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Biomedical subjects

M P Kaye

Publications and source records attributed to M P Kaye.

At least 19 recordsLinked to original sources

A new concept for successful long-term pulmonary preservation in a dog model.

We developed a dextran-glucose-based extracellular perfusion solution (DGX) that supports limited aerobic metabolism to maintain cellular integrity of an inflated donor lung during long-term ischemia and a storage temperature of 10 degrees C. In a dog model, we compared respiratory and hemodynamic function of orthotopically transplanted left lungs preserved using this method (DGX, group I, n = 6) with function of those preserved with EuroCollins solution (EC) stored at a temperature of 4 degrees C (group II, n = 6). All lungs were inflated with room air and stored for 12 hr. Pulmonary function was monitored for 5 hr of reperfusion. Values expressed below are group means with standard deviation. Statistical significance was calculated using a two-tailed t test. For PO2 (mmHg) (FiO2 = 0.4), group I (EC): control = 193 +/- 8, 30 min p.o. = 87 +/- 20*, 300 min p.o. = 174 +/- 13*; and group II (DGX): control = 217 +/- 28, 30 min p.o. = 184 +/- 46*, 300 min p.o. = 248 +/- 5*. For pulmonary vascular resistance (dynes), group I: control = 389 +/- 22, 30 min p.o. = 1209 +/- 301, 300 min p.o. = 1025 +/- 204*; and group II: control = 401 +/- 31, 30 min p.o. = 522 +/- 129, 300 min p.o. = 458 +/- 137* (*P < 0.05 DGX vs. EC). Gas analysis performed on air samples taken from the ischemic donor lung immediately after harvest and after 12-hr storage showed (calculated as group means) a significant decrease of PO2 and a significant increase of PCO2, respectively. Histology of the lungs after 5 hr of reperfusion showed essentially normal-appearing lungs in the DGX group, whereas lungs in the EC group showed thickening of the intra-alveolar septi, marked cellular infiltration, and accumulation of protein-like material in the alveoli. In this study, preservation with DGX resulted in satisfactory respiratory and hemodynamic function of the transplanted lung even after 12 hr of ischemia. It does not cause an increase of pulmonary vascular resistance as seen after preservation with EC. Data from the intrabronchial air analysis of the donor lung suggest that aerobic metabolism continues even under preservation conditions.

Animals↗

The relationship of clinical outcomes to status as a Medicare-approved heart transplant center.

This study reports the evaluation of the validity and utility of the Medicare heart transplant center selection process, as outlined in its 1986 Heart Coverage Regulations. A total of 9401 heart transplants performed in the U.S. between 1986 and 1991 were analyzed. The outcomes assessed were mortality and the occurrence of infection during the hospital stay. Outcomes experienced by centers with and without Medicare approval were compared directly and following adjustment for patient risk factors. Patients at centers that satisfied the Medicare criteria experienced lower mortality. The risk-adjusted hazard ratio for death over the five years of observation was 0.874 (P = 0.005). The probability of death following a transplant at a Medicare-approved center was 7.0 +/- 0.4% at 30 days and 16.2 +/- 0.6% at one year, and 9.2 +/- 0.4% and 19.2 +/- 0.6%, respectively, at centers without Medicare approval (P = 0.001). The difference appeared to be principally associated with death within 30 days of admission due to nonspecific graft failure. The posttransplant infection rate at Medicare-approved centers was 0.743 (P < 0.001) but this result is strongly confounded with differences in reporting patterns of the two types of centers. Criteria used by HCFA identify medical centers where outcomes of heart transplantation, as measured by mortality, are superior. This difference is established early, persists over time, and is not attributable to the numerous risk factors considered in our models. Overall, the results of the present study suggest that "centers of excellence" can be identified through the evaluation of center characteristics and outcomes, and that this approach chosen by HCFA may have broad health care systems applications.

Adolescent↗

Pulmonary retransplantation for obliterative bronchiolitis. Intermediate-term results of a North American-European series.

