Chemical epicardiectomy. A method of myocardial denervaion.
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Biomedical subjects
Publications and source records attributed to M P Kaye.
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With 111In-labeled platelets and 125I-labeled bovine fibrinogen, regional mapping of platelet and fibrinogen deposition on leaflets and sewing rings was obtained. Ten Holstein calves received 25-mm mitral valves (ISLM) and were killed 1, 14, and 30 days after implantation. Twenty-four hours before the calves were killed, 350 to 450 microCi of 111In-labeled platelets and 200 to 250 microCi of 125I-labeled bovine fibrinogen were administered intravenously. The components of the tissue valves, i.e., three leaflets and sewing rings, were separated. Each leaflet was cut into four sections: free edge, central zone, flexion zone, and attachment zone. From the radioactivity in blood, leaflet zones, sewing rings, area of leaflet zones, platelet count, and fibrinogen level in blood, the mean regional density of adherent platelets, fibrinogen-fibrin, and fibrinogen/platelet were calculated. The density of platelets and fibrinogen deposited on the components of the valves decreases with time postimplantation. The number of fibrinogen molecules per platelet is fivefold to 20-fold higher than that of the receptor concentration on platelets on leaflet zones, suggesting the heterogeneity of fibrinogen-fibrin in thrombus and components of the valve.
Platelet deposition on bovine pericardial-tissue mitral-valve prostheses in 11 dogs was observed noninvasively by use of 111In-labeled platelets and quantified after sacrifice at one (n = 3), 14 (n = 3), and 30 (n = 5) days postimplantation (300-400 microCi of labeled platelets having been injected 24 hours previously). Thrombosis on the sewing ring and pericardial leaflets at one and 14 days and on the leaflets at 30 days was delineated in scintiphotos. In vitro quantification (% injected dose) indicated that the leaflets, sewing ring, and perivalvular tissue retained 0.904% of labeled platelets at one day postimplantation, 0.198% at 14 days, and 0.040% at 30 days. Platelet half-life was reduced to 38 hours at 21 days postimplantation but returned toward the normal (50 hours) with fibrous ingrowth in the sewing ring. Microembolism in lung and kidney, as measured by tissue/blood radioactivity ratio, also was decreased significantly at 30 days. 111In-labeled platelets thus provide a sensitive marker for noninvasive imaging and in vitro quantification of platelet deposition on valvular prostheses and microemboli trapped in viscera, although histochemical confirmation will be necessary to correlate the increase in tissue/blood ratio with the presence of microembolism.
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Less than 25 years since the first human-human heart transplantation, the worldwide experience exceeds 16,000 heart and 1600 lung transplantations from more than 200 centers. Excellent results in heart transplantation have been achieved in a wide variety of patients. During the past few years, lung transplantation has come of age. The specific indications for each technique continue to evolve. Although much progress has been made, it is hoped that future developments in immunosuppression will solve the problems of chronic rejection and decrease the risk of infections. On behalf of the Society, we would like to take this opportunity to sincerely thank each of the participants throughout the world who took the time and care to submit their data to the Registry. Through this compilation of the world's experience, the state of the art in thoracic transplantation may be shared with the transplant community. The extensive Registry data base will permit risk assessment of thoracic transplant recipients while avoiding the problems associated with small sample sizes. Each participant's continued diligence in providing follow-up reports on all recipients is essential for an accurate evaluation of the long-term prognosis of heart and lung transplantation.
