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Biomedical subjects

M P Kaye

Publications and source records attributed to M P Kaye.

At least 73 records · Page 4Linked to original sources
PubMed1982

A new in vivo model of arterial thrombosis: the effect of administration of ticlopidine and verapamil in dogs.

An in vivo model of arterial thrombosis was developed in which either polytetrafluoroethylene (PTFE [Gore-Tex]) or autologous vein grafts were used to replace a segment of the femoral arteries of dogs. In one series of studies, 5 cm of PTFE and 5 cm of autologous femoral vein were used in each animal and blood flow was resumed for 1 hour. 111In-labeled autologous platelets accumulated in greater amounts on the PTFE grafts (93.6 X 10(6) platelets/cm) than on the vein grafts (2.6 X 10(6) platelets/cm) (P less than 0.001). Orally administered ticlopidine (30 mg/kg/day for 2 days), an established inhibitor of platelets, reduced platelet deposition on the PTFE grafts to 10.5 X 10(6) platelets/cm (P less than 0.01). In a second series of studies, PTFE grafts were interposed on both sides in each animal, and blood flow was resumed for 3 hours. With intravenously administered verapamil, a calcium antagonist, given perioperatively at 7.5 ug/kg/min, 12 of 16 grafts in eight dogs were patent compared with only 2 of 16 grafts in eight control dogs (P less than 0.001). Furthermore, platelet deposition on the grafts was reduced from 1,090 X 10(6) platelets/cm to 303 X 10(6) platelets/cm (P less than 0.001). Thus, both ticlopidine and verapamil are effective antithrombotic agents as a result of their inhibition of platelet activity in this model, and these results provide further evidence of a central role for calcium in platelet activation.

Administration, Oral↗
PubMed1982

Patency of polytetrafluoroethylene microarterial prostheses improved by ibuprofen.

Because of the increasing need for a reliable prosthetic microvascular graft, we investigated the patency of expanded PTFE with and without platelet inhibitor medication as an arterial prosthesis (1 by 10 mm) placed in the aorta of the rat using standard microsurgical technique. In 10 animals without platelet-inhibitor medication, one graft (10 percent) was patent at 30 days. When the platelet inhibitor ibuprofen was given for the initial 15 days to 10 animals, all 10 grafts (100 percent) remained patent at 30 days without further use of the drug. There was a significant difference between the patency achieved with the drug and that obtained without it (p less than 0.0001). The results of this experimental study demonstrate that expanded PTFE can successfully be used as a microvascular graft in the rat with excellent patency (100 percent at 30 days) when combined with ibuprofen therapy.

Animals↗
PubMed1982

Arteriosclerosis in normal and von Willebrand pigs: long-term prospective study and aortic transplantation study.

In a long-term prospective study, five normal control pigs and five pigs with homozygous von Willebrand's disease received a nonfatty diet from age 3 months to 4 years; then the aortas were analyzed. The fibrous arteriosclerotic plaques in the distal abdominal aortic region involved an average of 28% of the surface area in control pigs and only 7% of the surface area in pigs with von Willebrand's disease (P less than 0.01). In a subsequent study of 3-month-old pigs, the distal abdominal aortic segments from nine normal pigs were cross-transplanted with segments from nine other normal pigs (control study), and aortic segments from four normal pigs were transplanted into four host pigs with von Willebrand's disease (exchange study). All pigs received a 2% cholesterol diet for up to 6 months; then the transplanted aortic segments were analyzed. The donor normal aortic segments in the host normal pigs developed arteriosclerosis that involved an average of 20% of the surface; the endothelial fluorescent pattern of von Willebrand factor was identified. In contrast, the donor normal aortic segments in the host pigs with von Willebrand's disease had arteriosclerosis that involved an average of only 4% of the surface (P less than 0.01); the endothelial cell von Willebrand factor was not identified. The long-term prospective study indicates that pigs with von Willebrand's disease are resistant to the development of spontaneous arteriosclerosis. The aortic transplantation data are compatible with the hypothesis that the absence of von Willebrand factor in pigs with von Willebrand's disease may cause impairment of platelet-arterial wall interaction and resistance to arteriosclerosis.

