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Background. Non-heart-beating donors (NHBDs) have been proposed for the critical shortage of donors for cardiac and pulmonary transplantation. We determined the effects of prearrest hypoxia and postarrest warm ischemia on cardiac and pulmonary allografts procured from NHBDs undergoing hypoxic arrest. Methods. Rabbit hearts and lungs were procured from separate donors and placed on isolated blood perfusion circuits. Controls were excised and perfused without ischemia. Hearts from NHBDs underwent either prearrest hypoxic perfusion alone or consecutive periods of prearrest hypoxic perfusion and 20 minutes of postarrest warm ischemia. A third group of hearts underwent 30 minutes of warm, global ischemia alone. Two groups of pulmonary allografts were studied using similar hypoxic perfusion/20-minute ischemia and 30-minute ischemia donors. Results. Prearrest hypoxic perfusion clearly causes significant dysfunction of cardiac allografts from NHBDs compared with nonischemic controls. Prearrest hypoxic perfusion combined with postarrest ischemia results in an additive degree of dysfunction more severe than a similar period of warm ischemia alone. Both groups of experimental lungs displayed function similar to that of nonischemic controls in terms of pulmonary hemodynamics, airway resistance, and oxygenation potential. Conclusions. We conclude that prearrest hypoxic perfusion significantly contributes to the dysfunction of NHBD cardiac allografts. Pulmonary allografts may be more amenable to procurement of NHBDs.

Single-lung transplantation has been abandoned for the treatment of pulmonary hypertension by many centers because of overperfusion of the graft following implantation. Euro-Collins solution is currently used for lung preservation despite the vasoconstrictive effect of this intracellular-type solution. We hypothesized that high-flow reperfusion, alone or in combination with Euro-Collins–induced vasoconstriction, may cause lung dysfunction. Twenty-eight New Zealand White rabbit lungs were harvested and studied in an isolated, blood-perfused model of lung function after 4 hours of cold ischemia. Control lungs were preserved with 50 ml/kg cold saline solution flush and reperfused at either normal flow (60 ml/min) or high flow (120 ml/min). Experimental lungs were preserved with 50 ml/kg cold Euro-Collins solution and reperfused at normal or high flow rates. The arteriovenous oxygen gradient at the end of the 30-minute reperfusion period was significantly lower in the high-flow versus the low-flow experimental group (31.1 ± 4.2 vs 130.6 ± 41.6 mm Hg, p < 0.05). The pulmonary vascular resistance was increased in the high-flow groups and the experimental groups, with a statistically significant difference between low-flow experimental and control groups (64374.4 ± 5722.6 vs 37041.5 ± 2110.9 dynes•sec•cm–5, p < 0.001). The percentage decrease in dynamic airway compliance in the high-flow experimental group was markedly different from that in the high-flow control group (–51% ± 13.3% vs –10.15% ± 3.4%, p < 0.05). Similarly, the wet/dry ratio of the lungs in the high-flow experimental group (13.92 ± 2.32) was significantly greater than that in the low-flow experimental group (6.27 ± 0.19, p < 0.01) and than that in the high-flow control group (5.88 ± 0.23, p < 0.001). These data demonstrate that high-flow reperfusion and preservation with Euro-Collins solution are deleterious to lung function, both individually and in combination, in an ex vivo rabbit lung model. Lung preservation with Euro-Collins solution may not be optimal when high-flow reperfusion is anticipated, as in the setting of unilateral lung transplantation for pulmonary hypertension. (J Thorac Cardiovasc Surg 1996;112:111-6)

Background. Lung procurement from recently deceased cadavers has been suggested to enlarge the limited donor pool. We hypothesized that lungs harvested from non-heart-beating donors (NHBD) would function as well as those harvested from heart-beating donors. Methods. Sixteen adult swine underwent left lung allotransplantation. Controls received lungs procured from heart-beating donors, NHBD pigs received lungs immediately harvested from donors after death from asphyxiation, and NHBD-15 and NHBD-30 pigs received lungs harvested after 15 and 30 minutes after asphyxiation. Results. After 1 week of survival, mean dynamic airway compliance (mL/cm H2O ± standard error of the mean) was 16.3 ± 0.7 in controls, and 17.3 ± 1.0, 16.4 ± 6.0, and 7.3 ± 1.6 in the NHBD, NHBD-15, and NHBD-30 groups, respectively (p = 0.02, NHBD-30 versus others combined). No significant differences were noted in the pulmonary venous partial pressure of oxygen or pulmonary vascular hemodynamics compared with controls. Conclusions. The decrease in airway compliance noted in the NHBD-30 group may reflect an exacerbation of reperfusion injury caused by 30 minutes of warm ischemia during organ retrieval. We conclude that posttransplantation lung function using an NHBD with up to 15 minutes of warm ischemia is equivalent to lung function after heart-beating harvest.

