Sixty patients underwent heart-lung transplantation at our institution between April 1984 and March 1989. The first five donor organs were removed in an adjacent operating room. Subsequently, organs were removed from distant centers. The method of preservation consisted of cold crystalloid cardioplegic arrest of the heart followed by a cold colloid pulmonary artery flush of a perfusate developed at Papworth Hospital. The lung perfusate is preceded by an infusion of prostacyclin into the pulmonary artery, during preliminary dissection of the donor organs. The total ischemic time ranged from 48 to 51 minutes (mean, 49.6 minutes) for the near-procurement group and from 70 to 249 minutes (mean, 157.6 minutes) for the distant-procurement group. Function of the lungs was assessed by gas exchange, pulmonary function tests, extubation, and survival data. Serial x-ray films were used to monitor graft performance in the postoperative period. We record our clinical experience of early graft function after heart-lung transplantation.
The presence of high pulmonary vascular resistance (PVR) greater than 4 Wood units contributes to significant early posttransplant mortality, and remains a negative predictor of long-term survival. Current trends have been toward exclusion of the recipient with high PVR from the orthotopic procedure; elective heterotopic allograft placement is increasingly advocated. A patient with a PVR of 6 Wood units underwent orthotopic transplantation; the cardiac allograft from a 12 kg heavier donor was implanted after an ischemic time of 115 minutes. Early graft failure at 4 hours and subsequent cardiac arrest were followed by reinstitution of cardiopulmonary bypass, during which time optimal pharmacologic manipulation of the pulmonary vasculature was undertaken, including the use of high-dose prostacyclin. Refractory right heart failure indicated the requirement for right ventricular assistance (RVA) for patient survival. RVA with a Bio-Medicus pump was instituted in association with high-dose prostacyclin; an intraaortic balloon pump was inserted 12 hours later. Maintenance immunosuppression consisted of cyclosporine and azathioprine alone. RVA was maintained for 3 days; during this time the patient was totally pump dependent. Over an 18-hour period the patient was weaned and successfully withdrawn from RVA. Intraaortic balloon pump counterpulsation and the prostacyclin infusion were continued for 6 and 10 days, respectively. The clinical implications of the various interventions that resulted in the patient's survival are discussed.
During the past decade we have witnessed a continuing evolution in intrathoracic transplantation. The role of heart transplantation in end-stage heart disease has been well established; and combined heart-lung and lung transplantation techniques developed during the past 10 years have been applied to an expanding array of diseases associated with end-stage pulmonary failure. Recently a plateau in number of transplants per year has become evident. Although the areas of pediatric heart and single lung transplantation continue to expand, it appears that further overall growth in heart and lung transplantation is now limited by donor availability. Although operative mortality has shown gradual improvement, organ preservation and other intraoperative complications remain major factors associated with early death, especially in combined heart-lung and lung transplantation. Infection and rejection are the most common causes of late deaths for all types of intrathoracic transplantation. Although long-term survival has shown improvement over the past 10 years, an increasing number of patients now require retransplantation because of chronic rejection. Results with heart, combined heart-lung, and lung retransplantation, in operative mortality and in long-term survival, have not been as encouraging as with the primary transplant procedure. We await further developments in heart and lung transplantation during the new decade.
Current experimental models of heart transplantation include a period of ischemia after donor harvest, resulting in rhythm disturbances, myocardial distention, and reperfusion injury on implantation. A model of cervical heterotopic heart transplantation that avoids ischemia by using retrograde perfusion was developed. More than 100 consecutive successful transplantations have been performed both as control protocols and as a part of experimental protocols. The advantages of this technique include: avoidance of ischemia and reperfusion injury, prevention of myocardial damage caused by overdistention, and potential evaluation of pretreatment regimens for transplanted hearts.
The treatment for recurrent cardiac allograft rejection refractory to conventional immunotherapy is retransplantation. When retransplantation is not possible, alternative approaches must be undertaken. This report reviews the successful management of persistently recurring rejection using five serial 14-day courses of OKT3 in a 35-year-old man after two heart transplantations.
