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Biomedical subjects

H Reichenspurner

Publications and source records attributed to H Reichenspurner.

At least 127 records · Page 7Linked to original sources

Adenosine cardioplegia: reducing reperfusion injury of the ischaemic myocardium?

Hyperkalaemia-induced hypopolarization of the sarcolemnal membrane during standard crystalloid cardioplegic arrest potentiates calcium influx during reperfusion and is associated with depletion of high-energy phosphate reserves. Adenosine has been shown to induce fast cardiac arrest whilst preserving membrane hyperpolarization in an isolated rat heart model. In this study we compared the efficacy of adenosine, both as an arresting agent and as an ultrastructural, haemodynamic and high-energy phosphate preserving agent, in an in situ global ischemia model in the baboon with St. Thomas' Hospital solution No. 2 (ST2; n = 8) and with Krebs-Henseleit buffer (KHB; n = 7). The addition of 10 mM adenosine to the non-cardioplegic KHB (ADO; n = 8) improved haemodynamic recovery significantly in terms of cardiac index (91.6% +/- 7.2 vs 59.9% +/- 9.9) and stroke volume index (101.6% +/- 8.9 vs 55.6 +/- 10.0) and was not statistically distinguishable from the ST2 with regard to cardiac index (91.6% +/- 7.2 vs 94.8% +/- 5.8), stroke volume index (101.6% +/- 8.9 vs 114.0% +/- 8.3) or left ventricular dP/dt (73.1% +/- 9.9 vs 87.0% +/- 12.4). Adenosine triphosphate was best preserved with ADO (103.5% +/- 21.1 vs 67.9% +/- 9.3 and 48.5% +/- 8.7) although this was not statistically significant. This suggests therefore that the mechanism of cardioprotection by adenosine occurs by means other than its role as high-energy phosphate precursor.

Adenosine↗

Heart-lung transplantation in 1990--indications, surgical technique, postoperative complications and outcome.

Using cyclosporine A (CyA), long-term results after heart-lung transplantation became possible. Since 1981, 761 clinical heart lung transplantations have been registered at the International Society for Heart Transplantation. Candidates for this operation reveal signs of irreversible heart and lung diseases which are caused by cardiac lesions (e.g. valvular disease, Eisenmenger reaction due to congenital malformation) or pulmonary disorders (e.g. primary pulmonary hypertension, emphysema, fibrosis). The standard surgical procedure necessitates three anastomoses which combine donor and recipient tracheae, right atria and aortae. Immunosuppression consists of CyA (blood levels of 300-500 ng/ml), azathioprine (1-2 mg/kg/d) and rabbit antithymocyte globuline (RATG) (IgG: 2-4 mg/kg/d). After the first 2 postoperative weeks, RATG is replaced by low dose methylprednisolone (0.3-0.1 mg/kg/d). As an alternative, RATG may be omitted completely. Postoperatively, a variety of complications may evolve. Early problems (within the first month) comprise acute pulmonary rejection, bacterial pneumoniae, and multiorgan failure. Diagnosis of acute lung rejection proves difficult; it includes clinical signs, chest radiographic appearances and cytoimmunological monitoring of the peripheral blood. Transbronchial lung biopsies are for precise diagnosis of similar value to endomyocardial biopsies after heart transplantation. Late postoperative complications comprise viral, bacterial, fungal, and protozoal infections and chronic obliterative bronchiolitis. With increasing experience, the 30 day mortality fell to below 20% according to the International Society for Heart Transplantation. The one-year survival rate between 1986 und 1988 was reported to be 61%. The results of some individual groups are even better.

Bronchiolitis Obliterans↗

15-Deoxyspergualin for induction of graft nonreactivity after cardiac and renal allotransplantation in primates.

