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Biomedical subjects

M P Kaye

Publications and source records attributed to M P Kaye.

At least 55 records · Page 3Linked to original sources
PubMed1984

Ibuprofen in experimental vascular surgery.

Animal studies have been conducted to determine the effectiveness of ibuprofen in reducing early platelet deposition on small diameter (4 mm) Gore-Tex (polytetrafluoroethylene) arterial grafts and larger (10 mm) Gore-Tex grafts placed in the inferior vena cava. These studies demonstrated a significant reduction in platelet deposition at one and three hours. Additional studies of animals undergoing treatment with ibuprofen and subjected to arterial replacement with 1 or 4 mm Gore-Tex grafts demonstrated enhanced patency at 30 days. Cautious evaluation of ibuprofen as an adjunct in vascular surgery appears warranted.

Animals↗
PubMed1984

Morphologic quantitation of pseudointima and effects of antiplatelet drugs on vascular prostheses in goats.

The natural process of endothelialization, pseudointimal formation, and connective tissue incorporation of the expanded PTFE grafts in the goat was documented through histologic examination of specimens harvested at 2, 4, 6, and 8 weeks. The goats demonstrated a progressive increase in pseudointimal pannus ingrowth from the anastomoses at a rate of 11.3 mm over a 12 week period. Histologic changes according to time of vascular graft incorporation in the goat model were found to be comparable to those of the dog, pig, and calf models reported in the literature. Platelet-inhibiting drugs, aspirin, dipyridamole, nifedipine, and ibuprofen were administered to goats after replacement of their infrarenal aorta with 5 cm of 8 mm diameter expanded PTFE grafts. The effects of the drugs on graft endothelialization and anastomotic pseudointimal formation was compared with those in the untreated control group after 12 weeks. Aspirin and dipyridamole had no detrimental effect on the healing process compared with the untreated control group. Studies with nifedipine and ibuprofen did not demonstrate a decrease in pseudointimal hyperplasia. Antiplatelet treatment resulted in no significant change in the rate of endothelialization of expanded PTFE grafts.

Animals↗
PubMed1984

Platelet deposition on and calcification of bovine pericardial valve.

Platelet deposition on bovine pericardial mitral valves was quantified in healthy adult mongrel dogs at 1, 14 and 30 days post-implantation and 24 h after i.v. injection of 400-500 microCi of autologous 111In-platelets. In vitro quantitation of platelet deposition on components of the prosthesis indicated maximal activity at one day with a successive decrease in activity at 14 and 30 days. At one day, platelet-associated radioactivity on the sewing ring was 3-4 times as great as on the leaflets, but at 14 and 30 days this had dropped to approximately half of the value on the leaflets. Calves underwent mitral valve replacement with a bovine pericardial valve. Thirty days post-operatively, 111Indium labeled labeled platelets were administered i.v.; 24 h later, calves were sacrificed and sections of each valve leaflet were analyzed for platelet and calcium deposition. Platelet deposition per mm2 of surface was greatest at the free edge of the leaflet, followed by the central zone and flexion point. Calves treated with sodium hydroxyethylene diphosphonate (5 mg kg-1 day-1 s.c.) had reduced platelet deposition but no reduced calcium content on the valves after 30 days compared with untreated calves. In flow chamber studies, platelet deposition from the heparinized blood of normal calves was significantly less on the smooth (inner) than on the rough (outer) surface of fixed bovine pericardium.

Animals↗
PubMed1984

A new technique for producing pure aortic stenosis in animals.

To date, techniques used to produce an animal model of valvular aortic stenosis have been unsuccessful. We have developed a new technique for producing pure subcoronary aortic valvular stenosis, which results in left ventricular hypertrophy in a short time. Five adult mongrel dogs weighing 18-24 kg were anesthetized with Brevital (0.5 mg/kg), intubated, and mechanically ventilated with halothane-oxygen. The chest was opened through the right 4th intercostal space, and cardiopulmonary bypass was established between the right atrium and femoral artery. When the esophageal temperature was reduced to about 25 degrees C, the aorta was cross clamped and incised. A piece of Teflon felt covered by pericardium was sutured into each of the sinuses of Valsalva below the coronary orifices. Two to four weeks after the operation, the animals were catheterized. The average pressure gradient between left ventricle (LV) and aorta was 52 +/- 15 mmHg. Mean LV mass-to-body weight ratio was 6.16 +/- 0.28 g/kg vs. 4.24 +/- 0.27 for controls. End-diastolic volume and ejection fraction remained normal, and no aortic regurgitation was seen on aortic root angiography. This preparation creates a hemodynamic representation of valvular aortic stenosis and produces a useful model for examining the myocardial response to this disease. Although hypertrophy develops rapidly, slowly developing hypertrophy may also be possible with this technique.

