The role of calcium in the enhanced myocardial contractility of the hyperthyroid rat heart.
The hyperthyroid rat myocardium exhibits enhanced contractility. There is evidence that altered calcium handling by the myocardium may be responsible for this enhanced state. To investigate this, isolated hyperthyroid and euthyroid hearts were perfused in the working mode and exposed to alterations in external calcium concentration. Heart rate was not significantly different in either group of hearts, nor was it altered by the change in calcium. The concentration of calcium needed to elicit half-maximal contractility (dP/dtmax) was lower in the hyperthyroid (0.81 +/- 0.07 mM) than in the euthyroid hearts (1.12 +/- 0.09 mM, p less than 0.05). This increase in calcium sensitivity was unlikely to be at the site of the sarcolemma as verapamil exerted equal negative inotropic effects on both groups of hearts. Dantrolene, which blocks calcium release from the sarcoplasmic reticulum, exerted a significantly greater (p less than 0.01) depression in dP/dtmax after 12 min in the hyperthyroid (50 +/- 7%) than in the euthyroid heart (15 +/- 2%). We conclude from our results that the enhanced contractile state of the hyperthyroid rat heart is likely to involve an altered mechanical response to calcium which is possibly at the level of enhanced calcium release from the sarcoplasmic reticulum.
Butkow
N
N
Department of Physiology, University of the Witwatersrand Medical School, Johannesburg, South Africa.
Wheatley
A M
AM
Lippe
I T
IT
Marcus
R H
RH
Rosendorff
C
C
D000818:Animals; D002118:Calcium / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D003620:Dantrolene / Q000494:pharmacology; D003864:Depression, Chemical; D006339:Heart Rate; D006980:Hyperthyroidism / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013974:Thyroxine; D014700:Verapamil / Q000494:pharmacology
D014700:Verapamil; D003620:Dantrolene; D013974:Thyroxine; D002118:Calcium