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Background: Heart transplantation is an established therapy for cardiomyopathy but is limited by organ shortage and expense. As a result, alternative operations have been proposed including coronary bypass, mitral valve repair, and left ventricular reconstruction. Because it is unknown whether alternative operations are less expensive than replacing the diseased heart, we compared in-hospital costs and early outcome of these operations with elective heart transplantation., Methods: We compared clinical and financial data of 268 patients with ejection fraction less than 30% who underwent elective heart transplantation (n = 52, UNOS status 2 only), coronary bypass (n = 176), mitral repair (n = 15), or left ventricular reconstruction (n = 25). Data were evaluated for between-group differences, with p less than 0.05 as significant., Results: Preoperative ejection fraction, although similar for heart transplantation (21.2% +/- 1.3%), coronary bypass (25.8% +/- 0.4%), mitral repair (22.9% +/- 1.5%), and left ventricular reconstruction (24.2% +/- 2.1%), was significantly different between the former two (p < 0.001). There was no difference in operative mortality: 5.8% (3 of 52), 3.4% (7 of 176), 6.7% (1 of 15), and 4.0% (1 of 25), respectively (p = 0.8). However, total hospital cost of heart transplantation was significantly greater than all others: $75,992 +/- $5,380, $25,008 +/- $1,446, $32,375 +/- $2,379, and $26,584 +/- $4,076, respectively (p < 0.001). Organ procurement expenses alone comprised 39.7% ($30,169) of total transplant cost. Kaplan-Meier survival analysis failed to show any survival difference between the various groups (p = 0.86), Conclusions: Compared with heart transplantation, alternative operations yield a comparable early outcome and long-term survival, and are markedly less expensive. The cost of transplantation, which is largely due to procurement expenses, is yet another reason to attempt alternative operations for cardiomyopathy whenever feasible.

Background: We hypothesized that the use of aprotinin would ameliorate the reperfusion injury observed after lung transplantation because of a reduction in the inflammatory response., Methods: We used an isolated, whole blood-perfused, ventilated rabbit lung model to study the effects of aprotinin during reperfusion. The control animals (group A, n = 8) underwent lung harvest after pulmonary arterial prostaglandin E1 injection and Euro-Collins preservation flush before saline storage for 18 hours at 4 degrees C. The experimental groups received either a low dose (3,000 KIU/mL; group B, n = 8) or a high dose (10,000 KIU/mL; group C, n = 8) of aprotinin added to the pulmonary flush before storage. Each lung was reperfused at 37 degrees C at a rate of 60 mL/min., Results: The arterial partial pressure of oxygen values of group B (low-dose aprotinin) were significantly higher than those of group A (control) after 10 minutes of reperfusion (69.19 +/- 5.69 mm Hg versus 264.30 +/- 48.59 mm Hg, respectively, p = 0.001). Similar results were recorded at 20 and at 30 minutes of reperfusion. Similarly, after 10 minutes of reperfusion, the differences between groups A and C were 69.19 +/- 5.69 mm Hg versus 235.91 +/- 28.63 mm Hg, respectively (p = 0.001)., Conclusions: The addition of aprotinin to the Euro-Collins pulmonary flush significantly improves arterial oxygenation in the early reperfusion period. The enhanced oxygenation suggests that aprotinin may offer protection against early reperfusion injury.

Objective: Epidermal growth factor has been shown to play an important role in prenatal and postnatal lung development, but little is known about its effects on adult lung growth. We hypothesized that postpneumonectomy compensatory lung growth can be augmented by the administration of epidermal growth factor., Methods: Adult Sprague-Dawley rats were divided into 3 groups. Sham left thoracotomy was performed in the first group (group C), left pneumonectomy in the second group (group P), and left pneumonectomy with administration of epidermal growth factor (0.2 microgram/g body weight intraperitoneally, at 72-hour intervals) in the third group (group E). The right lung growth was studied in each group 1, 3, 5, 10, and 21 days after the operation. Lung weights (in grams) and volumes (in milliliters) were expressed as a ratio to the total body weight (in kilograms) (lung weight and volume indices). Epidermal growth factor receptor was quantitated by using Western blotting., Results: Using analysis of variance and contrast analysis, we noted a significant increase in lung weight index in group E versus group P rats at 3 days (3.08 vs 2.75; P =.034) and 21 days (4.62 vs 3.61; P =.006). Lung volume index was significantly increased in group E versus group P rats at 5 (16.98 vs 15.09), 10 (24.48 vs 18.81), and 21 (28.54 vs 21.01) days (P <.001). Epidermal growth factor receptor was noted to be up-regulated in the lungs of animals that received exogenous epidermal growth factor., Conclusions: This study demonstrates that administration of exogenous epidermal growth factor has a significant effect on postpneumonectomy lung growth. This process may be mediated by an up-regulation of growth factor receptor expression in the contralateral lung.

A central role for nuclear factor-kappaB (NF-kappaB) in the induction of lung inflammatory injury is emerging. We hypothesized that NF-kappaB is a critical early regulator of the inflammatory response in lung ischemia-reperfusion injury, and inhibition of NF-kappaB activation reduces this injury and improves pulmonary graft function. With use of a porcine transplantation model, left lungs were harvested and stored in cold Euro-Collins preservation solution for 6 h before transplantation. Activation of NF-kappaB occurred 30 min and 1 h after transplant and declined to near baseline levels after 4 h. Pyrrolidine dithiocarbamate (PDTC), a potent inhibitor of NF-kappaB, given to the lung graft during organ preservation (40 mmol/l) effectively inhibited NF-kappaB activation and significantly improved lung function. Compared with control lungs 4 h after transplant, PDTC-treated lungs displayed significantly higher oxygenation, lower PCO(2), reduced mean pulmonary arterial pressure, and reduced edema and cellular infiltration. These results demonstrate that NF-kappaB is rapidly activated and is associated with poor pulmonary graft function in transplant reperfusion injury, and targeting of NF-kappaB may be a promising therapy to reduce this injury and improve lung function.

