B. Reichart

Prevention of Myocardial Injury During Brain Death by Total Cardiac Sympathectomy in the Chacma Baboon

In a previous study, structural myocardial damage was found to occur in 60% of baboons after brain death had been induced by a rapid increase in intracranial pressure. In the present study, we attempt to clarify the causative mechanisms involved in the development of such injury. Three groups of baboons were subjected to brain death: group A, the control; group B, those with previous surgical or pharmacological cardiac sympathectomy or cardiac denervation; and group C, those with bilateral vagotomy, incomplete sympathectomy, or bilateral adrenalectomy. Electrocardiographic and hemodynamic responses to brain death were greatly modified in group B baboons compared with responses in groups A and C. Groups A and C showed a high incidence of myocardial necrosis, whereas no myocyte damage was seen in the hearts of group B baboons. The histological appearance of innervated hearts following brain death (groups A and C) may closely resemble that seen during an acute rejection episode following cardiac transplantation. We suggest that myocardial damage occurring during the process of dying may be related to endogenous catecholamine release (possibly resulting in increased calcium uptake by the myocardial cells), inducing various forms of myocyte necrosis. This may result in early failure in a donor heart following cardiac transplantation.

Pathophysiology of pulmonary edema following experimental brain death in the chacma baboon.

Systemic and pulmonary hemodynamics have been studied during the induction of brain death in the chacma baboon. In 11 animals brain death was induced by acute intracranial hypertension. Continuous recording of blood flow through both the pulmonary artery and the aorta was obtained by electromagnetic flow meters placed around these vessels. Mean arterial, central venous, pulmonary arterial, and left atrial pressures were recorded continuously. Systemic and pulmonary vascular resistances were calculated. During the agonal period marked sympathetic activity occurred, with significant increases in circulating catecholamines and systemic vascular resistance. The great increase in systemic resistance resulted in acute left ventricular failure. Mean left atrial or pulmonary capillary wedge pressure rose above the mean pulmonary arterial pressure in 9 animals. As the systemic vascular resistance rose, a significant difference between pulmonary artery and aortic blood flows occurred, leading to blood pooling within the lungs. A mean of 72% of the total blood volume of the animal accumulated within these organs. The increase of left atrial pressure to levels higher than pulmonary artery pressure indicated a state of pulmonary capillary blood flow arrest. This, associated with the blood pooling within the lungs, almost certainly resulted in disruption of the anatomic integrity of the pulmonary capillaries (blast injury); 4 animals developed pulmonary edema, with alveolar septal interstitial hemorrhage.

In situ cannulation, microgrid follow-up and low-density plating provide first passage endothelial cell masscultures for in vitro lining

A rapid and reliable harvest and culture technique was developed to provide a sufficient number of autologous endothelial cells for the confluent in vitro lining of cardiovascular prostheses. Enzymatic endothelial cell detachment was achieved by the in situ application of collagenase to short vessel segments. This harvest technique resulted in a complete lack of contaminating smooth muscle cells in all of 124 cultures from nonhuman primates and 13 cultures from human adults. The use of a microgrid technique enabled the daily in situ quantification of available endothelial cells. To assess ideal plating densities after passage the population doubling time was continuously related to the cell density. Surprisingly, a low plating density of 1.5 X 10(3) endothelial cells/cm2 achieved 43% shorter cell cycles than the usual plating density of 1.0 X 10(4) endothelial cells/cm2. Moreover, low density plating enabled mass cultures after one single cell passage, thereby reducing the cell damaging effect of trypsin. When the growth characteristics of endothelial cells from five anatomically different vessel sites were compared, the external jugular vein--which would be easily accessible and dispensable in each patient--proved to be an excellent source for endothelial cell cultures. By applying in situ administration of collagenase, low density plating and microgrid follow-up to adult human saphenous vein endothelial cells, 14,000,000 first passage endothelial cells--sufficient for the in vitro lining of long vascular prostheses--were obtained 26.2 days after harvest. (95% confidence interval:22.3 to 32.2 days).

Endothelial cell toxicity of solid-organ preservation solutions

Endothelial cell damage caused by myocardial cardioplegic solutions (Bretschneider HTK and St. Thomas Hospital No. 2) or renal and hepatic cold storage solutions (modified Collins and University of Wisconsin solution) was assessed in monolayer cultures of adult human venous endothelial cells at 4 degrees to 10 degrees C with phase-contrast microscopy. St. Thomas Hospital solution caused the cells to contract, resulting in disruption of monolayer integrity and opening of intercellular gaps, and resulted in a 24-hour postexposure survival of 51.0% +/- 2.4%. Bretschneider HTK solution altered cellular morphology less and produced the best postexposure survival (80.2% +/- 2.6%; p less than 0.001). Although morphology was altered the least with University of Wisconsin solution, postexposure survival with this solution, which was similar to that with modified Collins solution, was superior to that with St. Thomas (p less than 0.01) but inferior to that with Bretschneider HTK (p less than 0.05). The superior protection provided by Bretschneider HTK was due to its additives histidine, tryptophan, and KH-2-oxygluterate (p less than 0.005), and to its low chloride content (p less than 0.005). Furthermore, modifying St. Thomas solution by decreasing its chloride content improved cell survival to 71.2% +/- 2.3% (p less than 0.001). Normothermic (37 degrees C) exposure to Bretschneider HTK, modified Collins, and University of Wisconsin solution was cytotoxic, whereas normothermic exposure to St. Thomas cardioplegia was not. In conclusion, the preservation solution that is the least harmful to endothelial cells at hypothermia is Bretschneider HTK cardioplegic solution.

