John C. Kerr

Heparinization reduces endothelial permeability and hydrogen ion accumulation in a canine skeletal muscle ischemia-reperfusion model

Skeletal muscle injury after revascularization (ischemia-reperfusion) continues to be a major clinical problem. Although heparinization has been recommended, its action in an experimental model of I-R has not been evaluated. We investigated the ability of heparinization to decrease I-R injury in 10 anesthetized dogs (nonheparinized, n = 5; heparinized, n = 5), subjecting one gracilis muscle to 6 hours of ischemia followed by 1 hour of reperfusion while the identically prepared contralateral muscle served as a nonischemic control. Skeletal muscle infarction was determined by Tc-PYP uptake. Endothelial permeability was quantified by measurement of skeletal muscle 125I-Alb activity after intravenous injection. Interstitial hydrogen ion (H+) accumulation was determined by a miniature pH electrode inserted into the gracilis muscle. Isotopic activities from the ischemic muscle were calculated as a percentage of the contralateral nonischemic muscle (mean +/- SEM). Nonheparinized ischemic muscles had an increase in the activities of Tc-PYP and 125I-Alb of 684% +/- 149% and 742% +/- 130%, which were reduced to 218% +/- 54% and 378% +/- 85% by heparinization, respectively (p less than 0.05). During ischemia, the nonheparinized muscles accumulated 1223 +/- 121 nmol of H+ compared with 785 +/- 95 nmol in the heparinized animals (p less than 0.01). This significant reduction in I-R injury may be causally related to diminished endothelial permeability and H+ accumulation.

Primate mesenteric blood flow: Effects of vasopressin and its route of delivery

The effects of vasopressin on blood flow in the superior mesenteric artery and on mean arterial pressure and portal venous pressure were measured in 7 rhesus monkeys. Vasopressin was injected, as either a bolus, or infused both intravenously and intraarterially to assess the influence of the route of administration upon hemodynamic responses. Dose-dependent decreases in superior mesenteric arterial flow were observed during both intraarterial and intravenous injections of vasopressin. No statistically significant differences between the two routes of administration, the decrease in flow, and changes in pressure were observed. Based upon these observations, one might anticipate that intravenously administered vasopressin will be as effective as intraarterially administered vasopressin in reducing mesenteric blood flow, and thus portal venous pressure, in man.

Distribution and Arteriovenous Shunting of Gastric Blood Flow in the Baboon: Effect of Epinephrine and Vasopressin Infusions

The effects of 60-min intraarterial infusion of vasopressin (0.005 U per kg-min) and epinephrine (0.05 mu per kg-min) on gastric hemodynamics were studied in anesthetized baboons. Total gastric blood flow was measured electromagnetically and radioactive microspheres (15 +/- 5 mu) with three labels were used to determine regional distribution of gastric blood flow and arteriovenous shunting. Control flow was 55 +/- 8 ml per min, with 77.4 +/- 2.7% of flow going to the gastric mucosa and 1.7 +/- 0.4% of injected spheres appearing in the liver. Epinephrine infusion resulted in a sustained vasoconstriction to 18 +/- 5 ml per min with no autoregulatory escape and no changes in arterial pressure or cardiac output. Vasopressin resulted in a decrease in flow to 14 +/- 3 ml per min with no excape. Whereas cardiac output did not change, there was a singificant hypertensive effect during the vasopressin infusion. There was neither redistribution of flow nor change in arteriovenous shunting with either epinephrine or vasopressin. Transmucosal electrical potential difference was 62 +/- 8 mv and did not change significantly with either infusion.

Influence of Vasopressin on Colon Blood Flow in Monkeys

Inferior mesenteric arterial blood flow was measured with an electromagnetic blood flowmeter in five anesthetized rhesus monkeys. The effects of vasopressin on this vasculature were determined to evaluate the optimal, safe concentration of this agent during its clinical application in the management of hemorrhagic lesions of the colon. Control flow was 29 +/- 3 (SE) ml min-1; aortic pressure was 124 +/- 4 mm Hg. Intraarterial injections of vasopressin, in doses ranging logarithmically from 5 X 10(-5) to 5 X 10(-2) U kg-1, caused dose-dependent decreases in flow. At the highest dose, vasopressin reduced flow by 50% and increased arterial pressure by 9 mm Hg. When infused, at a rate of 5 X 10(-3) U kg-1 min-1, vasopressin produced a significant and sustained reduction in inferior mesenteric arterial blood flow. Autoregulatory escape was not observed. At this rate, vasopressin increased arterial pressure 10 mm Hg, by the 6th minute of infusion. This hypertension was unaccompanied by significant bradycardia. After cessation of the infusion, flow gradually returned to control values over a period of minutes. These observations indicate that vasopressin is a potent constrictor in the inferior mesenteric arterial circulation of the monkey, and support the use of this agent to control lower intestinal bleeding in man. At a dose of 5 X 10(-3) U kg-1 min-1, vasopressin causes a significant reduction in flow without adverse systemic side effects.

Vasopressin: route of administration and effects on canine hepatic and superior mesenteric arterial blood flows.

Blood flows through the canine hepatic (HBF) and superior mesenteric arteries (MBF) were measured with electromagnetic flowmeters, during infusions of vasopressin, by three routes of administration: 1) intra-hepatic-arterially (IHA), 2) intra-portal-venously (IPV) and 3) intra-systemic-venously (IV). Mean control HBF was 148 ± 17 (S.E.) ml min; MBF was 243 ± 27 ml min; aortic pressure (AP) was 126 ± 3 mm Hg; portal venous pressure (PVP) was 8.8 ± 1.0 mm Hg. Infusions of vasopressin, at a rate of 5 × 10 units kg min, IHA, reduced HBF significantly (p <.001) to 121 ± 21 ml min, within one minute. Flow returned to control, despite continued drug infusion; and at the end of the fifth minute of infusion, the value (134 ± 21 ml min) was not significantly (p >.05) different from control. During the same infusion, MBF fell to 129 ± 28 ml min (p <.001), by the sixth minute of the infusion and remained at this level for the duration of the infusion. AP increased to 137 ± 13 mm Hg, by the sixth minute of the infusion and was sustained at this level for the duration of the infusion. PVP decreased to 7.0 ± 1.0 mm Hg, by the tenth minute of the infusion. The responses to IPV vasopressin were indistinguishable from those following IHA vasopressin, with the exception that HBF was reduced to only 147 ± 22 ml min (from a preinfusion control of 160 ± 23 ml min), at one minute. HBF returned to control, despite continuation of the infusion. IV vasopressin, at the same concentration, caused no change in HBF throughout the ten minute infusion. These observations indicate that the canine hepatic arterial circulation responds to vasopressin with vasoconstriction characterized by autoregulatory escape. By any of the three routes of administration, vasopressin causes a significant and sustained reduction in blood flow through the superior mesenteric artery. Autoregulatory escape, from vasopressin-induced mesenteric arterial constriction, is not observed. Based on these observations, significant changes in mesenteric arterial blood flow can be anticipated without associated significant changes in hepatic arterial blood flow, regardless of the route of administration of vasopressin.