Purpose: Spinal cord injury and the resultant postoperative paraplegia are devastating complications of thoracic aortic surgery, for which no widely accepted protective interventions exist. We hypothesized that retrograde venous perfusion-cooling of the spinal cord with a hypothermic saline and adenosine solution would protect it from ischemic injury caused by thoracic aortic occlusion., Methods: Adult domestic swine of either sex (weight range, 20 to 30 kg) were intubated and ventilated. A left thoracotomy was performed. The accessory hemiazygous vein was divided, and a catheter was inserted distally. The aorta was clamped at the left subclavian artery. The venous catheter was not used in the animals in the control group (n = 7); in the animals in the experimental group (n = 7), a cold (4 degrees C) saline and adenosine solution was infused into the accessory hemiazygous vein. After 30 minutes, the clamp and catheter were removed, and the chest was closed. A blinded observer evaluated the animals' hind-leg motor activity 24 hours later. The Tarlov scale was used: 0, complete paralysis; 1, minimal movement; 2, stands with assistance; 3, stands alone; 4, weak walk; 5, normal gait. The animals' rectal temperatures were measured at the end of the experiment, and blood pressure was measured throughout. Two other groups were studied to assess the effect of the intervention on spinal cord temperature., Results: The animals in the control group had a mean Tarlov score of 1.7 +/- 0.6; the animals in the experimental group had a mean Tarlov score of 4.9 +/- 0.1 (P <.01). The animals in the experimental group had a significantly greater drop in spinal cord temperature than those in the control group (4. 05 +/- 0.6 degrees C vs 0.58 +/- 0.12 degrees C; P <.01). No significant difference in rectal temperatures was found, nor did any arrhythmias or hypotensive episodes occur in either group. Perfusion of the spinal cord was confirmed with angiography by using this approach., Conclusion: Retrograde venous perfusion-cooling of the spinal cord with a hypothermic saline and adenosine solution protects the cord from ischemic injury caused by clamping of the thoracic aorta.

Background: Neuronal voltage-dependent sodium channel antagonists have been shown to provide neuroprotection in focal and global cerebral ischemic models. We hypothesized that retrograde spinal cord venous perfusion with phenytoin, a neuronal voltage-dependent sodium channel antagonist, would provide protection during prolonged spinal cord ischemia., Methods: In a rabbit model, spinal cord ischemia was induced for 45 minutes. Six groups of animals were studied. Controls (group I, n = 8) received no intervention during aortic cross-clamping. Group II (n = 8) received systemic phenytoin (100 mg). Group III (n = 4) received systemic phenytoin (200 mg). Group IV (n = 8) received retrograde infusion of room temperature saline (22 degrees C) only. Group V (n = 8) and group VI (n = 9) received retrograde infusion of 50 mg and 100 mg of phenytoin, respectively, (infusion rate: 0.8 mL x kg(-1) x min(-1) during the ischemic period). Mean arterial blood pressure was monitored continuously. Animals were allowed to recover for 24 hours before assessment of neurologic function using the Tarlov scale., Results: Tarlov scores (0 = complete paraplegia, 1 = slight lower limb movement, 2 = sits with assistance, 3 = sits alone, 4 = weak hop, 5 = normal hop) were as follows (mean +/- SEM): group I, 0.50 +/- 0.50; group II, 0.25 +/- 0.46; group IV, 1.63 +/- 0.56; group V, 4.13 +/- 0.23; and group VI, 4.22 +/- 0.22 (p < 0.0001 V, VI versus I, II, IV by analysis of variance). No differences in mean arterial blood pressure were observed. All animals in group III became profoundly hypotensive and died before the conclusion of the 45-minute ischemic time., Conclusions: Retrograde venous perfusion of the spinal cord with phenytoin, a voltage-sensitive sodium channel blocker, is safe and provides significant protection during prolonged spinal cord ischemia.

Objective: We evaluated the utility of retrograde venous perfusion to cool the spinal cord and protect neurologic function during aortic clamping. We hypothesized that hypothermic adenosine would preserve the spinal cord during ischemia., Methods: Six swine (group I) underwent thoracic aortic occlusion for 30 minutes at normothermia. Group II animals underwent spinal cooling by retrograde perfusion of the paravertebral veins with hypothermic (4 degrees C) saline solution during aortic occlusion. The spinal cords of group III animals were cooled with a hypothermic adenosine solution in a similar fashion. Intrathecal temperature was monitored and somatosensory evoked potentials assessed the functional status of spinal pathways., Results: Spinal cooling without systemic hypothermia significantly improved neurologic Tarlov scores in group III (4.8 +/- 0.2) and group II (3.8 +/- 0.4) when compared with group I scores (1.3 +/- 0.6) (P <.001). Furthermore, 5 of the 6 animals in group III displayed completely normal neurologic function, whereas only one animal in group II and no animals in group I did (P =.005). Somatosensory evoked potentials were lost 10.6 +/- 1.4 minutes after ischemia in group I. In contrast, spinal cooling caused rapid cessation of neural transmission with loss of somatosensory evoked potentials at 6.9 +/- 1.2 minutes in group II and 7.0 +/- 0.8 minutes in group III (P =.06). Somatosensory evoked potential amplitudes returned to 85% of baseline in group III and 90% of baseline in group II compared with only 10% of baseline in group I (P =.01)., Conclusions: We conclude that retrograde cooling of the spinal cord is possible and protects against ischemic injury and that adenosine enhances this effect. The efficacy of this method may be at least partly attributed to a more rapid reduction in metabolic and electrical activity of the spinal cord during ischemia.

The authors sought to determine if patients with stroke and a high-grade carotid stenosis benefited from a delay before carotid endarterectomy. A retrospective study of 45 patients undergoing carotid endarterectomy after stroke is presented. The patients were divided into two groups: group I (early group, n = 20), composed of patients who had carotid endarterectomy less than 6 weeks after stroke, and group II (late group, n = 25), comprised of patients who had carotid endarterectomy more than 6 weeks after stroke. As assessed by cerebral angiography, 100% of patients in group I and 64% of patients in group II had carotid artery stenoses > 76% (P < 0.001). The median interval from stroke to carotid endarterectomy was 14 days in group I and 129 days in group II. There was no mortality in either group. No patients in either group demonstrated any neurological deterioration. The authors conclude that, in select patients, carotid endarterectomy may be done safely less than 6 weeks after stroke in order to avoid new events or carotid occlusion while awaiting surgery.

