Cellular basis for contractile dysfunction in the diaphragm from a rabbit infarct model of heart failure.
Abnormal respiratory muscle function is thought to contribute to breathlessness and exercise intolerance in heart failure but little is known about possible alterations in the function of such muscle. We have measured tetanic force and intracellular Ca(2+) concentration ([Ca(2+)](i)) in isolated, arterially perfused hemidiaphragm preparations from a rabbit coronary artery ligation model of heart failure. Increasing stimulation frequency (10-100 Hz) caused a progressive increase of force and [Ca(2+)](i) in control preparations, whereas force and [Ca(2+)](i) only increased between 10 and 25 Hz stimulation (decreasing at higher frequencies) in preparations from ligated animals. Cyclopiazonic acid produced a dose-dependent shift in the relationship between stimulation frequency and [Ca(2+)](i) in control preparations that was similar to the shift observed in the diaphragm of coronary-ligated animals. These data indicate that the in vitro contractile characteristics of the diaphragm are significantly altered in our model and that altered [Ca(2+)](i) regulation contributes to the reduced diaphragm strength observed in heart failure.
MacFarlane
N G
NG
Institute of Biomedical Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom. N.MacFarlane@bio.gla.ac.uk
Darnley
G M
GM
Smith
G L
GL
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002303:Cardiac Output, Low / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D003331:Coronary Vessels; D003964:Diaphragm / Q000378:metabolism / Q000503:physiopathology*; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism; D007537:Isometric Contraction; D008026:Ligation; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000150:complications*; D009994:Osmolar Concentration; D010791:Phrenic Nerve / Q000503:physiopathology; D011817:Rabbits; D012016:Reference Values
D004791:Enzyme Inhibitors; D007211:Indoles; D002118:Calcium; C000543:cyclopiazonic acid