Animals↗
PubMed1982

Fate of indium 111-labeled platelets during cardiopulmonary bypass performed with membrane and bubble oxygenators.

To elucidate the effects of bubble and membrane oxygenators on platelet integrity, we developed a quantitative method of determining platelet lysis during cardiopulmonary bypass. Two groups of dogs whose platelets had been labeled with indium 111 were subjected to 1 hour of cardiopulmonary bypass. In Group A (bubble oxygenator), platelet lysis as measured by free plasma 111In levels increased from 6% +/- 1% to 33% +/- 7% during bypass. In Group B (membrane oxygenator), plasma 111In levels increased from 5% +/- 2% to 10% +/- 6% during bypass (p less than 0.01). After 1 hour of bypass, the ratio of 111In-labeled platelets to prebypass levels was 36% +/- 8% in Group A and 67% +/- 9% in Group B. Platelet deposition on the oxygenator was greater in bubble oxygenators (19% +/- 4% of total injected 111In) than in membrane oxygenators (12% +/- 3% of total injected 111In). These data indicated that membrane oxygenators maintain a higher circulating platelet count both intraoperatively and postoperatively and result in less platelet destruction than bubble oxygenators following 1 hour of cardiopulmonary bypass in dogs.

Animals↗
PubMed1981

Reduction of thrombosis in canine coronary bypass vein grafts with dipyridamole and aspirin.

The potential benefit of platelet inhibitor drugs in reducing early thrombosis of coronary arterial vein bypass grafts was assessed in dogs. There were 26 control dogs and 24 dogs treated with dipyridamole, 55 mg/day plus aspirin, 325 mg/day. The dogs in both groups were killed at 2 hours and 1, 2, 3, 7 and 14 days after operation. The grafts were perfused with fixative in vivo, harvested and examined with light microscopy. Severe alterations of the graft wall were observed in the dogs in both groups. The grafts in the control group had a high incidence rate of thrombosis, which occurred early after the operation; those in the treated group had a significantly reduced incidence of thrombosis (p = 0.025). Our study indicates that a combined regimen of dipyridamole and aspirin is effective in reducing early graft thrombosis in dogs.

Animals↗
PubMed1981

Specific binding of nerve growth factor to normal and denervated canine heart.

Preparations of membranes from normal and surgically denervated canine heart were tested for binding of radiolabeled nerve growth factor. Specific binding was detected in both normal and denervated hearts. Binding was nonsaturable and complex for normal atria and ventricles and denervated atria but appeared to be saturable for denervated ventricles. Nerve growth factor bound per microgram of protein was lower in denervated ventricles than normal ventricles, whereas slightly higher binding to denervated atria than normal atria was observed. This binding could not be displaced by cytochrome c, insulin, or epidermal growth factor. The data indicate that a large part of binding to normal ventricles could be due to nerve terminals attached to the heart, but specific binding detected in the denervated ventricles may be an intrinsic property of the tissue itself. These sites may serve as storage or uptake sites to direct sympathetic innervation in the developing or reinnervating myocardium.

Animals↗
PubMed1980

Mechanical properties of the canine aorta following hypercholesterolemia.

The effect of hypercholesterolemia on the transverse wall properties of the upper descending thoracic aorta was studied in canines. Hypothyroid animals were fed a free diet supplemented with cholesterol, prophylthiouracil, and saturated fat (lard) for 11 mo. The mechanical properties of the wall showed marked changes following experimental pathology. The failure stress, failure elongation, and energy to failure decreased following hypercholesterolemia. The tensile response was bilinear in both the pathological and control tissues. In the initial region, which is controlled by elastic fibers, the response was left unchanged by the experimental pathology. In the secondary region, which is controlled by stretching of the collagen fibers, the intercept with the strain axis and the slope were decreased by the pathology. This indicates that there are changes in the strength-bearing collagen and its interaction with the amorphous matrix. However, no significant parallel histological changes were observed in the structure of collagen and elastic fibers. Although this phenomenon precedes the development of atherosclerotic plaques which are characteristic of a diagnosed human disease, the aortic wall is already "hardened" because of its reduced compliance resulting from the shift in the onset of secondary (collagen) response.

