title: Enalapril protects against myocardial ischemia/reperfusion injury in a swine model of cardiac arrest and resuscitation.
abstract: There is strong evidence to suggest that angiotensin-converting enzyme inhibitors (ACEIs) protect against local myocardial ischemia/reperfusion (I/R) injury. This study was designed to explore whether ACEIs exert cardioprotective effects in a swine model of cardiac arrest (CA) and resuscitation. Male pigs were randomly assigned to three groups: sham‑operated group, saline treatment group and enalapril treatment group. Thirty minutes after drug infusion, the animals in the saline and enalapril groups were subjected to ventricular fibrillation (8 min) followed by cardiopulmonary resuscitation (up to 30 min). Cardiac function was monitored, and myocardial tissue and blood were collected for analysis. Enalapril pre‑treatment did not improve cardiac function or the 6-h survival rate after CA and resuscitation; however, this intervention ameliorated myocardial ultrastructural damage, reduced the level of plasma cardiac troponin I and decreased myocardial apoptosis. Plasma angiotensin (Ang) II and Ang‑(1‑7) levels were enhanced in the model of CA and resuscitation. Enalapril reduced the plasma Ang II level at 4 and 6 h after the return of spontaneous circulation whereas enalapril did not affect the plasma Ang‑(1‑7) level. Enalapril pre-treatment decreased the myocardial mRNA and protein expression of angiotensin-converting enzyme (ACE). Enalapril treatment also reduced the myocardial ACE/ACE2 ratio, both at the mRNA and the protein level. Enalapril pre‑treatment did not affect the upregulation of ACE2, Ang II type 1 receptor (AT1R) and MAS after CA and resuscitation. Taken together, these findings suggest that enalapril protects against ischemic injury through the attenuation of the ACE/Ang II/AT1R axis after CA and resuscitation in pigs. These results suggest the potential therapeutic value of ACEIs in patients with CA.
authors.affiliation: Department of Emergency Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Guoxing
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Emergency Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing Key Laboratory of Cardiopulmonary Cerebral Resuscitation (NO.BZ0370), Beijing 100020, P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Emergency Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing Key Laboratory of Cardiopulmonary Cerebral Resuscitation (NO.BZ0370), Beijing 100020, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yuan
authors.affiliation: Department of Emergency Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing Key Laboratory of Cardiopulmonary Cerebral Resuscitation (NO.BZ0370), Beijing 100020, P.R. China.
authors.forename: Junyuan
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Emergency Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing Key Laboratory of Cardiopulmonary Cerebral Resuscitation (NO.BZ0370), Beijing 100020, P.R. China.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Li
mesh_terms: D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D002316:Cardiotonic Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D004656:Enalapril / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006323:Heart Arrest / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D046529:Microscopy, Electron, Transmission; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000503:physiopathology / Q000628:therapy
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D002316:Cardiotonic Agents; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D004656:Enalapril; D007703:Peptidyl-Dipeptidase A