The purpose of this study was to analyze the utilization, cost profile, and predictors of intensive care unit (ICU) services after carotid endarterectomy. A retrospective medical record review of all patients undergoing isolated carotid endarterectomy by a vascular surgery service at one university hospital during a 12-month period was performed. Eighty-four patients undergoing 91 carotid endarterectomies were identified for review. All carotid endarterectomy patients at the authors' institution were routinely admitted to an ICU postoperatively. Sixty-five of the 91 patients (71.4%) required ICU interventions, the majority of which were intravenous antihypertensive therapy. There were no deaths in the group. There was one non-fatal stroke (1.1%), and one non-fatal myocardial infarction (1.1%). There were three reoperations (3.3%): two for hematoma and one for a change in neurological status. One patient required reintubation. Five of the six major adverse events after carotid endarterectomy occurred within 12 hours postoperatively. No preoperative factors predicted a significant risk for complications following carotid endarterectomy. There is no reliable predictor that carotid endarterectomy patients will require postoperative interventions or develop adverse outcomes. Mandatory intensive care immediately after carotid endarterectomy upholds high safety standards, avoids the uncertainty of preoperative ICU planning, and avoids the high cost of a recovery room stay to determine the need for intensive care. In addition, costs may be further reduced as the ICU length of stay may be decreased if there are no necessary interventions or complications after 12 hours of intensive care.

Objective: The purpose of this article was to examine the influence of reimplantation of patent intercostal and lumbar arteries on the incidence of postoperative paraplegia/paraparesis in patients undergoing clamp-and-sew surgical repair of thoracoabdominal aortic aneurysms., Methods: Data from January 1987 through December 1997 were retrospectively collected on 132 patients. Ninety-one patients in group I underwent aneurysm repairs before January 1995 and did not undergo intercostal artery reimplantation. Group II included the more recent 41 patients who had vessels between the eighth thoracic intercostal and the second lumbar arteries reimplanted to the graft or preserved at the aortic anastomoses., Results: The operative mortality rate was 13.2% (12/91) in group I and 4.9% (2/41) in group II (P =.22). The incidence of postoperative paraplegia was significantly lower in the more recent cohort of patients (8.8% [8/91] in group I vs 0% [0/41] in group II, P =.05). The overall rate of spinal cord dysfunction was lowered from 9.9% (9/91) in group I to 2.4% (1/41) in group II (P =.17). However, a multivariable logistic regression analysis identified only aneurysm extent (Crawford type I and type II) as a predictor of less postoperative spinal cord injury (P =.08). The average aortic crossclamp time in group I was 30.3 +/- 11.5 (SD) minutes, and the time of aortic occlusion in group II was not significantly prolonged, with an average crossclamp time of 31.0 +/- 21.0 (SD) minutes (P =. 88)., Conclusions: An aggressive approach to maintain intercostal artery patency during clamp-and-sew repair of thoracoabdominal aortic aneurysms may effectively lower the incidence of spinal cord injury without prolonging aortic crossclamp time.

Background: Paraplegia remains a devastating complication following thoracic aortic operation. We hypothesized that retrograde perfusion of the spinal cord with a hypothermic, adenosine-enhanced solution would provide protection during periods of ischemia due to temporary aortic occlusion., Methods: In a rabbit model, a 45-minute period of spinal cord ischemia was produced by clamping the abdominal aorta and vena cava just below the left renal vessels and at their bifurcations. Four groups (n = 8/group) were studied: control, warm saline, cold saline, and cold saline with adenosine infusion. In the experimental groups, saline or saline plus adenosine was infused into the isolated cavae throughout the ischemic period. Clamps were removed and the animals to recovered for 24 hours before blinded neurological evaluation., Results: Tarlov scores (0 = paraplegia, 1 = slight movement, 2 = sits with assistance, 3 = sits alone, 4 = weak hop, 5 = normal hop) were (mean +/- standard error of the mean): control, 0.50 +/- 0.50; warm saline, 1.63 +/- 0.56; cold saline, 3.38 +/- 0.26; and cold saline plus adenosine, 4.25 +/- 0.16 (analysis of variance for all four groups, p < 0.00001). Post-hoc contrast analysis showed that cold saline plus adenosine was superior to the other three groups (p < 0.0001)., Conclusion: Retrograde venous perfusion of the spinal cord with hypothermic saline and adenosine provides functional protection against surgical ischemia and reperfusion.

Background: There is evidence that lung ischemia reperfusion injury is a result of the activation of components of the inflammatory cascade. However, the role of neutrophils in lung reperfusion injury continues to be a source of controversy., Methods: Using an isolated, whole blood-perfused, ventilated rabbit lung model, we sought to characterize the pattern of reperfusion injury and investigate the contribution of neutrophils to this injury. Donor rabbits underwent lung harvest after pulmonary arterial prostaglandin E1 injection and Euro-Collins preservation solution flush. Group I lungs (n = 8) were immediately reperfused without ischemic storage. Group II lungs (n = 8) were stored for 18 h at 4 degrees C before reperfusion. Group III lungs (n = 10) underwent 18 h of ischemic storage and were reperfused with whole blood that was first passed through a leukocyte-depleting filter. All lungs were reperfused for 2 h., Results: Arterial oxygenation in group III progressively improved, and was significantly higher than that of group II after 2 h of reperfusion (272.58+/-58.97 vs 53.58+/-5.34 mm Hg, p = 0.01). Both pulmonary artery pressure and pulmonary vascular resistance were significantly reduced in group III when compared with group II (27.85+/-1.45 vs 44.15+/-4.77 mm Hg, p = 0.002; and 30,867+/-2,323 vs 52,775+/-6,386 dynes x sec x cm(-5), p = 0.003, respectively). Microvascular permeability in group III lungs was reduced to 73.98+/-6.15 compared with 117.16+/-12.78 ng Evans blue dye/g tissue in group II (p = 0.005). Group III myeloperoxidase activity was 56.92+/-6.31 deltaOD/g/min compared with 102.84+/-10.41 delta0d/g/min in group II (p = 0.002)., Conclusions: Leukocyte depletion of the blood reperfusate protects against microvascular permeability and significantly improves pulmonary graft function. The neutrophil plays a major role in amplifying lung injury later during reperfusion, and this lung ischemia reperfusion injury may be reversed through the interruption of the inflammatory cascade and the interference with neutrophil infiltration.

