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Biomedical subjects

M K Dewanjee

Publications and source records attributed to M K Dewanjee.

At least 73 records · Page 4Linked to original sources
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

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↗
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

A sensitive new method of "ex vivo" platelet deposition.

In 1978, an "in vivo" quantitative method of platelet aggregation based on the increment of weight of a rabbit tendon when superfused with flowing blood (3 ml/min) derived from a carotid artery of a cat and reentering the contralateral jugular vein was reported. TO increase the sensitivity of the method, we labeled platelets with indium-111 and reinjected them after two hours; then, with a gamma counter, we quantitated the 111In-labeled platelets deposited on the superfused rabbit tendon. Results of the radioactivity method and of the weight method were compared. We found that the 111In-labeling of platelets was more precise and reproducible method, rendering possible the use of a small amount of blood without need for reentry into the venous system.

Animals↗
PubMed1982

Comparative evaluation of red cell-labeling parameters of three lipid-soluble- 111In-chelates: effect of lipid solubility on membrane incorporation and stability constant on transchelation.

A rabbit red cell model was used to determine the cell labeling properties of three lipid-soluble 111In-complexes: 111In-oxine, 111In-acetylacetone, and 111In-tropolone. Partition coefficients (olive oil/buffer) were measured to determine the lipid solubility and were 3.54, 7.93, and 18.18 for 111In-oxine, 111In-acetylacetone, and 111In-tropolone respectively. The effect of the concentration of these three chelating agents on labeling efficiencies was studied. The factors influencing the labeling efficiencies of these complexes such as cell density, time of incubation, influence of temperature, pH, effect of plasma proteins, and citrate ion concentration in the cell-labeling medium were studied. Labeling yields as high as 95.15 +/- 4.15% were achieved with 111In-tropolone after a 10-min incubation at 37 degrees C. The optimum pH for cell labeling was 6.5. Excess citrate ion (greater than 3.02 mg/ml) and small amounts of plasma proteins (greater than 10 microliter/ml) decreased the labeling efficiencies in all three cases. Distribution of these 111In-complexes in membrane, membrane fragments, and hemoglobin was studied after hemolysis. In spite of the higher lipid solubility of 111In-tropolone, the transchelation capacity appears to be similar to that of 111In-oxine. 111In-acetylacetone had the highest transchelation capacity.

Animals↗
PubMed1982

Indium-111 tropolone, a new tracer for platelet labeling.

Platelets have been labeled with a new neutral, lipid-soluble metal complex of indium 111 (111In) and tropolone. Unlike oxine, which is soluble in ethyl alcohol, tropolone is soluble in isotonic saline. Platelet labeling with 111In tropolone can be performed in both acid-citrate-dextrose (ACD) plasma and ACD saline within two hours. Labeling efficiency has been 80% to 90%. 111In tropolone in ACD saline and ACD plasma at tropolone concentrations of 5 and 10 micrograms/ml, respectively, and incubation of the platelets with the tracer at room temperature for 20 minutes were optimal conditions for labeling. The authors have developed an ACD-saline kit for convenient preparation of 111In-labeled platelets. No adverse effect of 111In tropolone on platelets has been observed in studies of biodistribution, recovery, and survival of platelets in rabbits and dogs.

Animals↗
PubMed1982

Imaging of platelets in right-sided extracardiac conduits in humans.

As a connection between the systemic venous ventricle and the pulmonary artery, valved Dacron extracardiac conduits have remarkably influenced the surgical approach to many complex congenital heart defects. Obstruction of the conduit, however, can reduce the long-term effectiveness of this corrective procedure. In addition to stenosis of the porcine valve, formation of thick fibrous neointima plays a major role in the pathogenesis of conduit obstruction. The purpose of this study was to determine whether platelet deposition could be demonstrated in these conduits by external imaging with In-111-labeled autologous platelets. After injection of labeled platelets either immediately after operation or on the fifth to eighth postoperative day, imaging was performed by standard procedures. Eight of nine patients had platelet accumulation in the conduit, and treatment with aspirin and dipyridamole caused no recognizable change in platelet deposition. This study demonstrates the feasibility of imaging platelet deposition in Dacron conduits and shows that the pattern of deposition varies with time.

Adolescent↗
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

Distribution and dosimetry of 111In-labeled platelets.

The distribution of 111In-labeled platelets was studied in five young, healthy men. The radioactivity in the lungs, heart, liver, spleen, kidneys, and testes was determined from areas-of-interest in computed gamma-camera scans at intervals up to 75 hours after injection. After the first four hours, the activity in each organ studied except the liver and kidney decreased at roughly the physical decay rate. In the liver and kidney, the curves were relatively flat, indicating continued accumulation of the radiotracer. The calculated mean radiation absorbed dose per unit administered activity was 0.60 +/- 0.07 rad/mCi (0.16 +/- 0.02 Gy/GBq) for the total body, and was 34 +/- 6 rad/mCi (9.0 +/- 1.5 Gy/GBq) for the spleen.

Blood Platelets↗
PubMed1981

Indium-111 tropolone, a new high-affinity platelet label: preparation and evaluation of labeling parameters.

Platelets were isolated with a new neutral, lipid-soluble metal complex of indium-111 and tropolone. Unlike oxine, which must be dissolved in ethyl alcohol, tropolone is soluble saline. Platelet labeling with In-111 tropolone can be performed in both acid-citrate-dextrose (ACD)-plasma and ACD-saline media within two hours' time. Labeling efficiency has been 80-90% in ACD-saline and 60-70% in the ACD-plasma medium. Optimum concentrations for the labeling of platelets with In-111 tropolone were 5 micrograms/ml in ACD-saline and 10 micrograms/ml in ACD-plasma, using a 15-min incubation at room temperature. A kit formulation for convenient routine preparation of In-111-labeled platelets has been developed. Seven parameters of platelet labeling were studied: concentration of tropolone, citrate, plasma proteins, and calcium ions; also platelet density, temperature, and pH of incubation medium. Their effects on the mechanism of platelet labeling with lipid-soluble tracers are discussed.

Affinity Labels↗