Vasodilation, fibrinolysis, and thrombolysis with intraarterial infusion of urokinase in the canine superior mesenteric artery.
Urokinase, the plasminogen activator from human urine, produces a dose-dependent increase in blood flow in the canine superior mesenteric artery when injected intraarterially at doses from 10(-1) to 10(3) units kg-1. This vasodilation persists despite blockade of beta-adrenergic and histamine H1 and H2 receptors as well as inhibition of plasminogen activation, suggesting that these mechanisms are not involved. Infusion of urokinase at 10(2) CTA (Committee on Thrombolytic Agents) units kg-1 min-1 does not produce a sustained vasodilation, but is effective in achieving complete lysis of thrombi within 100 min in the superior mesenteric arterial circulation. Increasing the dose slightly to 125 CTA units kg-1 min-1 results in unwanted clotting abnormalities without attaining a vasodilator level. Decreasing the dose to 75 CTA units kg-1 min-1 still results in complete thrombolysis. In contrast to the results in the femoral circulation, the dose required for fibrinolysis-thrombolysis does not overlap with that for vasodilation in the superior mesenteric artery. Nevertheless, these experiments provide some basis for the use of intraarterial urokinase infusion in the treatment of nonocclusive mesenteric ischemia and, perhaps, thrombotic occlusion of the superior mesenteric artery.
D000818:Animals; D004285:Dogs; D010450:Endopeptidases / Q000494:pharmacology*; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D005343:Fibrinolytic Agents; D007261:Infusions, Intra-Arterial; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors; D015849:Plasminogen Inactivators; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D013997:Time Factors; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage / Q000494:pharmacology*; D014665:Vasodilator Agents
D005343:Fibrinolytic Agents; D015849:Plasminogen Inactivators; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D014665:Vasodilator Agents; D010450:Endopeptidases; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator