Both systolic and diastolic dysfunction characterize nonischemic inhibition of myocardial energy metabolism: an experimental strain rate echocardiographic study

J Am Soc Echocardiogr. 2004 Dec;17(12):1239-44. doi: 10.1016/j.echo.2004.08.015.

Abstract

Background: Ischemia is primarily a metabolic event. However, regional functional changes can be affected by structural alterations. We developed an experimental model of sole myocardial energy metabolism inhibition and characterized the resulting regional dysfunction.

Methods: In 12 pigs, we regionally inhibited creatine kinase (CK) and, consequently, myocyte high-energy phosphate transfer by intracoronary administration of iodoacetamide. Myocardial biopsies for CK activity and structural analyses and strain rate (SR) echocardiography scans were obtained at baseline and 60 minutes after iodoacetamide administration. Plasma levels of the CK isoenzyme MB and troponin I were assessed to determine possible myocardial damage.

Results: CK activity in the iodoacetamide-perfused myocardium decreased to 0.5% of the original value and was accompanied by a reduction in peak systolic SR ( P < .0001), end-systolic strain ( P < .0001), and peak SRs of myocardial early and late filling waves ( P < .0001). Microscopy showed contracture without sarcomere disruption. Plasma levels of CK isoenzyme MB and troponin I did not change.

Conclusions: Regional inhibition of myocyte energetics leads to both systolic and diastolic dysfunction by SR echocardiography, but the presence of a residual phosphotransfer protects microstructural integrity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Creatine Kinase / antagonists & inhibitors
  • Diastole / drug effects
  • Diastole / physiology
  • Echocardiography
  • Energy Metabolism / drug effects
  • Enzyme Inhibitors / pharmacology
  • Iodoacetamide / pharmacology
  • Models, Animal
  • Myocardial Contraction / drug effects
  • Myocardial Contraction / physiology
  • Myocardial Ischemia / diagnostic imaging*
  • Myocardial Ischemia / physiopathology
  • Myocardium / enzymology
  • Myocardium / metabolism*
  • Swine
  • Systole / drug effects
  • Systole / physiology
  • Ventricular Dysfunction / diagnostic imaging*
  • Ventricular Dysfunction / enzymology
  • Ventricular Dysfunction / metabolism

Substances

  • Enzyme Inhibitors
  • Creatine Kinase
  • Iodoacetamide