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Biomedical subjects

H Reichenspurner

Publications and source records attributed to H Reichenspurner.

At least 109 records · Page 6Linked to original sources
PubMed1994

Reduction of cyclosporine-induced nephrotoxicity by cilastatin following clinical heart transplantation.

The objective of this prospective, randomized, placebo-controlled, single-blinded study in 28 heart-transplanted patients was to investigate whether the dehydropeptidase inhibitor cilastatin reduces cyclosporine-induced nephrotoxicity. Cilastatin is available only in combination with imipenem, a beta-lactam antibiotic to which it is added for reduction of nephrotoxic side-effects of the antimicrobial agent. Patients received either 100 ml placebo (n = 12) or 100 ml (500 mg) imipenem/cilastatin (n = 16) twice perioperatively, and 4 times daily for the first 7 postoperative days. Serum creatinine and urea, as well as urine concentrations of N-acetyl-beta-D-glucosaminidase, which is directly correlated with tubular cell damage, were used as markers for renal function. Thromboxane B2 and 6-keto-prostaglandin F1-alpha serum concentrations were determined to investigate whether there is an imbalance in synthesis of thromboxane A2 and prostacyclin as a possible mechanism for cyclosporine-induced nephrotoxicity. Two placebo patients and 6 patients receiving imipenem/cilastatin had to be excluded from further analysis. Three of 10 placebo patients required hemofiltration, and 2 of them even required hemodialysis, as compared with none in the imipenem/cilastatin group. Creatinine concentrations increased significantly from the second to the fourth postoperative day in the placebo group, but remained nearly normal in cilastatin patients (P < 0.05 for intergroup comparison on postoperative days 2-4). The same trend was observed in urea and N-acetyl-beta-D-glucosaminidase concentrations, without the difference reaching statistical significance. For thromboxane B2 and 6-keto-prostaglandin F1-alpha no differences between the groups could be found. These results suggest that imipenem/cilastatin can counteract acute cyclosporine-induced nephrotoxicity, which appears to be associated with alterations of tubular cell function. The combined use of cyclosporine and imipenem/cilastatin appears to be advantageous in patients following heart transplantation during the initial postoperative period.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Reduction of the incidence of rejection by adjunct immunosuppression with photochemotherapy after heart transplantation.

In this study, photochemotherapy (PCT) was used for adjunct immunosuppression in the first six months after heart transplantation (HTx). Fifteen patients after orthotopic HTx were included in the study; all received standard triple-drug immunosuppression including cyclosporine, azathioprine and glucocorticoids, but no adjunct therapy with mono- or polyclonal antibodies. The patients were divided into three groups: group I served as control with no additional treatment; group II received adjunct treatment with 10 courses of PCT (single-day treatments); and group III received 20 PCT courses since it was given each time on two consecutive days. PCT was started in both groups on day one after HTx; it was applied with a higher frequency in the early postoperative period and thereafter continued at four-week intervals for a total of 6 months. The photopheresis method for PCT included extracorporeal UVA irradiation of mononuclear cells that were treated with the photosensitive drug 8-methoxypsoralen (8-MOP) and subsequently retransfused to the patient. A new liquid form of 8-MOP was added directly to the buffy coat, resulting in reliable and sufficient drug levels in the cell suspension during the irradiation period; problems caused by oral application due to unpredictable variations in gastrointestinal absorption were thus prevented. Analysis of the total numbers of acute rejection episodes (AREs) within the first four weeks after HTx revealed a more impressive decrease by double PCT (group III, 3 AREs) than by single PCT (group II, 5 AREs) in comparison with the control (group I, 6 AREs). Over the total observation time (mean: 9.6 months), however, both PCT schedules reduced the total number of AREs observed in the control group (20 AREs) equally by more than 50% (9 AREs each in groups II and III) (P = 0.007). Furthermore, PCT treated patients had significantly fewer infections (6 infections in each group) than control group patients (15 infections) (P = 0.026); this, however, may be accounted for by the higher number of acute rejections in the control group and consequent increase in unspecific immunosuppression treatment. Our results suggest that PCT is a safe and effective method of adjunct immunosuppression that can be applied early in the postoperative period; it reduces the number of rejection episodes and does not increase the risk of infections.

Adult↗
PubMed1994

Heart-lung transplantation in a patient with pulmonary atresia and ventricular septal defect.

Operation for pulmonary atresia and ventricular septal defect is challenging, as in most patients the pulmonary arteries are hypoplastic, nonconfluent, or in part absent. In these cases, combined heart-lung transplantation may be the surgical treatment of choice. In the described case, the morphology of pulmonary atresia and ventricular septal defect was present in combination with completely atretic main, left, and right pulmonary arteries. In this patient, successful heart-lung transplantation was performed.

