Biomedical subjects
Publications and source records attributed to H Reichenspurner.
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BACKGROUND: To extend the applications of minimal access cardiac surgery, an endovascular cardiopulmonary bypass (CPB) system that allows cardioplegia delivery and cardiac venting was used to perform bilateral internal mammary artery (IMA) bypass grafting in six dogs. METHODS: The left IMA (LIMA) was taken down thoracoscopically from three left lateral chest ports, followed by the right IMA (RIMA) from the right side. One left-sided port was extended medially 5 cm with or without rib resection, to expose the pericardium. Both IMAs were divided and exteriorized through the left anterior mediastinotomy. Flow and pedicle length were satisfactory in all cases. Femoral-femoral bypass was used and the heart arrested with antegrade delivery of cardioplegic solution via the central lumen of a balloon catheter inflated to occlude the ascending aorta. All anastomoses were made through the mediastinotomy under direct vision. In five studies the RIMA was attached to the left anterior descending artery (LAD) and the LIMA to the circumflex, and in one study the RIMA was tunneled through the transverse sinus to the circumflex and the LIMA was anastomosed to the LAD. All animals were weaned from CPB in sinus rhythm without inotropes. CPB duration was 108 +/- 27 minutes (mean +/- SD) and the clamp duration was 54 +/- 10 minutes. RESULTS: Preoperative and postoperative cardiac outputs were 2.9 +/- 0.71/min and 2.4 +/- 0.31/min, respectively (p = NS), and corresponding pulmonary artery occlusion pressures were 6 +/- 3 mmHg and 7 +/- 2 mmHg, respectively (p = NS). All 12 grafts were demonstrated to be fully patent. Postmortem examination revealed well aligned pedicles and correctly grafted target vessels. CONCLUSION: This canine model demonstrates the potential for a less invasive approach to the surgical management of left main coronary artery disease in humans.
The histologic findings in a total of 112 experimental heart transplants comprising allografts (baboon to baboon: n = 37), concordant xenografts (vervet monkey to baboon: n = 52), and discordant xenografts (pig to baboon: n = 23), in which the roles of ABO blood group incompatibility, corcordance, and immunosuppression were evaluated, are described. Hyperacute (vascular, humoral) rejection was characterized by disruption of the microcirculation, with interstitial hemorrhage and edema, rather than by intravascular thrombosis; the features were basically similar whether hyperacute rejection occurred in an ABO-incompatible allograft, concordant xenograft, or discordant xenograft. Hyperacute rejection was noted in all 23 discordant xenografts, in 12 to 52 concordant xenografts, and in four of 17 ABO-incompatible allografts. A unique mixture of acute and hyperacute rejection was observed in three ABO-incompatible allografts and in 10 concordant xenografts. Intensive antirejection therapy was associated with a reduced incidence of hyperacute rejection in corcordant xenografts but also with a significant number of fatal treatment-related complications.
To assess the hemodynamic contribution of both hearts after heterotopic heart transplantation, we examined recipients by cardiac catheterization and Doppler echocardiography. Since September 1984, immunosuppression consisted of cyclosporine, azathioprine, methylprednisolone, and antithymocyte globulin. In this time interval, 55 orthotopic and 14 heterotopic transplants have been performed. The indications for heterotopic transplant were elevated pulmonary vascular resistance (greater than 4 Wood units), in 10 patients, or gross (greater than 20%) donor-recipient weight mismatch, in six patients. Two patients belonged to both groups. The 1-year survival rate was 63%; currently seven of the 14 patients are alive. Cardiac output (as measured by dye dilution curves and by the Fick method) increased from 4.2 L/min preoperatively to 6.1 L/min in both groups postoperatively (mean follow up, 5.3 months; p less than 0.0005); the transpulmonary gradient fell from 18.5 to 12.3 mm Hg, the pulmonary vascular resistance from 4.4 to 2.4 Wood units (p less than 0.01). The echocardiographic findings were as follows: left ventricular end-diastolic diameter (mm) in the recipient heart was 67.4 +/- 12 and in the donor heart, 42.6 +/- 8.7. Fractional shortening (%) in the recipient heart was 7.1 +/- 2.9 and in the donor heart, 30.4 +/- 10.4. The Doppler technique revealed a cardiac output contribution-ratio (CO donor/CO recipient) of 3.0 +/- 0.61 on average. In all recipient hearts mild and moderate mitral and tricuspid regurgitation was discovered. In the donor heart all mitral and tricuspid valves were found to be incompetent; this was severe in 66% and 11% of the mitral and tricuspid valves, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Xenogeneic heart transplantation is becoming increasingly attractive because of the shortage of suitable donor organs. In small infants and neonates, for whom suitable human grafts are difficult to obtain, this may play a particularly important role. To evaluate the optimal immunosuppressive regimen after xenogeneic transplantation, cervical heterotopic heart transplantation was performed with vervet monkeys as donors and chacma baboons as recipients. The following groups were investigated: group 1 (n = 9): control, no immunosuppressive medication; group 2 (n = 5): cyclosporine in combination with azathioprine and methylprednisolone; group 3 (n = 6): cyclosporine, azathioprine, and methylprednisolone in combination with antithymocyte globulin for postoperative days 0 to 9; group 4 (n = 7): cyclosporine, azathioprine, and methylprednisolone in combination with 15-deoxyspergualin for postoperative days 0 to 9. Because of severe treatment-related side effects that were observed in group 4, further immunosuppression was modified as follows: group 5 (n = 5): 15-deoxyspergualin was combined with cyclosporine and methylprednisolone only. Acute rejection episodes were diagnosed by cytoimmunologic monitoring on alternate days and weekly myocardial biopsies and were treated with 500 mg methylprednisolone intravenously for 3 to 5 consecutive days. The graft survival after xenogeneic heart transplantation was best in group 3 with 43.3 days compared with 10.3 days in the control group. Still 2.3 acute rejections occurred, which in most cases led to graft failure in these animals. In group 4 the graft survival was prolonged to 20.1 days on average. Only 0.5 acute rejections per animal occurred, but severe gastrointestinal complications and infections were observed that made further experiments necessary to minimize these treatment-related complications.(ABSTRACT TRUNCATED AT 250 WORDS)
Considering a worldwide average 1-year survival rate of nearly 90% after orthotopic heart transplantation, the question arises as to whether there is still an indication for heterotopic heart transplantation. Since 1967, 132 heart transplantations have been performed at our institution. From 1974 to 1983 only heterotopic transplantations were performed. Since 1985, quadruple-drug therapy has been used for immunosuppression. This consists of low dose cyclosporine in combination with azathioprine, methylprednisolone (in lower dosages), and rabbit antithymocyte globulin (for the first 4 to 6 days after operation and as rescue therapy for severe rejections). Fifty-five transplantations have been performed with this therapy (44 orthotopic and 11 heterotopic). The indications for heterotopic transplantations were either elevated pulmonary vascular resistance (4 to 6 Wood units, n = 6), or a gross donor and recipient weight mismatch (more than 20%) in candidates who showed signs of severe cardiac decompensation (n = 6). One patient had both indications. The 1-year survival rate for those patients was 83%. Currently seven of the 11 patients are alive with life spans ranging from 6 months to 2.5 years after operation. Causes of deaths were infections (n = 3) and chronic graft rejection (n = 1). The recipients were restudied with right-sided heart catheterizations performed from 2 months to 2 years after transplantation. In all patients the cardiac output increased significantly from a mean of 4.0 to 5.8 L/min (p less than 0.0005). In patients with elevated pulmonary vascular resistance, this value decreased after heterotopic transplantation from a mean of 4.9 to 2.4 Wood units.(ABSTRACT TRUNCATED AT 250 WORDS)
An anomalous left superior vena cava (SVC) was identified in two recipients during combined heart-lung transplantation. In the first patient an interposition Gore-Tex graft was used to reconstitute the venous drainage from the aberrant left SVC to the right atrium. In the second patient a new method of reconstituting the drainage from the left SVC with the donor innominate vein is described. It is recommended that excision of the donor heart and lung should include the innominate vein, as it may be used to create a venous channel for an aberrant left SVC if present in the recipient.
