Role of calcium in acute hyperthermic myocardial injury

Thomas Everett, Sunil Nath, Carl Lynch, James M. Beach, James G. Whayne, David E. Haines

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Introduction: We hypothesized that intracellular calcium overload may play an important role in heat-induced myocardial injury. This postulate was investigated using a model of isolated guinea pig papillary muscle in which resting tension was measured as an indirect indicator of cytosolic free-calcium concentration and the fluorescence changes of Fluo-3 AM dye was measured as a direct indicator of cytosolic free-calcium concentration. Methods and Results: Excised guinea pig right ventricular papillary muscles were attached to a force transducer in a high-flow tissue bath and superfused with Tyrode's solution at 37° ± 0.5°C. The temperature was rapidly changed to between 38.0° and 56.0°C for 60 seconds and then returned to 37.0°C. Hyperthermia caused a reversible increase in resting tension at temperatures between 45° and 50°C and irreversible contracture at ≥50°C. Rapid cooling contracture experiments and experiments measuring fluorescence of myocytes loaded with 5 μM Fluo-3 AM dye demonstrated that the hyperthermia-induced rise in resting tension was likely due to an increase in intracellular calcium content. Inhibition of the sarcoplasmic reticulum calcium pump with 20 μM thapsigargin resulted in irreversible contracture of the papillary muscles at temperatures between 45° and 50°C and significant increases in Fluo-3 fluorescence at 48°C. Blockade of sarcolemmal calcium channels with 0.5 mM cadmium or 40 μM verapamil did not attenuate the heat-induced increase in resting tension and Fluo-3 fluorescence. Conclusion: Hyperthermia causes an increase in resting tension of cardiac muscle that most likely is mediated by a calcium channel-independent increase in calcium permeability of the sarcolemmal membrane and/or release of stored intracellular calcium.

Original languageEnglish (US)
Pages (from-to)563-569
Number of pages7
JournalJournal of Cardiovascular Electrophysiology
Volume12
Issue number5
StatePublished - 2001
Externally publishedYes

Fingerprint

Calcium
Wounds and Injuries
Papillary Muscles
Contracture
Fluorescence
Calcium Channels
Temperature
Guinea Pigs
Fever
Coloring Agents
Hot Temperature
Induced Hyperthermia
Thapsigargin
Sarcoplasmic Reticulum
Verapamil
Transducers
Cadmium
Baths
Muscle Cells
Permeability

Keywords

  • Calcium
  • Hyperthermia
  • Injury
  • Myocardium

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology

Cite this

Everett, T., Nath, S., Lynch, C., Beach, J. M., Whayne, J. G., & Haines, D. E. (2001). Role of calcium in acute hyperthermic myocardial injury. Journal of Cardiovascular Electrophysiology, 12(5), 563-569.

Role of calcium in acute hyperthermic myocardial injury. / Everett, Thomas; Nath, Sunil; Lynch, Carl; Beach, James M.; Whayne, James G.; Haines, David E.

In: Journal of Cardiovascular Electrophysiology, Vol. 12, No. 5, 2001, p. 563-569.

Research output: Contribution to journalArticle

Everett, T, Nath, S, Lynch, C, Beach, JM, Whayne, JG & Haines, DE 2001, 'Role of calcium in acute hyperthermic myocardial injury', Journal of Cardiovascular Electrophysiology, vol. 12, no. 5, pp. 563-569.
Everett T, Nath S, Lynch C, Beach JM, Whayne JG, Haines DE. Role of calcium in acute hyperthermic myocardial injury. Journal of Cardiovascular Electrophysiology. 2001;12(5):563-569.
Everett, Thomas ; Nath, Sunil ; Lynch, Carl ; Beach, James M. ; Whayne, James G. ; Haines, David E. / Role of calcium in acute hyperthermic myocardial injury. In: Journal of Cardiovascular Electrophysiology. 2001 ; Vol. 12, No. 5. pp. 563-569.
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