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Biomedical subjects

H G Borst

Publications and source records attributed to H G Borst.

At least 307 records · Page 17Linked to original sources

Emergency lung transplantation after extracorporeal membrane oxygenation.

In some patients with acute respiratory failure, the native lungs do not recover during extracorporeal membrane oxygenation (ECMO), or complications occur that preclude the meaningful continuation of ECMO therapy. In such cases, emergency lung transplantation (LTx) represents the only therapeutic alternative. Between May 1988 and April 1993, the authors have performed LTx after ECMO support in five of 111 lung or heart-lung transplantations (4.5%). Two patients presented with early graft failure after unilateral LTx. In these patients, ECMO was used as a bridging device to unilateral re-LTx for 1, resp. 11 days. One patient died 6 months post-operatively from chronic rejection; the other underwent a third LTx and is doing well after 42 months. In three further patients already treated with ECMO for 5 to 12 days for ARDS (n = 2) or acute respiratory failure after liver and kidney transplantation, the native lungs did not recover (n = 2) or pulmonary hemorrhage developed. The last patient (unilateral LTx) and one of the former (bilateral LTx for ARDS) are long-term survivors (12, 30 months). The remaining patient (unilateral LTx for ARDS) had severe multiorgan failure at the time of his operation and died intraoperatively. The authors conclude that ECMO no longer represents a contraindication to subsequent LTx. Their results also support the continued investigation of this combined therapeutic approach.

Adult↗

Regional distribution of beta-adrenoceptors in the human heart: coexistence of functional beta 1- and beta 2-adrenoceptors in both atria and ventricles in severe congestive cardiomyopathy.

We evaluated the amount of beta 1- and beta 2-adrenoceptors in human right and left atrium as well as in right and left ventricular wall obtained from heart transplant recipients who suffered from end-stage congestive cardiomyopathy. The total number of myocardial beta-adrenoceptors was assessed with the nonsubtype selective beta-adrenoceptor radioligand (-)[125I]iodocyanopindolol (ICYP); concomitantly, the number of beta 1-adrenoceptors was determined with the selective beta 1-adrenoceptor radioligand (-)[3H]bisoprolol. The number of beta 2-adrenoceptors was calculated by subtracting (-)[3H]bisoprolol binding sites from ICYP binding sites. With this technique, a beta 1/beta 2-ratio of approximately 65/35% for both atria and of approximately 75/25% for both ventricles was found. Identical results were obtained when the beta 1/beta 2-ratio was calculated indirectly by nonlinear regression analysis of competition curves of the selective beta 1-adrenoceptor antagonist bisoprolol and the selective beta 2-adrenoceptor antagonist ICI 118,551 with ICYP binding. In addition, on atria and on ventricles, adenylate cyclase was activated by norepinephrine (presumably by beta 1- and beta 2-adrenoceptor stimulation) and by procaterol (by beta 2-adrenoceptor stimulation). It is concluded that in the human heart functional beta 1- and beta 2-adrenoceptors coexist on both atria and both ventricles. In end-stage congestive cardiomyopathy, there appears to be a selective down-regulation of cardiac beta 1-adrenoceptors, whereas beta 2-adrenoceptors are obviously not affected. This may explain the beneficial effects of beta 2-adrenoceptor agonists in severe heart failure.

Adenylyl Cyclases↗

Aortic dissection.

Acute and chronic aortic dissection is described in terms of diagnostics, surgical indications and present day operative treatment. The need for prompt decision making and intervention is highlighted. The results to be expected from surgery are outlined.

Acute Disease↗

Donor heart-related variables and early mortality after heart transplantation.