Adult↗
PubMed1994

Comparison of UW versus HTK solution for myocardial protection in heart transplantation.

In order to evaluate the protective effect of University of Wisconsin (UW) solution in heart transplantation, a retrospective comparative study with histidine-tryptophane-ketoglutarate (HTK) solution was initiated. In group I, we included 160 patients with HTK preservation, while group II consisted of 50 patients who had their transplant protected with UW solution. All patients received standard quadruple drug therapy for immunosuppression. The average ischaemic time of the donor hearts in group I was 142+/-44 min, ranging from 83 to 235 min. Acute immediate perioperative graft failure occurred in six cases (3.8%). Statistical analysis including the chi-square test, revealed a significant increase in the incidence of acute perioperative graft failure when compared with duration of ischaemic time (P < 0.01). Within the first 30 postoperative days, 24 patients died (15% early mortality). The same statistical correlation was evident between the incidence of early mortality and duration of graft ischaemic time. The 30-day and 6-month survival rates were 81% and 78%, respectively. The average ischemic time of the donor hearts in group II was 193+/-50 min ranging from 100 to 360 min, which was significantly longer in comparison with the group I (P < 0.05). Acute perioperative graft failure occurred once (2%); the patient was retransplanted successfully. Five patients died within the first 30 postoperative days (10% early mortality). There was no correlation between length of ischaemic time and incidence of acute graft failure or early mortality. The 30-day and 6-month survival rates were 90% and 88%, respectively and, thus, better when compared with group I. In both groups similar results were achieved with regard to postoperative NYHA status of the patients and incidence of cardiac arrhythmias. Myocardial preservation with HTK solution showed satisfying results as long as the ischaemic time did not exceed 4 h. The early functional results achieved with UW graft protection were excellent, even with ischaemic times longer than 4 h and not depending on lenght of ischaemic period.

Adenosine↗
PubMed1994

Studies of the nucleoside transporter inhibitor, draflazine, in the human myocardium.

1. The aim of the present study was to determine the effect of the nucleoside transporter inhibitor, draflazine, on the force of contraction in human myocardium and the affinity of the compound for the nucleoside transporter. Nucleoside transport inhibitors, like draflazine, are of potential importance for cardiopreservation of donor hearts for heart transplantation. 2. Functional experiments were performed in isolated electrically driven (1 Hz, 1.8 mmol l-1 Ca2+) human atrial trabeculae and ventricular papillary muscle strips. The affinity of draflazine for the myocardial nucleoside transporter was studied in isolated membranes from human ventricular myocardium and human erythrocytes in radioligand binding experiments using [3H]-nitrobenzylthioinosine ([3H]-NBTI). Dipyridamole was studied for comparison. 3. In membranes from human myocardium and erythrocytes, [3H]-NTBI labelled 1.18 pmol mg-1 protein and 23.0 pmol mg-1 protein, respectively, nucleoside transporter molecules with a KD value of 0.8 nmol l-1. Draflazine concentration-dependently inhibited binding of [3H]-NBTI to myocardial and erythrocyte membranes with a K(i)-value of 4.5 nmol l-1. The potency as judged from the K(i) values was ten times greater than that of dipyridamole in both myocardial and erythrocyte membranes. 4. Draflazine, at concentrations up to 100 mumol l-1, did not produce negative inotropic effects in atrial and ventricular myocardium. (-)-N6-phenylisopropyladenosine (R-PIA) and carbachol did not reduce force of contraction in ventricular myocardium, but exerted concentration-dependent direct negative inotropic effects in atrial myocardium. 5. The data provide evidence that draflazine specifically binds to the nucleoside transporter of the human heart and erythrocytes with high affinity. The compound does not produce negative inotropic effects at concentrations as high as 100 micromol 1-1.6. Draflazine could be a useful agent for cardio preservation because it does not produce cardio depressant effects. Thus, it may be possible to perfuse explanted hearts directly with this agent without the hazard of cardiodepression.

Adult↗
PubMed1993

Extended cardiopulmonary preservation: University of Wisconsin solution versus Bretschneider's cardioplegic solution.