Animals↗
PubMed1980

Gore-Tex (polytetrafluoroethylene) in canine coronary artery bypass.

Because of the occasional need for a prosthesis in coronary artery operations, we investigated the potential use of microporous polytetrofluoroethylene (PTFE) with and without antiplatelet drugs as an aorta-coronary bypass graft in 43 dogs. In 13 animals without antiplatelet drugs, no grafts were patent at 1 month. When antiplatelet drugs were used (25 dogs), the 1 month patency rate increased to 64%. The addition of antibiotic treatment 1 month patency rate to 80%. The 6 month patency rate in dogs treated with antiplatelet drugs, preoperative bowel preparation, and systemic antibiotics was 60%. Our data indicate that microporous PTFE grafts used as coronary artery bypass grafts in dogs can be maintained patent for at least 6 months when the animals are treated with antiplatelet drugs.

Animals↗
PubMed1980

Noninvasive radioisotopic technique for detection of platelet deposition in mitral valve prosthesis and renal microembolism in dogs.

At 24 hrs after implantation of Björk-Shiley mitral prosthesis in 5 dogs, in vivo images were obtained with a gamma camera after intravenous administration (0.5-0.6 mCi) one hour postoperatively of autologous Indium-111-labeled platelets. The site of platelet deposition in the teflon ring and perivascular damaged cardiac tissue is clearly delineated in the scintiphoto. In vitro biodistribution (mean % +/- SD of injected dose) at 24 hrs after injection of the 5 implanted and 7 normal dogs performed with a gamma counter demonstrated that (45.1 +/- 10.6)% and (0.7 +/- 0.4)% were in blood and kidneys in normal dogs and (28.5 +/- 6.8)%, (1.6 +/- 0.6)%, (0.3 +/- 0.1)%, and (0.2 +/- 0.1)% were in blood, kidneys, teflon rings, and perivascular damaged cardiac tissue, respectively. The strut and pyrolytic carbon-coated disc retained only (0.0033 +/- 0.0004)% and (0.0031 +/- 0.0003)%, respectively. There was a 2.3-fold increase of labeled platelets in kidneys of implanted dogs due to renal trapping of microembolism. Also, three- to fivefold increase in ratios of lung, brain, cardiac, and skeletal muscle to blood indicates that internal organs and whole body work as filter for microembolism generated by cardiovascular surgery and mitral prosthesis. Twenty percent of the administered platelets are consumed in surgical repair of damaged tissue. Indium-111-labeled platelets thus provide a sensitive marker for noninvasive imaging of Björk-Shiley mitral prosthesis, thromboembolism after implantation of prosthetic device, and in vitro quantitation of surgical consumption.

Animals↗
PubMed1979

Reduction of intimal thickening in canine coronary bypass vein grafts with dipyridamole and aspirin.

The potential benefit of platelet inhibitor drugs on coronary arterial bypass vein grafts was assessed in dogs with magnification-corrected angiographic luminal measurements and quantitative histologic evaluation of the vein grafts. There were 11 control animals and 11 animals treated with dipyridamole, 55 mg/day, plus aspirin, 325 mg/day. Eighteen animals with patent grafts were studied when electively killed 2, 4 or 6 months after grafting. At 14 days, there was greater angiographic narrowing in the most distal 1 cm of vein grafts in control than in treated dogs (P less than 0.01). This same angiographic narrowing persisted in control dogs until they were killed (P less than 0.03). Computer-assisted measurements of the entire area of intimal thickening were done on vein graft cross sections taken 1 cm from the distal anastomosis. The circumference of the vein grafts at the intimal-media junction was measured from the same section and the potential maximal luminal area calculated. The calculated luminal narrowing due to intimal thickening was greater in control than in treated dogs (P less than 0.03). These data correlate well with the demonstrated angiographic narrowing. The findings indicate that the degree of early intimal thickening that persists 2 to 6 months postoperatively in canine coronary bypass vein grafts may be reduced by the platelet inhibitor combination of dipyridamole plus aspirin.

