title: Inhibition of endoplasm reticulum stress by anisodamine protects against myocardial injury after cardiac arrest and resuscitation in rats.
abstract: 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.
authors: Department of Emergency, Chinese PLA General Hospital, Beijing, China.
authors: Xue-Lian
authors: XL
authors: Yin
authors: Hong
authors: H
authors: Shen
authors: Wei
authors: W
authors: Zhang
authors: Yang
authors: Y
authors: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016887:Cardiopulmonary Resuscitation; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects*; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006323:Heart Arrest / Q000150:complications* / Q000628:therapy; D006335:Heart Injuries / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D008297:Male; D009206:Myocardium / Q000166:cytology; D011897:Random Allocation; D051381:Rats; D015427:Reperfusion Injury / Q000150:complications*; D012991:Solanaceous Alkaloids / Q000627:therapeutic use*
chemical_list: D004365:Drugs, Chinese Herbal; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D012991:Solanaceous Alkaloids; C003922:anisodamine