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Biomedical subjects

R L Kormos

Publications and source records attributed to R L Kormos.

At least 127 records · Page 7Linked to original sources

Lessons learned in pediatric heart transplantation.

Between February 1, 1982, and June 30, 1988, 32 children underwent cardiac transplantation for treatment of congenital heart disease (10) and other cardiomyopathies (22). The 6-year actuarial survival was a disappointing 36% because of a high perioperative mortality (12 of 32, 37.5%) and because of five late deaths due to uncontrolable rejection. The perioperative mortality was a staggering 60% (6 of 10) for the patients with congenital heart disease. Four of the 6 recipients with congenital heart disease died because of acute failure of the donor right ventricle. This included 2 patients who required reconstruction of the pulmonary arteries for stenosis secondary to previous systemic-to-pulmonary shunts and 2 others in whom the pulmonary vascular resistances were underestimated because of undetected recent pulmonary emboli (1) and complicated pulmonary vascular anatomy (1). Five of the six late deaths were due to rejection-related events, and all were patients with acquired cardiomyopathy.

Actuarial Analysis↗

Coronary artery fistula in the heart transplant patient. A potential complication of endomyocardial biopsy.

All follow-up annual cardiac catheterizations performed on recipients of orthotopic heart transplant were reviewed, and 14 patients with coronary artery fistula were identified. The prevalence (8.0%, 14 of 176 patients) was strikingly higher than that for patients without transplant (0.2%) who underwent routine cardiac catheterization. These 14 patients had 21 coronary artery fistulas: single in nine and multiple in five patients. Fifty-two percent arose from the right, 43% from the left anterior descending, and 5% from the circumflex coronary artery. All drained into the right ventricle. Four patients underwent oximetric evaluation, and left-to-right shunting was not detectable. No patient had symptoms attributable to the fistula. Hemodynamic measurements were similar to those of a control group of 28 age- and sex-matched recipients of heart transplant without coronary artery fistula; however, the cardiac index (p = 0.02) and pulmonary artery oxygen saturation (p = 0.03) were significantly higher, and the arteriovenous oxygen difference (p = 0.01) was significantly lower in the group with coronary artery fistula. The histologic features of rejection, large arterioles, or epicardial fat on any biopsy specimen predating coronary artery fistula diagnosis were not associated with the development of the fistula when the two groups were compared. Nine patients (11 coronary artery fistulas) had follow-up studies performed, and three fistulas were larger, three were unchanged, two were smaller, and three had resolved. No complications of coronary artery fistula developed during a mean follow-up of 28 months (range, 12-42 months).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Infections in mortally ill cardiac transplant recipients.

A total of 351 cardiac transplantations performed between June 1, 1980, and Sept. 30, 1987, were reviewed to determine if infectious complications were more frequent in those patients requiring preoperative intravenous inotropic support, placement of an intraaortic balloon pump, or mechanical support with a left ventricular assist device or total artificial heart. One hundred forty-nine transplants (45%) were performed in these mortally ill patients. There was no statistically significant difference between patients with and without infection within each support group for the following: the number of in-patient days awaiting a donor heart, the number of days receiving support, the percent of patients with preoperative tracheal intubation, the length of the operation, and the percent of patients requiring reoperation for bleeding. The need for invasive methods of support (intraaortic balloon pump, left ventricular assist device, or total artificial heart) in patients awaiting heart transplantation increases the prevalence of perioperative nonviral infection. Preoperative mechanical support with a left ventricular assist device or total artificial heart significantly increases the risk of infection-related mortality.

Adult↗

Clinical utilization of the artificial heart.

During the past 30 years the artificial heart has evolved from a bioengineering concept to clinical reality. To date four patients have had an artificial heart implanted as a permanent device, while over 150 artificial hearts have been utilized temporarily as a bridge to cardiac transplantation. Increased use of this device requires that a number of issues be critically addressed: (1) criteria for patient selection; (2) operative techniques for implantation including size of device and its position in the mediastinum; and (3) management of the patient in the intensive care unit (ICU), in particular, regimens of anticoagulation, assessment of adequacy of organ perfusion, and prevention of sepsis. This chapter is a discussion of these bioengineering and clinical concerns with respect to the Jarvik total artificial heart (TAH). Clinical data are presented which highlight the current problems with these devices and the areas of future research that need to be undertaken.

Heart Transplantation↗

Biomechanics of the arterial wall under simulated flow conditions.

A perfusion apparatus is employed to reproduce quantifiable pulsatile hemodynamics within freshly excised canine carotid arteries. From measurements of pulsatile intraluminal and transmural pressure and the dynamic radial motion of the vessel wall, calculations are made of the vascular incremental modulus of elasticity and hoop, axial, and radial wall stresses. The results of this investigation suggest that an increase in transmural pressure from 120/80 to 240/120 mmHg produces a marked elevation in incremental modulus and arterial wall stress. These parameters are reduced when transmural pressure is lowered while maintaining intraluminal pressure at physiologic values.

Animals↗

The artificial heart: infection-related morbidity and its effect on transplantation.

