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Biomedical subjects

M K Dewanjee

Publications and source records attributed to M K Dewanjee.

At least 55 records · Page 3Linked to original sources
PubMed1985

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↗
PubMed1985

Drug effects on platelet deposition after endothelial injury of the rabbit aorta.

Factors released from platelets deposited on injured endothelium have lately been increasingly implicated in the pathogenesis of atherosclerosis and neointimal hyperplasia. Inhibition of platelet activity has therefore been postulated to protect injured vessels from progressive degenerative disease. The objective of this study was to evaluate the effectiveness of platelet inhibiting drugs in decreasing the deposition of platelets after a standardized endothelial injury of the rabbit aorta. The aortic endothelium of 53 rabbits was denuded with a balloon catheter. Morphological changes were studied with light and electron microscopy in five rabbits. The influence of ibuprofen, acetylsalicylic acid, dipyridamole, verapamil, and prostacyclin upon the deposition of indium-111-labeled autogenous platelets 1 hr after injury was evaluated in 48 animals. The morphological studies demonstrated that platelets were deposited on the denuded aorta but no major platelet aggregation or thrombus formation occurred. The radionuclide studies showed that none of the drugs tested had any significant influence on the deposition of platelets. It is concluded that platelets immediately adhere to injured vessels but that the secondary platelet aggregation is minimal if the injury is limited to the endothelium. Conventional drugs mainly affecting platelet aggregation are ineffective in these circumstances.

Animals↗
PubMed1985

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↗
PubMed1985

Balloon angioplasty. Natural history of the pathophysiological response to injury in a pig model.

The restenosis or occlusion that frequently follows balloon angioplasty is poorly understood. Thus, the pathophysiological response to angioplasty of the common carotid artery in 38 heparinized normal pigs was investigated by quantification of the 111In-labeled platelet deposition and histological and electron microscopic examination from 1 hour to 60 days after angioplasty. At 1 hour, the following findings were noted: complete endothelial denudation in all arteries, marked platelet deposition (44.7 +/- 20.7 X 10(6)/cm2), mural thrombus in seven of 10 pigs, and a medial tear extending through the internal elastic lamina in nine of 18 arteries. All nine arteries with tears had associated mural thrombus and severe platelet deposition (76 X 10(6)/cm2); in contrast, the nine arteries without a tear had no mural thrombus and much lower platelet deposition (6 X 10(6)/cm2). Necrosis of medial smooth muscle cells was evident at 24 hours. Platelet deposition remained high at 24 hours (40.5 +/- 20.6 X 10(6)/cm2), but was markedly reduced at 4 days (4.4 +/- 1.5 X 10(6)/cm2), coincident with partial regrowth of endothelium or periluminal lining cells. No significant platelet deposition was noted at 7 days, when the endothelial cell type of regrowth was largely complete. Intimal proliferation of smooth muscle cells was mild and patchy at 7 days, significantly greater and more uniform at 14 days, and unchanged at 30 and 60 days after angioplasty. Complete thrombotic occlusion occurred in four (11%) of the 38 pigs. A significant stenosis present at 30 days after angioplasty was shown by histological examination to be due to organization of mural thrombus.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗
PubMed1985

Comparison of indium-labeled-leukocyte imaging with sequential technetium-gallium scanning in the diagnosis of low-grade musculoskeletal sepsis. A prospective study.

