title: Cardioprotective effect of therapeutic hypothermia for postresuscitation myocardial dysfunction.
abstract: Mild-to-moderate therapeutic hypothermia after resuscitation from cardiac arrest is neuroprotective, but its effect on postresuscitation myocardial dysfunction is not clear. We hypothesized that therapeutic hypothermia is cardioprotective in postresuscitation. Male adult Wistar rats underwent asphyxia-induced cardiac arrest and manual resuscitation with epinephrine. Therapeutic hypothermia is induced immediately after successful resuscitation and the return of spontaneous circulation (ROSC). One hour after ROSC, the rats achieved a target temperature of 30 degrees C to 31 degrees C, which was maintained for 1.5 h and then transitioned to the passive rewarming process in the hypothermia group. A temperature between 36.5 degrees C and 37.5 degrees C was maintained in the normothermia group. Echocardiography revealed that hypothermia resulted in significantly better systolic function of fractional shortening in 60 and 120 min after ROSC (both P < 0.05). The benefit of cardioprotection was also confirmed by the general linear mixed-models analysis of dP/dt, which revealed significantly better systolic function in positive dP/dtR(40) and diastolic function in maximal negative dP/dt (both P < 0.001). The 4-h and 3-day survival analyses both revealed better outcomes in the hypothermia groups in the log-rank test (P < 0.001 for the 4-h analysis, and P < 0.05 for the 3-day analysis). Serum level of heart-type, fatty acid-binding protein at 4 h after resuscitation as the myocardium damage marker was also significantly lower in the hypothermia group (52.4 ng/mL vs 186.5 ng/mL in the normothermia group; P < 0.05). Western blotting of myocardium showed that myocardial Akt and ERK1/2 were more activated in the hypothermia group 2 h after spontaneous circulation returned. In conclusion, postresuscitation mild-to-moderate therapeutic hypothermic is cardioprotective in the asphyxia-induced cardiac arrest animal model. It stabilizes hemodynamics, improves short-term survival, and decreases myocardial damage. The cardioprotective effect is associated with Akt and ERK1/2 activation in signal transduction.
authors.affiliation: Department of Emergency Medicine, National Taiwan University Medical College and Hospital, Taipei, Taiwan.
authors.forename: Chiung-Yuan
authors.initials: CY
authors.lastname: Hsu
authors.forename: Chien-Hua
authors.initials: CH
authors.lastname: Huang
authors.forename: Wei-Tien
authors.initials: WT
authors.lastname: Chang
authors.forename: Huei-Wen
authors.initials: HW
authors.lastname: Chen
authors.forename: Hsiao-Ju
authors.initials: HJ
authors.lastname: Cheng
authors.forename: Min-Shan
authors.initials: MS
authors.lastname: Tsai
authors.forename: Tzung-Dau
authors.initials: TD
authors.lastname: Wang
authors.forename: Zui-Shen
authors.initials: ZS
authors.lastname: Yen
authors.forename: Chien-Chang
authors.initials: CC
authors.lastname: Lee
authors.forename: Shyr-Chyr
authors.initials: SC
authors.lastname: Chen
authors.forename: Wen-Jone
authors.initials: WJ
authors.lastname: Chen
mesh_terms: D000818:Animals; D001237:Asphyxia / Q000097:blood / Q000150:complications / Q000000981:diagnostic imaging / Q000628:therapy; D004452:Echocardiography; D004837:Epinephrine / Q000494:pharmacology*; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins / Q000097:blood; D006323:Heart Arrest / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology / Q000628:therapy*; D007036:Hypothermia, Induced; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012151:Resuscitation; D015398:Signal Transduction / Q000187:drug effects; D013566:Sympathomimetics / Q000494:pharmacology*; D013599:Systole / Q000187:drug effects; D013997:Time Factors
chemical_list: C509948:FABP3 protein, rat; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins; D013566:Sympathomimetics; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D004837:Epinephrine