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 Bretschneiders 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 Bretschneiders 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 Bretschneiders solution as compared with University of Wisconsin solution after an ischemic period of up to 16 hours.

Acute Isolated Pulmonary Rejection Following Transplantation of the Heart and Both Lungs: Experimental and Clinical Observations

Early observations following transplantation of the heart and both lungs have suggested that acute rejection occurs simultaneously in both organs. Endomyocardial biopsy could, therefore, be used to monitor rejection in both heart and lungs. We present here our experience with heart-lung transplantation in the baboon, and in two recently observed human patients. The evidence we provide suggests that acute rejection may occur earlier in the lungs than in the heart, and that monitoring the heart alone may prove inadequate. Of 12 baboons that survived heart and lung transplantation, 11 died from acute isolated pulmonary rejection; 10 of these 11 animals showed no features of cardiac rejection. In 2 of 6 human patients who have undergone this operation, an episode of acute pulmonary rejection is believed to have occurred in the absence of cardiac rejection. There is no 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 be directed toward developing tests that indicate acute rejection but are not organ specific, rather than relying on techniques that diagnose cardiac rejection only.

Surgical management of heart-lung transplantation☆

Using cyclosporin A, long-term survival after heart-lung transplantation became possible. The drug blocks the immune system more selectively and leaves the tracheal wound healing unimpaired. Since 1981, 501 clinical cases have been collected by the registry of the International Society for Heart Transplantation. Candidates for heart-lung transplantation reveal signs of irreversible heart and lung diseases that may have been caused by cardiac lesions (valvular diseases, Eisenmenger reaction due to congenital malformations) or by pulmonic disorders (primary pulmonary hypertension, emphysema, fibrosis). The standard surgical procedure, which combines donor and recipient tracheas, right atria, and aortas, makes three anastomoses necessary. Immunosuppressive regimen includes cyclosporin A (blood trough levels of 300 to 500 ng/mL), azathioprine (1 to 2 mg/kg), and rabbit antithymocyte globulin (1 to 4 mg immunoglobulin G/kg). After the first two postoperative weeks, rabbit antithymocyte globulin is replaced by methylprednisolone (0.3 to 0.1 mg/kg; 500 mg are given intravenously after opening the aortic cross-clamp; 3 x 125 mg on postoperative day 1). After heart-lung transplantation an extreme variety of problems may evolve. Early postoperative complications (within the first postoperative month) comprise acute isolated lung rejection, multiorgan failure, and bacterial pneumonia. Diagnosis of acute lung rejection proves difficult; it includes clinical signs, chest radiographic appearances, and cytoimmunological monitoring. Transbronchial lung biopsies are of similar value for precise diagnosis as are endomyocardial specimens after heart transplantation. Late postoperative complications (after 1 postoperative month) comprise viral pneumonia, fungal infection, tuberculosis, and chronic obliterative bronchiolitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of pH shifts induced by oxygenating crystalloid cardioplegic solutions

Oxygenation of a bicarbonate-containing crystalloid cardioplegic solution alters the partial pressure of both oxygen (O2) and carbon dioxide (CO2). Therefore, oxygenating St. Thomas Hospital II plus glucose (11 mmol/L) cardioplegic solution with 95% O2 + 5% CO2 induces a pH shift to 7.0 (10 degrees C) as opposed to pH 9.3 with 100% O2. In an isolated working rat heart model, we show that pH 7.0 (10 degrees C) improves mechanical postischemic recovery in the absence or presence of O2. However, in the absence of O2, pH 7.0 appears to inhibit glycolysis and diminish the stability of cellular membranes. The provision of O2 independently improved mechanical recovery and at pH 7.0, improved the preservation of the sarcolemma. Increasing the O2 content by including a perfluorocarbon (FC-43) in the oxygenated St. Thomas plus glucose cardioplegia is not additionally beneficial. St. Thomas Hospital plus glucose cardioplegic solution should be oxygenated, but with 95% O2 + 5% CO2 and not 100% O2.

Left heart assist device: a simple method to conserve associated blood loss

Left or right monoventricular and biventricular circulatory assist devices are being used increasingly for postoperative low cardiac output syndrome following cardiac surgery.’--6 One of the major problems of the temporary left heart assist device is excessive bleeding which may be related to the prolonged period of cardiopulmonary bypass used in resting the heart and attempting to wean from cardiopulmonary bypass ;7,8 in some patients, it may be related to the need for systemic heparinization to prevent clot formation and

Klinischer Einsatz eines roboterunterstützten Instrumentier- und Endoskopiesystems zur Durchführung endoskopischer koronarer Bypassanastomosen

Hintergrund: Ziel der minimal invasiven Bypasschirurgie ist die Durchfuhrung von endoskopischen Koronaranastomosen. In dieser Studie wurde ein Computer- und sprachunterstutztes Instrumentier- und Endoskopie-System (Zeus, Computer Motion Inc., Goleta, CA) klinisch bei der Durchfuhrung von endoskopischen koronaren Bypassanastomosen getestet.