Animals↗
PubMed1984

Quantification of platelet retention in aortocoronary femoral vein bypass graft in dogs treated with dipyridamole and aspirin.

Autologous femoral vein segments were implanted as aortocoronary bypass grafts in 50 dogs, 25 of which were treated with dipyridamole and aspirin to inhibit platelet deposition and 25 that were not. Autologous platelets labeled with indium-111 were injected into some dogs 48 hr before they were killed on the first day after surgery; other dogs were injected 24 hr before they were killed (3, 7, 30, and 90 days after surgery). Radioactivity on the grafts and on control specimens of contralateral femoral veins was converted to quantification of platelets adhering to the vessel wall (platelets/cm2). The treated group had fewer graft platelets per square centimeter than the untreated group on postoperative days 3, 7 (p less than .01), and 30 (p less than .05). Graft and control vein platelets per square centimeter were nearly equal by day 90. Comparison of graft and control specimens by scanning electron microscopy nearly equal by day 90. Comparison of graft and control specimens by scanning electron microscopy revealed deendothelialization at 1 and 7 days after grafting and reendothelialization at 30 and 90 days. The data suggest that indefinite prolongation of therapy to inhibit platelet deposition after bypass grafting may be unnecessary (although other atherosclerotic vessels may benefit from therapy).

Animals↗
PubMed1984

Endothelial seeding of venous prostheses.

To evaluate the potential benefit of endothelial seeding of venous prostheses, 20 dogs were subjected to iliocaval reconstruction with expanded polytetrafluoroethylene grafts protected by an arteriovenous fistula. Grafts seeded with enzymatically derived endothelial cells were compared with control grafts that were sham seeded with culture medium and blood. Five seeded and seven sham-seeded grafts remained patient and were perfusion fixed in situ 4 to 6 weeks after operation. Specimens were examined by light, scanning, and transmission electron microscopy. No statistical difference in early patency was noted. The mean thrombus-free surface area was 80% in the seeded and 71% in the sham-seeded group. Light microscopy of these areas revealed a monocellular layer lining the lumen in all grafts. Scanning electron microscopy demonstrated a thin cellular lining covering 50% to 100% of the specimens' surface area in four of the five seeded and five of seven sham-seeded grafts. Transmission electron microscopy revealed these cells to exhibit characteristics typical of endothelial cells. The subcellular layer was equally thin in both groups. Early patency rates were not benefited by endothelial seeding of grafts placed in the venous system. Seeding of grafts with enzymatically derived endothelial cells provides a good endothelial cover with a thin subendothelial layer but not to a greater extent than does sham seeding of the venous prostheses.

Animals↗
PubMed1984

The effect of preclotting on surface thrombogenicity and thromboembolic complications of Dacron grafts in the canine thoracic aorta.

Previous reports have advocated preclotting and autoclaving of Dacron grafts to prevent graft hemorrhage, yet no data delineate possible changes in surface thrombogenicity or thromboembolic risks. To assess these factors, preclotted and preclotted-autoclaved woven Dacron prostheses were implanted in the thoracic aorta of 31 dogs. Grafts were harvested 1 week to 1 month following implantation, and the thrombus-free surface of each graft was calculated by computerized morphometry. Values for thrombus-free surface were lowest in autoclaved grafts preclotted in nonheparinized blood (72%) or in heparinized blood (78%). Grafts preclotted in platelet-rich plasma and autoclaved had a thrombus-free surface value of 85%. Regular preclotted grafts or grafts without preclotting had the greatest thrombus-free surface value (97% and 99%). Distal embolization to the kidneys was detected in seven of 31 animals (23%). No emboli were found in animals with grafts that were not preclotted or if grafts were preclotted with platelet-rich plasma and autoclaved. Thrombus-free surface values were lower (p less than 0.01) in grafts with embolic complications (71% versus 91%). These data suggest that, if the risk of severe bleeding in fully heparinized patients precludes the use of a woven Dacron graft without preclotting, autoclaving a graft preclotted with platelet-rich plasma appears to be the method of choice.

Animals↗
PubMed1984

Overcoming failure of venous vascular prostheses.