In the model of heterotopic intrathoracic heart transplantation, rejections of the graft are not lethal for the recipient animal. Therefore it is possible to follow the immunologic rejection mechanism to the final stage. Allogeneic dog hearts (n = 6) and xenogeneic fox hearts (n = 6) were transplanted. Immunosuppression therapy included cyclosporine and methylprednisolone. Cytoimmunologic monitoring was done every second day. Due to fluctuations of lymphocyte subpopulations and their immature forms, endomyocardial biopsies were performed. The transplanted allogeneic hearts survived for 53.2 +/- 14.8 days if treated with cyclosporine (historical control group without immunosuppression 6.8 +/- 0.8 days). Xenogeneic fox hearts stopped beating after 20.2 +/- 4.1 days (historical control 8.4 +/- 1.9 days). The allogeneic grafts were all rejected in an acute cellular fashion, whereas xenogeneic transplanted hearts showed humoral and cellular rejection mechanisms. Monitoring of circulating inflammatory cells allowed differentiation between humoral and cellular rejection, which was confirmed by histology. Both types of rejection were accompanied by an increase of lymphocytes and their activated forms. Differentiation of lymphocyte subpopulations revealed a significant increase of surface IgG-positive B-lymphocytes under humoral rejection, whereas acute cellular rejection episodes showed a substantial increase of surface IgG-negative lymphocytes. Humoral rejection that developed even with cyclosporine administration was not influenced, whereas cellular rejections were controlled by increasing methylprednisolone to 250 mg/day for 3 days.
Between December 1967 and July 1987, 110 heart transplantations (61 heterotopic and 49 orthotopic) and 12 heart-lung transplantations were done at Groote Schuur Hospital in Cape Town, South Africa. Twelve procedures were retransplantations, including two third interventions. The patients were divided into three groups: Group A (n = 55) from 1967 to 1982 received so-called conventional treatment of azathioprine, methylprednisolone, and antithymocyte globulin. Group B (n = 15) from 1983 to 1984 had cyclosporine in high dosages together with methylprednisolone. Group C (n = 30) received quadruple drug therapy of low-dosage cyclosporine, together with azathioprine, methylprednisolone in lower dosages, and antithymocyte globulin (for the first 4 to 6 days and rescue antithymocyte globulin for severe rejection). From Group A, nine of 55 patients are alive up to 17 years after transplantation. The main causes of death were acute rejections and infections (in 60% altogether). From group B, six of 15 patients are alive. Acute rejections and infections were the causes of death in 12% of the patients, but multiple organ failure was a major cause in 24% most probably because of the high dosages of cyclosporine. From group C, 23 of 30 patients have survived. In this group the results after heterotopic heart transplantation do not differ significantly from orthotopic transplantation, which justifies this procedure in particular situations. If all heterotopic and orthotopic transplantations are compared, orthotopic procedures have a substantially better outcome. With the modified immunosuppressive regimen (group C) combined with precise donor and recipient selection and more sophisticated rejection monitoring, the actuarial survival rate within the last 12 months is 94%.
