Low-dose vasopressin infusion results in increased mortality and cardiac dysfunction following ischemia-reperfusion injury in mice.
BACKGROUND
Arginine 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.


METHODS
We 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 microg/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.


RESULTS
Baseline 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.


CONCLUSIONS
Arginine 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.
Indrambarya
Toonchai
T
Critical Care Research Laboratories, Heart + Lung Institute, University of British Columbia, Vancouver, British Columbia V6Z 1Y6, Canada. toonchai@hotmail.com
Boyd
John H
JH
Wang
Yingjin
Y
McConechy
Melissa
M
Walley
Keith R
KR
D000818:Animals; D001127:Arginine Vasopressin / Q000008:administration & dosage / Q000009:adverse effects*; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use; D004280:Dobutamine / Q000494:pharmacology / Q000627:therapeutic use; D006333:Heart Failure / Q000188:drug therapy; D007262:Infusions, Intravenous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D012769:Shock / Q000188:drug therapy*; D013318:Stroke Volume / Q000187:drug effects*; D016019:Survival Analysis; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000009:adverse effects*; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced* / Q000473:pathology
D002316:Cardiotonic Agents; D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin; D004280:Dobutamine