Background: As many as 40% of patients with left-sided bacterial endocarditis will sustain a neurologic insult. The importance of a neurologic change as an indication or a contraindication for valve replacement remains controversial., Methods: We performed a retrospective analysis of the records of 33 patients admitted to the University of Virginia Health Sciences Center between January 1, 1978, and June 30, 1996, with a diagnosis of endocarditis and a neurologic change., Results: All 33 patients had echocardiographic or pathologic evidence of left-sided endocarditis; 23 were seen with focal neurologic findings and had a mortality rate of 22% (5 of 23), and 10 patients were seen with nonfocal, diffuse encephalopathy and had a mortality rate of 60% (6 of 10) (p<0.05). Of the 33 patients, 14 underwent operation and 19 were treated medically. The mortality rate was 21.4% (3 of 14) in the surgical group and 42.1% (8 of 19) in the medical group (p = not significant). In 71% (10 of 14) of the surgical patients, the operation was done within 1 week of the neurologic event. Additional neurologic deterioration occurred in 18.2% (2 of 11) of survivors in the surgical group and 9.1% (1 of 11) in the medical group (p = not significant)., Conclusions: Choosing therapy for a patient with endocarditis and a neurologic change remains a difficult challenge. Initial findings of nonfocal, global dysfunction on examination are a predictor of a poor outcome. By comparing surgical and medical groups derived from the same series of patients, it is clear that patients with bacterial endocarditis and central nervous system changes face substantial mortality regardless of intervention. However, these data demonstrate that when compared with a similar group of medical patients, surgical patients who require and receive operation early in the course of their illness do comparatively well. Improving outcomes by delaying surgical intervention may serve to "select out" hardier patients but will lead to the death of patients who might benefit from such intervention.

Lipopolysaccharide (LPS)-induced septic shock, which triggers nitric oxide (NO) overproduction, multiple organ dysfunction, and death, can be affected by gender and sex hormones. We hypothesized that NO is beneficial during endotoxemia and that this beneficial effect is influenced by sex hormones. C57BL/6 wild-type (WT) mice and congenic inducible NO synthase knockout (KO) mice were injected with LPS, and mortality was recorded for 4 days. After 5 mg/kg LPS, female KO mice had significantly higher mortality than WT. After 12.5 mg/kg LPS, both male and female KO mice had significantly higher mortality than WT. Ovariectomy did not alter mortality, but orchiectomy dramatically increased mortality in KO mice. After 5 mg/kg LPS, exogenous testosterone completely prevented the increased mortality in KO female and orchiectomized KO male mice. WT survival was not affected by exogenous testosterone. After 12.5 mg/kg LPS, exogenous testosterone significantly improved survival of female KO mice. Serum enzymes and organ edema, which may not correlate with mortality, were significantly and similarly increased in both WT and KO endotoxemic mice; however, edema was not observed in KO hearts. Thus, NO plays a protective role in endotoxemia while having differential effects on different organs. Importantly, testosterone is beneficial in endotoxemia when NO production is deficient, and may be therapeutic in certain septic patients.

Background: Cyclic guanosine monophosphate (cGMP) is a potent second messenger for the nitric oxide pathway in the pulmonary vasculature. Increased cytosolic cGMP levels elicit pulmonary vasodilatation resulting in decreased pulmonary vascular resistance and maximized pulmonary function after ischemia-reperfusion injury. We hypothesized that the addition of a membrane-permeable cGMP analogue (8-bromo-cGMP) to a Euro-Collins (EC) preservation solution would ameliorate pulmonary reperfusion injury better than prostaglandin E1 injection alone after prolonged hypothermic ischemia., Methods: All lungs from New Zealand White rabbits (weight, 3 to 3.5 kg) were harvested en bloc, flushed with EC solution, and reperfused with whole blood for 30 minutes. Group 1 lungs (immediate control) were immediately reperfused. Group 2 lungs (control) were stored inflated at 4 degrees C for 18 hours before reperfusion. Groups 3 and 4 lungs were flushed with EC solution containing 200 micromol/L 8-bromo-cGMP and stored at 4 degrees C for 18 and 30 hours, respectively. Fresh, nonrecirculated venous blood was used to determine single-pass pulmonary venous-arterial oxygen gradients at 10-minute intervals. Assays for cGMP, cyclic adenosine monophosphate, nitric oxide synthase activity, and myeloperoxidase were performed on all lung tissue samples. Wet to dry weight ratios were determined after 2 weeks of passive desiccation., Results: Oxygenation (venous-arterial oxygen gradient), pulmonary artery pressure, pulmonary vascular resistance, and edema formation were significantly improved in groups 3 and 4 (addition of 8-bromo-cGMP to EC plus 18 or 30 hours of hypothermic ischemia). Hypothermic storage (groups 2, 3, and 4) decreased both nitric oxide synthase activity and myeloperoxidase levels compared with immediate reperfusion (group 1)., Conclusions: These results suggest that the addition of a membrane-permeable cGMP analogue to an EC pulmonary flush solution improves pulmonary function after prolonged storage compared with EC and prostaglandin (E1) preservation alone. The finding of myeloperoxidase reduced levels after hypothermic storage and subsequent reperfusion may suggest a more important role for pulmonary hemodynamic control in mitigating pulmonary reperfusion injury.