This study assessed the ability of immunomonitoring to differentiate between acute cardiac rejection and viral, bacterial or fungal infections, using data of thirty-five cyclosporine treated heart and heart-lung transplant recipients. Peripheral blood samples were analyzed daily for 20 days, then three times weekly until the patient's discharge. Later, peripheral blood was examined every fourteen days on an outpatient basis. White blood cells were counted and differentiated. A mononuclear concentrate was obtained by the Ficoll-Hypaque gradient and centrifugation method, and cytocentrifuged onto slides. The cells were stained by a five minute method. Percentages of lymphocytes, prelymphoblasts, lymphoblasts, large granular lymphocytes and monocytes were calculated. When activated cells were detected, aliquots of the mononuclear concentrate were labeled using monoclonal antibodies. In these thirty-five patients, more than 60 acute rejection episodes were diagnosed by the cytoimmunological method. Acute rejection was characterized by a significant rise of the number of leukocytes, lymphocytes, prelymphoblasts and lymphoblasts. The T-lymphocyte population increased while the B-cells remained normal. Ninety-five percent of all acute rejection episodes were diagnosed using cytoimmunological parameters. During viral infection more than 20% of the mononuclear cells were large granular lymphocytes and the OKT4/OKT8 ratio was less than one. During bacterial and fungal infections the B-lymphocytes increased to 40% of the mononuclear cells. In addition, juvenile polymorphs appeared in the mononuclear concentrate and the OKT4/OKT8 ratio was within normal limits (1.5 to 2.5).(ABSTRACT TRUNCATED AT 250 WORDS)
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Protozoal infections such as toxoplasmosis are known complications in heart transplant recipients. Diagnosis of the disease is often difficult. This article describes the course of a patient who had a febrile illness with leukocytosis and neurologic disorders after heart transplantation; all microbiologic and serologic tests of the peripheral blood and the cerebrospinal fluid failed to identify the responsible pathogen. Infection with Toxoplasma gondii was finally diagnosed by endomyocardial biopsy. We conclude that in heart transplant recipients with infections of unclear origin and neurologic disorders, endomyocardial biopsy may be helpful in the diagnosis, especially in cases of toxoplasmosis.
We report the first successful reuse of a previously transplanted heart after perioperative brain death of the first recipient. The second recipient was a 66-year-old man suffering from end-stage ischemic cardiomyopathy. The intra- and postoperative course of the retransplantation was completely uneventful. At the time of writing, more than 2 years after reuse of the graft, the patient remains in New York Heart Association class I. This procedure, which proved to be possible under certain optimal conditions, should be considered in the case of brain death of a graft recipient, particularly with regard to the ongoing donor shortage.
OKT3 is recommended as rescue therapy for cases of steroid-resistant, clinically persistant acute rejection episodes after heart transplantation. In this study we determined the efficacy of such treatment. One hundred thirty-two patients were included in this study. The postoperative immunosuppressive regimen consisted of triple-drug therapy and perioperative antithymocyte globulin. During a follow-up of 10 to 108 weeks (mean, 51 +/- 20 weeks) 281 treatment-requiring acute rejection episodes (International Society for Heart and Lung Transplantation > or = II) were observed. In 29 cases (10.3%) the grade of the acute rejection episodes was either unchanged after two series of intravenous steroid pulse therapy, was worsened after the first steroid course, or the patient experienced clinical deterioration as a result of the acute rejection episodes. These patients were considered to have steroid-resistant acute rejection episodes and received a 10-day rescue therapy with OKT3, followed by control endomyocardial biopsy. In 17 cases, control endomyocardial biopsy revealed normal myocardium (group I). In 10 cases acute rejection episodes remained unchanged (group II); twice a deterioration was found (group III). However, 12 of the 17 patients from group I experienced a rebound of the acute rejection episodes (International Society for Heart and Lung Transplantation > or = II) 1 to 3 weeks later. Side effects of OKT3 treatment were fever, chills, intestinal complications, hemodynamic response, convulsions, and viral infections.(ABSTRACT TRUNCATED AT 250 WORDS)
In this study, registration of thoracic electrical bioimpedance was used for early detection of acute rejection after heart transplantation. Thirty-five heart transplant recipients were monitored by registration of thoracic electrical bioimpedance signals during the immediate postoperative period and during the outpatient follow-up. At the same time, endomyocardial biopsy specimens were taken. In addition to cardiac stroke volume index and ejection fraction, the acceleration index (seconds -2) was calculated. This acceleration index describes the acceleration of blood volume and represents a function parameter of the myocardial inotropy. Seventeen acute rejection episodes were diagnosed during the follow-up period. The average acceleration index value during the 17 rejection episodes was 92.5 +/- 11.7 sec-2 and thus significantly lower when compared with the nonrejection levels (p < 0.05). The acceleration index values decreased during acute rejections by an average of 36.4 +/- 19.3 sec-2 (28%). The sensitivity of this diagnostic parameter in the examined patients was 71%, and the specificity was 100%. Thus registration of thoracic electrical bioimpedance and calculation of the acceleration index represents a quick and noninvasive monitoring technique and can ideally be used in the outpatient clinic as a supplement to invasive endomyocardial biopsies.