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Biomedical subjects

M P Kaye

Publications and source records attributed to M P Kaye.

At least 37 records · Page 2Linked to original sources

Left ventricular preparation with an extrathoracically adjustable balloon occluder.

We developed a hydraulic occluder that could be adjusted percutaneously through a subcutaneous reservoir. Because of the potentially high pressures that may occur in preparing patients with transposition of the great vessels for an atrial switch procedure, the band on that hydrauler was modified to withstand arterial pressure and was subjected to studies involving banding of the aorta. Data indicate the suitability of this hydraulic occluder to withstand and maintain pressure in the systemic circulation.

Animals↗

Superoxide generation during cardiopulmonary bypass: is there a role for vitamin E?

The cytotoxic metabolites of oxygen [superoxide (O-2), hydrogen peroxide (H2O2), and hydroxyl (OH.)] have been demonstrated to be involved in the peroxidation of membrane lipids consequently altering membrane composition, morphology, and function. Of all the lines of defense adopted by living organisms against toxic oxygen free radicals, vitamin E is most effective in the prevention of membrane damage. Cardiopulmonary bypass (CPB) has been shown to activate complement and cause sequestration of leukocytes which can recruit, adhere, and stimulate release of cytotoxic oxygen radicals. A prospective study of 30 patients evaluated the effects of CPB with and without an exogenous free radical scavenger (Group I, N = 20, control) and (Group II, N = 10, vitamin E) on H2O2 (a marker of oxygen free radicals) malonaldehyde (a marker of lipid peroxidation), transpulmonary leukosequestration, and plasma levels of vitamins E and C. Group I showed a progressive increase in H2O2 during CPB from 65 +/- 6 to 130 +/- 11 micron/ml (P less than 0.0001); plasma vitamin E decreased from 15 +/- 3 to 6 +/- 1 mg/liter (P less than 0.0001) while vitamin C increased from 1.6 +/- .3 to 2.3 +/- .3 mg/dl (P less than 0.0001). Group II showed no significant increase in H2O2 (from 78 +/- 8 to 93 +/- 5 microns/ml) during CPB and a significant reduction in H2O2 levels compared to Group I (P less than 0.001); plasma vitamins E and C did not change significantly in Group II.(ABSTRACT TRUNCATED AT 250 WORDS)

Ascorbic Acid↗

Xenograft seeding of Dacron grafts in dogs.

The benefit of autologous endothelial cell seeding in dogs has been widely accepted. This experiment seeks to determine if a similar effect accompanies the use of xenograft (porcine) endothelial cells in dogs. Thirty-two mongrel dogs underwent thoracoabdominal aortic bypass with 25- to 30-cm segments of double velour Dacron 8-mm grafts. Endothelial cell seeding was performed with whole blood suspensions of either autologous endothelial cells (Group I) or heterologous endothelial cells from pigs (Group II). Cell-free culture medium was added to whole blood for preclotting in unseeded control animals (Group III). Ten animals in each group were sacrificed at 30 days and all grafts were patent. Thrombus-free surface areas were Group I = 61.7 (+/- 6.4%, SEM); Group II = 53.2 (+/- 6.8%, SEM); and Group III 42.2 (+/- 8.0%, SEM). There was a significant difference between autologous-seeded and unseeded grafts (P less than 0.04). Endothelialization was confirmed by scanning and transmission electron microscopy in all groups but was better in both seeded groups: Group I-9/10 grafts, Group II-8/10 grafts, and Group III-4/10 grafts. Factor VIII immunofluorescent staining confirmed the presence of endothelium on selected grafts in each group. These results raise questions concerning the proposed mechanism of endothelial seeding since xenograft cells seem to facilitate healing in the canine model. If heterograft cells can be effective, it may not be necessary to harvest cells from the recipient in order to achieve the benefits of seeding.

Animals↗

Identification of new collagen formation with 125I-labeled antibody in bovine pericardial tissue valves implanted in calves.

Failure of bovine pericardial tissue valve used in young patients may be due to a slow rejection process. Polyclonal anticollagen (Type I) antibody (IgG) was made in rabbits and purified by protein A affinity column. Two milligrams of IgG was labeled with 2 mCi of 125I by the Iodogen method. Free iodide was separated by G-10 column. Affinity of 125I-IgG was checked by radioimmunoassay. Two hundred and fifty microcuries of 125I-IgG was injected in calves immediately after tissue valve implantation, and the calves were killed 4 h post-injection. After harvesting the valve, each of the three leaflets was separated into four zones, and radioactivity in each section was mapped with a gamma counter. The radioactivity in tissue valve section was compared to that of normal aortic valve. The sections of tissue valve retain five to ten times more 125I-IgG than control aortic valve. Iodine-IgG thus provides a sensitive technique for determination of residual antigenicity in tissue valve.