Animals↗
PubMed1979

Nerve growth factor-enhanced reinnervation of surgically denervated canine heart.

Nerve growth factor (NGF) was administered in doses of 25,000 U daily for the first 5 postoperative days to dogs subjected to cardiac denervation. These dogs and untreated cardiac-denervated dogs were killed at 1, 2, 3, and 6 mo postoperatively. Tritiated norepinephrine ([3H]NE) was administered prior to death, after which the hearts were removed and eight segments (right and left atria, right ventricular conus and sinus, left ventricular base and apex and high and low ventricular septum) analyzed to determine myocardial NE content and uptake of [3H]NE. Our data demonstrated enhanced cardiac reinnervation of the left ventricular base in NGF-treated dogs.

Animals↗
PubMed1979

The unbalanced heart. Animal models of cardiac dysrhythmias.

The heart often appears to function independently because it can maintain regular activity even when isolated from the rest of the body. Likewise, it maintains its regularity in the midst of powerful but balanced neural and pressure influences. Experimental situations designed to unbalance these forces produce rhythm disturbances resembling those encountered clinically. Unbalancing of the sympathetic supply with the parasympathetic supply totally obliterated, leads to tachycardias of various origin which are eliminated by adrenergic blockade. Removing the sinoatrial node results in atrial brady-tachyarrhythmia, eliminated by cholinergic blockade. Unbalancing the pressure load results in premature ventricular contractions that are clearly not mediated by external neural controls. Cardiac rhythm disturbances thus result from a variety of forces that may be readily tolerated when balanced by opposing forces but cannot be controlled without that buffer.

Animals↗
PubMed1979

Noninvasive radioisotopic technique for detection of platelet deposition in coronary artery bypass grafts in dogs and its reduction with platelet inhibitors.

At 8 and 32 hours after saphenous vein bypass graft surgery in six dogs, in vivo images of the graft were obtained with a gamma camera after intravenous injection, 2 hours postoperatively of autologous platelets labeled with indium-111. Platelet deposition in the grafts could be imaged in vivo from the scintiphotos. In vitro images of the excised heart showed saphenous vein graft uptake confirming the in vivo image. In vitro determination of radioactivity in the graft averaged 17 +/- 14 times greater than in blood and 33 +/- 26 times greater than in the lung. Under identical conditions, in eight dogs treated with dipyridamole (55 mg/day) plus aspirin (325 mg/day), the grafts appeared to have considerably less platelet deposition as estimated by imaging. In vitro determination of radioactivity in the graft averaged 5 +/- 2 times greater than in blood and 8 +/- 4 times greater than in the lung (p less than 0.01). This noninvasive technique may be a promising tool for a better understanding of the role played by platelets in the process of occlusion of saphenous vein bypass grafts in man and its prevention with platelet inhibotors.

Animals↗
PubMed1979

Measurement of postoperative cardiac output by thermodilution in pediatric and adult patients.

Serial cardiac output determinations were made by the thermodilution technique in 51 patients by means of a No. 2 Fr. thermistor catheter placed directly into the pulmonary artery at cardiac operation. Correlations were determined prospectively between thermodilution measurements of cardiac output and other commonly used indirect clinical parameters. Serial indicator dye-dilution curves were performed in 24 of these patients and compared with simultaneous thermodilution measurements. A high correlation (r = 0.97) was noted between dye curve measurements of cardiac output and thermal measurements. Statistically significant correlations were also seen between cardiac output and both the quality of the peripheral pulses and the duration of cardiopulmonary bypass, but no significant correlations were found between the measured cardiac outputs and other variables. This study confirms the necessity for direct measurement of cardiac output for its accurate assessment.

Adolescent↗