The treatment of cardiac allograft rejection remains complex and is influenced by a number of factors, including hemodynamic compromise, severity of biopsy grade, time after transplantation, gender, and local institutional bias. This article reports the response of 43 rejection episodes in 67 patients who underwent orthotopic heart transplantation in a 3-year period and who were treated with triple-drug immunosuppression only. Eighty-eight percent (38 of 43) of the rejection episodes were treated initially with one course (3 gm) of intravenous methylprednisolone, and 82% (31 of 38) responded. Another 7% responded to a second course of intravenous corticosteroids, and the remaining 11% of the episodes eventually required the use of antilymphoblast globulin for resolution. Twelve percent of the rejections (n = 5) were initially treated with antilymphoblast globulin, and three responded. The response of cardiac allograft rejection to intravenous corticosteroids is greater than 85%, and this should be the initial treatment in most cases of rejection. The role of advanced biopsy grade, dose of corticosteroids used, and complications resulting from this form of therapy are discussed.
The ability of cytoimmunologic monitoring to detect acute rejection in heart and heart-lung transplant recipients was assessed. Seventeen heart and nine heart-lung transplant patients treated with cyclosporine as the primary immunosuppressive agent were monitored after operation. Seventeen acute rejection episodes occurred in the heart-only recipients and 12 in the combined heart-lung recipients. These acute rejection reactions were accompanied by increased numbers of "activated" lymphocytes in all but one case, providing cytoimmunologic monitoring a sensitivity of 100% in the heart-lung recipients and 94% in the heart recipients. The specificity was, however, low (68% in the heart recipients and 55% in the heart-lung recipients). Seventy-two percent of the false-positive results were associated with viral infections, particularly cytomegalovirus infections.
The treatment for recurrent cardiac allograft rejection refractory to conventional immunotherapy is retransplantation. When retransplantation is not possible, alternative approaches must be undertaken. This report reviews the successful management of persistently recurring rejection using five serial 14-day courses of OKT3 in a 35-year-old man after two heart transplantations.
Single flush perfusion of the lung represents one concept of pulmonary preservation that has provided satisfactory results in both experimental and clinical situations. The technique has allowed successful distant organ procurement, with consequent enlargement of the available donor pool. Both cold modified blood (CMB) and modified Euro-Collins solution (ECS) are currently used as perfusates, although the volumes of each used clinically are different. CMB is administered at 20 ml/kg and ECS at 60 ml/kg. Both techniques combine the use of a prostaglandin to enhance preservation. In this study these two perfusion techniques were compared in a canine model of unilateral left lung allotransplantation after 6 hours of storage, with subsequent ligation of the recipient's contralateral pulmonary artery and bronchus. Equal volumes of both solutions were used (20 ml/kg) to determine whether the blood vehicle was necessary to provide good preservation at this volume. Assessment of pulmonary preservation was determined by animal survival, blood gas analyses, hemodynamic values, and measurement of lung water content. All animals survived the 24-hour experimental period in stable condition. Postoperative oxygenation was well maintained at control values throughout this period with no significant difference between groups. The pulmonary vascular resistance index was significantly higher in the CMB group at 1 hour (p less than 0.05). Lung compliance, assessed by peak-inspiratory pressure, was impaired to a greater extent in the CMB group than in the ECS animals (p less than 0.01 at 12 and 24 hours).(ABSTRACT TRUNCATED AT 250 WORDS)
Acute lung rejection after orthotopic left lung transplantation and Mycoplasma pulmonis infection were studied immunohistologically by bronchoalveolar lavage (BAL) in inbred rats using monoclonal antibodies differentiating lymphocyte and macrophage subpopulations. Twenty transplants in a major histocompatibility complex (MHC)-different strain combination (Brown-Norway/Lewis) were examined 2, 4, and 6 days after transplantation. Thirty isotransplants (Lewis/Lewis) and normal Lewis rats were used as controls. Eight Lewis rats with acute Mycoplasma pulmonis infection and six Lewis rats with chronic Mycoplasma infection also underwent BAL. Mononuclear cell subpopulations were analyzed using a panel of monoclonal antibodies to MHC and macrophage differentiation antigens: ED1 monocyte/macrophages, ED2 inflammatory tissue macrophages, OX19 T lymphocytes, and OX12 B lymphocytes. The following results were obtained: (1) All allotransplants developed acute rejection on day 2, and it advanced until day 6, demonstrating severe perivascular and peribronchiolar infiltration of inflammatory tissue macrophages (ED1+/ED2+): (2) the proportion and number of inflammatory macrophages (ED2+) in BAL fluid increased on day 6; (3) in BAL the proportion and number of T lymphocytes (OX19+) increased more prominently than B lymphocytes (OX12+) on day 6 of acute rejection; (4) in infection with Mycoplasma pulmonis the increase of T lymphocytes (OX19+) in BAL was more prominent than that of B lymphocytes (OX12+). In conclusion, serial analysis of macrophage, T- and B-lymphocyte antigens was performed. The increase of the proportion of inflammatory macrophages (ED2+) and lymphocytes (OX19+, OX12+) in BAL fluid occurred rather late in the rejection response. This limits the use of BAL as an early diagnostic method of allografted lung rejection.(ABSTRACT TRUNCATED AT 250 WORDS)