The effects of hypothermic lung preservation were evaluated in 12 mongrel dogs receiving double lung allografts. Animals underwent transplant procedures after 12 hours of static preservation at 4 degrees C following pulmonary artery flush with 60 to 80 ml/kg cold modified Collins solution. Donors were pretreated with allopurinol and recipients with methylprednisolone and perireperfusion deferoxamine. Six donor animals received a PGE1 infusion (20 to 500 ng/kg/min) for 20 minutes before harvest at doses causing a significant reduction in pulmonary vascular resistance. After implantation, recipients were maintained at ventilator settings identical to those used in donors. A fixed FIO2 (0.4) was maintained, except for 15-minute periods of FIO2 1.0 that were used to measure left-to-right intrapulmonary shunt fraction (Qs/Qt) and alveolar-arterial oxygen gradients (PAO2-PaO2). Cardiopulmonary function was studied for 20 hours. Pretreatment with PGE1 resulted in reduced survival (p less than 0.05) and increased PAO2-PaO2 (p less than 0.05) and Qs/Qt (p less than 0.05) 30 minutes after reperfusion. After 60 minutes of reperfusion, mean arterial pO2 (FIO2 0.4) was 148 mm Hg in controls and 80.5 mm Hg in the PGE1 group (p less than 0.02). There was no significant difference in pulmonary vascular resistance, cardiac output, mixed venous oxygen saturation, airway resistance, compliance and physiologic dead space between groups at any time after implantation. After 20 hours of reperfusion, pO2 (FIO2 0.4) in the control group was well maintained at 140 (+/- 52) mm Hg. The method of lung preservation in control animals resulted in good survival and adequate gas exchange after 12 hours of ischemia and 20 hours of reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
The physiologic effects of 12-hour lung preservation were assessed in six mongrel dogs studied for 20 hours after double-lung allograft implantation. Donor animals were pretreated with allopurinol (30 mg/kg) and methylprednisolone (500 mg) intravenously at anesthesia induction. Heart-lung blocks were harvested after cardioplegic arrest, and a simple pulmonary artery flush of 4 degrees C modified Collins' solution was administered at 15 ml/kg/min. The lungs were ventilated with 100% nitrogen during flushing and inflation. Recipient animals received an infusion of deferoxamine (20 mg/kg) during implantation and were pretreated with methylprednisolone (500 mg) intravenously. All six implantations were technically successful. Two animals died of cardiac standstill 12 and 24 hours postoperatively. Gas exchange deteriorated after implantation compared with donor levels but remained in a range compatible with survival, and at 20 hours arterial oxygen tension (FiO2 0.4) was 138 +/- 91 mm Hg. Similar changes were seen in alveolar-arterial oxygen gradients and arterial-alveolar oxygen tension fraction. Elimination of carbon dioxide was satisfactory. Pulmonary venous shunt fraction rose significantly at the end of the study. Hemodynamic changes consisted of a gradual increase in pulmonary vascular resistance and a reduction in cardiac output. Lung mechanics also deteriorated, with a gradual rise in airway resistance and a fall in compliance. The double-lung model allows detailed assessment of the early effects of preservation and may have certain advantages over heart-lung models of preservation. The preservation technique warrants further study.
During the past decade we have witnessed a continuing evolution in intrathoracic transplantation. The role of heart transplantation in end-stage heart disease has been well established; and combined heart-lung and lung transplantation techniques developed during the past 10 years have been applied to an expanding array of diseases associated with end-stage pulmonary failure. Recently a plateau in number of transplants per year has become evident. Although the areas of pediatric heart and single lung transplantation continue to expand, it appears that further overall growth in heart and lung transplantation is now limited by donor availability. Although operative mortality has shown gradual improvement, organ preservation and other intraoperative complications remain major factors associated with early death, especially in combined heart-lung and lung transplantation. Infection and rejection are the most common causes of late deaths for all types of intrathoracic transplantation. Although long-term survival has shown improvement over the past 10 years, an increasing number of patients now require retransplantation because of chronic rejection. Results with heart, combined heart-lung, and lung retransplantation, in operative mortality and in long-term survival, have not been as encouraging as with the primary transplant procedure. We await further developments in heart and lung transplantation during the new decade.
