Effect of timing of vagal stimulation on heart rate in the dog.
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Animals↗
Biomedical subjects
B A Reitz
Publications and source records attributed to B A Reitz.
An analysis of the toxic actions of purified streptolysin O on the isolated heart and separate cardiac tissues of the guinea pig.
The response of isolated guinea pig hearts to perfusion with purified streptolysin O is characterized by a rapid, but transient, decrease in rate and amplitude of contraction; these reactions are superimposed upon a gradual, irreversible, loss of ventricular contractility. At ventricular standstill, the atria continue to beat spontaneously in a normal way. Isolated ventricle strips prepared from such preparations can be driven electrically, and their behavior is functionally indistinguishable from that of similar preparations made from normal hearts. Tests on spontaneously beating isolated atrial pairs show that the toxin induces a dose-dependent, reversible, decline in rate and amplitude which is accompanied by a marked, but transient, increase in the velocity of repolarization of the intracellular potential. The atrial reactions were completely blocked by atropine and potentiated by eserine. Acetylcholine was detected in the perfusates obtained by incubating a large pool of atrial tissue with active toxin, supporting the inference that the transient mechanical and electrophysiological reactions to toxin might be consequences of the release of acetylcholine from these tissues by the active toxin. Control studies showed that only the active toxin had the capacity to induce the cardiac responses. The toxin was active only in the reduced but not the oxidized form. The effects of the active toxin were modified if it were heated prior to challenge, and they could be neutralized by specific antiserum and inhibited by cholesterol. Since the driven ventricle strip was mechanically and electrophysiologically insensitive to streptolysin O, the irreversible changes in the whole heart must have occurred because of a defect in the atrioventricular conduction system.
Acetylcholine↗
Significant reduction in the number of fungal infections after lung-, heart-lung, and heart transplantation using aerosolized amphotericin B prophylaxis.
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Adult↗
Effect of low molecular weight heparin on graft vascular disease in the rat cardiac allograft model.
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Animals↗
Revascularization of tracheal anastomosis following heart-lung transplantation.
The mechanism by which tracheobronchial arterial supply is reconstituted following heart-lung transplantation was investigated in seven monkeys (3 allografts, 2 autografts, and 2 nontransplanted control monkeys) and three patients. Descending tracheal branches of the thyrocervical arteries provided the major tracheal vascular supply. A collateral branch arising from atrial branches of the left coronary artery supplied tracheobronchial branches in the region of the carina in one allograft. In the three patients studied to date by coronary arteriography, a similar collateral supply to the region of the carina and proximal bronchi was demonstrated from atrial branches of both the left and right coronary circulation.
Adult↗
Port-access bilateral internal mammary artery grafting for left main coronary artery disease: canine feasibility study.
BACKGROUND: To extend the applications of minimal access cardiac surgery, an endovascular cardiopulmonary bypass (CPB) system that allows cardioplegia delivery and cardiac venting was used to perform bilateral internal mammary artery (IMA) bypass grafting in six dogs. METHODS: The left IMA (LIMA) was taken down thoracoscopically from three left lateral chest ports, followed by the right IMA (RIMA) from the right side. One left-sided port was extended medially 5 cm with or without rib resection, to expose the pericardium. Both IMAs were divided and exteriorized through the left anterior mediastinotomy. Flow and pedicle length were satisfactory in all cases. Femoral-femoral bypass was used and the heart arrested with antegrade delivery of cardioplegic solution via the central lumen of a balloon catheter inflated to occlude the ascending aorta. All anastomoses were made through the mediastinotomy under direct vision. In five studies the RIMA was attached to the left anterior descending artery (LAD) and the LIMA to the circumflex, and in one study the RIMA was tunneled through the transverse sinus to the circumflex and the LIMA was anastomosed to the LAD. All animals were weaned from CPB in sinus rhythm without inotropes. CPB duration was 108 +/- 27 minutes (mean +/- SD) and the clamp duration was 54 +/- 10 minutes. RESULTS: Preoperative and postoperative cardiac outputs were 2.9 +/- 0.71/min and 2.4 +/- 0.31/min, respectively (p = NS), and corresponding pulmonary artery occlusion pressures were 6 +/- 3 mmHg and 7 +/- 2 mmHg, respectively (p = NS). All 12 grafts were demonstrated to be fully patent. Postmortem examination revealed well aligned pedicles and correctly grafted target vessels. CONCLUSION: This canine model demonstrates the potential for a less invasive approach to the surgical management of left main coronary artery disease in humans.