Background: Patients with large (> or = 5.0 cm) abdominal aortic aneurysms (AAA) frequently have marked associated coronary artery disease. We hypothesized that a single operation for coronary artery bypass grafting (CABG)/AAA would provide equivalent, if not improved, patient care while decreasing postoperative length of stay and hospital costs compared with staged procedures., Methods: Eleven patients to date have undergone a combined procedure at our institution. Ten underwent CABG followed by AAA repair, whereas one patient received an aortic valve replacement before aneurysm repair. We performed a retrospective analysis comparing the postoperative length of stay and hospital costs for this single procedure to a combined cohort of 20 randomly selected patients who either received AAA repair (n = 10) or standard CABG (n = 10) during the same time period., Results: No operative mortality has been reported. There were no episodes of neurologic deficit or cardiac complication after these procedures. The postoperative length of stay was significantly decreased for the CABG/AAA group compared with the combined postoperative length of stay for the AAA plus CABG group (7.44+/-0.88 days versus 14.10+/-2.00; p = 0.012). Total hospital costs were also significantly decreased for the CABG/AAA group compared with total hospital costs for the AAA plus CABG group ($22,941+/-$1,933 versus $34,076+/-$2,534; p = 0.003)., Conclusions: A single operation for coronary revascularization and AAA repair is safe and effective. Simultaneous CABG and AAA repair substantially decreases postoperative length of stay and hospital costs while avoiding possible interim aneurysm rupture and repeat anesthesia.

Background: The role of nitric oxide synthase in myocardial ischemia-reperfusion injury is complex. Our hypothesis was that inducible nitric oxide synthase has a role in the regulation of coronary flow after ischemia., Methods: Four groups of isolated blood-perfused rabbit hearts underwent sequential periods of perfusion, ischemia, and reperfusion (20, 30, and 20 minutes). Two groups underwent 40 minutes of perfusion. Ischemic groups received saline vehicle, N omega-nitro-L-arginine methyl ester (L-NAME) or the highly specific inducible nitric oxide synthase inhibitor 1400W in low or high doses during reperfusion. Two nonischemic groups were treated with saline vehicle or 1400W during the last 20 minutes of perfusion. Left ventricular developed pressure and coronary flow were measured after each perfusion period. Ventricular levels of myeloperoxidase and cyclic guanosine monophosphate were measured at the end of the second perfusion period., Results: Coronary flow was significantly increased in both 1400W groups versus L-NAME (p < 0.001) and in high-dose 1400W versus control (p < 0.001). Coronary flow was not significantly different between the nonischemic groups. Left ventricular developed pressure was not significantly different among the ischemic groups or between the two nonischemic groups. There were no differences in cyclic guanosine monophosphate levels in any of the ischemic hearts. Myeloperoxidase levels were significantly elevated in L-NAME versus high-dose 1400W, nonischemic 1400W, and nonischemic saline groups (p < 0.02)., Conclusions: Highly selective inhibition of inducible nitric oxide synthase results in increased coronary flow after ischemia but not after continuous perfusion. This occurs with decreased neutrophil accumulation and a trend toward increased contractility without elevation of cyclic guanosine monophosphate levels.

Background: Improved techniques in cerebral and myocardial protection have made replacement of the chronically aneurysmal ascending thoracic aorta a safe and effective procedure. We hypothesized that patients with severe ascending or aortic arch atherosclerosis were at greater risk for operative complications during ascending aortic replacement because of the diffuse nature of their atherosclerotic process., Methods: We retrospectively analyzed the records of 17 patients who received ascending aortic replacement during elective coronary artery bypass grafting (CABG) because of the intraoperative finding of severe atherosclerosis. All 17 patients underwent tube graft replacement of the ascending aorta under hypothermic circulatory arrest and retrograde cerebral perfusion before coronary artery bypass grafting. The outcomes for these patients were compared with those of a control group of 89 consecutive patients who underwent replacement for ascending thoracic aortic aneurysm., Results: The hospital mortality rate for replacement of the ascending thoracic aorta for severe atherosclerosis was 23.5% (4/17) versus 2.25% (2 of 89) for the control group (p=0.006). The incidence of cerebrovascular accident in the atherosclerotic group was 17.6% (3/17) and 3.37% (3/89) for the control group (p=0.051). Nine of 17 atherosclerotic patients (52.9%) had operative morbidity. Only 20.2% (18 of 89) of the control patients had nonfatal postoperative complications., Conclusions: The severely atherosclerotic ascending aorta is a marker of diffuse atherosclerosis. Despite improved techniques of myocardial and cerebral protection, we have been unable to duplicate our success with ascending thoracic aneurysm repair. Preoperative screening of the ascending aorta by chest computed tomography may be appropriate in select high-risk patients to determine operability.

Objective: The purpose of this study was to investigate the safety and efficacy of a period of deep hypothermic circulatory arrest (DHCA) during elective replacement of the ascending thoracic aorta., Summary Background Data: DHCA has been implemented in ascending thoracic aortic aneurysm resection whenever the anatomy or pathology of the aorta or arch vessels prevents safe or adequate cross-clamping. Profound hypothermia and retrograde cerebral perfusion have been shown to be neurologically protective during ascending aortic replacement under circulatory arrest., Methods: The authors conducted a retrospective analysis of 91 consecutive patients who underwent repair of chronic ascending thoracic aortic aneurysms from 1986 to present. The authors hypothesized that patients undergoing DHCA with or without retrograde cerebral perfusion during aneurysm repair were at no greater operative risk than patients who received aneurysm resection while on standard cardiopulmonary bypass., Results: There were no significant differences in hospital mortality, stroke rate, or operative morbidity between patients repaired on DHCA when compared to those repaired on cardiopulmonary bypass., Conclusions: DHCA with or without retrograde cerebral perfusion does not result in increased morbidity or mortality during the resection of ascending thoracic aortic aneurysms. In fact, this technique may prevent damage to the arch vessels in select cases and avoid the possible complications associated with cross-clamping a friable or atherosclerotic aorta.