Neonatal lung hypoplasia is frequently a fatal condition often associated with congenital diaphragmatic hernia. Unilateral lung transplantation rarely has been performed for this indication, although it is a potential solution. It is not known whether the transplant needs to function permanently or to act as a bridge until the native lung develops. It is also not known whether the native lung will grow in the face of an immunosuppressed state and chronic rejection of the transplanted lung. We therefore developed a porcine model of left lung rejection to study this. Infant swine underwent left lung transplantation. Chronic rejection occurred in all, resulting in nonfunction of the transplanted lung. The right lungs of these animals were compared with the right lungs of size-matched and age-matched control animals not given immunosuppressive treatment and not undergoing transplantation. There were no differences in terms of the functional residual capacity, airway compliance, and airway resistance among the groups. There was a significant increase in the pulmonary vascular resistance in the animals with transplanted lungs. There was also a significant increase in the lung weight in these animals. Unilateral pneumonectomies were done in 4 infant pigs to serve as controls. Three of the 4 did not survive the operation because of acute pulmonary failure. In conclusion, the study group exhibited evidence of compensatory growth that was not seen in the control animals, as shown by the increase in lung weight. This suggests that contralateral lung growth occurs in a growing animal, despite the effects of immunosuppression therapy and chronic rejection of the transplanted lung.

Background . An outbreak of excessive bleeding after cardiac operations occurred at our institution when 5% albumin was in short supply and hetastarch became the preferred intraoperative colloid. As hetastarch may impair coagulation, we investigated the effects of its intraoperative administration on post-cardiac surgical hemostasis. Methods . Indices of postoperative hemostasis were analyzed in 189 consecutive patients undergoing coronary artery bypass grafting. Three groups were compared: one group (n = 68) received a mean of 796 mL of hetastarch only in the operating room (a few minutes after cessation of cardiopulmonary bypass), another group (n = 59) received a mean of 856 mL postoperatively only, and a third group (n = 62) received no hetastarch. Results . Compared with the other two groups, those patients administered hetastarch intraoperatively exhibited significant reductions in hematocrit and platelet count, a significant prolongation in the prothrombin time, and significant increases in both blood loss and hemostatic drug requirement. Also identified were obvious trends toward a greater transfusion requirement and reexploration rate for bleeding in the latter group. Conclusions . Hetastarch infusion just after weaning from cardiopulmonary bypass produces a clinically important impairment in post-cardiac surgical hemostasis. Intraoperative use of this agent during heart operations should be avoided until the safe timing of its administration is clarified. (Ann Thorac Surg 1997;63:78–83)

Background: Reperfusion injury remains a significant problem after lung transplantation and is thought to be in part mediated by neutrophils. Ulinastatin inhibits release of elastase and cathepsin G from neutrophil granules. We hypothesized that inhibition of these neutrophil endopeptidases (proteases) would attenuate pulmonary reperfusion injury. Methods: With an isolated, whole blood–perfused, ventilated rabbit lung model, we studied the effects of ulinastatin. All lungs were flushed with cold Euro-Collins solution, harvested en bloc, stored inflated at 4° C for 18 hours, and reperfused with whole blood. The 18-hour control lungs ( n = 8) were stored and reperfused. Low-dose ( n = 8) and high-dose ( n = 7) groups were treated with total doses of ulinastatin of 25,000 and 50,000 units, respectively, during flush and reperfusion. An additional control group of lungs ( n = 8) was harvested, flushed, and immediately reperfused. Results: The pulmonary artery pressure was significantly lower in the high-dose group than in the 18-hour control group (36.7 ± 1.8 vs 44.8 ± 2.9 mm Hg, p = 0.034). The percentage decrease in dynamic airway compliance was significantly less in the high-dose group than in the 18-hour control group (-13.8% ± 4.4% vs -25.1% ± 3.7%, p = 0.032). Both low-dose and high-dose ulinastatin treatments did not result in a significant improvement in oxygenation with respect to the 18-hour control group (72.2 ± 25.8 vs 32.5 ± 4.9 mm Hg, p = 0.21). Conclusions: Ulinastatin diminishes reperfusion injury after 18 hours of hypothermic pulmonary ischemia, with resultant improvements in pulmonary artery pressure and airway compliance. Improvement in pulmonary function after preservation and reperfusion with a neutrophil endopeptidase inhibitor confirms the role of endopeptidases in reperfusion injury and suggests an intervention to reduce their detrimental effects on early graft function. (J THORAC CARDIOVASC SURG 1996;112:607-13)