Animals↗

Percutaneously adjustable pulmonary artery band.

Conventional banding techniques result in up to 50% mortality as a result of improper and fixed constriction of the pulmonary artery in patients in unstable condition. We developed a percutaneously adjustable band with a fluid-filled reservoir that allows variable constriction without thoracotomy or other surgical procedures. Six pigs ranging in weight from 7 to 10 kg underwent pulmonary artery banding. Swan-Ganz catheterization, ultrasound studies, and Doppler studies were used to adjust and monitor the pressure gradient across the band. Thirty days after banding, the pigs were killed; their hearts were sectioned, weighed, and compared with hearts from a control group of six pigs weighing 11 to 13 kg. The ratio of mean total heart weight to total body weight (X 10(-3] was 6.3 +/- 0.7 in the banded group and 4.4 +/- 0.3 in the controls (p less than 0.001). The ratio of left ventricular weight to right ventricular weight was 0.76 +/- 0.1 in the banded group and 1.6 +/- 0.1 in the controls (p less than 0.001). The thickness of the right ventricular free wall was 4.9 +/- 0.5 mm in the banded group and 2.6 +/- 0.5 mm in the controls (p less than 0.001). Right ventricular free wall weight in the banded group was 25.9 +/- 5.8 gm compared with 11.1 +/- 1.3 gm in the controls (p less than 0.001). These results demonstrate the effectiveness of the band in inducing right ventricular hypertrophy. Since the band is easily placed and simply adjusted percutaneously, this device promises to be of importance clinically in improving the safety of pulmonary artery banding procedures.

Animals↗

Are seeded endothelial cells the origin of neointima on prosthetic vascular grafts?

Although endothelial cell seeding has been demonstrated to be effective in producing uniform endothelial coverage on prosthetic grafts, no one has demonstrated that the seeded cells are the genetic precursors of the endothelial cells that ultimately line the graft. This study was performed to determine whether seeded endothelial cells were the source of the neoendothelial surface on Dacron vascular grafts implanted in the pig. Eight pairs of littermate male and female pigs were selected at birth and allowed to grow until their weight reached 20 to 25 kg. Endothelial cells were enzymatically harvested from the jugular vein of the female siblings and seeded onto 8 mm diameter grafts, 25 cm in length. The grafts were then implanted as a thoracoabdominal bypass into the male siblings. Seven other randomly selected pigs of similar size (four males and three females) had thoracoabdominal bypass with similar grafts, which were preclotted with autologous blood only, but not seeded. After 4 weeks, grafts in both groups were covered with a neointima that was more than 90% thrombus-free. The graft surface cells were grown in culture and were documented to be endothelium. Chromosome analysis demonstrated that the surface cells on the seeded grafts were from the male host and did not originate from the donor female cells. We conclude that seeded endothelial cells are not the source for the neointima on Dacron grafts in the porcine model. In addition, we have again documented that spontaneous endothelial coverage of grafts does occur without endothelial seeding.

Animals↗

Flow capacity of the canine internal mammary artery.

The internal mammary artery has excellent long-term patency when used as a conduit for coronary artery bypass, and clinical and experimental studies have shown that blood flow through an internal mammary artery graft is satisfactory for most coronary artery branches. Multiple distal anastomoses from a single internal mammary artery, either with sequential anastomoses or with a Y-graft, might require additional blood flow through the vessel, and there has been concern that the flow capacity of the internal mammary artery is insufficient with these techniques. To better define the immediate postoperative flow capacity and pattern of the internal mammary artery, we performed experiments in seven dogs in which the left internal mammary artery was anastomosed to the circumflex coronary artery. In situ, blood flow in the internal mammary artery was 27 ml/min. Blood flow was 63 ml/min in the circumflex coronary artery and 42 ml/min in the left anterior descending coronary artery. After anastomosis of the left internal mammary artery to the circumflex coronary artery, the left main coronary artery was ligated; flow through the bypass graft increased to 92 ml/min, and systemic hemodynamics remained stable. Isoproterenol stimulation further increased flow through the left internal mammary artery graft to 160 ml/min. This study suggests that the canine internal mammary artery is capable of substantial early increase in flow and can, in fact, support the entire left coronary circulation.

Animals↗

Heart and heart-lung transplantation: the Canadian and world experience from December 1967 to September 1985.

