Control of oxygen cytotoxicity with allopurinol and superoxide dismutase: a canine model of global myocardial ischemia-reperfusion injury.

The purpose of this study was to assess the effects of acute pharmacological interventions on the ischemia-reperfusion damage in a canine model of hypothermic global myocardial ischemia. Three experimental groups each consisting of seven animals were subjected to 2 h of global ischemia followed by 1 h of reperfusion. Group A (control) used Tyers' iso-osmolar potassium cardioplegia solution; group B received allopurinol (40 mg/kg), 95% intravenously (IV) systemically with 5% added to the final infusion of Tyers' solution. In group C, superoxide dismutase (6.5 mg/kg) was used, one third of the total dose in the final delivery of the Tyers' cardioplegia solution and two thirds IV during the initial 5 min of reperfusion. In all three groups, myocardial temperature was maintained between 15 and 19 degrees C. Methods of evaluation included hemodynamic and echocardiographic parameters of ventricular function. Assessment was performed at three time periods: pre-cardiopulmonary bypass (control), 60 min postreperfusion and immediately post-volume loading (at 2 h after cardiopulmonary bypass). No significant deterioration of myocardial function was observed in either of the experimental groups after the use of these preservation techniques. Comparison of regression slopes based on analysis of covariance for myocardial performance, systolic function, and diastolic compliance did not demonstrate any significant differences between the groups. Two hours of global ischemia was not sufficient to cause measurable damage to the myocardium on the basis of which the pharmacological intervention with allopurinol and superoxide dismutase could be evaluated. The controversy surrounding the use of allopurinol and superoxide dismutase is discussed with the findings of this experimental protocol and is brought up for scientific dialogue.

Simplified technique of heart-lung transplantation.

Well-known complications of heart-lung transplantation include mediastinal bleeding and phrenic nerve injury. Conventional technique places the hila behind the phrenic nerves. We have placed the hila in front of the phrenic nerve in our last 10 patients, using direct caval anastomoses when feasible. This minimizes traction on and dissection around the phrenic nerves, and allows anterior rotation of the heart-lung block for easier hemostasis of the posterior mediastinum after implantation.

Successful treatment of early infective endocarditis and mediastinitis in a heart transplant recipient.

We report a case of bacterial endocarditis in a heart transplant recipient that was diagnosed 6 weeks after operation when a transesophageal echocardiogram revealed vegetations on both sides of the atrial septum. The patient also had postoperative mediastinitis and pericarditis. He underwent two mediastinal explorations, pericardiectomy, and 22 weeks of antibiotics and is free of infection 1 year after transplantation. We presume that the source of infection was contamination of the donor heart by the donor's right lung, which was harvested en bloc with the heart.

Heart transplantation in patients with treated breast carcinoma.

Since 1987, five women with end-stage cardiomyopathy and a history of treated breast carcinoma have undergone transplantation at our institution. All patients underwent extensive multidisciplinary pretransplantation evaluation to rule out metastatic disease. Disease-free interval before heart transplantation ranged from 5 to 11 years (mean, 7.6 years). All patients received immunosuppression in accordance with a standard protocol of rabbit antithymocyte globulin, cyclosporine, prednisone, and azathioprine. Mean postoperative follow-up is 49 months. All patients are alive and have no symptoms 18 to 73 months after transplantation. In carefully selected patients with a history of breast carcinoma, heart transplantation can be performed with good functional results and satisfactory late survival.

Management of complications of Sideris transcatheter devices for atrial septal defect closure.

Various devices that can be inserted transvenously to close an ostium secundum atrial septal defect are undergoing clinical trials. Although these are safe and effective in most instances, they may occasionally dislodge or fail to "button" properly, causing migration and embolization. We report two cases in which the occluder and counteroccluder of the Sideris device for transvenous atrial septal defect occlusion (Custom Medical Devices, Amarillo, Tex.) failed to "button" appropriately, migrating in the right atrium in one patient and embolizing to the pulmonary artery in the second patient. An emergency operation was required to retrieve the device and repair the atrial septal defect.