Thrombogenicity of graft material, low velocity of blood flow, and wall collapsibility have been cited as the main factors responsible for the high occlusion rate of vascular prostheses placed in the venous system. This study was performed to analyze the effects of measures taken to overcome each of these factors. The thrombogenicity of expanded polytetrafluoroethylene (ePTFE) was evaluated by determination of the 3-hour deposition of radionuclide-labeled platelets and fibrin on grafts placed in the infrarenal vena cava of 18 dogs. Wetting the prosthesis with heparin before implantation significantly decreased platelet deposition at the cranial anastomosis (p less than 0.025) and on the graft surface (p less than 0.01), whereas the decrease of fibrin deposition was not statistically significant. The effects of flow velocity and graft support were studied in 44 dogs subjected to iliocaval bypass. The results of these studies demonstrated that a flow-increasing arteriovenous fistula was necessary to maintain patency of ePTFE grafts (p less than 0.01) but did not enhance patency of autogenous vein grafts. External ring support of ePTFE grafts did not significantly improve early patency. Decreasing thrombogenicity by wetting the grafts with heparin and increasing the blood flow by constructing an arteriovenous fistula helps in overcoming failure of venous vascular prostheses.

Animals↗
PubMed1984

Quantitative evaluation of ibuprofen treatment on thrombogenicity of expanded polytetrafluoroethylene vascular grafts.

To evaluate the effect of ibuprofen on graft thrombogenicity and early patency, expanded polytetrafluoroethylene (ePTFE) (Gore-tex) grafts with an inside diameter of 4 mm and length of 5 cm were implanted into the femoral artery in 43 dogs. Autogenous vein bypass was performed on the contralateral side. 111In-labeled platelets were injected into 16 dogs 24 hours prior to operation, and eight of these received 12.5 mg ibuprofen/kg intravenously 15 minutes prior to cross-clamping. The grafts were removed after 3 hours and radioactivity in five segments of the grafts, including both anastomoses, was determined with a gamma-well counter. Of 27 additional dogs, 13 received oral ibuprofen (150 mg three times daily till the time of sacrifice) and 14 served as controls. The grafts were harvested at 5 days and at 30 days and patency was evaluated. At 30 days, thrombus thickness and extent of intimal hyperplasia on the specimens were measured by light microscopy. At 3 hours, radioactivity per unit of weight (counts per minute per gram) of ePTFE graft to vein graft decreased from 8.46 to 1.34 (P less than 0.001) with ibuprofen treatment. The median radioactivity ratio of ePTFE to blood decreased from 11.62 to 0.89 (P less than 0.01). Platelet deposition was reduced in all segments of treated grafts. The median platelet count was 9.43 X 10(6)/mm2 in control and 0.27 X 10(6)/mm2 in treated grafts (P less than 0.01). The patency of vein grafts did not change significantly, whereas the patency of the ePTFE grafts significantly improved in the treated group at 5 days (P = 0.01) and at 30 days (P less than 0.01). These data demonstrate that ibuprofen effectively reduces early platelet deposition and improves patency of ePTFE grafts.

Animals↗
PubMed1984

Experimental replacement of the inferior vena cava: factors affecting patency.

To evaluate factors influencing graft patency in the venous system, we replaced the inferior vena cava (IVC) in 50 dogs. Expanded polytetrafluoroethylene ( ePTFE ) grafts with external support were implanted into 32 animals while autogenous, spiral jugular vein grafts were used to replace the IVC in 18 dogs. 111In-labeled autologous platelets and 125I-labeled canine fibrinogen were utilized to evaluate early thrombus formation. A distal arteriovenous (AV) fistula significantly (P less than 0.05) decreased both platelet and fibrin deposition on ePTFE grafts 3 hours following implantation. Patency rate of 12 ePTFE grafts with a temporary AV fistula was higher (75%) than that of grafts without fistula (25%) at 3 months (P less than 0.05). Spiral vein grafts with fistula showed 91% patency at 3 months; without fistula patency was only 67%. Venograms confirmed patency in five grafts followed up to 6 months. Antiplatelet therapy resulted in 100% patency in ePTFE and vein grafts during its administration, and vein grafts maintained patency after discontinuation of antiplatelet treatment. Spiral vein grafts showed no decrease in cross-sectional area at 3 months, while the cross-sectional area of ePTFE grafts decreased significantly (59%). Distal AV fistula decreases platelet and fibrin deposition leading to early occlusion in ePTFE grafts and produces excellent patency in spiral vein grafts. Antiplatelet therapy appears to further improve patency.

Animals↗
PubMed1983

Quantitative effects of antiplatelet therapy on healing of the endarterectomized canine aorta.