By Sept. 1, 1985, 62 centres around the world were identified as having participated in heart transplantation; of these 14 had also performed combined heart-lung transplantation. Between December 1967 and December 1984, 1599 recipients had undergone 1644 transplant procedures. By September 1985, 112 heart-lung transplant procedures had been performed in 110 patients. Overall survival at 1 and 3 years respectively, excluding perioperative mortality, averaged 80% and 65%; for heart transplantation alone survival rates were 85% and 75%, respectively. In Canada, of 81 heart and 5 heart-lung transplant procedures that were performed in nine centres between April 1981 and September 1985, 38 heart and 2 heart-lung transplants were carried out in the first 9 months of 1985. Sixty-four of the heart and 2 of the heart-lung transplant recipient were alive from 20 days to 4.42 years postoperatively.

Adolescent↗

Quantification of regional platelet and calcium deposition on pericardial tissue valve prostheses in calves and effect of hydroxyethylene diphosphonate.

Mitral valves were replaced with 25 mm bovine pericardial tissue valve prostheses (Ionescu-Shiley) in 45 calves (23 controls and 22 treated daily with hydroxyethylene diphosphonate). Before being killed 1, 14, 30, and 90 days later, the calves received In-labeled autologous platelets intravenously. Regional variations in platelet deposition were measured by a new technique. Thrombus was noted early on the flexion zone of the valve; with time it increased on the free edge and central zone. Platelet deposition was initially high on the flexion zone, attachment zone, sewing ring, and perivalvular tissue but decreased with time. Hydroxyethylene diphosphonate treatment tended to decrease platelet deposition in all zones. Calcium content was high in thrombus and increased in all zones with time, in both groups, but the deposition was less in the group treated with hydroxyethylene diphosphonate. Collagenous tissue and adherent thrombus appear to provide nucleation sites for calcification.

Animals↗

Influence of antioxidants (mannitol and allopurinol) on oxygen free radical generation during and after cardiopulmonary bypass.

Oxygen-derived free radicals (O2-, H2O2, OH.) are produced during oxidative metabolism, ischemia and reperfusion, and cardiopulmonary bypass (CPB). When oxygen free radical production exceeds scavenging capacity, peroxidation of structural lipids in cell membranes can occur with potentially injurious consequences. In this prospective study, 45 patients were evaluated to determine the effect of CPB on oxygen free radical generation. Twenty patients in group I were controls. Exogenous oxygen free radical antioxidants were administered before bypass to patients in group II (n = 15, mannitol) and group III (n = 10, allopurinol). In group I, plasma H2O2 increased during extracorporeal circulation from 65 +/- 6.0 to 125 +/- 12 microM/ml (p less than .001). At similar sampling intervals, plasma H2O2 levels were significantly lower in group II (p less than .03) and group III (p less than .05) when compared with those in group I. Red blood cell H2O2 did not change in group I or group II. White blood cell H2O2 levels decreased in group I (p less than .04) and group II during CPB. (Intracellular concentrations of H2O2 were not obtained in group III patients). We conclude that cytotoxic oxygen radicals are generated during CPB and that pretreatment with free radical antioxidants, mannitol or allopurinol, may minimize the free radicals available for lipid peroxidation of biomembranes.

Allopurinol↗

Complement activation during cardiopulmonary bypass. Comparison of bubble and membrane oxygenators.

A prospective randomized trial involving 91 patients undergoing cardiopulmonary bypass compared the effects of bubble oxygenators (with and without methylprednisolone sodium succinate) and membrane oxygenators on complement activation and transpulmonary sequestration of leukocytes. Patients were divided as follows: Group I, 30 patients, bubble oxygenator; Group II, 31 patients, bubble oxygenator and methylprednisolone sodium succinate (30 mg/kg); Group III, 30 patients, membrane oxygenator. In Group I, C3a increased from 323 +/- 171 ng/ml during cardiopulmonary bypass to 1,564 +/- 785 ng/ml at 25 minutes after bypass (p less than 0.0001). A significant decrease in C3a was found in Groups II and III compared to Group I (p less than 0.0001). C5a did not change significantly during cardiopulmonary bypass in any group. Reestablishment of pulmonary circulation at the end of bypass produced significant transpulmonary leukocyte sequestration in Group I; the median cell difference was 1,700/microliter. Transpulmonary sequestration was significantly (p less than 0.0001) less in Group II (median cell difference = 200/microliter) and in Group III (median cell difference = 400/microliter) than in Group I. We conclude that cardiopulmonary bypass with a bubble oxygenator alone initiates significantly (p less than 0.0001) more C3a activation and leukocyte sequestration than when methylprednisolone sodium succinate (30 mg/kg) is given 20 minutes before the start of cardiopulmonary bypass with a bubble oxygenator or when a silicone membrane oxygenator is used.

