Cellular basis for contractile dysfunction in the diaphragm from a rabbit infarct model of heart failure

Abnormal respiratory muscle function isthought to contribute to breathlessness and exercise intolerance inheart failure but little is known about possible alterations in thefunction of such muscle. We have measured tetanic force andintracellular Ca²⁺ concentration([Ca²⁺]_i) in isolated, arteriallyperfused hemidiaphragm preparations from a rabbit coronary arteryligation model of heart failure. Increasing stimulation frequency(10-100 Hz) caused a progressive increase of force and[Ca²⁺]_i in control preparations,whereas force and [Ca²⁺]_i onlyincreased between 10 and 25 Hz stimulation (decreasing at higherfrequencies) in preparations from ligated animals. Cyclopiazonic acidproduced a dose-dependent shift in the relationship between stimulationfrequency and [Ca²⁺]_i in controlpreparations that was similar to the shift observed in the diaphragm ofcoronary-ligated animals. These data indicate that the in vitrocontractile characteristics of the diaphragm are significantly alteredin our model and that altered[Ca²⁺]_i regulation contributes tothe reduced diaphragm strength observed in heart failure.