Faculty Collaboration Database

Cross-bridge kinetics modeled from myoplasmic [Ca2+] and LV pressure at 17 degrees C and after 37 degrees C and 17 degrees C ischemia. Am J Physiol Heart Circ Physiol 2003 Apr;284(4):H1217-29

Date

01/18/2003

Pubmed ID

12531735

DOI

10.1152/ajpheart.00816.2002

Scopus ID

2-s2.0-0037377557 (requires institutional sign-in at Scopus site)   15 Citations

Abstract

We modeled changes in contractile element kinetics derived from the cyclic relationship between myoplasmic [Ca(2+)], measured by indo 1 fluorescence, and left ventricular pressure (LVP). We estimated model rate constants of the Ca(2+) affinity for troponin C (TnC) on actin (A) filament (TnCA) and actin and myosin (M) cross-bridge (A x M) cycling in intact guinea pig hearts during baseline 37 degrees C perfusion and evaluated changes at 1) 20 min 17 degrees C pressure, 2) 30-min reperfusion (RP) after 30-min 37 degrees C global ischemia during 37 degrees C RP, and 3) 30-min RP after 240-min 17 degrees C global ischemia during 37 degrees C RP. At 17 degrees C perfusion versus 37 degrees C perfusion, the model predicted: A x M binding was less sensitive; A x M dissociation was slower; Ca(2+) was less likely to bind to TnCA with A x M present; and Ca(2+) and TnCA binding was less sensitive in the absence of A x M. Model results were consistent with a cold-induced fall in heart rate from 260 beats/min (37 degrees C) to 33 beats/min (17 degrees C), increased diastolic LVP, and increased phasic Ca(2+). On RP after 37 degrees C ischemia vs. 37 degrees C perfusion, the model predicted the following: A x M binding was less sensitive; A x M dissociation was slower; and Ca(2+) was less likely to bind to TnCA in the absence of A. M. Model results were consistent with reduced myofilament responsiveness to [Ca(2+)] and diastolic contracture on 37 degrees C RP. In contrast, after cold ischemia versus 37 degrees C perfusion, A x M association and dissociation rates, and Ca(2+) and TnCA association rates, returned to preischemic values, whereas the dissociation rate of Ca(2+) from A x M was ninefold faster. This cardiac muscle kinetic model predicted a better-restored relationship between Ca(2+) and cross-bridge function on RP after an eightfold longer period of 17 degrees C than 37 degrees C ischemia.

Author List

Rhodes SS, Ropella KM, Audi SH, Camara AK, Kevin LG, Pagel PS, Stowe DF

Authors

Said Audi PhD Professor in the Biomedical Engineering department at Marquette University
Amadou K. Camara PhD Professor in the Anesthesiology department at Medical College of Wisconsin
David F. Stowe MD, PhD Professor in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Actins
Animals
Blood Pressure
Calcium
Cold Temperature
Fluorescent Dyes
Guinea Pigs
Heart Rate
Hot Temperature
Indoles
Kinetics
Mathematics
Models, Biological
Myocardial Ischemia
Myocardial Reperfusion Injury
Myocardium
Myosins
Spectrometry, Fluorescence
Troponin C
Ventricular Function, Left