Between October, 1985, and September, 1987, a total of 195 patients received cardiac allografts and 15 candidates required mechanical support with the Jarvik-7 total artificial heart. Seven of the 15 died within 60 days of total artificial heart implant. There have been no late deaths, and survivors are unrestricted. Six of 7 deaths were related to infection (mediastinitis, 5; pneumonia and sepsis, 1), and the remaining 1 was due to failure of the transplanted heart. Respiratory tract infection occurred in each of the recipients who died with infection, and the same organisms appeared to be related to subsequent mediastinitis in 3 patients (Serratia marcescens, 2; Pseudomonas, 1) and caused fatal sepsis in another (Enterobacter aerogenes, Candida albicans). One patient died with pneumonia and sepsis prior to transplantation, and another succumbed with mediastinal infection known to be present before transplantation.

Heart Transplantation↗

Role of the antibody to vascular endothelial cells in hyperacute rejection in patients undergoing cardiac transplantation.

Traditionally, the human lymphocyte antigens have been considered to be the major barrier to successful transplantation, and lymphocytes have been used as the target cell in evaluating histocompatibility. The presence in the serum of recipients of preformed antibodies, cytotoxic to donors lymphocytes, is associated with a high probability of hyperacute rejection. We identified 11 patients in whom, despite a compatible direct lymphocytotoxic cross-match, acute failure of the cardiac homograft was associated with histologic and immunologic findings consistent with hyperacute rejection. Direct immunofluorescence and immunohistochemical staining showed the presence of antibodies on the surface of vascular endothelial cells in each of these 11 patients. The serum of these recipients was found to contain antibodies against a panel of endothelial cells. In contrast, cytotoxic antibodies to vascular endothelial cells were not present in a control group of 18 heart transplant recipients who did not experience hyperacute rejection. Thus the presence of antibodies against vascular endothelial cells seems to be related to hyperacute rejection of the cardiac allograft.

Antibodies↗

Patient selection and results of cardiac transplantation in patients with cardiomyopathy.

Cardiac transplantation for the treatment of end-stage congestive heart failure has been shown to be of benefit regardless of the etiology. With few exceptions, the evaluation of patients with end-stage heart failure is the same, regardless of the etiology. In those with cardiomyopathy not as a result of CAD, special attention must be given to exclude secondary causes of cardiomyopathy such as amyloidosis, hemochromatosis, and sarcoidosis, as well as generalized systemic illnesses that may also involve the heart, either secondary or hereditary, because special consideration must be given to these patients on a case-by-case basis to determine that there is no general systemic involvement of the illness that would preclude satisfactory rehabilitation after transplantation. Before cardiac transplantation becomes widely available, there must be a greater number of donor hearts, the lack of which now severely limits the number of transplants performed in comparison with the estimated need.66 Additionally, more effective and specific immunosuppressive agents must be identified in order to reduce the incidence of rejection, infection, and accelerated atherosclerosis that now limits the longevity of transplant recipients. Furthermore, the ideal immunosuppressive agent should be associated with fewer side effects than those currently available. The emotional and economic burdens placed on the patient, the family, and society must be balanced against the benefits generated by the procedure. Despite these limitations, cardiac transplantation continues to offer hope for the terminally ill patient, which must be tempered by an understanding of the real limitations of transplantation.

Adolescent↗

Temporary use of the Jarvik-7 total artificial heart before transplantation.

Between October 24, 1985, and July 31, 1986, the Jarvik-7 total artificial heart was implanted into six moribund patients in an attempt to test its potential as a bridge from almost certain death to cardiac transplantation. Four of these patients are now well and at home after implantation of the device and subsequent cardiac transplantation. Before transplantation, one patient died with sepsis and multiorgan failure that preceded implantation of the artificial heart. Another patient died with acute rejection 60 days after cardiac transplantation. Fifty-two days of total mechanical support with the artificial heart were accumulated in these six patients, and although the device worked flawlessly and no clinically apparent thromboembolic events occurred, each artificial heart contained areas of macroscopic aggregations of platelets and thrombi. The results of this trial indicate that in properly selected cases, direct benefit to the patient can be obtained when the Jarvik-7 artificial heart is used as a bridge to transplantation.

Adult↗

Effect of variations in pressure and flow on the geometry of isolated canine carotid arteries.

A study is described in which the effects of hemodynamics on arterial geometry are investigated in vitro. A novel perfusion apparatus is employed to deliver pulsatile flow through excised canine carotid arteries under carefully controlled conditions. Data of perfused vessel diameter and arterial wall thickness are derived from the radial displacement of the pulsating vessel as measured using a scanning laser micrometer whose accuracy is determined to be 0.0125 mm (0.0005 in). The results of 30 perfusion experiments suggest that the hemodynamic variables of transmural pressure, pulse pressure and flow rate influence vessel size and radial strain. The physiologic implications of these findings are discussed.

Animals↗

Hemodynamics and the vascular endothelial cytoskeleton.

