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Biomedical subjects

D Novitzky

Publications and source records attributed to D Novitzky.

103 records · Page 6Linked to original sources
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Triiodothyronine therapy for heart donor and recipient.

Both (1) brain-dead donors and (2) transplant recipients on cardiopulmonary bypass suffer a depletion in plasma-free triiodothyronine (T3), which leads to metabolic changes (from inhibition of mitochondrial function), resulting in myocardial energy store depletion. Replacement therapy with T3 reverses these changes in both donor and recipient. Donor heart energy stores and function will be maintained at optimum levels if T3 therapy is administered to both donor and recipient at the time of transplantation.

Cardiopulmonary Bypass↗
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Prediction of acute cardiac rejection by changes in left ventricular volumes.

Sixteen patients underwent heart transplantation (11 orthotopic, five heterotopic). Monitoring for acute rejection was by both endomyocardial biopsy (EMB) and multigated equilibrium blood pool scanning with technetium 99m-labelled red blood cells. From the scans information was obtained on left ventricular volumes (stroke, end-diastolic, and end-systolic), ejection fraction, and heart rate. Studies (208) were made in the 16 patients. There was a highly significant correlation between the reduction in stroke volume and end-diastolic volume (and a less significant correlation in end-systolic volume) and increasing acute rejection seen on EMB. Heart rate and ejection fraction did not correlate with the development of acute rejection. Correlation of a combination of changes in stroke volume and end-diastolic volume with EMB showed a sensitivity of 85% and a specificity of 96%. Radionuclide scanning is therefore a useful noninvasive tool for monitoring acute rejection.

Biopsy↗
PubMedDate not supplied

Acute pulmonary rejection precedes cardiac rejection following heart-lung transplantation in a primate model.

Twelve Chacma baboons underwent transplantation of the heart and both lungs from donor baboons matched for size and AB blood group. Cyclosporine was given daily orally, by twice daily intravenous injections, or by a single intravenous injection (together with oral azathioprine and, after 2 weeks, methylprednisolone); whole blood trough levels were inadequate in all groups. Survival was from 4 to 29 days, with death resulting from acute rejection of the lungs in 11 and from bronchopneumonia in one. In the 11 animals dying from rejection, histologic examination showed that the heart was spared from severe rejection in all cases but one. In the inadequately immunosuppressed baboon, therefore, acute rejection occurs earlier in the lungs than in the heart. We have now observed what we believe to have been acute pulmonary rejection in the absence of cardiac rejection on five occasions in three patients in our clinical transplantation program. We would suggest that pulmonary rejection must always be strongly suspected if there are any suggestive features, particularly pulmonary shadowing on chest radiographs, despite negative results of tests indicating rejection of the heart. In the absence of any easy method of confirming pulmonary rejection directly (other than open-lung biopsy, which is clearly contraindicated as a routine procedure), we suggest that more attention should be directed toward developing tests for rejection that are not organ specific, rather than relying on techniques that diagnose cardiac rejection only.

Animals↗
PubMedDate not supplied

Successful orthotopic heart-lung transplantation in the baboon after five hours of cold ischemia with cardioplegia and Collins' solution.

En bloc transplantation of the heart and lungs was performed in 15 chacma baboons; the donor organs were stored between 4 and 6 hours before transplantation. The hearts were perfused in the donor animals with 15 ml/kg Wicomb's cardioplegic solution at 4 degrees C, the lungs with either 20 ml/kg 4 degrees C Collins' solution with an added 2.5% dextrose and 12 mEq magnesium sulfate (Collins' solution, group 1, n = 8), Collins' solution plus superoxide dismutase (40,000 U/L superoxide dismutase, group 2, n = 4), or Collins' solution plus superoxide dismutase plus peroxidase (5000 U/L peroxidase plus mannitol, group 3, n = 3). The pulmonary artery perfusion pressure was not allowed to exceed 50 cm water; the lungs were maintained at 30% to 50% inflation, and external cooling was applied. After explantation the thoracic organs were stored in 0.9% saline solution at 4 degrees C. In groups 1 (Collins' solution) and 2 (Collins' plus superoxide dismutase) all surviving baboons revealed normal blood gas values and normal light and electron microscopic histology at 24 hours. Three animals had further biopsies at intervals between 1 and 9 days, at which time the histology of the lungs proved normal and well preserved. All three baboons in group 3 (Collins' plus superoxide dismutase plus peroxidase) had grossly abnormal blood gas values from the time of operation, and all died within 9 hours; light microscopy of the lungs showed early lung infarctlike lesions and in one case pulmonary edema. These preclinical findings proved that storage of the lungs in Collins' solution with or without superoxide dismutase is possible for up to 5 hours; the addition of peroxidase had a detrimental effect.