Animals↗
Ultrastructural evidence of cell-mediated endothelial cell injury in cardiac transplant-related accelerated arteriosclerosis.
Accelerated arteriosclerosis secondary to chronic allograft rejection is a major long-term complication of heart transplantation. Accelerated arteriosclerosis has been associated with an endothelialitis, and the majority of the involved inflammatory cells are T lymphocytes and macrophages. Coronary arteries from six heart allograft recipients with transplant-related arteriosclerosis were examined by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Four hearts were explants from heart transplant recipients with severe accelerated arteriosclerosis who were undergoing retransplantation, and two were obtained from autopsied recipients. The patients ranged in age from 6 to 60 years (mean, 44 years). The graft survival for these six hearts ranged from 1.4 to 5.6 years (mean, 4.3 years). Lymphocytes, macrophages, and smooth muscle cells were identified by TEM in the intimas of all the vessels examined. The lymphocytes were often in contact with macrophages or in close proximity to injured endothelial cells. Areas of endothelial injury were characterized by vacuolization of endothelial cells and partial denudation of the endothelium with fibrin deposition. SEM also revealed endothelial cell injury with disorganization of the endothelium and gaps between endothelial cells. Leukocytes and platelets were often noted in these gaps. These findings suggest that accelerated arteriosclerosis in heart transplant recipients is associated with an accumulation of macrophages, lymphocytes, and smooth muscle cells in the intima as well as with lymphocyte-directed endothelial injury.
Adult↗
Adapted indications for lung transplantation: discussion report.
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Cystic Fibrosis↗
Severe lymphocytic endothelialitis associated with coronary artery spasm in a heart transplant recipient.
Coronary artery spasm plays an important role in ischemic heart disease, particularly variant angina. We report the case of a 59-year-old man who developed severe diffuse coronary artery spasm 11 months after he received a heart transplant. The spasm was reversed by a single dose of sublingual nitroglycerin; however, the patient died 9 days later of Pneumocystis carinii pneumonia. Postmortem examination of this patient's heart revealed accelerated arteriosclerosis, with a prominent diffuse lymphocytic endothelialitis in the coronary arteries. The lymphocytic endothelialitis was characterized by the presence of numerous T lymphocytes and macrophages in the subendothelial space and by histologic changes suggesting injury to the endothelial cells. Although an association does not prove a causal relationship, the findings of accelerated arteriosclerosis and lymphocytic endothelialitis in a patient with coronary artery spasm suggests that these processes may be etiologically linked.
Coronary Artery Disease↗
Comparison of rejection in the atrioventricular node and bundles with the working myocardium in transplanted hearts.
At present the monitoring of heart transplant patients for rejection is done by endomyocardial biopsy. It has been proposed that ECG assessments of conduction delay may provide a noninvasive means of detecting rejection. To determine whether rejection in the atrioventricular node and conduction bundles reflects rejection in the working myocardium, we studied 21 transplanted hearts from 21 cardiac allograft recipients. Twenty of the hearts were obtained at autopsy, and one was obtained from a patient who underwent a second transplant procedure. The atrioventricular conduction tissues, the ventricular and atrial free walls, and the interventricular and interatrial septa from these hearts were examined for histologic evidence of rejection. Of the 21 hearts, 17 showed histologic changes of acute allograft rejection. Of the 17, rejection involved the conducting system and the myocardium equally in 11. In 6 of the 17 hearts, rejection involved the working myocardium more severely than it did the conducting system. Of interest, nonrejection pathologic changes were also noted in the conducting systems of several hearts. Severe accelerated arteriosclerosis was found in the artery to the atrioventricular node in one case, and lesser degrees of accelerated arteriosclerosis in this artery were found in two additional cases. In one case, lymphoid infiltrates, consistent with posttransplant lymphoproliferative disorder, were noted in the vicinity of the atrioventricular node, and several hearts demonstrated operative trauma or ischemic changes that appeared to involve the conducting system. These results suggest that although there may be a morphologic basis for using electrophysiologic changes in the conducting system to monitor heart allograft recipients for rejection, caution should be exercised in interpreting these changes.
