In:
American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 279, No. 2 ( 2000-08-01), p. H702-H708
Abstract:
Catecholamines and elevated extracellular Ca 2+ concentration ([Ca 2+ ] o ) augment contractile force by increased Ca 2+ influx and subsequent increased sarcoplasmic reticulum (SR) Ca 2+ release. We tested the hypothesis that pyruvate potentiates Ca 2+ release and inotropic response to isoproterenol and elevated [Ca 2+ ] o , since this might be of potential importance in a clinical setting to circumvent deleterious effects on energy demand during application of catecholamines. Therefore, we investigated isometrically contracting myocardial preparations from rabbit hearts at 37°C, pH 7.4, and a stimulation frequency of 1 Hz. At a [Ca 2+ ] o of 1.25 mM, pyruvate (10 mM) alone increased developed force (F dev ) from 1.89 ± 0.42 to 3.62 ± 0.62 (SE) mN/mm 2 ( n = 8, P 〈 0.05) and isoproterenol (10 −6 M) alone increased F dev from 2.06 ± 0.55 to 25.11 ± 2.1 mN/mm 2 ( P 〈 0.05), whereas the combination of isoproterenol and pyruvate increased F dev overproportionally from 1.89 ± 0.42 to 33.31 ± 3.18 mN/mm 2 ( P 〈 0.05). In a separate series of experiments, we assessed SR Ca 2+ content by means of rapid cooling contractures and observed that, despite no further increase in F dev by increasing [Ca 2+ ] o from 8 to 16 mM, 10 mM pyruvate could still increase F dev from 26.4 ± 6.8 to 29.7 ± 7.1 mN/mm 2 ( P 〈 0.05, n = 9) as well as the Ca 2+ load of the SR. The results show that the positive inotropic effects of pyruvate potentiate the inotropic effects of isoproterenol or Ca 2+ , because in the presence of pyruvate, Ca 2+ and isoproterenol induced larger increases in inotropy than can be calculated by mere addition of the individual effects.
Type of Medium:
Online Resource
ISSN:
0363-6135
,
1522-1539
DOI:
10.1152/ajpheart.2000.279.2.H702
Language:
English
Publisher:
American Physiological Society
Publication Date:
2000
detail.hit.zdb_id:
1477308-9
SSG:
12
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