An international series of pulmonary retransplantation was updated to identify the predictors of survival in the intermediate-term after reoperation for obliterative bronchiolitis. The study cohort included 32 patients with end-stage obliterative bronchiolitis who underwent retransplantation in 15 North American and European centers between 1988 and 1992. Five types of retransplantation procedures were done, including repeat ipsilateral single lung transplantation (7 patients), repeat contralateral single lung transplantation (8 patients), repeat double lung transplantation (3 patients), double lung transplantation after a previous single lung transplantation (3 patients), and single lung transplantation after a previous double lung or heart-lung transplantation (11 patients). The mean interval between transplants was 564 +/- 51 days (range 187 to 1589 days). Postoperative follow-up was 100% complete and the average follow-up in surviving patients was 678 +/- 63 days. Actuarial survival was 72%, 53%, 50%, 41%, and 33% at 1, 3, 6, 12, and 24 months, respectively. Survival did not differ according to the age, preoperative diagnosis, ambulatory or ventilator status, or cytomegalovirus serologic status of the recipient before reoperation. Life-table and Cox proportional hazards analysis identified the type of retransplantation procedure and the year of reoperation as significant (p < 0.05) predictors of postoperative survival. Actuarial survival was significantly better in patients without an old, retained contralateral graft after retransplantation and in patients who underwent reoperation between 1990 and 1992, as opposed to between 1988 and 1989. Infection was the most common cause of death at all time intervals after retransplantation, although all deaths beyond 2 years resulted from obliterative bronchiolitis of the second graft. Most surviving patients are in a satisfactory clinical condition, with a mean forced expired volume in 1 second of 59% +/- 13% of predicted (repeat double lung transplant recipients) or 41% +/- 6% of predicted (repeat single lung transplant recipients). We conclude that pulmonary retransplantation for obliterative bronchiolitis is associated with significantly worse survival than after primary lung transplantation. The absence of an old contralateral graft after retransplantation and reoperation after 1989 are important predictors of survival. Additional data and follow-up are required to determine the merit of pulmonary retransplantation for obliterative bronchiolitis.

Actuarial Analysis↗

The relation between experience and outcome in heart transplantation.

BACKGROUND: Current policies related to organ transplantation in the United States are designed to ensure that centers and physicians with experience in transplantation perform these procedures. It is essential to confirm the validity of such policies, since they may limit access to transplantation services. METHODS: To determine the relation between experience with heart transplantation and mortality after the procedure, we merged data from the registry of the International Society for Heart and Lung Transplantation with data from a survey that provided additional information about patients and transplantation centers. Our study included 1123 patients who received a heart transplant at one of 56 hospitals in the United States from 1984 through 1986. We used univariate and bivariate techniques, as well as logistic regression, to analyze our data. RESULTS: We observed an institutional learning curve for heart transplantation. Patients who received one of a center's first five transplants had higher mortality rates than patients who received a subsequent transplant (20 percent vs. 12 percent; P = 0.002; relative risk = 2.2; 95 percent confidence interval, 1.6 to 3.4). In addition, we found a correlation between the training of key personnel on the transplantation team and mortality at new transplantation centers. For example, new centers staffed by cardiologists with previous training in heart transplantation had lower mortality rates among heart-transplant recipients than centers without experienced cardiologists (7 percent vs. 16 percent; P = 0.001; relative risk = 2.7; 95 percent confidence interval, 1.3 to 5.9). By contrast, the previous training of the surgeons who performed transplantations was not related to the mortality rate associated with the procedure. CONCLUSIONS: Experience with heart transplantation is associated with a better outcome for patients after that procedure. Opportunities exist to refine transplantation policies on the basis of the experience of a center and its transplantation team and to develop similar policies for other forms of organ transplantation.

Cardiac Care Facilities↗

Registry report: International Society for Heart and Lung Transplantation.

Orthotopic heart transplantation continues to be a highly successful therapy for end-stage cardiac disease. Recent advances have extended the benefits of this procedure to neonatal patients. The number of patients undergoing single- and double-lung transplantation increases steadily and the indications for transplantation are being expanded. Evaluation of the early results indicates that patients undergoing lung transplantation for vascular disease do not fare as well as those undergoing transplantation for parenchymal disease. Presently, the results of retransplantation are far inferior to primary transplantation and require ongoing evaluation.

Adolescent↗

Canine double-lung allotransplantation: operative technique and results for 12-h preservation studies.

A canine double-lung allotransplantation model was developed to study the effects of 12-h static pulmonary preservation. This model has not been used extensively for such experiments but allows a detailed evaluation of the quality of preservation. An operative technique is described in which cautery dissection and preliminary devascularization of the recipient right lung allows the period of cardiopulmonary bypass to be limited and reduces postoperative bleeding. Six double-lung blocks were successfully orthotopically transplanted and recipient animals were studied for 12 h postoperatively. All animals survived the study period and had a mean PO2 (FIO2 0.4) of 141 mm Hg, 12 h following reimplantation suggesting adequate pulmonary preservation. There was no evidence of pulmonary edema at any time following implantation, although airway pressures and pulmonary vascular resistance were elevated. The role of this model in lung preservation studies is discussed.

Animals↗

The Registry of the International Society for Heart Transplantation.

