Anisodamine is a multi-functional bio-
alkaloid with vascular activity. Our previous studies have revealed that
anisodamine protects the heart from
ischemia/reperfusion (I/R) injury induced by
cardiac arrest (CA) and
resuscitation. This study aimed to explore whether the protective effect of
anisodamine is mediated by inhibition of the endoplasmic reticulum stress (ERS) response, which has been demonstrated to implicate in various I/R
injuries. After 5 min of CA induced by electric stimulation, Wistar rats were randomly selected to receive
cardiopulmonary resuscitation (
CPR, including chest compression and
epinephrine infusion) with or without
anisodamine injection (n = 50/group). Hearts were harvested 24 h after the return of spontaneous circulation (ROSC).
Sham-operated animals served as non-ischemic controls (n = 10). The survival rate, cardiomyocyte apoptosis, and the
protein expression of ERS markers were detected. Thirty-three of the 50 rats in the Ani + CA/R group were successfully resuscitated, whereas only 18 of the 50 rats in the CA/R group gained ROSC. Survival to 24 h was significantly improved in the
anisodamine treatment group (Ani + CA/R, n = 22/50) compared to the group with standard
CPR (CA/R, n = 8/50).
Anisodamine markedly decreased the number of apoptotic cardiomyocytes, the
protein expression of
GRP78, CHOP, and the active form of Caspase3 compared to the CA/R group. Our data suggest that
anisodamine protects against cellular damage in rat hearts after CA and
resuscitation, at least in part, by inhibiting myocardial ERS.