The binding of leukocytes to intercellular adhesion molecules expressed on endothelial surfaces during ischemia and subsequent reperfusion initiates leukocyte-mediated reperfusion injury. Interruption of this leukocyte-endothelium interaction may therefore prevent reperfusion injury. In an isolated, ventilated, blood-perfused rabbit lung preparation, we studied the effect of a monoclonal anti–intercellular adhesion molecule antibody on lung function during reperfusion. Lungs were harvested with 50 ml/kg cold Euro-Collins flush and 30 μg prostaglandin E 1 before storage for 18 hours at 4o C. Experimental groups received low-dose (100 μg) or high-dose (200 μg) anti–intercellular adhesion molecule antibody added to the pulmonary flush at harvest and to the initial reperfusate. Eighteen-hour control preparations were preserved for 18 hours and received saline solution vehicle. Immediate control preparations were harvested and immediately reperfused. The oxygen tension in the recirculated pulmonary venous effluent was measured after 30 minutes of reperfusion. Histologic specimens were graded by blinded observers for degree of leukocyte infiltration (0, normal, to 4, severe infiltration). The mean oxygen tensions (±standard error of the mean) were 138.29 ± 6.23, 58.86 ± 9.14, 86.87 ± 11.32, and 139.33 ± 16.15 mm Hg in immediate control preparations, 18-hour control preparations, low-dose antibody group, and high-dose antibody group, respectively ( p = 0.0001). The leukocyte grades (mean ± standard error of the mean) were 1.5 ± 0.723, 3.0 ± 0.955, 1.9 ± 0.899, and 1.2 ± 0.834, respectively ( p = 0.0002). We conclude that anti–intercellular adhesion molecule antibody added to the pulmonary flush and initial reperfusate results in a dose-dependent enhancement of the reperfused lung's ability to oxygenate blood, possibly as a result of decreased leukocyte sequestration. (J THORAC CARDIOVASC SURG 1996;111:941-7)

OBJECTIVE: The authors reviewed the morbidity and mortality of surgical resection of the descending thoracic and thoracoabdominal aorta using the clamp-and-sew technique. BACKGROUND: Paraplegia remains a devastating complication after thoracoabdominal aortic resection, despite many strategies for spinal cord protection. Because of its simplicity, clamp and sew has been the preferred technique at the University of Virginia for the thoracoabdominal aortic resection when proximal control is possible. METHODS: Between 1987 and 1994, the authors reviewed 91 consecutive patients who underwent thoracic aortic resection using clamp-and-sew techniques without any additional adjuncts for spinal cord protection. RESULTS: The average age of patients was 60.8 years; 57.1% were male. No intraoperative deaths occurred. In-hospital mortality was 13% (12/91), with an overall incidence of postoperative spinal cord injury manifested as paraparesis or paraplegia of 9.9% (9/91). Eighty-nine percent (81/91) of all repairs were completed with aortic clamp times of 40 minutes or less, and nearly six out of ten were completed in 30 minutes or less (53/91). Cross-clamp times were not significantly different between those patients who sustained neurologic injury and those who had no deficits. CONCLUSIONS: The authors conclude that clamp and sew is still a viable technique for thoracoabdominal aortic resection. Nearly all resections can be completed within 40 minutes of aortic occlusion. However, the "safe" duration of thoracic aortic occlusion remains unknown, and spinal cord injury can occur even with short clamp times. Reproducible, safe, and technically simple means of spinal cord protection must be developed.

