Abstract
IntroductionArginine vasopressin is a vasoactive drug commonly used in distributive shock states including mixed shock with a cardiac component. However, the direct effect of arginine vasopressin on the function of the ischemia/reperfusion injured heart has not been clearly elucidated.MethodsWe measured left ventricular ejection fraction using trans-thoracic echocardiography in C57B6 mice, both in normal controls and following ischemia/reperfusion injury induced by a one hour ligation of the left anterior descending coronary artery. Mice were treated with one of normal saline, dobutamine (8.33 μg/kg/min), or arginine vasopressin (0.00057 Units/kg/min, equivalent to 0.04 Units/min in a 70 kg human) delivered by an intraperitoneal micro-osmotic pump. Arterial blood pressure was measured using a micromanometer catheter. In addition, mortality was recorded and cardiac tissues processed for RNA and protein.ResultsBaseline left ventricular ejection fraction was 65.6% (60 to 72). In normal control mice, there was no difference in left ventricular ejection fraction according to infusion group. Following ischemia/reperfusion injury, AVP treatment significantly reduced day 1 left ventricular ejection fraction 46.2% (34.4 to 52.0), both in comparison with baseline and day 1 saline treated controls 56.9% (42.4 to 60.2). There were no significant differences in preload (left ventricular end diastolic volume), afterload (blood pressure) or heart rate to account for the effect of AVP on left ventricular ejection fraction. The seven-day mortality rate was highest in the arginine vasopressin group. Following ischemia/reperfusion injury, we found no change in cardiac V1 Receptor expression but a 40% decrease in Oxytocin Receptor expression.ConclusionsArginine vasopressin infusion significantly depressed the myocardial function in an ischemia/reperfusion model and increased mortality in comparison with both saline and dobutamine treated animals. The use of vasopressin may be contraindicated in non-vasodilatory shock states associated with significant cardiac injury.
Highlights
Arginine vasopressin is a vasoactive drug commonly used in distributive shock states including mixed shock with a cardiac component
There were no significant differences in preload, afterload or heart rate to account for the effect of arginine vasopressin (AVP) on left ventricular ejection fraction
Following ischemia/reperfusion injury, we found no change in cardiac V1 Receptor expression but a 40% decrease in Oxytocin Receptor expression
Summary
Arginine vasopressin is a vasoactive drug commonly used in distributive shock states including mixed shock with a cardiac component. With the increasing medical complexity of the critically ill, shock due to a combination of vasodilation and cardiac dysfunction is increasingly frequent. Two common clinical examples of this are first, vasodilation following cardiopulmonary bypass surgery and, second, the cardiac dysfunction during septic shock. These mixed shock conditions are routinely treated with intravenous fluids plus inotropes combined with a vasopressor such as norepinephrine or arginine vasopressin (AVP). Vascular V1R appear to mediate the majority of effects of vasopressin in reversing vasoplegia and catecholamine tolerance [4,10]
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