In order to assess the immunosuppressive potentials of 15-deoxyspergualin (15-DS) in a preclinical experiment, heterotopic cardiac (n = 27, group I) and classic renal (n = 25, group II) allotransplantations were performed in Chacma baboons. The following immunosuppressive regimens were applied: Groups IB and IIB were treated with 15-DS alone (4 mg/kg/day) for p.o. days 0-9. Groups IC and IIC were treated with cyclosporine A (10-40 mg/kg/day) for p.o. days 0-30. Groups ID and IID received a combination of 15-DS (for p.o. days 0-9) and CsA (for p.o. days 0-30). Groups IA and IIA served as control and received no medication. The mean graft survival was 11.0 days for group IA, 28.2 days for group IB (P less than 0.05; IB vs. IA), 32.4 days for group IC, and 43.1 days for group ID (P less than 0.025; ID vs. IA). After renal transplantation, the corresponding figures were 12.3 days for group IIA, 8.5 days for group IIB, 30.4 days for group IIC and 148.9 days for group IID (P less than 0.025; IID vs. IIA). After cardiac and renal transplantation, acute rejection was the main cause of graft failure. Treatment-related side effects, mainly gastrointestinal complications, were observed only in primates, who were treated with 15-DS alone. After cardiac transplantation, permanent graft non-reactivity was not achieved, but a delayed rejection occurred within a mean of 21.8 days after immunosuppression had been stopped. Following renal transplantation, graft nonreactivity was also not achieved in groups IIB and IIC. In group IID, however, 4 of 8 animals (50%) were graft-tolerant 340, 256, 244, and 164 days after treatment discontinuation. Thus, the combination of 15-DS and CsA led to a significant prolongation of graft survival in both groups. Long-term nonreactivity was achieved only after renal transplantation, when initially treated with 15-DS and CsA.

Animals↗

Heart transplantation--the treatment of choice for patients with end-stage ischaemic heart disease.

Between December, 1967 and August, 1988, 147 heart transplants (64 orthotopic, 68 heterotopic procedures; 15 heart-and-lung replacements) were performed on 128 patients. In the majority of the recipients, dilated cardiomyopathy or end-stage ischaemic heart disease was diagnosed. From 1985 to the present, 70 transplants (45 orthotopic, 11 heterotopic and 14 heart-lung) took place. Seventeen of these patients (mean age 46.6 years) suffered from end-stage disabling (NYHA IV) coronary artery disease; in each case the angiogram verified severe stenosis or occlusion of the three main coronary artery systems. Their histories revealed a total of 22 previous myocardial infarctions; 8 patients needed a total of 9 surgical revascularization procedures. The left ventricular ejection fraction (LVEF) ranged from 9% to 24% (mean 15.3%). Before transplantation three patients required intraaortic balloon pump (IABP) support. Fourteen of the 17 patients are at present still alive with post operative periods ranging from 8 weeks to 3.5 years (the actuarial 90-days and 1-year-survival rates being respectively 91.7% and 81.5%). Twelve of the patients are in NYHA class I; 2 are in class II. Three late deaths occurred: one from pneumocystic carinii/cytomegalovirus pneumonia, a second from atypical pneumonia and a third from chronic graft rejection. Radionuclide ventricular studies demonstrated postoperative left ventricular ejection fractions ranging from 54%-81% (mean 71%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Blood platelets in cardiopulmonary bypass operations. Recovery occurs after initial stimulation, rather than continual activation.

