected by a block of the nervous supply to the trauma sites, including the peripheral sympathetic outflow.