Background: The role of nitric oxide in myocardial ischemia-reperfusion is controversial. Although many studies claim that nitric oxide ameliorates reperfusion injury, others suggest that it exacerbates such injury, possibly through peroxynitrite production. These discordant results may be attributable to a dose-dependent phenomenon., Methods: Isolated rabbit hearts sustained sequential periods of blood perfusion (20 minutes), warm ischemia (30 minutes), and reperfusion (20 minutes). During reperfusion, four groups underwent intracoronary infusion of saline solution (n = 6), or the nitric oxide donor sodium nitroprusside (100 nm/min [SNP100, n = 6], 1 nmol x L(-1)/min(-1) [SNP1, n = 6], or 0.01 nmol x L(-1) x min(-1) [SNP0.01]). Left ventricular-developed pressure and oxygen consumption were measured after preischemic perfusion and reperfusion. Levels of myocardial nitrotyrosine, a marker for peroxynitrite, were measured after reperfusion with an immunoradiochemical assay., Results: Postischemic-developed pressure and myocardial oxygen consumption were significantly higher in the saline group than all nitroprusside-reperfused groups (p < 0.01 for both parameters). However, there were no differences in either parameter between SNP100, SNP1, or SNP0.01. Nitrotyrosine levels were similar among the four groups (p = 0.43)., Conclusions: Nitroprusside exacerbates myocardial ischemia-reperfusion injury over a wide range of doses, although the mechanism does not appear to be mediated by peroxynitrite.

Background: We previously have shown that extracellular preservation solutions provide superior pulmonary protection after 18 hours of cold ischemia at 4 degrees C in an isolated, whole-blood-perfused, rabbit lung model. We also reported that the addition of 20% whole blood to a low-potassium dextran solution (BLPD) conferred no discernible advantage over low-potassium dextran (LPD) alone in this same model. Our current study was aimed at documenting the importance of blood in buffering extracellular preservation solutions during 24 to 48 hours of hypothermic ischemia., Methods: We studied three groups of lungs using an isolated, whole-blood-perfused, ventilated, rabbit lung model. Lungs were flushed with Euro-Collins, LPD, or BLPD solution, and then were reperfused after 24, 36, or 48 hours of hypothermic storage at 4 degrees C. Continuous measurements of pulmonary artery pressure, pulmonary vascular resistance, left atrial pressure, tidal volume, and dynamic airway compliance were obtained. Fresh, non-recirculated venous blood was used to determine single-pass pulmonary venous-to-arterial O2 gradients., Results: The 24-hour Euro-Collins group could not be completed because of immediate reperfusion failure. The 36-hour LPD group oxygenated significantly better than the 36-hour BLPD group (363.3 +/- 65.1 versus 145.3 +/- 40.3 mm Hg, respectively; p = 0.015). The 48-hour LPD group also experienced significant improvements in oxygenation when compared with the 48-hour BLPD group (pulmonary venous-arterial O2 difference of 239.4 +/- 48.4 versus 70.7 +/- 19.5 mm Hg, respectively; p = 0.012). The 48-hour LPD group also displayed significant improvements in pulmonary artery pressure (34.72 +/- 0.96 versus 55.52 +/- 7.37 mm Hg, respectively; p = 0.031) and pulmonary vascular resistance (39,737 +/- 1,291 versus 67,594 +/- 9,467 dynes.s.cm-5, respectively; p = 0.027) when compared with the 48-hour BLPD group. There were no significant differences between the three LPD groups., Conclusions: Extracellular solutions provide improved pulmonary preservation in an isolated rabbit lung model after 48 hours of cold ischemia. The addition of blood to extracellular preservation solutions diminishes pulmonary function when combined with ischemic periods of 36 to 48 hours.

Background: In the repair of total anomalous venous connection, vertical vein ligation is recommended to eliminate left-to-right shunting. However, the small left heart chambers may not always tolerate the immediate increase in blood flow after combined repair and vein ligation., Methods: A retrospective review of 23 infants and children undergoing correction of total anomalous pulmonary venous connection was undertaken to determine whether vertical vein ligation is a necessary component of successful surgical repair. In 14 patients this vein was ligated, whereas in 9 it was left patent. Six patients who underwent ligation and 5 who did not had pulmonary venous obstruction before operation., Results: The operative mortality rate was 36% (5 of 14 patients) for the ligated group compared with 0% (0 of 9 patients) for the nonligated group (p = 0.06). All deaths occurred in patients with preoperative obstruction and a low mean left atrial pressure, and four of the deaths were directly attributable to left heart failure. Follow-up echocardiography in patients in whom the vertical vein was not ligated revealed adequate cardiac function and no residual left-to-right flow through the previously patent venous conduit., Conclusion: Vertical vein ligation during the repair of total anomalous pulmonary venous connection is not routinely necessary and actually may be undesirable in patients with preoperative obstruction, in whom the left heart chambers are particularly small.

Objective: The authors performed a retrospective cost analysis for patients undergoing revascularization of their left anterior descending (LAD) coronary artery either by standard coronary artery bypass grafting (CABG), percutaneous transluminal coronary angioplasty (PTCA), or minimally invasive coronary artery bypass grafting (MICABG)., Summary Background Data: Minimally invasive CABG has become a safe and effective alternative treatment for single-vessel coronary artery disease. However, the acceptance of this procedure as a routine alternative for the treatment of coronary artery disease will depend on both long-term graft patency rates as well as a competitive market cost., Methods: The authors conducted a retrospective analysis of three patient groups undergoing LAD coronary revascularization from January 1995 to July 1996. Ten patients were selected randomly from this period after PTCA of an LAD lesion with or without stenting. Nine patients underwent standard CABG on cardiopulmonary bypass with a left internal mammary artery. Nine patients received MICABG via a limited left anterior thoracotomy and left internal mammary artery to LAD grafting without the use of cardiopulmonary bypass., Results: Percutaneous transluminal coronary angioplasty (n = 10) was unsuccessful in two patients. One patient in the MICABG group (n = 9) was converted successfully to conventional CABG because of an intramyocardial LAD and dilated left ventricle. There was no operative morbidity or mortality in any group. Average length of stay postprocedure was decreased significantly for both the MICABG and PTCA groups when compared with that of conventional CABG (n = 9) (2.7 + 0.26, p = 0.009, and 2.6 + 0.54, p = 0.006, vs. 4.8 + 0.46, respectively). Total hospital costs for the MICABG and PTCA groups were significantly less when compared with those of standard CABG ($10,129 + 1104, p = 0.0028, and $9113 + 3,039, p = 0.0001, vs. $17,816 + 1043, respectively). There were no statistically significant differences between the MICABG and PTCA groups., Conclusions: The final role of minimally invasive CABG is unclear. This procedure is clearly cost effective when compared with that of PTCA and conventional CABG. The long-term patency rates for MICABG will determine its overall efficacy.