Clinical significance of weight difference between donor and recipient in heart transplantation.

A standard and important criterion for donor acceptance is to match the donor's body weight to within 20% of the recipient's body weight. However, to meet the increasing demand of patients who need heart transplantation, frequently a heart that is below the standard criteria for donation is accepted. Of the 200 consecutive patients who underwent heart transplantation at the University of Arizona, 27 patients received a heart from a smaller donor with a weight difference of more than 30% (range 30% to 46%). The early mortality and late survival of these 27 patients were not different when compared with those of the patients who received transplants from donors with a weight difference of less than 30%. The probability of freedom from rejection and infection and postoperative ejection fraction were also similar between the two groups. Therefore, we believe that the widely accepted donor-recipient weight-match criterion of 20% can be safely extended.

Dialysis access via a right ventricular assist device.

In this report, we describe the successful utilization of an external right ventricular assist device as vascular access for hemodialysis and continuous arteriovenous hemodialysis in a critically ill patient on biventricular mechanical assist support. Utilization of the right ventricular assist device lines provided relatively easy and safe dialysis access and temporarily reduced the risks associated with the conventional vascular access techniques.

Coccidioidomycosis and heart transplantation.

Eleven episodes of Coccidioides immits infection (cocci) were documented in nine of 199 heart transplant recipients. Cocci was confirmed by fungal cultures and treated with 1 gram of intravenous amphotericin B, after which all patients were put on ketoconazole 200 mg orally twice a day. Two recurrent cocci episodes were noted, both occurring when ketoconazole maintenance therapy was discontinued. When compared with the group of patients without cocci, actuarial survival at 1 and 5 years was identical. We conclude that cocci does not seem to affect the early and late clinical outcome and that prophylactic use of ketoconazole (or other oral antifungal agents) after successful treatment of the initial infection is recommended.

New technique for improving hemostasis in aortic root replacement with composite graft.

By using both aortic annular and supraannular aortic wall tandem suture lines, we have, in our experience, markedly improved hemostasis in aortic root replacement with composite conduits of two types. Using this technique, 4 of 5 patients required 2 units or less of transfused red blood cells. Two patients did not receive transfusions. The technique consists of using interrupted mattress sutures to anchor the lower part of the valve sewing ring to the aortic annulus. The upper part of the sewing ring is then anchored with a running suture line to the cut edge of the supraannular aortic wall.

Incidence and recurrence of gastrointestinal cytomegalovirus infection in heart transplantation.

Cytomegalovirus (CMV) infection of the upper gastrointestinal tract is a major cause of morbidity in heart transplant recipients. Since April 1985, 201 patients underwent heart transplantation at our institution. Immunosuppressive therapy was with a triple drug regimen of cyclosporin A, prednisone, and azathioprine. Fifty-three of these patients had upper gastrointestinal symptoms, which primarily consisted of abdominal pain or nausea and vomiting despite prophylactic treatment with antacids, H2 blockers, or both. A total of 79 esophagogastroduodenoscopies were performed in this group; 15 patients required more than one esophagogastroduodenoscopy for recurrent symptoms. Of these 53 patients with persistent gastrointestinal symptoms, 16 (30.2%) had diffuse erythema or ulceration of the gastric mucosa (14), esophagus (1), and duodenum (1) with biopsy results that were positive for CMV on viral cultures (incidence, 8%). All patients with positive biopsy results were treated with intravenous ganciclovir at a dose of 10 mg.kg-1.day-1 in two divided doses for a period of 2 weeks. Recurrence developed in 6 patients (37.5%) and necessitated repeated therapy with ganciclovir. None of the 16 patients died as a result of gastrointestinal CMV infection. Patients who were seronegative for CMV and received a seropositive heart experienced earlier clinical manifestation of CMV infection. Infection of the upper gastrointestinal tract with CMV is a major cause of morbidity in cardiac transplant patients that may progress to a life-threatening complication if left untreated. Early diagnosis with esophagogastroduodenoscopy and biopsy for viral cultures is essential for documentation and proper management.

