Captopril Pretreatment Produces an Additive Cardioprotection to Isoflurane Preconditioning in Attenuating Myocardial Ischemia Reperfusion Injury in Rabbits and in Humans.
BACKGROUND
Pretreatment with the angiotensin-converting inhibitor captopril or volatile anesthetic isoflurane has, respectively, been shown to attenuate myocardial ischemia reperfusion (MI/R) injury in rodents and in patients. It is unknown whether or not captopril pretreatment and isoflurane preconditioning (Iso) may additively or synergistically attenuate MI/R injury.


RESULTS
Patients selected for heart valve replacement surgery were randomly assigned to five groups: untreated control (Control), captopril pretreatment for 3 days (Cap3d), or single dose captopril (Cap1hr, 1 hour) before surgery with or without Iso (Cap3d+Iso and Cap1hr+Iso). Rabbit MI/R model was induced by occluding coronary artery for 30 min followed by 2-hour reperfusion. Rabbits were randomized to receive sham operation (Sham), MI/R (I/R), captopril (Cap, 24 hours before MI/R), Iso, or the combination of captopril and Iso (Iso+Cap). In patients, Cap3d+Iso but not Cap1hr+Iso additively reduced postischemic myocardial injury and attenuated postischemic myocardial inflammation. In rabbits, Cap or Iso significantly reduced postischemic myocardial infarction. Iso+Cap additively reduced cellular injury that was associated with improved postischemic myocardial functional recovery and reduced myocardial apoptosis and attenuated oxidative stress.


CONCLUSIONS
A joint use of 3-day captopril treatment and isoflurane preconditioning additively attenuated MI/R by reducing oxidative stress and inflammation.
Department of Anesthesiology, Haikou Municipal Hospital, Affiliated Haikou Hospital Xiangya School of Medicine, Central South University, Haikou 570208, China.
Yi
Y
Tian
Department of Anesthesiology, The University of Hong Kong, Hong Kong.
Haobo
H
Li
Department of Anesthesiology, Hainan Municipal Corps Hospital, Chinese People's Armed Police Force, Haikou 570203, China.
Peiyu
P
Liu
Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
Jun-mei
JM
Xu
Department of Anesthesiology, The University of Hong Kong, Hong Kong.
Michael G
MG
Irwin
Department of Anesthesiology, The University of Hong Kong, Hong Kong ; Department of Anesthesiology, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524023, China.
Zhengyuan
Z
Xia
Department of Anesthesiology, Haikou Municipal Hospital, Affiliated Haikou Hospital Xiangya School of Medicine, Central South University, Haikou 570208, China.
Guogang
G
Tian
D000328:Adult; D000818:Animals; D002216:Captopril / Q000627:therapeutic use*; D004357:Drug Synergism; D005260:Female; D006801:Humans; D019194:Ischemic Preconditioning / Q000379:methods; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D007530:Isoflurane / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011817:Rabbits
D002216:Captopril; D007530:Isoflurane