Urocortin Treatment Improves Acute Hemodynamic Instability and Reduces Myocardial Damage in Post-Cardiac Arrest Myocardial Dysfunction.
OBJECTIVE
Hemodynamic instability occurs following cardiac arrest and is associated with high mortality during the post-cardiac period. Urocortin is a novel peptide and a member of the corticotrophin-releasing factor family. Urocortin has the potential to improve acute cardiac dysfunction, as well as to reduce the myocardial damage sustained after ischemia reperfusion injury. The effects of urocortin in post-cardiac arrest myocardial dysfunction remain unclear.


RESULTS
We developed a preclinical cardiac arrest model and investigated the effects of urocortin. After cardiac arrest induced by 6.5 min asphyxia, male Wistar rats were resuscitated and randomized to either the urocortin treatment group or the control group. Urocortin (10 μg/kg) was administrated intravenously upon onset of resuscitation in the experimental group. The rate of return of spontaneous circulation (ROSC) was similar between the urocortin group (76%) and the control group (72%) after resuscitation. The left ventricular systolic (dP/dt40) and diastolic (maximal negative dP/dt) functions, and cardiac output, were ameliorated within 4 h after ROSC in the urocortin-treated group compared to the control group (P<0.01). The neurological function of surviving animals was better at 6 h after ROSC in the urocortin-treated group (p = 0.023). The 72-h survival rate was greater in the urocortin-treated group compared to the control group (p = 0.044 by log-rank test). Cardiomyocyte apoptosis was lower in the urocortin-treated group (39.9±8.6 vs. 17.5±4.6% of TUNEL positive nuclei, P<0.05) with significantly increased Akt, ERK and STAT-3 activation and phosphorylation in the myocardium (P<0.05).


CONCLUSIONS
Urocortin treatment can improve acute hemodynamic instability as well as reducing myocardial damage in post-cardiac arrest myocardial dysfunction.
Department of Emergency Medicine, National Taiwan University Medical College and Hospital, Taipei, Taiwan.|Division of Cardiology, Department of Internal Medicine, National Taiwan University Medical College and Hospital, Taipei, Taiwan.
Chien-Hua
CH
Huang
Department of Emergency Medicine, National Taiwan University Medical College and Hospital, Taipei, Taiwan.
Chih-Hung
CH
Wang
Department of Emergency Medicine, National Taiwan University Medical College and Hospital, Taipei, Taiwan.
Min-Shan
MS
Tsai
Department of Emergency Medicine, National Taiwan University Medical College and Hospital, Taipei, Taiwan.
Nai-Tan
NT
Hsu
Division of Cardiology, Department of Internal Medicine, Cardinal Tien Hospital Yunghe Branch, New Taipei City, Taiwan.
Chih-Yen
CY
Chiang
Division of Cardiology, Department of Internal Medicine, National Taiwan University Medical College and Hospital, Taipei, Taiwan.
Tzung-Dau
TD
Wang
Department of Emergency Medicine, National Taiwan University Medical College and Hospital, Taipei, Taiwan.
Wei-Tien
WT
Chang
Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Huei-Wen
HW
Chen
Department of Emergency Medicine, National Taiwan University Medical College and Hospital, Taipei, Taiwan.|Division of Cardiology, Department of Internal Medicine, Lotung Poh-Ai Hospital, Yilan County, Taiwan.
Wen-Jone
WJ
Chen
D061605:Administration, Intravenous; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology*; D006323:Heart Arrest / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009206:Myocardium / Q000473:pathology; D017208:Rats, Wistar; D054832:Urocortins / Q000008:administration & dosage / Q000627:therapeutic use*
D054832:Urocortins