Use of the Symbion biventricular assist device in bridging to transplantation.

From 1988 to 1991 13 patients received Symbion biventricular assist devices in attempts to bridge them to cardiac transplantation. All 7 of those who had cardiac transplants survived to hospital discharge. One death occurred 60 days after transplantation because of rejection. All other patients who received transplants are surviving. Implant times in this group varied from 10 to 164 days (mean, 55 days). There were two embolic neurologic events and two significant infections, and 2 of the survivors were dialyzed for reversible renal failure before transplantation. Of those who died on device support, 3 presented on centrifugal pump support. The three other deaths were caused by graft rejection, multiple organ failure, and multiple peripheral emboli. Biventricular assist devices optimally provide cardiac outputs of 4 to 5 L/min, can be quickly inserted often without requiring cardiopulmonary bypass, are easily explanted, and seem best suited for patients weighing less than 80 kg.

Sinoatrial node dysfunction in recipients of domino heart transplants: complication of a surgical harvesting technique.

Two of six domino transplantations performed at our institution required permanent pacemaker implantation as a result of persistent sinoatrial node dysfunction and symptomatic nodal rhythm. Retrospective analysis of several potential etiologic factors showed that the only obvious difference between these two patients and the remaining four domino transplant recipients without this complication was the technique used during harvesting of the cardiac graft. The hearts from the two patients with sinoatrial node dysfunction were harvested using a "right atrial cuff preservation" technique, and the hearts of the remaining four patients were harvested with a standard bicaval division technique. Based on this experience, we think that this right atrial cuff preservation harvesting technique carries a potential risk for sinoatrial node damage, and we do not recommend its use for domino transplantation.

Peripheral vascular disease in heart transplant recipients.

The improved longevity of heart transplant recipients demands heightened awareness of the long-term complications of the procedure. Between 1979 and 1990, 232 patients received 241 heart transplants at our institution. Accelerated coronary atherosclerosis occurred in 45 (19%) of the 232 patients, typically appearing within 2 years of transplantation, whereas peripheral vascular disease (PVD) appeared in 23 (10%) of the 232 patients, usually within 3 years of transplantation. In the patients with PVD, 13 had occlusive disease, nine had aneurysms, and one patient suffered a vertebral artery dissection. Accelerated coronary atherosclerosis afflicted 12 (52%) of the 23 patients affected by PVD (p < 0.05) and preceded the development of PVD in all 12. Logistic regression analysis revealed risk factors predictive of the development of PVD after transplantation to be a pretransplant history of ischemic cardiomyopathy and posttransplant hypertension and hypertriglyceridemia (p < 0.05), with the presence of more than one risk factor increasing the probability of development of PVD. Those patients thus identified as at risk should be closely monitored for the development of PVD. Aggressive medical management of hypertension and hyperlipidemia in this subpopulation may forestall or prevent the development of peripheral vascular disease after heart transplantation.

Futility of yearly heart biopsies in patients undergoing heart transplantation.

Three hundred thirty-eight endomyocardial biopsies, performed as part of the routine annual evaluation at 1 or more years after transplantation in 211 patients, were reviewed. In only two instances (0.6%) were the histologic findings suggestive, but not pathognomonic, of acute rejection. Both patients were treated for rejection and are doing well at 4 and 6 years postoperatively. On the basis of the results of this study, we believe that routine yearly heart biopsies in asymptomatic patients are not necessary for long-term care of patients after heart transplantation, and we believe they should be performed only if there is clinical suspicion of rejection or as part of a research protocol.

Long-term bridge to transplantation with the Symbion acute ventricular assist device system.