Animals↗
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Hemodynamic and myocardial histologic and ultrastructural studies on baboons from 3 to 27 months following autotransplantation of hearts stored by hypothermic perfusion for 24 or 48 hours.

Hemodynamic and myocardial histologic studies have been made in four baboons, each of whom had undergone heart excision and storage, followed by autotransplantation. The excised baboon heart was stored by continuous hypothermic perfusion for 24 or 48 hours and then replaced orthotopically, the baboon being maintained alive in the interim by an orthotopic cardiac allograft. Follow-up of the autotransplanted baboons has been from 3 to 27 months. Cardiac catheterization revealed normal function both early and late after the period of storage. In three animals, myocardial histology was normal on light microscopy, although some dilation of the T tubules was seen on electron microscopy. In the fourth baboon, whose heart had been stored for 48 hours with follow-up for 13 months, light microscopy revealed some variation of staining of the myofibers and mild interstitial edema; ultrastructural studies showed mild intracellular edema, focal scanty loss of myofilaments, and a lack of dilation of the T tubular system. With this one possible exception, this study confirms that the system of hypothermic perfusion storage developed in our laboratory does not have any significant damaging effects on myocardial function or structure. There would appear, therefore, to be no contraindication to its use in clinical heart transplantation.

Animals↗
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Regression of Kaposi's sarcoma after reduction of immunosuppressive therapy in a heart transplant patient.

The de novo development of Kaposi's sarcoma, confirmed by lymph node biopsy 17 months after heart transplantation in an 18-year-old patient, is described. Constitutional symptoms and axillary and inguinal lymphadenopathy were the presenting features. Surveillance for systemic involvement was negative, and the tumor seemed to be confined to the lymphoreticular system alone. Chemotherapy with vincristine and cyclophosphamide resulted in severe leukopenia and was discontinued. Immunosuppressive therapy, consisting of cyclosporine and methylprednisolone, was gradually reduced, resulting in regression of symptoms and lymphadenopathy. One year later the patient was symptom free, and only one extremely small inguinal lymph node was palpable. Microscopic examination of this node, however, revealed persistent Kaposi's sarcoma. The patient's immunosuppressed state would now appear to be sufficient to prevent acute rejection and yet insufficient to lead to growth and spread of the tumor.

Adolescent↗
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Twenty years of heart transplantation at Groote Schuur Hospital.

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%.

Antilymphocyte Serum↗
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Is pulmonary ischemia a factor in the reperfusion response? An experimental study in the chacma baboon.

A reimplantation or reperfusion response has been described in both the experimental animal and the human patient after various procedures involving pulmonary ischemia. We have investigated this phenomenon in a primate model. Ten chacma baboons were placed on cardiopulmonary bypass and cooled to 20 degrees C. Circumferential segments of the right main bronchus and pulmonary artery were denuded of all surrounding tissue. Each structure was then cross-clamped, which rendered the lung ischemic, during which time the organ was immersed in cold saline solution. Ischemia was maintained for 1.5 to 5 hours; after reperfusion and discontinuation of bypass, the right lung was biopsied and the chest closed. Chest radiographs, lung biopsies, and arterial blood gases were taken at intervals for up to 16 to 28 days. Right lung shadowing on chest radiography with concomitant histopathologic changes, indicative of a reperfusion reaction, were seen in only one animal, which had undergone lung ischemia for 1.5 hours. In one other animal that was ischemic for 5 hours, patchy opacification of the lung was seen on two occasions (days 8 and 15) with concomitant mild histopathologic changes. In conclusion, therefore, a major reperfusion response after pulmonary ischemia in the chacma baboon is possible but unusual. This would suggest that the appearance of pulmonary opacification on chest radiography within the first 4 weeks after heart-lung transplantation in humans is most likely attributable to some other condition, such as isolated lung rejection or infection.

Animals↗
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Does the electrocardiogram detect early acute heart rejection.

Changes in electrocardiographic parameters, particularly a reduction of the voltage of the QRS complex, have been held to indicate acute rejection of a transplanted heart. In a series of heterotopic heart recipients, changes in electrocardiographic parameters were correlated with histopathological evidence of acute rejection seen on endomyocardial biopsies obtained by the percutaneous transvenous technique. No statistically significant correlation was found between the electrocardiographic changes and the histopathological features. The electrocardiogram appears to be an unreliable predictor of early acute rejection in patients with heterotopic heart transplants.

