Decreased creatine kinase is linked to diastolic dysfunction in rats with right heart failure induced by pulmonary artery hypertension
Ventricular trabeculae from rat heart were chemically skinned with Triton-X100, which disrupts all cellular membranes including the sarcoplasmic reticulum. Trabeculae developed a maintained rigor contracture when adenosine triphosphate was withdrawn from the bathing medium. In all preparations, the final level of rigor force developed in the presence of caffeine (10–40 mM) was greater than under control conditions. However, caffeine failed to increase rigor tension when applied after contracture had fully developed. The effect of caffeine on rigor was maximal at about 15 mM; concentrations greater or less than 15 mM were less effective. On average, caffeine decreased the time required to develop half-maximum rigor force. The caffeine-induced potentiation of rigor force occurred in the effective absence of Ca2+ (10−9 M), in solutions strongly Ca2+-buffered with [ethylenebis(oxonitrilo)]tetraaceticacid (10–50 mM). In all preparations, rigor force was found to be independent of [Ca2+] over the range 10−10 M to about 10−7 M. These results suggest that caffeine affects rigor force by a direct effect on the myofilaments via a mechanism that is independent of Ca2+.