We previously demonstrated that standard preservation using Euro-Collins solution impairs lung function in the setting of high-flow reperfusion because of potassium-induced vasoconstriction. Preservation strategies for single-lung transplantation are an important factor in patients with pulmonary hypertension. This study investigates the hypothesis that low-potassium preservation solution will improve function of lungs subjected to high-flow reperfusion.Twenty-one New Zealand white rabbit lungs were harvested and studied on an isolated, blood-perfused model of lung function after 4 hours of cold ischemia at 4 degrees C. Control lungs were preserved with 50 mL/kg of cold saline solution flush (group I). Experimental lungs were preserved with low-potassium solution (group II) or Euro-Collins solution (group III) at similar temperatures and volumes.The pulmonary arteriovenous oxygen gradient at the end of the 30-minute high-flow reperfusion period was significantly higher in group II compared with group III (121.3 +/- 19.2 mm Hg versus 31.1 +/- 4.2 mm Hg; p0.001). The pulmonary vascular resistance was significantly lower in group II than in group III (46.3 +/- 1.8 x 10(3) dynes x s x cm(-5) versus 79.8 +/- 8.4 x 10(3) dynes x s x cm(-5); p0.01. The percent decrease in dynamic airway compliance in group III was significantly greater than in group I and II (-51.0% +/- 13.3% versus -10.2% +/- 3.4% and -11.2% +/- 2.8%, respectively; p0.001). Similarly, the wet to dry ratio of the lungs in group III was significantly greater than in groups I and II (13.9 +/- 2.3 versus 5.9 +/- 0.2 and 6.0 +/- 0.4, respectively; p0.001).These data demonstrate that a low-potassium preservation solution yields improved lung function after high-flow reperfusion in an ex vivo rabbit lung model. Lung preservation should be aimed at the clinical setting.

Spinal cord injury occurring as the result of surgical repair of thoracic and thoracoabdominal aortic disease remains a devastating complication. The incidence of postoperative neurologic deficits varies from 4% to 38%. Factors associated with a greater risk for injury include the presence of dissection or extensive thoracoabdominal disease, and a prolonged cross-clamp time. Spinal cord ischemia initiates a deleterious cascade of biochemical events that ultimately result in an increased intracellular calcium concentration. Calcium-activated proteases, lipases, and nucleases mediate the processes that cause cell injury. The accumulation of oxygen-derived free radicals and the occurrence of hyperemia during reperfusion are also contributing causes of spinal cord injury. Increasing the spinal cord blood flow with shunts, oxygenated bypass circuits, cerebrospinal fluid drainage, the intrathecal administration of vasodilators, and the reattachment of intercostal arteries has been tried in an effort to increase spinal cord perfusion. Pharmacologically based measures to prevent spinal cord injury have been pursued, and these have consisted of hypothermia, anesthetic agents, calcium channel blockers, free radical scavengers, and immune system modulation. However, no single technique has proved to be consistently effective in preventing ischemia-induced spinal cord injury.

OBJECTIVE: The authors ascertained the optimal timing of repair of an abdominal aortic aneurysm (AAA) after coronary artery revascularization. SUMMARY BACKGROUND DATA: Cardiac events are the most common cause of death after elective repair of AAA. Preoperative coronary revascularization has significantly reduced postoperative cardiac complications after elective AAA repair. Currently, most patients undergo repair of asymptomatic AAA within 6 months after the coronary revascularization. METHODS: The authors performed a retrospective review of patients who underwent repair or scheduled repair of an asymptomatic AAA within 6 months after coronary artery bypass graft (CABG) between March 1988 and October 1993. RESULTS: There was no mortality in the group of patients (n = 14) who underwent repair of AAA simultaneously or within 14 days of coronary revascularization. In contrast, there was a significantly increased mortality rate of 3 of 9 (33%) in patients scheduled to undergo repair of the AAA more than 2 weeks after coronary revascularization (p < 0.05). All nonsurvivors died between 16 and 29 days after CABG, and died as a result of ruptured AAA. CONCLUSION: Elective AAA repair should be undertaken simultaneously or within 2 weeks of coronary artery revascularization because of an increased risk of postoperative AAA rupture seen after this time period. In addition, simultaneous or early postoperative AAA repair does not increase the overall operative risk.