Dynamic cardiomyoplasty was conceived to enhance cardiac performance by assisting myocardial contraction. Technically, this procedure consists of placing a pedicled latissimus dorsi muscle flap around the heart and subsequent muscle electrostimulation in synchrony with ventricular systole. Three types of dynamic cardiomyoplasty can be considered. (1) Atrial or ventricular reinforcement is accomplished by wrapping the latissimus dorsi muscle flap around the heart to support hypokinetic or akinetic areas secondary to congenital or acquired diseases. The atrial reinforcement may be performed to improve atrial output after Fontan-type procedures. (2) Ventricular substitution is performed to replace a portion of the ventricular wall. Autologous pericardium is used to create a neoendocardium and facilitate hemostatic closure of the ventricle. The pedicled latissimus dorsi is then secured to replace the resected myocardium. (3) The two previous techniques of ventricular substitution and reinforcement are combined. This reconstructive procedure, which normalizes the ventricular geometrical shape, is particularly useful after extended cardiac resections, such as is done in treatment of large ventricular aneurysms, cardiac tumors, or echinococcal cyst formations. At present, improvement in ventricular function has been obtained in 12 patients at our institution. Preoperative severe cardiac dysfunction was present in all of these patients (New York Heart Association functional class III or IV). Postoperative echocardiography, multigated acquisition scan, and hemodynamic studies demonstrate an improvement in ventricular function and no impairment of ventricular compliance by the muscle flap. After a mean follow-up period of 18 months, all patients are in functional class I or II. We believe that dynamic cardiomyoplasty prolongs and improves the quality of life of patients suffering from severe chronic and irreversible myocardial dysfunction by improving ventricular contraction and limiting cardiac dilatation.
Current experimental models of heart transplantation include a period of ischemia after donor harvest, resulting in rhythm disturbances, myocardial distention, and reperfusion injury on implantation. A model of cervical heterotopic heart transplantation that avoids ischemia by using retrograde perfusion was developed. More than 100 consecutive successful transplantations have been performed both as control protocols and as a part of experimental protocols. The advantages of this technique include: avoidance of ischemia and reperfusion injury, prevention of myocardial damage caused by overdistention, and potential evaluation of pretreatment regimens for transplanted hearts.
The physiologic effects of 12-hour lung preservation were assessed in six mongrel dogs studied for 20 hours after double-lung allograft implantation. Donor animals were pretreated with allopurinol (30 mg/kg) and methylprednisolone (500 mg) intravenously at anesthesia induction. Heart-lung blocks were harvested after cardioplegic arrest, and a simple pulmonary artery flush of 4 degrees C modified Collins' solution was administered at 15 ml/kg/min. The lungs were ventilated with 100% nitrogen during flushing and inflation. Recipient animals received an infusion of deferoxamine (20 mg/kg) during implantation and were pretreated with methylprednisolone (500 mg) intravenously. All six implantations were technically successful. Two animals died of cardiac standstill 12 and 24 hours postoperatively. Gas exchange deteriorated after implantation compared with donor levels but remained in a range compatible with survival, and at 20 hours arterial oxygen tension (FiO2 0.4) was 138 +/- 91 mm Hg. Similar changes were seen in alveolar-arterial oxygen gradients and arterial-alveolar oxygen tension fraction. Elimination of carbon dioxide was satisfactory. Pulmonary venous shunt fraction rose significantly at the end of the study. Hemodynamic changes consisted of a gradual increase in pulmonary vascular resistance and a reduction in cardiac output. Lung mechanics also deteriorated, with a gradual rise in airway resistance and a fall in compliance. The double-lung model allows detailed assessment of the early effects of preservation and may have certain advantages over heart-lung models of preservation. The preservation technique warrants further study.
Since its inception in 1985, the Combined Registry for the Clinical Use of Mechanical Ventricular Assist Pumps and the Total Artificial Heart has compiled data on more than 1200 patients. In 400 of these patients circulatory support was used in conjunction with heart transplantation