Adult↗
Coronary blood flow does not decrease during allograft rejection in heterotopic heart transplants.
To evaluate changes in coronary blood flow during allograft rejection, 16 beagles with cervical cardiac allografts from mongrel donors were immunosuppressed postoperatively for 7 days with cyclosporine (20 mg/kg orally) and prednisone (0.5 mg/kg orally). They were weaned from immunosuppression over 3 days and then treated with methylprednisolone (30 mg/kg/day IV), cyclosporine (20 mg/kg orally), and prednisone (0.5 mg/kg orally) for 4 days. Previous experiments with this model have suggested the utility of phosphorus 31 nuclear magnetic resonance spectroscopy (31P NMR) in the diagnosis of rejection. Therefore in 10 dogs (NMR group) bioenergetic changes during rejection were assessed using the 31P NMR index of the ratio of phosphocreatine to inorganic phosphate (PCr/Pi). To correlate coronary blood flow and graft ischemia with allograft rejection, six dogs (FLOW group) underwent placement of a magnetic flow probe on the left anterior descending coronary artery to determine mean and peak coronary flow. In both NMR and FLOW groups, grafts were evaluated by endomyocardial biopsy (grading 0 to 8 for increasing rejection), and measurement of lactate production and left ventricular end-diastolic pressure. During the initial 7 days of immunotherapy, cellular rejection was effectively suppressed, and the bioenergetic status of the grafts remained stable (day 7: PCr/Pi = 70% of baseline, biopsy score = 2.0). During weaning of immunotherapy, however, the metabolic profile of the grafts decayed (day 10: PCr/Pi = 45% of baseline, biopsy score = 5.8; p less than 0.05 vs day 0). After 4 days of augmented immunosuppression, PCr/Pi recovered to 83% of baseline; this metabolic recovery corresponded with an improvement in mean biopsy score to 3.2.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Twelve-hour cardiopulmonary preservation using donor core cooling, leukocyte depletion, and liposomal superoxide dismutase.
Because leukocytes and oxygen radical species contribute to ischemic and reperfusion injury during organ preservation, we examined the effects of a long-acting liposomal superoxide dismutase (liposomal SOD) and mechanical filtration of leukocytes on cardiopulmonary graft function after 12 hours of static preservation. Bovine heart-lung blocks were harvested, core cooled to 15 degrees C, stored in 4 degrees C donor blood for 12 hours, and then orthotopically transplanted (control group, n = 6). In the leukocyte-depletion group (n = 6), a leukocyte filter was incorporated in the bypass circuits of the donor and recipient. In the SOD group (n = 6), liposomal SOD (5000 U/kg) was administered in the cardioplegic solution, in the prime of the bypass circuits of donor and recipient, and immediately before recipient heart-lung reperfusion. In the combination group (n = 6), both leukocyte depletion (LD) and liposomal SOD were used. Only four of six control animals survived more than 2 hours after weaning from bypass, whereas all LD, SOD, and LD + SOD animals survived to be studied at 6 hours. Pulmonary function was assessed at 6 hours by arterial oxygen tension on 100% inspired oxygen (PO2), pulmonary vascular resistance (PVR), and postmortem wet/dry lung weight ratios. Arterial pO2 values (mm Hg) were as follows: control, 102 +/- 51; LD, 437 +/- 60*; SOD, 278 +/- 83; and LD + SOD, 504 +/- 54* (*p less than 0.05 vs controls). PVR values (dynes . sec . cm5) were as follows: control, 1975 +/- 697; LD, 682 +/- 131*; SOD, 607 +/- 191*; and LD + SOD 367 +/- 87* (*p less than 0.05 vs controls).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Inflation-fixed lungs: pathologic-radiologic (CT) correlation of lung transplantation.
