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Biomedical subjects

M Kapadvanjwala

Publications and source records attributed to M Kapadvanjwala.

24 records · Page 2Linked to original sources

Platelet preservation during cardiopulmonary bypass with iloprost and Duraflo-II heparin-coated surfaces.

To test the hypothesis that temporary platelet inhibition during cardiopulmonary bypass (CPB) with surface heparinized systems may result in platelet preservation, nine Yorkshire pigs were placed on CPB for 3 hours. Platelet labeling was done in all pigs with Indium-111 tropolone. CPB was instituted with a roller pump, a hollow fiber membrane oxygenator (Bentley CM-50 [Baxter-Bentley Laboratories, Irvine, CA]), and an arterial filter. The extracorporeal perfusion systems were surface-coated with the Duraflo-II heparin complex. Group A pigs (n = 5) were systemically heparinized (activated coagulation time longer than 400 sec). Group B pigs (n = 4) were placed on CPB without systematic heparinization, but have received the stable prostacyclin-analog Iloprost (ZK36374) at 1 ng/kg/min i.v. from 30 min before and during CPB. Platelet counts declined in group A pigs at 5 min, 1 hr, 2 hr, and 3 hr of CPB to 79.8% (mean), 66.5%, 71.3%, and 69.0% of pre-CPB values, respectively (p less than 0.05). In group B pigs, mean platelet count during CPB was higher than 90% of control value. Percentage of injected radioactivity detected in the oxygenator was 2.82% in group A pigs versus 0.73% in group B pigs (p = 0.0541). Surface heparinization with the Duraflo II heparin coating complex in combination with Iloprost-induced temporary platelet inhibition resulted in platelet count preservation during CPB in the pig model.

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Cardiopulmonary bypass with a surface-heparinized extracorporeal perfusion system.

To evaluate the effect of surface heparinization on platelet consumption during cardiopulmonary bypass (CPB) ten pigs were placed on CPB for 3 hours. All pigs were injected with autologous Indium-111 labeled platelets (300-420 uCi) 24 hours prior to CPB and were systemically heparinized prior to cannulation for CPB. CPB was established with a roller pump, a hollow fiber membrane oxygenator (HFMO, Bentley CM-50) and an arterial filter (AF, Bentley 1025). In six pigs the extracorporeal system was untreated whereas in four pigs it was surface heparinized with the Duraflo-II method. Cardiotomy suction was not used. Percent of injected radiation dose in HFMO and AF at 3 hours of CPB in the nontreated systems was 1.53 +/- 1.12 and 0.88 +/- 0.63%, whereas in the surface heparinized systems was 2.45 +/- 1.71 and 0.49 +/- 0.39% respectively (NS). (Values are mean +/- SD). Blood loss during (CPB) was 225 +/- 179 ml in the nontreated systems, and 263 +/- 103 ml in the surface heparinized systems (NS). Platelet counts were reduced by 12% or 21.8% at 3 hours of CPB in the two groups of pigs respectively (NS). No difference was observed in platelet consumption (in HFMO and in AF) or in platelet count reduction between the two groups of pigs. Surface heparinization did not improve platelet preservation in systemically heparinized pigs at 3 hours of CPB.

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Increase of intraplatelet free calcium ion during extracorporeal circulation with a hollow fiber oxygenator: arterial filter and dynamics of platelet thrombosis on oxygenator and filter in a pig model.

Intraplatelet free calcium (IPFC) ions provide a common pathway for platelet activation leading to thrombosis and embolization. IPFC levels were determined by chlorotetracycline fluorometry during extracorporeal circulation (ECC) with systemic heparin in eight Yorkshire pigs (weighing 30-40 kg; 3 control and 5 ECC); the ratio of slow phase organelle calcium sequestration to fast phase platelet-membrane binding is an index of free calcium. During 3 hr of ECC with a hollow fiber oxygenator (HFO) (Bentley CM-50) and AF (Bentley 1025), seven blood samples were collected 5 min before and during ECC. The platelet deposition (CPM/microCi) on HFO (PDHFO) was simultaneously measured with In-111-labeled autologous platelets (300-400 microCi) and a Geiger probe detector at -5, 0, 5, 30, 45, 60, 120, and 180 min. During ECC, IPFC and HFO thrombus increase significantly (p less than 0.05) at 45 min with respect to control IPFC values of 0.4 +/- 0.1, suggesting direct participation of calcium activated platelets in thrombosis on HFO. The decline of IPFC is due to extrusion and sequestration by dense granules, and decline in HFO thrombus is due to embolization. On the other hand, the embolus in the arterial filter was trapped in a linear fashion, with a consistent increase with time of ECC.