This study was designed to quantitatively evaluate the effects of an antiplatelet agent, ibuprofen, on mural thrombus formation and pseudointimal development in the endarterectomized canine aorta. A 3 cm segment of abdominal aorta was endarterectomized in 18 dogs. Nine dogs served as controls and nine dogs were treated with ibuprofen (12.5 mg/kg) given intravenously 1 hour preoperatively and orally (7.5 mg/kg) three times a day in the postoperative period. Three dogs were killed from each group at 7, 14, and 21 days. Healing of the endarterectomized aortic segment was assessed by means of computer-assisted surface morphometry, light microscopy, and both scanning and transmission electron microscopy. One week postoperatively, the thrombus-free surface in the treated dogs was 75 percent, compared with 20 percent in control animals; at 2 weeks 97 percent, compared with 38 percent and at 3 weeks 98 percent, compared with 38 percent (p less than 0.01 for each group). The thickness of the pseudointima was 9 percent of the aortic wall thickness in treated dogs compared with 60 percent in control animals 1 week postoperatively (p less than 0.001); at 2 weeks 24 percent in treated animals and 64 percent in control animals (p less than 0.001); and at 3 weeks 31 percent in treated animals and 55 percent in control animals (p less than 0.05). Partial reendothelialization was observed 1 week postoperatively and complete reendothelialization at 3 weeks in both the control and treated animals. These data suggest that administration of preoperative and maintenance therapy with ibuprofen significantly reduces mural thrombus formation and pseudointimal thickness in the endarterectomized canine aorta.

Animals↗
PubMed1983

Comparison of the antithrombotic action of calcium antagonist drugs with dipyridamole in dogs.

Because platelet activation is associated with fluxes of intracellular calcium, calcium antagonist drugs such as verapamil and nifedipine may have useful platelet inhibitor effects. Accordingly, the effect of these drugs was compared with that of dipyridamole, an established platelet inhibitor, in preventing the deposition of indium-111-labeled autologous platelets and thrombus development in polytetrafluoroethylene (Gore-Tex) grafts interposed in both femoral arteries in mongrel dogs. Eight dogs received verapamil 7.5 micrograms/kg/min perioperatively, 8 dogs received nifedipine 4 micrograms/kg/h perioperatively, 8 dogs received dipyridamole 50 mg orally given twice during the 24 hours before operation, and 16 control dogs received isotonic saline solution perioperatively. After 3 hours of perfusion, the median weight of the grafts and luminal thrombus was less in dogs treated with dipyridamole (465.1 mg), verapamil (453.7 mg), or nifedipine (389.7 mg) than in control dogs (680.2 mg) (p less than 0.001). In addition, the estimated total platelet deposition along the graft was reduced in dogs treated with dipyridamole was reduced in dogs treated with dipyridamole (2,073.2 X 10(6)) (p less than 0.01), verapamil (1,898.9 X 10(6)) (p less than 0.001), and nifedipine (1,474.8 X 10(6)) (p less than 0.001) as compared with controls (3,056.2 X 10(6)). When the mural thrombus was removed from 14 grafts, a median 73% of the platelets were located in the interface between thrombus and graft. We conclude that all 3 drugs prevent thrombus formation by inhibiting platelet activity in this model, and that the calcium antagonist drugs are as effective as dipyridamole.

Animals↗
PubMed1983

Inferior vena cava replacement: the role of antiplatelet therapy.

To evaluate the effect of ibuprofen on early thrombus formation following inferior vena cava (IVC) replacement, a 4-cm segment of IVC was replaced with a 5-cm (10-mm-i.d.) segment of reinforced polytetrafluoroethylene (PTFE) graft in 12 dogs. Autologous platelets and canine fibrinogen were labeled with 111In and 125I, respectively, and injected into each animal 24 hr prior to vena cava replacement. Six dogs served as controls and six were treated with 12.5 mg/kg ibuprofen intravenously 1 hr preoperatively. All dogs were heparinized with 100 U/kg intravenous heparin prior to crossclamping the IVC: heparin was not reversed at the end of the procedure. Three hours after normal circulation was restored, the grafts were removed and counts of radioactivity made. All grafts were patent. The mean platelet count for the control group was 12.8 X 10(6)/mm2, while in the grafts from the treated group it was 0.960 X 10(6)/mm2. The decreased platelet deposition was significant in all graft segments (P less than 0.01). Fibrin deposition was reduced from 3.38 micrograms/mm2 to 0.25 micrograms/mm2 (P less than 0.01) by ibuprofen. Although fibrin and red blood cells are the major constituents of venous thrombi, platelet aggregation appears to play an important role if prosthetic material is implanted into the venous system. Ibuprofen not only reduced platelet deposition by 13.5-fold, but also reduced fibrin deposition by 13.5-fold. The ratio of platelets to fibrin in control and treated animals was similar (3.84 and 3.79, respectively). These data suggest that antiplatelet medication combined with heparin therapy might decrease early thrombus formation in venous prostheses.