Adrenal Cortex Hormones↗

The natural history of microsurgical lymphovenous anastomoses: an experimental study.

Lymphovenous anastomoses have been suggested for the treatment of lymphedema, but the literature lacks evidence of late patency. To determine a method to verify patency, 57 lymphovenous anastomoses were performed in 34 dogs. In vivo cinelymphangiography gave convincing evidence of patency up to 8 months. Eight of 10 anastomoses were patent at 24 hours, 8 of 19 at 2 to 6 weeks, 4 of 6 at 3 months, and 2 of 6 at 8 months. Antiplatelet treatment did not decrease the thrombotic occlusion rate on the venous side, which was the main cause of failure. Scanning electron microscopy showed complete endothelial coverage of suture lines at 4 weeks. Because this study demonstrated that patency of lymphovenous anastomoses can be achieved, the procedure may be considered for the treatment of secondary lymphedema. The occlusion rate is high; therefore, chances of success are better with several anastomoses performed in the early stages of lymphedema, before significant tissue fibrosis and complete loss of lymphatic valvular function develop.

Angiography↗

Prevention of platelet deposition by ibuprofen and calcium dobesilate in expanded polytetrafluoroethylene vascular grafts.

This study was designed to evaluate the platelet-inhibiting effect of a new drug, calcium dobesilate, and to compare its efficacy to the known antiplatelet agent, ibuprofen. Five centimeter long expanded polytetrafluoroethylene grafts (internal diameter 4 mm) were used to replace 48 carotid arteries in 24 dogs. Autologous platelets were labeled with indium-111-labeled tropolone and reinjected into each animal 24 hours before operation. Six animals received an intravenous placebo, six received 12.5 mg/kg of intravenous ibuprofen, six received 100 mg/kg of intravenous calcium dobesilate, and six received 200 mg/kg of intravenous calcium dobesilate before cross-clamping. The grafts were removed after 3 hours, and radioactivity was measured and platelet deposition calculated. The results have indicated that preoperative administration of ibuprofen and calcium dobesilate in this animal model significantly diminishes early platelet deposition. Calcium dobesilate appears to be a dose-dependent, highly effective antiplatelet agent.

Animals↗

Quantification of deposition of neutrophilic granulocytes on vascular grafts in dogs with 111In-labeled granulocytes.

A new radioisotopic technique has been developed for quantification of deposition of neutrophilic granulocytes on vascular grafts. Nine healthy mongrel dogs underwent bilateral femoral artery resection and reconstruction with grafts of femoral vein and Gore-Tex. Pure granulocytes that had been separated from whole blood by centrifugal elutriation were labeled with 111In-tropolone in plasma. The granulocyte harvesting efficiency was 25 +/- 12%, and the labeling efficiency was 87 +/- 7%. Three hours after injection of labeled granulocytes and 2 hours after reperfusion, the grafts were harvested and cut into several segments for study of areas of anastomoses and midsections. On the basis of the radioactivity in the blood and in anastomotic and graft sections, the area of graft sections, and the neutrophilic granulocyte and differential leukocyte counts, the number of neutrophilic granulocytes adherent to a unit area and the total number of neutrophilic granulocytes on graft sections were calculated. These quantifications of the deposition of neutrophilic granulocytes indicated that the midsections of Gore-Tex grafts retained more neutrophilic granulocytes than did the midsections of vein grafts. Although the anastomotic areas retained more neutrophilic granulocytes than did the midsections of vein grafts, the opposite finding prevailed for the Gore-Tex grafts. A major fraction of neutrophilic granulocytes on Gore-Tex grafts was incorporated into thrombus. Semiquantitative information obtained by scintigraphy of the deposition of neutrophilic granulocytes on vascular grafts also confirmed this observation.

Animals↗

Cardiac function following prolonged preservation and orthotopic transplantation.

Donor dog hearts perfused with whole blood were preserved ex vivo, beating, for 12 hours before orthotopic implantation. Twenty-four to 48 hours following implantation, ventricular function was studied using sonomicrometric techniques and compared to that of acutely denervated and conventionally preserved transplanted hearts. Hearts preserved ex vivo for 12 hours and then implanted in an orthotopic position had ventricular function statistically equal to or better than acutely denervated or conventionally preserved transplanted hearts.

Animals↗