Abstract 202: Improved Cardiac Recovery With Sivelestat During Low Flow Following Global Ischemia
Introduction: Sivelestat, a neutrophil elastase inhibitor, has been shown to preserve post-ischemic cardiac function in the absence of neutrophils, when administered during full reperfusion following global ischemia. Such full flow conditions are unlikely to exist during resuscitative efforts following cardiac arrest in vivo.
Hypothesis: Sivelestat induces protection of left ventricular (LV) function prior to full reperfusion when administered during low flow following global ischemia in the buffer-perfused isolated rat heart.
Methods: Hearts isolated from male Sprague-Dawley rats (n=3/group) were perfused with 37.4° C Krebs-Henseleit buffer. Developed pressure and dP/dt were monitored through a latex LV balloon. Hearts were given 25 min of global no-flow ischemia, then a) full reperfusion (control), b) 3 min of low flow at 20% of baseline coronary flow (low flow), or c) 3 min of 20% low flow with Sivelestat (19 μM). All hearts received 60 min of full flow reperfusion. Creatine kinase (CK) release was determined in coronary effluent prior to ischemia and at 10, 30 and 60 min of full flow reperfusion. Following experimentation, hearts were stained with triphenyltetrazolium chloride for measurements of infarct size. Significance was set at p < 0.05.
Results: Administration of Sivelestat significantly improved recovery of dP/dt and developed pressure at 60 min of reperfusion as compared to untreated low flow hearts and resulted in recovery of LV function to the same levels as controls. CK release was significantly elevated at 10, 30 and 60 min reperfusion in untreated low flow hearts compared to hearts in the other two groups. At 30 and 60 min of reperfusion, Sivelestat treatment significantly reduced CK release as compared to control hearts. Infarct area was smallest in Sivelestat-treated hearts (10.7 ± 2.1%) as compared to untreated low flow hearts (28.3 ± 7.8%) and controls (14.7 ± 3.1%).
Conclusions: When administered during low flow following global ischemia, Sivelestat reduces infarction and CK release, and enhances recovery of LV function in the buffer-perfused isolated rat heart. Sivelestat may induce a pharmaceutical postconditioning response, which is effective under low flow reperfusion conditions such as may exist during CPR.
- © 2010 by American Heart Association, Inc.