Impaired donor heart function after heart transplantation results in the necessity for prolonged catecholamine and ventilatory support of the patient. Subsequently the risk of multiorgan impairment, infection, and rejection will be increased. In this retrospective analysis we tried to identify donor-related risk factors in patients who died early after transplantation. Of 174 patients undergoing heart transplantation from October 1985 through October 1988, 22 (12.6%) died early. Of the total, 39 cases were evaluated retrospectively for donor-related logistic and metabolic factors. All donors were analyzed with respect to the early mortality for age, weight, height, maximum dopamine concentration, thyroid hormone levels, and the duration from brain death until explantation and ischemia. Thirty patients were survivors (group A); nine patients died early (group B). By multiple regression analysis a significant influence (group A vs group B) of donor age, dopamine support, and ischemic time on early mortality could be demonstrated, whereas donor weight and height, hormone levels of triiodothyronine and thyroxine, and duration of brain death showed no correlation. From this limited experience we conclude that use of hearts from older donors with higher catecholamine support and longer ischemic times will result in an increased early mortality. In contrast, no influence of prolonged brain death times and metabolic factors could be demonstrated.

Adult↗

Comparison of mononuclear cell subpopulations in bronchoalveolar lavage fluid in acute rejection after lung transplantation and Mycoplasma infection in rats.

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)

Animals↗

Treatment of rejection after heart transplantation: what dosage of pulsed steroids is necessary?

Histologically proved rejection after heart transplantation is commonly treated with intravenous steroids, 1 gm/day for 3 days. This regimen may result in severe side effects, however, both metabolic and infectious. In a total of 663 rejection episodes, we treated 397 with conventional steroid therapy, 1000 mg per day for 3 days (group 1), 199 with 500 mg/day for 3 days (group 2), and 67 with 250 mg/day for 3 days (group 3). Response to treatment was assessed by control biopsy after 1 week and graded as ongoing, resolving, or resolved rejection. The efficacy of the three regimens showed no significant differences between the groups as determined by the results of the subsequent biopsy. Ongoing rejection, resolving rejection, and resolved rejection, respectively: group 1-3.3%, 66.5%, 30.2%; group 2-8.0%, 66.8%, 25.2%; group 3-4.5%, 73.1%, 22.4%. We conclude that comparable effects, even with a considerable reduction of pulsed steroids, may be obtained in the treatment of cardiac allograft rejection, if triple-drug immunosuppression is used for maintenance therapy. It seems likely that steroid side effects may be decreased without jeopardizing the graft.

Adult↗

Oxygen free radical scavengers to prevent pulmonary reperfusion injury after heart-lung transplantation.

Oxygen free radical scavengers, such as superoxide dismutase (SOD) and catalase (CAT), have been shown to reduce effectively myocardial reperfusion injury. No such data have been reported for cold global pulmonary ischemia, which is required in heart-lung transplantation. Heterotopic heart-left lung allotransplantation was performed in 18 dogs after single-flush perfusion of the lungs with Euro-Collins solution (60 ml/kg), cardioplegic arrest, and 6 hours of cold global ischemia. Six dogs served as controls. In six other dogs prostacyclin (PGI2) was administered both into the pulmonary artery (20 ng/kg/min) and to the Euro-Collins solution (15 mg/L) before explantation (group A). Grafts in six other dogs were preserved with Euro-Collins solution plus SOD (40,000 U/L) and CAT (100,000 U/L)(group B). In addition, SOD (1 mg/kg) and CAT (1.5 mg/kg) were given intravenously during the first 20 minutes of reperfusion. There was no significant difference in cardiac output, right and left atrial pressures, nor pulmonary arteriolar resistance among the groups. In contrast, left atrial oxygen pressure (PO2) values were best in group B. At all times, PO2 values in animals in groups A and B exceeded those in control animals. Compared with control animals with Euro-Collins solution preservation alone, animals with both PGI2 and SOD/CAT preservation had significantly improved pulmonary function after heart-lung transplantation. Better oxygenation in the SOD/CAT group (group B) suggests an important impact of oxygen free radicals during reperfusion.

Animals↗

Predictive implications of bioptic diagnosis in cardiac allografts.