Although there is considerable evidence to suggest that hemodynamics play an important role in vascular disease processes, the exact mechanisms are unknown. With this in mind, we have designed a pulsatile perfusion apparatus which reproducibly delivers pulsatile hemodynamics upon freshly excised canine carotid arteries in vitro. Quantifiable simulations included normotension with normal or lowered flow rates (120/80 mmHg, 120 and 40 ml/min), normotension with lowered or elevated transmural pressures (40-170 mmHg), and elevated pulse pressure (120 and 80 mmHg) with normal (150 ml/min) or elevated rates of flow (300 and 270 ml/min). Arterial biomechanical stresses and cellular behaviors were characterized biochemically and morphologically under all these stimulations which continued for 2-24 h. We found that increased pulse pressure alone had little effect on the total amount of radiolabeled [4-14C]cholesterol present within the medial compartment. However, normotension when coupled with altered transmural pressure yielded a three- to fourfold increase. Combinations of increased pulse pressure and flow potentiated cholesterol uptake by a factor of 10 when compared with normotension control values. Simulations that enhanced carotid arterial cholesterol uptake also influenced the endothelial cytoskeletal array of actin. Stress fibers were not present within the carotid endothelial cells of either the sham controls or the normotension and increased pulse pressure (normal flow) simulations. Endothelial cells lining carotids exposed to elevations in flow or those present within vessels perfused as per simulation b above assembled stress fibers (x = 4 and 10 per cell, respectively) within the time course of these studies. When endothelial cells were subjected to hemodynamic conditions that potentiated maximally cholesterol transport, no diffuse or stress fiber staining could be seen, but the cortical array of actin was intact. These results suggest that those biomechanical stresses that alter endothelial permeability and intimal integrity may do so via cytoskeletal actin signaling.

Animals↗

Heterotopic cardiac transplantation: current status.

Heterotopic cardiac transplantation first introduced by Bernard in 1974 currently is rarely used as the procedure of choice when orthotopic cardiac transplantation can be considered. Specific indications for heterotopic cardiac transplantation include elevation of pulmonary vascular resistance and availability of a small or poorly functioning donor organ for a mortally ill recipient. Most cardiac transplant centers have abandoned its routine use because the recipient's diseased and poorly functioning heart remains as a potential source for embolism, infection, and continued angina, because the operative procedure is more complicated. Pulmonary complications are common due to compressive atelectasis of the right lung. Experience indicates that the heterotopic procedure is useful for those selected individuals in whom the orthotopic procedure is not appropriate and that rates of survival are nearly equal.

Anastomosis, Surgical↗

Cardiac transplantation: improved quality of survival with a modified immunosuppressive protocol.

The effects on renal function on two different immunosuppressive protocols were evaluated retrospectively in two subsequent groups of heart transplant recipients. In group I, cyclosporine was given before the procedure at a loading dose of 17.5 mg/kg and then continued after the procedure to keep a whole blood level about 1000 ng/ml. In group II, cyclosporine was started only after the procedure at a lower dosage and was complemented by azathioprine, which was used for the first postoperative week. Group II showed a better perioperative renal function as determined by serum blood urea nitrogen and serum creatinine levels. Group II also showed a significant decrease of chronic nephrotoxicity secondary to long-term therapy with cyclosporine. Despite this improvement in late renal function, group II still shows a slow rise in serum creatinine. We think that even these lower dosages of cyclosporine can cause chronic nephrotoxicity and that further modification of the immunosuppressive regimen is required to completely abolish this toxic side effect.

Actuarial Analysis↗

Cardiac transplantation. Emerging from an experiment to a service.

Cardiac transplantation was resumed at the University Health Center of Pittsburgh in 1980 after a hiatus of 12 years. Prior to April 15, 1986, 270 hearts had been transplanted. Participants have been forced to reorder personal, professional, and institutional commitments to adapt to new demands of pre- and post-operative care and to develop flexibility in the operative scheduling of routine cardiac surgical cases. The actuarial survival has been 78, 69, and 64% at 1, 2, and 3 years. Much has been learned about evolving immunosuppression based on cyclosporine and of the allogenic response. An increasing proportion of recipients are mortally ill (54%), and for these urgent patients the wait for a donor organ continues to lengthen. The cardiac surgeon performing transplantations will need to grow with allied developments in xenotransplantation and mechanical cardiac support devices in order to keep pace with his evolving specialty.

Cyclosporins↗

Early function of cardiac homografts: relationship to hemodynamics in the donor and length of the ischemic period.

Twenty-four of 124 heart transplant recipients in our study group died in the perioperative period. In five patients the cause of death was unknown even after postmortem examination. The possibility that the cause of death was due either to poor donor selection or poor preservation of the donor heart was evaluated by reviewing the length of ischemic time of the cardiac homografts and the need for inotropic support in the donors before the hearts were harvested. Results of our retrospective analysis indicate that inotropic support in the form of 2 to 10 micrograms/kg/min dopamine and an ischemic time of up to 4 hr do not influence the early survival of heart transplant recipients.

Adult↗