Mechanisms underlying hypothermia-induced cardiac contractile dysfunction

Young Soo Han, Torkjel Tveita, Y. S. Prakash, Gary C. Sieck

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

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°C by measuring the intracellular Ca 2+ concentration ([Ca2+]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°C for 1.5 h before being rewarmed to the baseline temperature of 30°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 Ca2+-activated force (Fmax) and Ca2+ sensitivity of force in skinned papillary muscle fibers. F max was decreased by ∼30%, whereas the pCa required for 50% of Fmax was reduced by ∼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 Fmax. The reduced myocardial contractility is attributed to decreased Ca2+ sensitivity of force rather than [Ca2+]i itself, resulting from increased cTnI phosphorylation.

Original languageEnglish (US)
Pages (from-to)H890-H897
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume298
Issue number3
DOIs
StatePublished - Mar 1 2010

Keywords

  • Calcium sensitivity
  • Rat
  • Troponin I phosphorylation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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