We prospectively compared sequential technetium-gallium imaging with indium-labeled-leukocyte imaging in fifty patients with suspected low-grade musculoskeletal sepsis. Adequate images and follow-up examinations were obtained for forty-two patients. The presence or absence of low-grade sepsis was confirmed by histological and bacteriological examinations of tissue specimens taken at surgery in thirty of the forty-two patients. In these thirty patients, the sensitivity of sequential Tc-Ga imaging was 48 per cent, the specificity was 86 per cent, and the accuracy was 57 per cent, whereas the sensitivity of the indium-labeled-leukocyte technique was 83 per cent, the specificity was 86 per cent, and the accuracy was 83 per cent. When the additional twelve patients for whom surgery was deemed unnecessary were considered, the sensitivity of sequential Tc-Ga imaging was 50 per cent, the specificity was 78 per cent, and the accuracy was 62 per cent, as compared with a sensitivity of 83 per cent, a specificity of 94 per cent, and an accuracy of 88 per cent with the indium-labeled-leukocyte method. In patients with a prosthesis the indium-labeled-leukocyte image was 94 per cent accurate, compared with 75 per cent accuracy for sequential Tc-Ga imaging. Statistical analysis of these data demonstrated that the indium-labeled-leukocyte technique was superior to sequential Tc-Ga imaging in detecting areas of low-grade musculoskeletal sepsis.

Adolescent↗
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

Cardiac and vascular imaging with labeled platelets and leukocytes.

The contribution of platelets in atherosclerosis and thrombosis in animal models and in clinical studies has been quantified with 111In-platelet scintigraphy. New in vitro quantitative techniques have been developed using 111In-labeled platelets to determine the number of adherent platelets on deendothelialized surfaces of damaged vessel walls and synthetic vascular grafts. In vivo imaging techniques are semi-quantitative in nature; in these studies 111In radioactivity on thrombotic vessels or graft surfaces of iliac, femoral, or popliteal arteries is compared with contralateral vessels. Background 111In radioactivity in the circulating blood pool of venous and capillary networks and radioactivity in marrow decreases the sensitivity of these techniques. Despite these limitations, the dynamic process of platelet deposition in most of the denuded, atherosclerotic vessels and prostheses in the circulatory system can be recorded. This ongoing thrombosis and embolization has been observed in 5-10-year-old vascular grafts of Teflon and Dacron biomaterials. Currently used platelet function inhibitor drugs, eg, aspirin, Persantine, sulfinpyrazone, and Motrin, have a demonstrable effect on platelet deposition. Slight changes in reduction of platelet deposition on these surfaces due to medical intervention have been observed by noninvasive imaging with 111In-platelets. Subtraction of blood pool radioactivity with 99mTc-labeled autologous red cells and calculation of 111In radioactivity associated with platelet thrombus on vessel walls also have been performed for coronary, carotid, and femoral arteries. Although platelet concentrates are used frequently after open heart surgery (one to six per patient), consumption of platelets in the artificial lung or oxygenator, lysis of platelets during pumping, and suction of blood only recently have been quantified with the use of 111In-labeled platelets. These studies also demonstrated far less trauma to platelets with the use of a membrane rather than a bubble oxygenator. Further reduction in platelet consumption and trauma was observed with the use of prostacyclin, a short-acting drug with significant beneficial effect on platelet thrombus reduction and disaggregation of aggregated platelets. The role of polymorphonuclear leukocytes in inflammation, infection and myocardial infarction, and in vivo evaluation with 111In-leukocyte scintigraphy in animals and humans has been described.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
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

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

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

New "ex vivo" radioisotopic method of quantitation of platelet deposition - studies in four animal species.

We have developed a sensitive and quantitative method of "ex vivo" evaluation of platelet deposition on collagen strips, from rabbit Achilles tendon, superfused by flowing blood and applied it to four animal species, cat, rabbit, dog and pig. Autologous platelets were labeled with indium-111-tropolone, injected to the animal 24 hr before the superfusion and the number of deposited platelets was quantitated from the tendon gamma-radiation and the blood platelet count. We detected some platelet consumption with superfusion time when blood was reinfused entering the contralateral jugular vein after collagen contact but not if blood was discarded after the contact. Therefore, in order to have a more physiological animal model we decided to discard blood after superfusion of the tendon. In all species except for the cat there was a linear relationship between increase of platelet on the tendon and time of exposure to blood superfusion. The highest number of platelets deposited on the collagen was found in cats, the lowest in dogs. Ultrastructural analysis showed the platelets were deposited as aggregates after only 5 min of superfusion.