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During 1985 to 1986, 57 orthotopic heart transplantations have been performed at the University of Minnesota, Minneapolis. All patients received triple-drug immunosuppressive therapy of cyclosporine, azathioprine, and prednisone. Twenty-three patients were aged 55 years or older (mean age 58.0 +/- 2.6 years); 34 patients were under the age of 55 years (mean age 39.1 +/- 13.2 years). The initial in-hospital stay averaged 13 +/- 4 days in the older group and 16 +/- 13 days in the younger group. Perioperative mortality was similar in the two groups. The incidence of cerebrovascular accident was similarly low in the two groups, whereas incidence of steroid-induced diabetes (17% versus 9%) and significant osteoporosis (13% versus 3%) was significantly higher in older patients. The probability of survival and the actuarial freedom from rejection were identical in the two groups with 1-year survival of 96% and 94% of patients free of rejection at 12 months. Although the incidence of infection was not significantly higher in older patients (0.82 episode per patient) than in younger patients (0.78 episode per patient), life-threatening infections (Cryptococcus meningitidis, disseminated herpes simplex) were observed only in older patients. These data suggest that (1) heart transplantation is a valid therapeutic option even in elderly patients with end-stage heart failure, (2) it can be performed in selected patients at no increased operative risk with excellent long-term survival, (3) however, older patients are at higher risk for serious infections and for developing steroid-related complications.
Clinical double-lung transplantation has now been successfully performed at the University of Minnesota, Minneapolis. Donor care and operation are similar to heart-lung donor management. The most important parts of the recipient operation are to remove the lungs without injury to the phrenic, vagal, or recurrent nerves and to ensure hemostasis. In addition, the integrity of the tracheal anastomosis should be ensured by an omental wrap. The operative technique, developed and modified from our laboratory experience, is described.
A noncalcifying drug, aminodiphosphonate, was immobilized on pericardial collagen to inhibit calcification. The parameters of ADP binding were optimized by using labeled tracer. The effects of the detergents, Triton X-100 and sodium dodecyl sulfate, pH, and temperature on ADP binding to collagen in fresh pericardium, and stabilization of ADP-collagen bond by borohydride (BH) reduction, were optimized. These studies indicate that pretreatment of pericardium with SDS and TX-100 increases ADP binding three- to fivefold. Three-step cross-linking via Schiff-base reactions between collagen, ADP, and cross-linking via Schiff-base reactions between collage, ADP, and glutaraldehyde gives a high value of 30 to 35 molecules of ADP per collagen in pericardium. Twenty-five millimeter tissue valves were made with detergent (1% SDS, 1% TX-100) treated ADP-bound pericardium and implanted in the mitral annuli in calves, which were killed at 60 days post implantation. Regional calcium deposition was measured with atomic absorption spectrometry. The calcium level (micrograms/mg of tissue) in components of control and four processed valves were determined. Regional platelet deposition on zones of leaflets and components of tissue valves were quantified with 111In-labeled autologous platelets. The calcium levels in thrombus and flexion zones of treated valves are lower than that in the control valve. SEM studies of leaflet surfaces at 60 days indicate that these treatment processes reduce calcification and promote spontaneous cell coverage on leaflets around the smooth surface of the outflow tract.
To determine the feasibility of en bloc removal of the heart, lungs, liver, kidneys, and pancreas for preservation with warm blood autoperfusion, organs from 34 dogs were preserved ex vivo for periods of between 3 and 22 hours. The lungs were ventilated with a Bird Mark 7 respirator, and the heart served as the pump to perfuse all organs of the multiple organ block. In the first group of 28 animals, surgical and pharmacologic techniques were developed to permit management of the ex vivo model. The last six experiments were conducted in a standardized fashion for a period of 6 hours and evaluated on the basis of hemodynamic, biochemical, and pathologic measurements. In this group the pH level remained stable and blood gas levels remained within normal limits for inspired oxygen of 0.2. Serum and urine electrolyte levels were easily maintained within normal limits. Serum enzyme values were elevated initially after operation, and this increase persisted throughout the preservation period in most animals. Continuing refinements in surgical technique, pharmacologic management, and chamber development resulted in a dramatic reduction of the edema and organ damage seen on pathologic studies of the initial experiments. The presence of focal lymphatic congestion, however, was noted even in the animals in group II and may have been related to ligation of major lymphatic channels or to endothelial loss. These changes could contribute to the development of the pathologic changes seen in irreversible shock. Preservation of the multiple organ block by warm autoperfusion is an important step in understanding the physiology of organ preservation and has potential for permitting prolonged organ preservation. Studies are continuing to further analyze this model and prolong the time of preservation. Final assessment of the model will be transplantation of the preserved organs and evaluation of function after implantation.
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