Background: Hypoxia and warm ischemia produce severe injury to cardiac grafts harvested from non-heartbeating donors. To potentially improve recovery of such grafts, we studied the effects of intravenous phenylephrine preconditioning., Methods: Thirty-seven blood-perfused rabbit hearts were studied. Three groups of non-heart-beating donors underwent intravenous treatment with phenylephrine at 12.5 (n = 8), 25 (n = 7), or 50 microg/kg (n = 7) before initiation of apnea. Non-heart-beating controls (n = 8) received saline vehicle. Hypoxic cardiac arrest occurred after 6 to 12 minutes of apnea, followed by 20 minutes of warm in vivo ischemia. A 45-minute period of ex vivo reperfusion ensued. Nonischemic controls (n = 7) were perfused without antecedent hypoxia or ischemia., Results: Phenylephrine 25 microg/kg significantly delayed the onset of hypoxic cardiac arrest compared with saline controls (9.6 +/- 0.5 versus 7.7 +/- 0.4 minutes; p = 0.00001), yet improved recovery of left ventricular developed pressure compared with saline controls (57.1 +/- 5.3 versus 41.0 +/- 3.4 mm Hg; p = 0.04). Phenylephrine 25 microg/kg also yielded a trend toward less myocardial edema than saline vehicle (p = 0.09)., Conclusions: Functional recovery of nonbeating cardiac grafts is improved by preconditioning. We provide evidence that the myocardium can be preconditioned with phenylephrine against hypoxic cardiac arrest.

Background: Reperfusion injury is a significant cause of early allograft dysfunction after lung transplantation. We hypothesized that direct pulmonary arterial infusion of an intravascular nitric oxide donor, sodium nitroprusside (SNP), would ameliorate pulmonary reperfusion injury more effectively than inhaled nitric oxide without causing profound systemic hypotension., Methods: Using an isolated, ventilated, whole-blood-perfused rabbit lung model, we studied the effects of both inhaled and intravascular nitric oxide during lung reperfusion. Group I (control) lungs (New Zealand White rabbits, 3 to 3.5 kg) were harvested en bloc, flushed with Euro-Collins solution, and then stored inflated for 18 hours at 4 degrees C. Lungs were then reperfused with whole blood and ventilated with 60% oxygen for 30 minutes. Groups II, III, and IV received pulmonary arterial infusions of SNP at 0.2, 1.0, and 5.0 micrograms.kg-1.min-1, respectively, whereas group V was ventilated with 60% oxygen and nitric oxide at 80 ppm during reperfusion., Results: Pulmonary arterial infusions of SNP even at 0.2 microgram.kg-1.min-1 (group II) showed significant improvements in pulmonary artery pressure (31.35 +/- 0.8 versus 40.37 +/- 3.3 mm Hg; p < 0.05) and pulmonary vascular resistance (38,946 +/- 1,269 versus 52,727 +/- 3,421 dynes.s/cm-5; p < 0.05) when compared with control (group I) lungs after 30 minutes of reperfusion. Infusions of SNP at 1.0 microgram.kg-1.min-1 (group III) showed additional significant improvements in dynamic airway compliance (1.98 +/- 0.10 versus 1.46 +/- 0.02 mL/mm Hg; p < 0.05), venous-arterial oxygenation gradient (116.00 +/- 24.4 versus 34.43 +/- 2.5 mm Hg; p < 0.05), and wet-to-dry ratio (6.9 +/- 0.9 versus 9.1 +/- 2.2; p < 0.05) when compared with control (group I) lungs. Lungs that received inhaled nitric oxide at 80 ppm (group V) were significantly more compliant (1.82 +/- 0.13 versus 1.46 +/- 0.02 mL/mm Hg; p < 0.05) than control (group I) lungs., Conclusions: Pulmonary arterial infusion of low-dose SNP during lung reperfusion significantly improves pulmonary hemodynamics, oxygenation, compliance, and edema formation. These effects were achieved at doses of SNP that did not cause profound systemic hypotension. Direct intravascular infusion of SNP via pulmonary arterial catheters could potentially abate reperfusion injury immediately after allograft implantation.

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.

Background: Decreased airway compliance after lung transplantation has been observed with severe ischemia-reperfusion injury. Further, it has been shown that the surfactant system is impaired after lung preservation and reperfusion. We hypothesized that surfactant replacement after allograft storage could preserve airway compliance during reperfusion., Methods: Rabbit lungs were harvested after flush with 50 mL/kg of cold saline solution. Immediate control lungs were studied with an isolated ventilation/perfusion apparatus using venous rabbit blood recirculated at 40 mL/min, room-air ventilation at 20 breaths/min, and constant airway pressure (n = 8). Twenty-four-hour control lungs were preserved at 4 degrees C for 24 hours and then similarly studied (n = 7). Surfactant lungs underwent similar harvest and preservation for 24 hours, but received 1.5 mL/kg of intratracheal surfactant 5 minutes before reperfusion (n = 10). Airway pressure and flow were recorded continuously during 30 minutes of reperfusion. Tidal volume and airway compliance were calculated at 30 minutes., Results: Tidal volume was 33.67 +/- 0.57, 15.75 +/- 5.72, and 29.83 +/- 1.07 mL in the immediate control, 24-hour control, and surfactant groups, respectively (p = 0.004, surfactant versus 24-hour control). Airway compliance was 1.94 +/- 0.27, 0.70 +/- 0.09, and 1.46 +/- 0.10 mL/mm Hg in the immediate control, 24-hour control, and surfactant groups, respectively (p = 0.002, surfactant versus 24-hour control)., Conclusions: We conclude that surfactant administration before reperfusion after 24 hours of cold storage preserves tidal volume and airway compliance in the isolated ventilated/perfused rabbit model of lung reperfusion injury.

