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

Indrambarya T, Boyd JH, Wang Y, McConechy M, Walley KR - Crit Care (2009)

Bottom Line: 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.Following ischemia/reperfusion injury, we found no change in cardiac V1 Receptor expression but a 40% decrease in Oxytocin Receptor expression.The use of vasopressin may be contraindicated in non-vasodilatory shock states associated with significant cardiac injury.

View Article: PubMed Central - HTML - PubMed

Affiliation: Critical Care Research Laboratories, Heart + Lung Institute, University of British Columbia, Vancouver, British Columbia V6Z 1Y6, Canada. toonchai@hotmail.com

ABSTRACT

Introduction: 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.

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Kaplan Meier survival curve for mice in the three treatment groups. When compared with infusions of either saline (n = 6) or dobutamine (n = 6), vasopressin (n = 12) results in dramatically increased mortality. This difference begins as soon as day 1 following ischemia/reperfusion and persists throughout our seven day observation period.
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Figure 3: Kaplan Meier survival curve for mice in the three treatment groups. When compared with infusions of either saline (n = 6) or dobutamine (n = 6), vasopressin (n = 12) results in dramatically increased mortality. This difference begins as soon as day 1 following ischemia/reperfusion and persists throughout our seven day observation period.

Mentions: When compared with infusions of either saline or DOB, vasopressin results in dramatically increased mortality (Figure 3). This difference begins as soon as day 1 following I/R and persists throughout our seven-day observation period. The mice were no different in appearance (grooming, temperature, activity level) according to infusion group, and in general appeared healthy during routine monitoring.


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

Indrambarya T, Boyd JH, Wang Y, McConechy M, Walley KR - Crit Care (2009)

Kaplan Meier survival curve for mice in the three treatment groups. When compared with infusions of either saline (n = 6) or dobutamine (n = 6), vasopressin (n = 12) results in dramatically increased mortality. This difference begins as soon as day 1 following ischemia/reperfusion and persists throughout our seven day observation period.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2717470&req=5

Figure 3: Kaplan Meier survival curve for mice in the three treatment groups. When compared with infusions of either saline (n = 6) or dobutamine (n = 6), vasopressin (n = 12) results in dramatically increased mortality. This difference begins as soon as day 1 following ischemia/reperfusion and persists throughout our seven day observation period.
Mentions: When compared with infusions of either saline or DOB, vasopressin results in dramatically increased mortality (Figure 3). This difference begins as soon as day 1 following I/R and persists throughout our seven-day observation period. The mice were no different in appearance (grooming, temperature, activity level) according to infusion group, and in general appeared healthy during routine monitoring.

Bottom Line: 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.Following ischemia/reperfusion injury, we found no change in cardiac V1 Receptor expression but a 40% decrease in Oxytocin Receptor expression.The use of vasopressin may be contraindicated in non-vasodilatory shock states associated with significant cardiac injury.

View Article: PubMed Central - HTML - PubMed

Affiliation: Critical Care Research Laboratories, Heart + Lung Institute, University of British Columbia, Vancouver, British Columbia V6Z 1Y6, Canada. toonchai@hotmail.com

ABSTRACT

Introduction: 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.

Show MeSH
Related in: MedlinePlus