Mechanisms underlying hypothermia-induced cardiac contractile dysfunction.
Rewarming patients after profound hypothermia may result in acute heart failure and high mortality (50-80%). However, the underlying pathophysiological mechanisms are largely unknown. We characterized cardiac contractile function in the temperature range of 15-30 degrees C by measuring the intracellular Ca(2+) concentration ([Ca(2+)](i)) and twitch force in intact left ventricular rat papillary muscles. Muscle preparations were loaded with fura-2 AM and electrically stimulated during cooling at 15 degrees C for 1.5 h before being rewarmed to the baseline temperature of 30 degrees C. After hypothermia/rewarming, peak twitch force decreased by 30-40%, but [Ca(2+)](i) was not significantly altered. In addition, we assessed the maximal Ca(2+)-activated force (F(max)) and Ca(2+) sensitivity of force in skinned papillary muscle fibers. F(max) was decreased by approximately 30%, whereas the pCa required for 50% of F(max) was reduced by approximately 0.14. In rewarmed papillary muscle, both total cardiac troponin I (cTnI) phosphorylation and PKA-mediated cTnI phosphorylation at Ser23/24 were significantly increased compared with controls. We conclude that after hypothermia/rewarming, myocardial contractility is significantly reduced, as evidenced by reduced twitch force and F(max). The reduced myocardial contractility is attributed to decreased Ca(2+) sensitivity of force rather than [Ca(2+)](i) itself, resulting from increased cTnI phosphorylation.
Han
Young-Soo
YS
Dept. of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
Tveita
Torkjel
T
Prakash
Y S
YS
Sieck
Gary C
GC
D000818:Animals; D001831:Body Temperature / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D004558:Electric Stimulation; D005456:Fluorescent Dyes / Q000494:pharmacology; D016257:Fura-2 / Q000031:analogs & derivatives / Q000494:pharmacology; D007035:Hypothermia / Q000503:physiopathology*; D008297:Male; D023421:Models, Animal; D009200:Myocardial Contraction / Q000502:physiology*; D010210:Papillary Muscles / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D019210:Troponin I / Q000378:metabolism
D005456:Fluorescent Dyes; D019210:Troponin I; C049925:fura-2-am; D002118:Calcium; D016257:Fura-2