Animals↗
PubMed1983

Simplified method of heterotopic cardiac transplantation for left ventricular assist.

A method of heterotopic cardiac transplantation has been developed which is performed through a left thoracotomy and requires only two vascular anastomoses. Systemic heparinization and cardiopulmonary bypass are not necessary. Preliminary experiments demonstrated that this heterotopic transplant technique was effective for left ventricular assist; in some experiments, a multimode atrioventricular programmable pacemaker was used to provide sequential pacing for "counterpulsation." This technique or similar techniques may have potential clinical benefit for patients with intractable left ventricular failure.

Animals↗
PubMed1983

Light and electron microscopic evaluation of canine hearts orthotopically transplanted after 24 hours of extracorporeal preservation.

The hearts of 19 dogs were subjected to in vitro, moderately hypothermic, whole blood perfusion through the aorta for 24 hours. Sixteen of the hearts were reimplanted into recipient animals in the conventional orthotopic fashion and three were subjected to histologic study without reimplantation. Fourteen of the 16 reimplanted hearts successfully supported the recipients. Histologic and ultrastructural studies of the reimplanted hearts 24 hours and 7 days after implantation demonstrated good preservation of cellular and ultracellular structures. Some mild widening of the interstitium was noted.

Animals↗
PubMed1983

Noninvasive radioisotopic technique for detection of platelet deposition on bovine pericardial mitral-valve prosthesis and in vitro quantification of visceral microembolism in dogs.

Platelet deposition on bovine pericardial-tissue mitral-valve prostheses in dogs was observed noninvasively by use of 111In-labeled platelets and quantified after sacrifice at one, 14 and 30 days postimplantation (300-400 microCi of labeled platelets having been injected 24 hrs 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 sewing ring and perivalvular tissue retained 0.75% of labeled platelets at one day postimplantation, 0.084% at 14 days, and 0.0042% at 30 days. Platelet survival was reduced to 38 hrs at 21 days postimplantation but returned toward the normal (50 hrs) with endothelial covering of the sewing ring. Microemboli in lung and kidney, as measured by tissue/blood radioactivity ratio, 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.

Animals↗
PubMed1983

Noninvasive radioisotopic technique for detection of platelet deposition in mitral valve prostheses and quantitation of visceral microembolism in dogs.

A noninvasive technique has been developed in the dog model for imaging, with a gamma camera, the platelet deposition on Björk-Shiley mitral valve prostheses early postoperatively. At 25 hours after implantation of the prosthesis and 24 hours after intravenous administration of 400 to 500 microCi of platelets labeled with indium-111, the platelet deposition in the sewing ring and perivalvular cardiac tissue can be clearly delineated in a scintiphotograph. An in vitro technique was also developed for quantitation of visceral microemboli in brain, lungs, kidneys, and other tissues. Biodistribution of the labeled platelets was quantitated, and the tissue/blood radioactivity ratio was determined in 22 dogs in four groups: unoperated normal dogs, sham-operated dogs, prosthesis-implanted dogs, and prosthesis-implanted dogs treated with dipyridamole before and aspirin and dipyridamole immediately after operation. Fifteen to 20% of total platelets were consumed as a consequence of the surgical procedure. On quantitation, we found that platelet deposition on the components of the prostheses was significantly reduced in prosthesis-implanted animals treated with dipyridamole and aspirin when compared with prosthesis-implanted, untreated dogs. All prosthesis-implanted animals considered together had a twofold to fourfold increase in tissue/blood radioactivity ratio in comparison with unoperated and sham-operated animals, an indication that the viscera work as filters and trap platelet microemboli that are presumably produced in the region of the mitral valve prostheses. In the dog model, indium-111-labeled platelets thus provide a sensitive marker for noninvasive imaging of platelet deposition on mechanical mitral valve prostheses, in vitro evaluation of platelet microembolism in viscera, in vitro quantitation of surgical consumption of platelets, and evaluation of platelet-inhibitor drugs.

Animals↗