Decreased cAMP Level and Decreased Downregulation of β1-Adrenoceptor Expression in Therapeutic Hypothermia-Resuscitated Myocardium Are Associated With Improved Post-Resuscitation Myocardial Function

作者：Wang, Wei; Hua, Tianfeng; Li, Hao; Wu, Xiaobo; Bradley, Jennifer; Peberdy, Mary Ann; Ornato, Joseph P.; Tang, Wanchun^*

来源：Journal of the American Heart Association, 2018, 7(6): e006573.

DOI：10.1161/JAHA.117.006573

• adrenoceptor
• CPR
• epinephrine
• hypothermia
• post-resuscitation

Background-Epinephrine administered during cardiopulmonary resuscitation (CPR) is associated with severe post-resuscitation myocardial dysfunction. We previously demonstrated that therapeutic hypothermia reduced the severity of post-resuscitation myocardial dysfunction caused by epinephrine; however, the relationship between myocardial adrenoceptor expression and myocardial protective effects by hypothermia remains unclear. @@@ Methods and Results-Rats weighing between 450 and 550 g were randomized into 5 groups: (1) normothermic placebo, (2)normothermic epinephrine, (3) hypothermic placebo, (4) hypothermic epinephrine, and (5) sham (not subject to cardiac arrest and resuscitation). Ventricular fibrillation was induced and untreated for 8 minutes for all other groups. Hypothermia was initiated coincident with the start of CPR and maintained at 33 +/- 0.2 degrees C for 4 hours. Placebo or epinephrine was administered 5 minutes after the start of CPR and 3 minutes before defibrillation. Post-resuscitation ejection fraction was measured hourly for 4 hours then hearts were harvested. Epinephrine increased coronary perfusion pressure during CPR (27 +/- 6 mm Hg versus 21 +/- 2 mm Hg P<0.05). Post-resuscitation myocardial function was impaired in the normothermic epinephrine group compared with other groups. The concentration of myocardial cAMP doubled in the normothermic epinephrine group (655.06 +/- 447.63 mu mol/L) compared with the hypothermic epinephrine group (302.51 +/- 97.98 mu mol/L; P<0.05). Myocardial beta(1)-adrenoceptor expression decreased with normothermia cardiac arrest but not with hypothermia regardless of epinephrine. @@@ Conclusions-Epinephrine, administered during normothermic CPR, increased the severity of post-resuscitation myocardial dysfunction. This adverse effect was inhibited by intra-arrest hypothermia resuscitation. Declined cAMP with more preserved beta(1)-adrenoceptors in hypothermia-resuscitated myocardium is associated with improved post-resuscitated myocardial function in vivo.

• 出版日期2018-3-20
• 单位中山大学; 安徽医科大学