Pulmonary fibrin microembolism with Echis carinatus venom in dogs: effects of a synthetic thrombin inhibitor.
We produced pulmonary fibrin microembolism using an infusion of a prothrombin activator (Echis carinatus venom, 30 min, 0.5 NIH thrombin equivalent units/kg) in open-chest mongrel dogs. To determine the nonclotting effects of this venom on edemagenesis we infused an irreversible thrombin inhibitor, D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone (PPACK, 57 nmol X kg-1 X min-1 for 120 min), alone (n = 5) or with venom (Echis + PPACK, n = 5). The control group (n = 5) was given 1 ml of 0.9% NaCl. A decline in left atrial pressure (means +/- SE, 5.3 +/- 0.4 to 4.0 +/- 0.5 mmHg, P less than 0.05) and cardiac index (149 +/- 10 to 82 +/- 13 ml X min-1 X kg-1, P less than 0.01) in association with a marked increase in pulmonary arterial pressure (14.5 +/- 0.6 to 26.6 +/- 2.5 mmHg, P less than 0.001) and pulmonary vascular resistance (64 +/- 5 to 304 +/- 42 mmHg X ml-1 X min-1 X kg-1, P less than 0.001) was observed after 20 min of venom infusion. During this interval, pulmonary artery wedge pressure increased (4 +/- 1 to 12 +/- 4 mmHg, P less than 0.01) in four of eight animals. Fibrinogen declined below measurable levels and fibrin microemboli were seen in many pulmonary arterioles. These changes were not observed in the Echis + PPACK, PPACK, or control groups. Leukopenia and thrombocytopenia were observed in the Echis and Echis + PPACK groups.(ABSTRACT TRUNCATED AT 250 WORDS)
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology*; D000818:Animals; D001834:Body Water / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs / Q000502:physiology*; D005337:Fibrin / Q000502:physiology*; D005340:Fibrinogen / Q000378:metabolism; D006439:Hemodynamics; D007958:Leukocyte Count; D008168:Lung / Q000378:metabolism; D010976:Platelet Count; D011655:Pulmonary Embolism / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012119:Respiration; D013917:Thrombin / Q000037:antagonists & inhibitors*; D014757:Viper Venoms / Q000494:pharmacology*
D000590:Amino Acid Chloromethyl Ketones; D014757:Viper Venoms; D005337:Fibrin; D005340:Fibrinogen; D013917:Thrombin; C040308:phenylalanyl-prolyl-arginine-chloromethyl ketone