Animals↗
PubMed1983

Filter bleeding time: a new in vitro test of hemostasis. I. Evaluation in normal and thrombocytopenic subjects.

Disadvantages of current bleeding time methods include poor reproducibility, limited repeatability, and at times scar formation. We report a new, in vitro technique which circumvents these problems. Venous blood is collected in sodium citrate, stored capped in a siliconized tube at 37 degrees C until use, and made to flow under constant pressure through a filter of Woven Dacron. Flow rate progressively falls as platelet aggregates occlude the filter, as verified by scanning electron microscopy and 111Indium-labeled platelet radioactivity of the filter. Filter bleeding time (FBT) was 4.33 +/- 1.79 (means x +/- SD) min in 23 healthy human volunteers and 3.08 +/- 1.08 min in 14 normal dogs. Bleeding volume (BV) (number of drops) was 29 +/- 12 in the humans and 16 +/- 6 in the dogs. Initial bleeding rate (IBR) (number of drops during first minute) was 14 +/- 3 in citrated blood and 25 +/- 5 drops/min in EDTA blood of the humans (P = 9 X 10(-10)), 8 +/- 2 in citrated blood and 14 +/- 6 drops/min in EDTA blood of the dogs (P = .0004). Percent platelet reduction during passage of blood through the filter (PCR) was 27.5 +/- 7.2 in citrated blood and 4.9 +/- 2.6 in EDTA blood of the humans (P = 2 X 10(-12)), while in dogs it was 25.7 +/- 8.3 in citrated blood and 5.3 +/- 4.2 in EDTA blood (P = 8 X 10(-7)). The results of these parameters using human platelet rich plasmas (PRPs) were similar to those with human whole blood, but significant decrease of drop rate was not observed in canine PRPs during passage of PRP through the filter. FBT, BV, and IBR were correlated (r = -0.91, -0.84 and -0.62 respectively) with platelet count in 12 specimens obtained from 4 dogs in which thrombocytopenia (107 to 4 X 10(3) platelets/microliter) was induced by estradiol. This new test is unaffected by specimen transport by pneumatic tube, is sensitive to platelets, and should be useful for analysis of both quantitative and qualitative platelet abnormalities in man.

Animals↗
PubMed1983

In vivo quantitation of platelet deposition on human peripheral arterial bypass grafts using indium-111-labeled platelets. Effect of dipyridamole and aspirin.

Indium-111-labeled autologous platelets, injected 48 hours after operation, were used to evaluate the thrombogenicity of prosthetic material and the effect of platelet inhibitor therapy in vivo. Dacron double-velour (Microvel) aortofemoral artery bifurcation grafts were placed in 16 patients and unilateral polytetrafluoroethylene femoropopliteal grafts were placed in 10 patients. Half the patients in each group received platelet inhibitors before operation (dipyridamole, 100 mg 4 times a day) and after operation (dipyridamole, 75 mg, and acetylsalicylic acid, 325 mg 3 times a day); the rest of the patients served as control subjects. Five-minute scintigrams of the graft region were taken with a gamma camera interfaced with a computer 48, 72, and 96 hours after injection of the labeled platelets. Platelet deposition was estimated from the radioactivities of the grafts and expressed as counts per 100 pixels per microcurie injected. Dipyridamole and aspirin therapy significantly reduced the number of platelets deposited on Dacron grafts and prevented platelet accumulation over 3 days. With the small amount of platelet deposition on polytetrafluoroethylene femoropopliteal artery grafts even in control patients, platelet inhibitor therapy had no demonstrable effect on platelet deposition on these grafts. It is concluded that (1) platelet deposition on vascular grafts in vivo can be quantitated by noninvasive methods, and (2) dipyridamole and aspirin therapy reduced platelet deposition on Dacron aortofemoral artery grafts.

Adult↗