Circulation Research, Vol 69, 196-208, Copyright © 1991 by American Heart Association
ARTICLES |
A cellular mechanism for impaired posthypoxic relaxation in isolated cardiac myocytes. Altered myofilament relaxation kinetics at reoxygenation
HS Silverman, M Ninomiya, PS Blank, O Hano, H Miyata, HA Spurgeon, EG Lakatta and MD Stern
Laboratory of Cardiovascular Science, National Institute on Aging, Baltimore, Md.
Single, isolated rat ventricular myocytes were made hypoxic for 10 minutes and then reoxygenated. During hypoxia, there was a marked abbreviation of the mechanical twitch, without a decrease in its amplitude. Immediately after reoxygenation, both the time to peak shortening and the duration of relaxation were markedly prolonged, and they remained prolonged for 10-50 minutes. The alterations in contraction and relaxation were not associated with any change in the time course of either the transmembrane action potential or the cytosolic calcium transient, as recorded with the fluorescent probe indo 1. Intracellular pH, measured with a fluorescent probe (carboxyseminaphthorhodofluor), showed an acid shift during hypoxia and an alkaline rebound immediately after reoxygenation. The time courses of intracellular pH and contraction duration were not parallel during hypoxia or reoxygenation, and simulation of the alkaline pH shift by lowering PCO2 or superfusing NH4Cl (in the absence of exposure to hypoxia) did not quantitatively reproduce the prolongation of relaxation seen after reoxygenation. The prolongation of contraction after reoxygenation could be overridden by the beta-adrenergic agonist isoproterenol or the nonenzymatic phosphatase butanedione monoxime. We conclude that delayed relaxation after reoxygenation exists at the single cell level and is due to an alteration of the properties of the myofilaments. Intracellular pH is not the primary mediator of this alteration. We speculate that alteration of intracellular inorganic phosphate or covalent modification of the myofilaments might be involved.
This article has been cited by other articles:
 |
|
 |
|
  J.-M. Pei, J.-J. Zhou, J.-S. Bian, X.-C. Yu, M.-L. Fung, and T.-M. Wong Impaired [Ca2+]i and pHi responses to kappa -opioid receptor stimulation in the heart of chronically hypoxic rats Am J Physiol Cell Physiol, November 1, 2000; 279(5): C1483 - C1494. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Ito, Y. Kagaya, T. Ishizuka, N. Ito, N. Ishide, and K. Shirato Diacylglycerol delays pHi overshoot after reperfusion and attenuates contracture in isolated, paced myocytes Am J Physiol Heart Circ Physiol, November 1, 1999; 277(5): H1708 - H1717. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.A. Garcia-Fernandez, J. Azevedo, M. Moreno, J. Bermejo, N. Perez-Castellano, P. Puerta, M. Desco, C. Antoranz, J.A. Serrano, E. Garcia, et al. Regional diastolic function in ischaemic heart disease using pulsed wave Doppler tissue imaging Eur. Heart J., April 1, 1999; 20(7): 496 - 505. [Abstract] [PDF]
|
|
|
|
 |
|
 H. Kondo, T. Masuyama, K. Ishihara, T. Mano, K. Yamamoto, J. Naito, R. Nagano, S. Kishimoto, J. Tanouchi, M. Hori, et al. Digital Subtraction High-Frame-Rate Echocardiography in Detecting Delayed Onset of Regional Left Ventricular Relaxation in Ischemic Heart Disease Circulation, January 15, 1995; 91(2): 304 - 312. [Abstract] [Full Text]
|
|