Objective: Lung transplantation remains limited by donor organ ischemic time, inadequate graft preservation, and reperfusion injury. We evaluated lung preservation with use of an extracellular solution, with or without the addition of blood, as compared with preservation with the intracellular Euro-Collins solution., Methods: With use of an isolated, whole blood perfused/ventilated rabbit lung model, we studied three groups of animals. Lungs were flushed with Euro-Collins, low-potassium dextran, or 20% blood-low-potassium dextran solution. Lungs were harvested en bloc, stored inflated at 4 degrees C for 18 hours, and then reperfused at 60 ml/min with whole blood. Continuous measurements of pulmonary artery pressure, pulmonary vascular resistance, and dynamic airway compliance were obtained. Fresh, nonrecirculated venous blood was used to determine the single-pass pulmonary venous-arterial oxygen gradient., Results: Lungs preserved with Euro-Collins solution demonstrated elevated pulmonary artery pressure and pulmonary vascular resistance when compared with those preserved with low-potassium dextran and 20% blood-low-potassium dextran solutions (pulmonary artery pressure: 40.8 +/- 2.2 mm Hg vs 28.9 +/- 2.4 mm Hg and 28.3 +/- 1.5 mm Hg, respectively, p < 0.001; pulmonary vascular resistance: 46.0 +/- 3.1 x 10(3) dynes x sec x cm(-5) vs 29.0 +/- 4.2 x 10(3) dynes x sec x cm(-5) and 28.8 +/- 2.3 x 10(3) dynes x sec x cm(-5), respectively, p < 0.001). Euro-Collins solution-preserved lungs demonstrated a significant drop in compliance when compared with those preserved with low-potassium dextran and 20% blood-low-potassium dextran (-21.9% +/- 4.7% vs 1.8% +/- 3.3% and 1.4% +/- 6.2%, respectively; p = 0.002). Oxygenation was improved with low-potassium dextran and 20% blood-low-potassium dextran solutions as compared with that with Euro-Collins solution (296.3 +/- 54.6 mm Hg and 290.2 +/- 66.4 mm Hg, respectively, vs 37.2 +/- 4.6 mm Hg; p = 0.001)., Conclusions: Extracellular solutions provided superior preservation of pulmonary function in this rabbit lung model of ischemia-reperfusion. However, the addition of blood does not confer any demonstrable advantage over low-potassium dextran solution alone with use of an 18-hour period of cold ischemia.

Background: Hearts harvested from non-heart-beating donors sustain severe injury during procurement and implantation, mandating interventions to preserve their function. We tested the hypothesis that limiting oxygen delivery during initial reperfusion of such hearts would reduce free-radical injury., Methods: Rabbits sustained hypoxic arrest after ventilatory withdrawal, followed by 20 minutes of in vivo ischemia. Hearts were excised and reperfused with blood under conditions of high arterial oxygen tension (PaO2) (approximately 400 mm Hg), low PaO2 (approximately 60 to 70 mm Hg), high pressure (80 mm Hg), and low pressure (40 mm Hg), with or without free-radical scavenger infusion. Non-heart-beating donor groups were defined by the initial reperfusion conditions: high PaO2/ high pressure (n = 8), low PaO2/high pressure (n = 7), high PaO2/low pressure (n = 8), low PaO2/low pressure (n = 7), and high PaO2/high pressure/free-radical scavenger infusion (n = 7)., Results: After 45 minutes of reperfusion, low PaO2/ high pressure and high PaO2/low pressure had a significantly higher left ventricular developed pressure (63.6 +/- 5.6 and 63.1 +/- 5.6 mm Hg, respectively) than high PaO2/high pressure (40.9 +/- 4.5 mm Hg; p < 0.0000001 versus both). However, high PaO2/high pressure/free-radical scavenger infusion displayed only a trend toward improved ventricular recovery compared with high PaO2/ high pressure., Conclusions: Initially reperfusing nonbeating cardiac grafts at low PaO2 or low pressure improves recovery, but may involve mechanisms other than decreased free-radical injury.

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 neutrophi 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 degrees 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.

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 x sec x 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.

4ACKGROUND. 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. Heart 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.

Background: Adult respiratory distress syndrome remains a major cause of morbidity and mortality. We investigated the role of thromboxane receptor antagonism in an experimental model of acute lung injury that mimics adult respiratory distress syndrome., Methods: Three groups of rabbit heart-lung preparations were studied for 30 minutes in an ex vivo blood perfusion/ventilation system. Saline control (SC) lungs received saline solution during the first 20 minutes of study. Injury control (IC) lungs received an oleic acid-ethanol solution during the first 20 minutes. Thromboxane receptor blockade (TRB) lungs received the same injury as IC lungs, but a thromboxane receptor antagonist (SQ30741) was added to the blood perfusate just prior to study. Blood gases were obtained at 10-minute intervals, and tidal volume, pulmonary artery pressure, and lung weight were continuously recorded. Oxygenation was assessed by measuring the percent change in oxygen tension over the 30-minute study period. Tissue samples were collected from all lungs for histologic evaluation., Results: Significant differences were found between SC and IC lungs as well as TRB and IC lungs when comparing pulmonary artery pressure (SC = 33.1 +/- 2.2 mm Hg, TRB = 35.4 +/- 2.1 mm Hg, IC = 60.4 +/- 11.1 mm Hg; p < 0.02) and percent change in oxygenation (SC = -20.6% +/- 10.3%, TRB = -24.2% +/- 9.5%, IC = -57.1% +/- 6.2%; p < 0.03). None of the other variables demonstrated significant differences., Conclusions: Thromboxane receptor blockade prevents the pulmonary hypertension and the decline in oxygenation seen in an experimental model of acute lung injury that mimics adult respiratory distress syndrome.

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 micrograms prostaglandin E1 before storage for 18 hours at 4 degrees C. Experimental groups received low-dose (100 micrograms) or high-dose (200 micrograms) 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.

Background: 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., Methods: 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., Results: 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; p < 0.001). 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); p < 0.01. 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; p < 0.001). 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; p < 0.001)., Conclusions: 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.

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.