As of October 1990, the Registry of the International Society for Heart Transplantation has received data on over 14,000 heart and over 1,100 combined heart-lung or lung transplant recipients from over 200 centers worldwide. While the areas of single-lung transplantation and pediatric heart transplantation continue to expand rapidly, further growth in annual numbers of cardiac and pulmonary transplant procedures is now limited by donor supply. Operative mortality and late survival have improved during the past decade, however, infection and rejection continue to be the main causes of death. As the number of long-term survivors continues to increase, chronic rejection remains the major obstacle and results with retransplantation have not been very encouraging.

Age Factors↗

Effect of platelet inhibitors on platelet and fibrin deposition following transluminal angioplasty of the atherosclerotic rabbit aorta.

Experimental atherosclerosis was induced in a rabbit model by intimal damage of the infrarenal aorta followed by two months cholesterol feeding. The influence of four different antiplatelet drug regimens on acute platelet and fibrin deposition after transluminal angioplasty of the atherosclerotic abdominal aorta was then evaluated. The study group consisted of 32 New Zealand rabbits: 7 controls, 7 treated with prostacyclin (10 mg/kg/min i.v.), 5 treated with low-dose acetylsalicylic acid (2 mg/kg i.v.), 7 treated with acetyl-salicylic acid (5 mg/kg i.v.) and dipyridamole (2 mg/kg i.v.), and 6 treated with low molecular dextran (5 ml/kg). By 2 hours after angioplasty, there was a significant increase of the deposition of platelets (P less than 0.001) as well as fibrin (P less than 0.01) when comparing dilated to non-dilated segments in the control animals. There was no significant difference in the amount of platelets and fibrin deposition among the control and drug treated groups. Thus, in this animal model there appears to be no immediate benefit in using antiplatelet drugs during transluminal angioplasty. Although, this study did not address the potential long-term effects of antiplatelet drug therapy, future evaluation of the clinical benefits of these drugs in conjunction with transluminal angioplasty seems warranted.

Angioplasty, Balloon↗

The Registry of the International Society for Heart Transplantation.

The International Society of Heart Transplantation Registry has now received data on almost 12,000 transplants including over 11,000 heart transplants and almost 600 heart-lung and 100 lung transplants. Recently, a plateau in number of transplants per year has become evident. It appears that further growth is now limited by donor supply. Operative mortality and long-term survival rates continue to show gradual improvement. Organ preservation and other intraoperative complications remain a major factor associated with operative mortality, especially in heart-lung and lung transplantation. Infection and rejection remain the most common causes of early and late deaths. An increasing number of patients have now received second transplants. At the present time, results with retransplantation are significantly worse than for the initial transplant.

Heart Transplantation↗

Chronic hypoxia alters structure and transmitter dynamics in dog pulmonary artery.

Confinement of dogs to 10% oxygen for 14 days caused erythropoiesis and pulmonary hypertension. Histological sections of the lung tissue showed thickening of the smooth muscle component of muscular arteries and arterioles. Segments of pulmonary artery from dogs exposed to hypoxia were superfused under continuation of hypoxic conditions or after return to oxygenated conditions. Parallel segments of pulmonary artery from normal dogs were also studied. Norepinephrine stores were labeled with [3H]norepinephrine and measurements were made of [3H]norepinephrine and its radiolabeled metabolites (separated by column chromatography) in superfusates using liquid scintillation spectrometry. Chronic hypoxia (1) reduced neuronal uptake of NE from synaptic clefts, (2) reduced the content of DOPEG in superfusate from tissues studied during continuation of hypoxic conditions and in tissues studied after return to oxygenated conditions, (3) increased extraneuronal uptake of NE and (4) increased overflow of NE from synaptic clefts. In similar segments of pulmonary artery removed from the same lung, endogenous free and conjugated norepinephrine and dopamine were measured in pulmonary artery by liquid chromatography with electrochemical detection. The tissue content of free norepinephrine after stimulation was reduced, which was compatible with the reduction in neuronal uptake. Conjugated norepinephrine was a minor metabolite and was increased modestly compared to concentrations reported previously in pulmonary artery from normal dogs.

Animals↗

The International Society for Heart Transplantation Registry.

The Registry for the International Society for Heart Transplantation has collected data on some 6,500 heart transplant recipients and 344 heart-lung recipients. Operative mortality in heart transplantation has decreased substantially since 1985. There has been a recent increase in cardiac complications following heart transplantation. Congenital heart disease is a significant risk factor in heart transplantation. More patients are undergoing heart-lung transplantation for cystic fibrosis. Improved survival is seen with triple-drug immunosuppression in both heart and heart-lung recipients.

Adult↗