A 48-year-old man was supported for 164 days with Symbion biventricular assist devices. During that time, his cytotoxic antibody screen fell from 97% positivity to less than 10%, enabling cardiac transplantation. Complications during the implantation included a 3-minute episode of amaurosis fugax, one positive blood culture, and anemia, which responded to decreased frequency of blood drawing. He is now alive 7 months after transplantation.

Preservation techniques for heart transplantation: comparison of hypothermic storage and hypothermic perfusion.

Preservation of the donor heart is an important and controversial subject in heart transplantation. This study compares simple hypothermic storage and hypothermic perfusion in a swine model of heart transplantation (n = 14). The donor hearts of group A (n = 7) were placed in simple hypothermic storage for 5 hours. The donor hearts of group B (n = 7) were placed onto a perfusion apparatus for 5 hours, with pressure maintained at 28 cm of H2O and a myocardial temperature of 8 to 10 degrees C. In both groups the hearts were initially protected with isosmolar potassium cardioplegic solution. The perfusate in group B contained moderate sodium, mannitol, glucose, insulin, and oxygen. The ischemic interval within both groups was 6 hours including orthotopic transplantation. Investigation was conducted at three time periods: prepreservation, postpreservation, and immediately after loading. For both groups there was nonsignificant depression of myocardial function (cardiac index, stroke index, stroke work index, ejection fraction, and wall stress) at the postpreservation period. After volume loading, for the hypothermic perfusion group there was significant improvement of myocardial function (cardiac index, p less than 0.01; stroke index, p less than 0.01) with no significant change in heart rate, systemic vascular resistance, and systolic blood pressure. There was also significant improvement in myocardial performance (p less than 0.05) for the hypothermic perfusion group after volume loading. Ultrastructural changes were minimal for both groups, and there were no major heart transplantation after 6 hours of ischemia; however, hearts retain their contractile capacity better after hypothermic perfusion than after simple hypothermic storage.(ABSTRACT TRUNCATED AT 250 WORDS)

Mitral valve replacement six years after cardiac transplantation.

A 33-year-old man found to have increasing mitral regurgitation and decreasing exercise tolerance 6 years after cardiac transplantation received a mitral bioprosthesis. For 8 months he has been without complications from the valve replacement and is clinically and hemodynamically considerably improved.

Comparison of functional and metabolic assessments in preservation techniques for heart transplantation.

The present study compares simple hypothermic storage and hypothermic perfusion in a swine model of heart transplantation using metabolic and functional assessments. In both groups the hearts were initially protected with iso-osmolar potassium Tyers' cardioplegia. The donor hearts of group A were placed in simple hypothermic storage for 5 h. The donor hearts of group B were placed onto a perfusion apparatus for 5 h with perfusion pressure maintained at 28 cm of H2O and a myocardial temperature of 8-10 degrees C. The perfustate consisted of Tyers' solution with the addition of 2 mg/L of mannitol, 12.5 mg/L of glucose, 5 units/L of insulin, and 95% oxygen. The ischemic interval within both groups was 6 h, including orthotoipic transplantation. Investigation was conducted at three time periods: prepreservation (T1) in the donor, and postpreservation (T2) and immediately after loading (T3) in the recipient. Following volume loading for the hypothermic perfusion group there was significant improvement of myocardial function (cardiac index, p less than .05; stroke index, p less than .05) with no significant change in systemic vascular resistance, systemic blood pressure, and heart rate. There was also significant improvement in myocardial performance (p less than .05) for the hypothermic perfusion group following volume loading. Results of fatty acid turnover using 15-p-iodo (123I)-phenylpentodecanoic acid indicate significantly greater increase in metabolic rate for the perfusion group than for the hypothermic storage group. (p less than .05). This indicates improved metabolic status of the heart treated with the hypothermic perfusion technique. We conclude that a combination of functional and metabolic assessments is a good method for deduction of ischemic-reperfusion injury. We also conclude that hypothermic perfusion is superior to hypothermic storage for in vitro preservation of hearts for heart transplantation.