Adolescent↗
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The value of recipient heart assistance during severe acute rejection following heterotopic cardiac transplantation.

Acute rejection remains a major complication of cardiac transplantation. One of the advantages of heterotopic as opposed to orthotopic heart transplantation is that the recipient heart remains in situ, and may provide valuable support for the circulation if donor heart function is severely reduced during an acute rejection episode. Details are presented of 11 patients who underwent acute rejection severe enough to cause loss of significant function of the donor heart, during which time life was maintained by the patient's own diseased heart. In 5 cases the acute rejection proved reversible, with patient survival extending from 10 weeks to 61/2 years, though only 2 remain alive today. In 6 cases rejection was irreversible; 4 of these patients underwent a second heart transplant, but only 1 remains alive today.

Adult↗
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Preservation of competent rabbit lung function after 30 hours of storage with a low-potassium dextran solution.

BACKGROUND: The goal of organ preservation is maintenance of physiologic functions during extended extracorporeal storage. METHODS: This study was designed to evaluate the efficacy of using low-potassium (4 mmol/L) dextran (1%) solution on lung function after 30 hours hypothermic (10 degrees C) storage and to compare this with lung function after no storage. With low-potassium dextran solution rabbit lungs were flushed (10 degrees C, 40 ml/kg, 60 cm H2O), excised, inflated (with room air), and either not stored (control; no preservation; n = 9) or stored in low-potassium dextran solution (10 degrees C) 30 hours (experimental group; n = 9). RESULTS: During the flush the infusion pressure and pulmonary vascular resistance for the two groups did not differ (17.56 +/- 1.3 versus 16.74 +/- 1.5 mm Hg/ml/sec). After either no preservation or after 30 hours of storage, the lungs were first reperfused with low-potassium dextran solution (37 degrees C) for 4 minutes and then with blood (37 degrees C) for 30 minutes at 100 ml/min. During the reperfusion period the mean pulmonary artery pressure and end-inspiratory airway pressure for the control and experimental groups did not differ. After reperfusion the wet and dry weights of the left lung were determined. The wet/dry ratio for the two groups did not differ (5.32 +/- 2.20 versus 4.70 +/- 2.70, respectively). CONCLUSIONS: These data suggest that cold flush, cold storage, and initial warm perfusion with low-potassium dextran solution crystalloid preserve lung function after 30 hours of storage.

Animals↗
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Beneficial effect of initial warm crystalloid reperfusion in 6-hour lung preservation.

BACKGROUND: To achieve successful lung transplantation, it is essential to minimize reperfusion injury occurring as a result of metabolite accumulation during the preservation period or at the time of initial interaction of blood with constricted pulmonary vasculature. Initial reperfusion with warm crystalloid solution may be advantageous in preventing this injury. METHODS: This study was designed to evaluate the effect of low-potassium (4 mmol/L) dextran (1%) solution as the initial warming solution after 6 hours of hypothermic storage. In 23 New Zealand White rabbits the lungs were flushed with low-potassium dextran solution (10 degrees C, 40 ml/kg, 600 cm H2O), excised, inflated with room air, and stored in a low-potassium dextran solution (10 degrees C) for 6 hours. After storage, the lungs were divided into two groups. Group 1 (n = 8) was reperfused with warm low potassium dextran for 4 minutes, at 37 degrees C followed by blood reperfusion for 30 minutes at 37 degrees C. Group II (n = 15) was reperfused only with blood for 30 minutes at 37 C. The mean pulmonary vascular resistance measured during cold flush and prior to storage was similar in both groups (group I = 20.0 +/- 5.9 mm Hg.sec/ml, group II = 19.3 +/- 1.9 mm Hg.sec/ml). RESULTS: During reperfusion, only 4 of the 15 lungs in group II maintained an acceptable (< 80 mm Hg) mean pulmonary artery pressure; six failed immediately. All eight lungs in group I completed the 30-minute reperfusion (p < 0.005). The mean pulmonary artery pressure was significantly less, and effluent oxygen tension was significantly greater in group I during reperfusion. CONCLUSIONS: In this experimental model, initial warm reperfusion with low-potassium dextran ameliorated the deleterious effects of reperfusion, thus providing an environment to improve lung preservation.

Animals↗