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The dynamics of platelet thrombus formation rate, thrombus retention time, and rate of embolization on a control and heparin bonded polyurethane angio-catheter.

The dynamics of platelet deposition and embolization from control and heparin bonded polyurethane catheters (CPC and HBPC) was evaluated with In-111 labeled autologous platelets (IN-PLT) and a computerized gamma camera (CGC). Ten non-heparinized dogs (18-25 kg) were catheterized in both femoral arteries with 10 cm of CPC and HBPC (5 Fr., Cordis) 24 hr after injection of 300-420 microCi of In-PLT, and imaged for 3 hr with the computerized gamma camera. The regional platelet deposition curves (RPDC) indicated multiple peaks and valleys; the curves were analyzed for early rate of thrombus formation (upswing), thrombus retention time (full width at half maxima of the RPDC-peak), and rate of embolization (downswing) on both catheters. The four parameters (mean +/- SD) of thrombosis on catheters and integral of the radioactivity time curve for the 3 hr duration of imaging were calculated from normalized counts/sec. The rate of thrombus formation and rate of embolization are higher for the control than HBPC, suggesting that heparin-bonding decreases the early rate of thrombosis and embolization. The thrombus adhesivity and retention time appear shorter for the control catheter, indicating that the control thrombogenic catheter forms multiple thrombi and emboli than HBPC. The integral appears larger for the control catheter than HBPC. In vivo (dynamic) studies, in vitro studies, and critical analyses of the radioactivity time curve were essential for complete evaluation of thrombogenicity of catheters and other cardiovascular prostheses.

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In vitro and in vivo evaluation of the comparative thrombogenicity of cellulose acetate hemodialyzers with radiolabeled platelets.

Platelet consumption and platelet kinetics during hemodialysis were quantified in Yorkshire pigs with In-111 labeled platelets. Six anesthetized pigs (20-25 kg) were hemodialyzed at 150 ml/min for 3 hr. All pigs were injected with autologous In-111 labeled platelets (300-420 microCi) 24 hr before dialysis and were systemically heparinized (ACT > 400 sec) before cannulation. Hemodialysis was instituted with a Drake-Willock hemodialysis machine and a hollow fiber dialyzer (Cobe4, 0.6 m2). In vitro sham dialysis was carried out at 150 ml/min for 3 hr with six more dialyzers in a flow-loop with the blood reservoir maintained at 37 degrees C. In vitro thrombogenicity over-estimates (10-fold) in vivo values. In both systems, platelet deposition on dialyzers reached a steady state, suggesting a constant rate of thrombus formation and embolization in the hollow fiber system. The relative thrombus distribution after 3 hr of dialysis was similar in both systems, with adherent thrombi in the entry and exit ports and highest numbers in the midsection of the hemodialyzer. Biodistribution after 3 hr of dialysis indicated that thrombosis of the hemodialyzer and arterial and venous traps as well as embolization reduced the platelet pool in the blood and increased platelet emboli in lung, brain, kidneys, and skeletal muscle, as measured by the In-111 labeled platelets.

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A higher blood flow window of reduced thrombogenicity and acceptable fragmentation in a hollow fiber hemodialyzer.

The effect of pulsatile blood flow on platelet thrombogenicity and platelet fragmentation (PF) in a hollow fiber hemodialyzer (HFD) was quantified with 111In labeled platelets and 125I labeled fibrinogen; 150 ml of blood was collected from Beagle dogs, Yorkshire pigs, and a human volunteer (non-smoker). Platelets were labeled with 111In tropolone (300 microCi) and fibrinogen was labeled with 125I. Sham dialysis (SHD) was performed with 120 HFDs (0.9 meter2) at 37 degrees C, with flow-rates of 150, 250, 500, and 950 ml/min.; after SHD, the washed HD radioactivity was measured with an ionization chamber. PF was measured by flow cytometry with GP IIb-IIIa murine monoclonal antibody. Platelet deposition decreased significantly for 3 species at higher flow; fibrinogen deposition (10-12%, 55-65 mg/m2), was not affected by flow. Adherent platelet thrombus decreased from (8.2 +/- 3.4) to (3.1 +/- 1.0) with human blood as flow rate increased from 150 to 950 ml/min; platelet thrombus level also decreased significantly (p < 0.005) from (20.3 +/- 6.2) to (4.5 +/- 1.9) with canine blood. Higher values were obtained for canine than human and porcine platelets. Platelet fragmentation, on the other hand, increased from 2.1-2.2% to 10.2-11.3% with increase of flow. Like platelets, deposition of canine fibrinogen was slightly higher than that of pig and human. The studies of adherent thrombus and platelet fragmentation identified an important flow-window of reduced thrombogenicity and acceptable fragmentation, encouraging extracorporeal circulation at higher blood flow.

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