Plasma endothelin-1 level at the onset of ischemic ventricular fibrillation predicts resuscitation outcome

Abstract

Background: Endogenous vasopressors, including endothelin-1 (ET-1), have been shown to be elevated in patients following resuscitation from out-of-hospital cardiac arrest and are likely a physiologic response to global ischaemia. The importance of ET-1 in the setting of arrest and resuscitation has not been established. Prior work has demonstrated that ET-1 increases significantly after coronary occlusion. The purpose of this study was to assess changes in ET-1 following induction of ischaemia and VF.

Methods: VF was induced in 30 anesthetized and instrumented swine by balloon occlusion of the LAD. Blood was collected from the right atrium at baseline and at 5 min intervals following LAD occlusion until VF occurred. After 7 min of VF, resuscitation was attempted in accordance with guidelines. ET-1 and matrix metalloproteinase-9 (MMP-9), a measure of infarct size, were measured using ELISA.

Results: ET-1 and MMP-9 levels increased significantly from baseline within 20 min of occlusion of the LAD. Animals that could not be resuscitated had a higher ET-1 (p=0.031) at VF onset but similar ischaemia time (time to VF) and MMP-9, reflecting infarct size. An ET-1 level >4 pg/ml had a likelihood ratio of 4 for predicting resuscitation failure.

Conclusions: Elevated levels of ET-1 during acute ischaemia predict resuscitation failure independent of the time to VF. This finding may be due to the known effect of ET-1 on coronary vascular resistance or ventricular compliance, resulting in early ischemic contracture.

Figure 1. Plasma Endothelin-1 Concentrations After LAD Occlusion

Plasma endothelin-1 was measured prior to coronary occlusion (time = 0) and at 5 min intervals until spontaneous ventricular fibrillation occurred. Differences were not noted between groups at any time point. ET-1 was significantly greater (p < 0.05) than baseline values at the 20, 25, and 30 min time points.

Figure 2. Plasma MMP-9 Concentrations After LAD Occlusion

Plasma MMP-9 was measured prior to coronary occlusion (time = 0) and at 5 min intervals until spontaneous ventricular fibrillation occurred. Differences were not noted between groups at any time point. MMP-9 was significantly greater (p < 0.05) than baseline values at the 20, 25, and 30 min time points.

Figure 3. Endothelin-1 Level versus Resuscitation Outcome

Peak ET-1 concentration preceding spontaneous VF and outcome are plotted for each study animal. A concentration of >4 pg/ml yielded a likelihood ratio of 4 for resuscitation failure.