Pulmonary infections and lung rejection are the two major complications of lung transplantation. Although the therapies for these two processes differ greatly, they often cannot be differentiated using standard radiography. We applied high resolution CT (HRCT) to seven lung specimens that were obtained from patients who had received a heart-lung transplant. The lungs were fixed by a method that allows for direct one-to-one pathologic-radiologic correlation. We found: (a) that in contrast to the extensive changes present microscopically, acute lung allograft rejection was characterized by only minor changes on HRCT; (b) that bronchiolitis obliterans, the hallmark of chronic lung allograft rejection, was not reliably identifiable on HRCT; (c) that bronchiectasis with associated peribronchial inflammation and fibrosis, a common finding in lung allograft rejection, was identifiable on HRCT, but that the HRCT appearance of this lesion was not specific for rejection; and (d) that pulmonary infections were often identifiable as a mixed airway-interstitial process on HRCT.
Adult↗
Early phosphorus 31 nuclear magnetic resonance bioenergetic changes potentially predict rejection in heterotopic cardiac allografts.
The development of a noninvasive screening test for the detection of cardiac allograft rejection would improve the potential for management of heart transplant recipients. To assess the possibility that changes in myocardial high-energy phosphate metabolism precede frank rejection, 17 beagles received cervical cardiac allografts. Recipients underwent serial phosphorus 31 nuclear magnetic resonance spectroscopy, endocardial biopsy (blindly graded, 0 to 8), and left ventricular pressure measurements starting on the day of surgery. The first (less than 24 hours) spectrum was considered the baseline for all additional studies. The phosphocreatine to inorganic phosphate ratio (PCr/Pi), an index of myocardial bioenergetic supply/demand balance, was determined and expressed as a percentage of baseline of initial and all subsequent spectra. To evaluate the predictive utility of the PCr/Pi ratio, a 50% decrease from baseline was designated as a positive test and was correlated with biopsy-proved rejection (score greater than 3). When PCr/Pi values were compared with the subsequent day's biopsy score, we observed a 91% sensitivity, 90% specificity, and a predictive value of 92%. We conclude that the PCr/Pi ratio is sensitive in predicting heterotopic allograft rejection in its earliest stages. Thus phosphorus 31 nuclear magnetic resonance holds promise for clinical use in the noninvasive diagnosis and monitoring of cardiac rejection.
Animals↗
Persistent pulmonary hypertension after heterotopic heart transplantation: a case report.
Right-sided failure occurring in the donor heart immediately after transplantation is primarily caused by increased recipient pulmonary artery pressure and resistance and represents one of the leading causes of perioperative mortality associated with orthotopic heart transplantation. After transplantation pulmonary hypertension gradually declines, returning to near normal levels within 30 days of transplantation. This article describes a case report of the persistence of pulmonary hypertension after heterotopic heart transplantation. The heterotopic position was utilized because of marked elevation of the pulmonary artery resistance (18 Wood units) calculated at the time of operation. Cardiac catheterization data-obtained during the subsequent 6 months of follow-up showed persistent elevation of pulmonary artery pressure and pulmonary vascular resistance. The patient, however, clinically continues to feel well and remains asymptomatic without signs of right-sided heart failure. Indications, suggested advantages, and demonstrated disadvantages of heterotopic heart transplantation are discussed.
Adult↗
Successful four-hour heart-lung preservation with core-cooling on cardiopulmonary bypass: a simplified model that assesses preservation.