Application of the University of Wisconsin cold storage solution has rapidly expanded to include medium-term to long-term preservation of virtually all intraabdominal organs. Its use in intrathoracic organ transplantation has also been suggested. We therefore examined the efficacy of the University of Wisconsin solution in a primate allotransplantation model for preservation of hearts, and as a simple single-solution system for static preservation of heart-lung blocks, for periods of ischemia ranging from 6 to 24 hours. For comparison, we employed the histidine-tryptophane-ketoglutarate cardioplegic solution of Bretschneider. University of Wisconsin solution provided superior results with regard to clinical outcome and hemodynamic recovery of hearts after ischemic periods of up to 16 hours. This was in contrast to Bretschneider's solution, which allowed storage of hearts for periods of only up to 10 hours. Heart-lung blocks were equally well preserved with either University of Wisconsin or Bretschneider's solution after 6 to 12 hours, although the University of Wisconsin solution group exhibited a more notable increase in pulmonary water content. This was in accordance with histological data, which suggested that, although hemodynamic recovery of hearts stored for periods longer than 10 hours was poor, preservation of pulmonary ultrastructure was far superior using Bretschneider's solution as compared with University of Wisconsin solution after an ischemic period of up to 16 hours.

Adenosine↗
PubMed1993

Myocardial preservation using HTK solution for heart transplantation. A multicenter study.

Bretschneider HTK solution is commonly used for myocardial preservation. In order to evaluate its protective effect for heart transplantation, a retrospective study was initiated in cooperation with Eurotransplant and five heart transplant centers. Seventy-six female and 524 male patients who underwent cardiac transplantations between 1981 and 1991 were included in this study. Using standardized questionnaires, donor and recipient laboratory data, immunosuppressive therapy and the preoperative, intraoperative and postoperative organ function were documented. The average ischemic time of the donor hearts was 160 min, ranging from 75 min-304 min. Immediate postoperative graft failure was observed in 25 transplantations (4.2%). Within the first 30 days 71 organs (11.8%) failed. Using the chi2-test, a statistically significant increase of acute graft failure and early mortality was evident when they were correlated with the length of ischemic time (P = 0.01). In addition, a higher incidence of early graft failure was observed when the perfusion volume was less than 1500 ml. The 1- and 5-year survival rates were 72% and 63%, respectively. Organ preservation with HTK shows good results as long as the ischemic time does not exceed 4 h. The possibility that an increased perfusion volume allows longer ischemic times cannot be excluded with this study.

Cardioplegic Solutions↗
PubMed1993

Heart transplantation after Senning operation for transposition of the great arteries.

In a 17.5-year-old boy and a 21-month-old girl orthotopic heart transplantation was performed after intractable right-heart failure had developed 14.5 years and 15 months respectively after Senning operation for TGA. Before the atrial repair, combined with closure of the VSD in each case, initial operation had involved a banding of the pulmonary artery in the boy and a modified Blalock-Taussig shunt in the girl. A coarctation of the first patient remained untreated. After resection of the diseased organ a new intraatrial septum of glutaraldehyde-fixed bovine pericardium was created. 15 and 3 months respectively after orthotopic heart transplantation both patients belong to NYHA classification I.

Adolescent↗
PubMed1993

[Initial experience with the NOVACOR left heart assist system in transition for heart transplantation at the Grosshadern Clinic].

We recently used an electrically powered left ventricular assist device (NOVACOR Corp., Oakland, Calif.) to support the circulation of a 17-year-old man with profound circulatory impairment. He had been regularly listed for cardiac transplantation previously because of dilated cardiomyopathy, and decompensated acutely with severe biventricular failure before a suitable donor heart became available. Isolated left ventricular support with the NOVACOR system provided adequate haemodynamics and recovery of right ventricular, hepatic and renal function. After 2 days of support, orthotopic heart transplantation could be performed successfully. Five days after transplantation he developed a massive cerebral haemorrhage during a hypertensive crisis of which he recovered completely after neurosurgery without any residuals. He ist currently doing extremely well some 14 months after transplantation.

Adolescent↗
PubMed1992

[Incidence, prevention and therapy of cytomegalovirus and pneumocystis carinii infection after heart transplantation].

Diseases caused by cytomegalovirus (CMV) and pneumonia due to pneumocytis carinii (PCP) are problematic complications after allogeneic heart transplantation. Recipients of CMV-seropositive donors have a higher morbidity of CMV. By using an anti-CMV-immunoglobulin preparation in routine prophylaxis the incidence of CMV disease after heart transplantation could be reduced significantly. Ganciclovir 10 mg/kg is administered for treatment of CMV disease for at least 14 days. Recent investigations show that a prophylactic administration of ganciclovir after heart transplantation is safe, and it reduces the incidence of CMV-induced illness in CMV-seropositive patients. The incidence of PCP after heart transplantation varies according to the literature between 1 and 13%. The onset of the disease is located mostly between the third and the fifth month after heart transplantation. An effective prophylaxis can be achieved by low dose cotrimoxazole (960 mg at two days per week in adults) within the first six postoperative months. Cases of PCP are treated by cotrimoxazole or pentamidine and are associated with a mortality up to 60%.

Antibodies, Fungal↗