The prognostic value as represented by the predictive implications of the histopathologic bioptic diagnosis in cardiac allografts was studied in a total of 3209 biopsies from 111 patients under triple-drug immunosuppressive therapy after transplantation during a period of more than 2 years (0 to 782 days). The application of the so-called Hannover classification in the histopathologic diagnosis of rejection has revealed that there are certain configurations of histopathologic changes that lead significantly more frequently to the forms of acute rejection (moderate or severe) that require therapy. These are mild acute rejection with retrogressive changes in myocytes and a late-resolving phase of acute rejection with a severe vasculopathy. In cases with the simultaneous presence of the chronic phase of rejection, a slight prolongation of the interval taken by the conversion of these two diagnoses into the therapy-requiring forms of acute rejection could be observed. On average, however, the time interval of conversion of mild acute rejection with retrogressive changes in myocytes and of the late-resolving phase of acute rejection with interstitial vascular reaction into the therapy-requiring forms ranges between 7 and 10 days. Thus a second biopsy should be performed within this time interval.

Antilymphocyte Serum↗

Flush perfusion using Euro-Collins solution vs cooling by means of extracorporeal circulation in heart-lung preservation.

Single-flush perfusion using modified Euro-Collins solution and donor cooling by extracorporeal circulation represent two concepts of lung preservation currently in use for on-site heart-lung transplantation. The question of which technique is better for safe clinical application of heart-lung transplantation, including extended periods of ischemia and distant organ procurement, currently remains undetermined. Eighteen mongrel dogs, divided in three groups, underwent left lung, heterotopic heart transplantation, leaving the right lung and heart of the recipient in place. Donor organs were obtained from size-matched dogs. In all groups, myocardial preservation was achieved using 10 ml/kg cold potassium cardioplegia. Following flush perfusion of the lung (Euro-Collins solution, 60 ml/kg), six dogs were immediately transplanted (group I). Using the same preservation, organs were stored for 6 hours at 4 degrees C in group II. In group III, organs were cooled using extracorporeal circulation until reaching a rectal temperature of 16 degrees C, harvested, and thereafter stored as in group II. After transplantation, blood supply of the donor heart was assured by selective drainage of the superior vena cava into the right side of the donor heart. Outflow was obtained by end-to-side anastomosis of donor and recipient aorta. The dogs were kept anesthetized, and both lungs were ventilated selectively with an FiO2 of 0.4 for 20 hours or until death. During the postoperative course, the donor heart pumped about one third of the entire cardiac output in all groups. The lowest pulmonary vascular resistance of the transplanted lung was observed in group III. Oxygenation of the transplanted lung revealed no impairment in group I compared with the pretransplant values. By contrast, groups II and III showed a slight decrease of oxygenation within acceptable limits. We therefore conclude that both methods of cardiopulmonary preservation evaluated may allow for an extended ischemic time of up to 6 hours before heart-lung transplantation. Pulmonary vascular resistance was significantly lower in the group preserved by extracorporeal circulation, possibly reflecting superior preservation of lung function by this method.

Animals↗

Cytoimmunologic monitoring in early and late acute cardiac rejection.

The absolute concentration of circulating lymphoblasts and prelymphoblasts has been shown repeatedly to closely correlate with acute cardiac rejection in heart transplant recipients. Little information, however, is available with respect to the reliability of this measurement in the late postoperative course. Fifty-two heart transplant recipient operated on from October 1985 through September 1986 were studied with cytoimmunologic monitoring for lymphocyte activation in peripheral blood. Immunosuppressive therapy consisted of azathioprine, cyclosporine, and steroids. Endomyocardial biopsies were obtained at regular intervals. Cytoimmunologic monitoring was performed daily during hospitalization and together with endomyocardial biopsy at outpatient visits. A total of 768 endomyocardial biopsies and 1077 mononuclear concentrates for study of lymphocyte activation were obtained. Concentration of activated cells showed a significant increase during acute rejection. Cytoimmunologic monitoring had an overall sensitivity of 76% and a specificity of 79%. Within 90 days after transplantation cytoimmunologic monitoring showed a sensitivity of 84%, which decreased to 71% beyond 3 months. We therefore conclude that cytoimmunologic monitoring, a noninvasive adjunct for diagnosis of acute allograft rejection, cannot replace routine endomyocardial biopsy, particularly in view of a significant loss in sensitivity in the late postoperative course.

