Modest actomyosin energy conservation increases myocardial postischemic function

Bradford C. Blunt, Yi Chen, James D. Potter, Polly A. Hofmann

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

We have proposed that pharmacological pre-conditioning, leading to PKC-ε activation, in hearts improves postischemic functional recovery through a decrease in actomyosin ATPase activity and subsequent ATP conservation. The purpose of the present study was to determine whether moderate PKC-independent decreases in actomyosin ATPase are sufficient to improve myocardial postischemic function. Rats were given propylthiouracil (PTU) for 8 days to induce a 25% increase in β-myosin heavy chain with a 28% reduction in actomyosin ATPase activity. Recovery of postischemic left ventricular developed pressure (LVDP) was significantly higher in PTU-treated rat hearts subjected to 30 min of global ischemia than in control hearts: 57.9 ± 6.2 vs. 32.6 ± 5.1% of preischemic values. In addition, PTU-treated hearts exhibited a delayed onset of rigor contracture during ischemia and a higher global ATP content after ischemia. In the second part of our study, we demonstrated a lower maximal actomyosin ATPase and a higher global ATP content after ischemia in human troponin T (TnT) transgenic mouse hearts. In mouse hearts with and without a point mutation at F110I of human TnT, recovery of postischemic LVDP was 55.4 ± 5.5 and 62.5 ± 14.5% compared with 20.0 ± 2.9% in nontransgenic mouse hearts after 35 min of global ischemia. These results are consistent with the hypothesis that moderate decreases in actomyosin ATPase activity result in net ATP conservation that is sufficient to improve postischemic contractile function.

Original languageEnglish (US)
Pages (from-to)H1088-H1096
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume288
Issue number3 57-3
DOIs
StatePublished - Mar 1 2005

Keywords

  • Adenine nucleotides
  • Adenosinetriphosphatase
  • Hypothyroid
  • Left ventricular developed pressure
  • Preconditioning
  • Troponin T

ASJC Scopus subject areas

  • Physiology

Fingerprint Dive into the research topics of 'Modest actomyosin energy conservation increases myocardial postischemic function'. Together they form a unique fingerprint.

  • Cite this