This study was done to determine whether core-cooling could provide extended cardiopulmonary preservation and if reimplantation could be simulated and evaluated in the ex vivo autoperfused working heart-lung model. Twenty calves were divided into four groups and placed on cardiopulmonary bypass and rapidly cooled to 15 degrees C. Control heart and lungs were harvested after administration of cardioplegia through the aortic root and were subsequently resuscitated in the autoperfused working heart-lung circuit (group 1) or were orthotopically allotransplanted (group 2). Preserved heart and lungs were similarly excised but stored in a normal saline solution bath at 4 degrees C for 4 hours and then were resuscitated in the autoperfusion circuit (group 3) or were orthotopically allotransplanted (group 4). All groups received isoproterenol during explantation and reperfusion and were studied for 4 hours. Myocardial function was assessed by sonomicrometric techniques, and pulmonary preservation was evaluated by measurements of extravascular lung water, arterial oxygen tension on 100% inspired oxygen, and pulmonary vascular resistance. Cardiorespiratory function after 4-hour static preservation was similar in all four groups except that the arterial oxygen tension in group 1 was lower compared with group 3. Core-cooling on cardiopulmonary bypass without pulmonary artery flushing results in cold ischemic heart-lung preservation, comparable to other currently used modalities. In addition, reperfusion in the ex vivo autoperfusion circuit provides a simplified model to assess the adequacy of cardiopulmonary preservation techniques.
Animals↗
Autoperfused working heart-lung preparation versus hypothermic cardiopulmonary preservation for transplantation.
The effects of preserving the heart and lungs with an autoperfused working heart-lung preparation or simple hypothermia via cardiopulmonary bypass were studied in 18 dairy calves that had combined heart-lung transplantation. Group 1 (n = 6) served as the control group in which animals were cooled with cardiopulmonary bypass and immediately had allotransplantations. In group 2 (n = 6), cardiopulmonary function was maintained in the autoperfusion circuit for 4 hours, followed by transplantation. In group 3 (n = 6), the organs were harvested after cooling by cardiopulmonary bypass, stored in cold (4 degrees C) saline solution for 4 hours, and then transplanted. Cardiopulmonary function was compared between the three groups for 6 hours after implantation. Cardiac function was determined by the ratio of the end-systolic pressure to end-systolic dimension. Pulmonary function was evaluated by the measurement of extravascular lung water, arterial oxygenation on 100% inspired oxygen static lung compliance, and histologic lung injury score. All measurements in groups 2 and 3 were similar to those of the control group at 6 hours after implantation. One may use either the hypothermic cardiopulmonary preservation method after cardiopulmonary bypass or the autoperfused working heart-lung preparation for distant organ procurement and expect adequate cardiopulmonary function after transplantation.
Animals↗
Improved myocardial and pulmonary preservation by metabolic substrate enhancement in the autoperfused working heart-lung preparation.
The autoperfused working heart-lung (AWHL) preparation may provide successful cardiopulmonary preservation for up to 6 hours before transplantation. To determine whether the addition of metabolic substrate could prolong myocardial and pulmonary preservation in the AWHL model, 20 heart-lung blocks were harvested from calves. The brachiocephalic artery and superior vena cava were cannulated with extracorporeal tubing and connected to an elevated reservoir allowing total perfusion through a normothermic autoperfusion circuit. Eight heart-lung blocks were given dextrose and ribose followed by a continuous dextrose-insulin infusion, whereas the remaining 12 specimens received no additional substrates. Myocardial function was assessed by sonomicrometric techniques and pulmonary preservation evaluated by arterial oxygenation on 100% inspired oxygen, static lung compliance, and serial lung biopsies. The addition of substrate prolonged organ survival from 5 +/- 1 to 12 +/- 3 hours (p less than 0.001) and was associated with preservation of myocardial and pulmonary function. Application of substrate addition to the AWHL model will extend the interval of preservation for both heart and heart-lung transplantation.
Animals↗