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

Abstract：

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°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 μmol/L) compared with the hypothermic epinephrine group (302.51±97.98 μmol/L; P<0.05). Myocardial β1-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 β1-adrenoceptors in hypothermia-resuscitated myocardium is associated with improved post-resuscitated myocardial function in vivo.

journal_name

J Am Heart Assoc

journal_title

Journal of the American Heart Association

authors

Wang W,Hua T,Li H,Wu X,Bradley J,Peberdy MA,Ornato JP,Tang W

doi

10.1161/JAHA.117.006573

subject

Has Abstract

pub_date

2018-03-23 00:00:00

issue

issn

2047-9980

pii

JAHA.117.006573

journal_volume

pub_type

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