Adolescent↗

Changes of the intramyocardial electrogram after orthotopic heart transplantation.

Heart transplantation, including conventional immunosuppression, has allowed the use of the surface electrocardiogram to detect allograft rejection. With the use of cyclosporine this parameter is no longer sensitive, but voltage of the intramyocardial electrogram has correlated repeatedly with rejection. From July 1983 through February 1986, 98 patients had heart transplantation; 13 of those patients had a telemetry pacemaker simultaneously implanted. In previous studies, daytime dependent variabilities of the sum voltage of the surface electrocardiogram were reported. Therefore intramyocardial electrogram was measured at 7, 10, 13, 16, and 20 hours. In addition, the influence of exercise on intramyocardial electrogram voltage was studied in all patients. Analysis of the diurnal intramyocardial electrogram revealed substantial atrial and ventricular variability of both voltage measurements (p less than 0.05). Also, intramyocardial electrogram voltage was influenced by exercise, as demonstrated by a significant decrease after physical work at 25 W (-8%) and 50 W (-12%); p less than 0.05. Therefore we conclude that a high variability of intramyocardial electrogram may be found diurnally and on exercise testing after heart transplantation in humans. If intramyocardial electrogram is used to detect rejection, it should be applied at comparable hours and with the patients in a controlled resting state.

Adolescent↗

Transposition of the greater omentum for management of mediastinal infection following orthotopic heart transplantation: a case report.

A case of mediastinal infection following orthotopic heart transplantation is presented. A general survey of the available surgical management of this complication is given and an alternative operation involving extra-abdominal transposition of the greater omentum pedicled on the left gastroepiploic vessels is suggested for treating difficult cases.

Enterobacteriaceae Infections↗

The Carpentier-Edwards supra-annular bioprosthesis for aortic valve replacement. Clinical experience in 234 patients.

Between January 1980 through December 1983, aortic valve replacement (AVR) was performed in 234 patients with a Carpentier-Edwards supra-annular bioprosthesis. There were 177 isolated AVRs and 18 AVRs combined with coronary artery bypass grafting (CABG): one bypass was done in 9 patients, 2 in 7 and 3 in 2 patients. Additional valve surgery was: mitral valve reconstruction in 14, mitral valve replacement in 12 and additional tricuspid reconstruction in 2. AVR combined with various other procedures was performed in 11 other patients. Early mortality for isolated AVR was 5%. Follow-up information was obtained until June, 1984. During this observation period (19.8 +/- 7 months), late mortality was 4%. Follow-up information was obtained on 212 of the 234 patients (91%). Preoperatively, 77% of the patients were in NYHA class III, 16% were in class IV. Postoperatively, 82.5% had improved to functional class I and II (I: 42.5%, II: 40%), only 17% were in class III. A diastolic murmur indicating aortic regurgitation was noted in 25 patients (11%). The murmur occurred early in 3, and late within 2 years in 21 instances: 7 patients required reoperation. Intraoperative findings were: leaflet perforation (3), leaflet rupture (1), suture dehiscence (2), and endocarditis (1). Histology and electron microscopy of the 4 malfunctioning valves showed changes in collagen structure and minimal calcification. The possible causes of valve failure are discussed.

Adult↗

Partial repair followed by total correction in congenital heart anomalies.

A two stage corrective operative approach is required for a variety of complex heart anomalies. Different anomalies require different approaches in the various age groups. The technique, results, and complications of elective primary partial repair followed by full correction are described.

Aorta, Thoracic↗