The ultrastructure of blood platelets was related to platelet function and secretion products before, during, and after cardiopulmonary bypass. Circulating platelets from 15 patients undergoing aorta-coronary bypass operations were investigated at ten predetermined points of time by scanning and transmission electron microscopy. Simultaneously, platelet adenosine triphosphate, diphosphate, and serotonin, as well as plasma levels of platelet factor 4, beta-thromboglobulin, serotonin, thromboxane B2, lactic dehydrogenase, and free hemoglobin were measured. Moreover, platelet responsiveness toward adenosine diphosphate and collagen was determined by optical aggregometry. By scanning electron microscopy, the number of unactivated platelets dropped from 96% +/- 4% to 54% +/- 19% (p less than 0.05) 8 minutes after the onset of bypass. Simultaneously, the percentage of "shape changed" platelets significantly increased. No major release reaction was detected at this time. After the initial activation, platelet morphology began to recover although the bypass continued. During the late period of bypass, a highly significant correlation between increasing plasma levels of alpha-granule compounds (platelet factor 4 and beta-thromboglobulin) and lysis parameters (lactic dehydrogenase and free hemoglobin) was found. However, transmission electron microscopic analysis of the arterial filter and scanning electron microscopic findings of circulating platelets indicated that the release products in plasma were due not only to platelet lysis but also to a limited extent to secondary aggregation. In an inverse and probably causative manner, platelet morphology recovered, whereas the sensitivity of platelets to adenosine diphosphate and collagen decreased toward the end of bypass.

Adenosine Triphosphate↗

Initial experience with heart and lung transplantation.

Between February 1983 and July 1987, twelve patients underwent heart-lung transplantation at the University of Cape Town and the University of Munich. The patients included eight men and four women, whose ages ranged from 15 to 49 years (mean, 27 years). The underlying pathologic condition was idiopathic primary pulmonary hypertension in five cases, Eisenmenger's syndrome in four cases, idiopathic pulmonary fibrosis in one case, diffuse fibrosing alveolitis in one case, and chronic emphysema in one case. The immunosuppressive regimen consisted of cyclosporine A, azathioprine, and rabbit antithymocyte globulin (RATG) during the first 2 postoperative weeks; RATG was subsequently replaced by methylprednisolone. Pulmonary rejection frequently occurred in the absence of cardiac rejection; in one case, however, this situation was reversed. Two patients required retransplantation, which was undertaken for caseating pulmonary tuberculosis with obliterative bronchiolitis after 1 year in one case and for early pulmonary insufficiency after 2 days in the other case. There were no operative deaths, but three early deaths occurred, owing to respiratory insufficiency of unknown origin (10 days postoperatively), multiorgan failure (10 days postoperatively), and acute liver dystrophy (11 days postoperatively). Five weeks after operation, a fourth patient died of multi-organ failure. There were five late deaths, all of which resulted from infectious complications. Three patients, including one who underwent retransplantation, remain alive and well, 10 to 36 months postoperatively.

Journal Article↗

Frequency analysis of the surface electrocardiogram for recognition of acute rejection after orthotopic cardiac transplantation in man.

Recognition of acute rejection after heart transplantation has been based mainly on invasive methods until now. In this study we analyzed two well-defined surface electrocardiographic recordings by fast Fourier transform (FFT) (Blackman Harris window, 512 points) after low-noise, high-gain amplification (filter setting 0.5 to 300 Hz) each day for 4 weeks after cardiac transplantation in 27 patients. Twenty acute rejection crises requiring treatment were diagnosed by cytoimmunologic monitoring and endomyocardial biopsy. Single-beat analysis of the QRS complex by FFT revealed a progressive change of the spectral morphology (increase of the frequency content between 70 and 110 Hz) on the days of rejection in 19 of 20 patients. At that time there were no visible changes on the electrocardiogram in the time domain in most patients. At the same time, the frequency content of the ST segment decreased between 10 and 30 Hz in 16 of 20 patients. After successful treatment, the frequency spectra of the QRS complex and ST segment returned to control within 1 to 2 weeks in most patients. One false-positive result was seen in a patient with mediastinitis and large pericardial effusion. A drop in QRS amplitude (greater than 20%) occurred in 10 of 20 rejection crises and in 10 patients without rejection. Nine patients after cardiac transplantation without rejection and seven control patients after cardiac surgery (not transplantation) showed stable frequency plots from one day to the other after the first postoperative day, but with considerable changes in QRS amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