부산대학교 도서관

It is currently unclear whether left ventricular (LV) myofilament function is depressed in experimental LV hypertrophy (LVH) or congestive heart failure (CHF). To address this issue, we studied pressure overload-induced LV hypertrophy (POLVH) and myocardial infarction-elicited congestive heart failure (MICHF) in rats. LV myocytes were isolated from control, POLVH, and MICHF hearts by mechanical homogenization, skinned with Triton, and attached to micropipettes that projected from a sensitive force transducer and high-speed motor. A subset of cells was treated with either unphosphorylated, recombinant cardiac troponin (cTn) or cTn purified from either control or failing ventricles. LV myofilament function was characterized by the force-[[Ca.sup.2+]] relation yielding [Ca.sup.2+]-saturated maximal force ([F.sub.max]), myofilament [Ca.sup.2+] sensitivity ([EC.sub.50]), and cooperativity (Hill coefficient, [n.sub.H]) parameters. POLVH was associated with a 35% reduction in [F.sub.max] and 36% increase in [EC.sub.50]. Similarly, MICHF resulted in a 42% reduction in [F.sub.max], and a 30% increase in [EC.sub.50]. Incorporation of recombinant cTn or purified control cTn into failing cells restored myofilament [Ca.sup.2+] sensitivity toward levels observed in control cells. In contrast, integration of cTn purified from failing ventricles into control myocytes increased [EC.sub.50] to levels observed in failing myocytes. The [F.sub.max] parameter was not markedly affected by troponin exchange, cTnI phosphorylation was increased in both POLVH and MICHF left ventricles. We conclude that depressed myofilament [Ca.sup.2+] sensitivity in experimental LVH and CHF is due, in part, to a decreased functional role of cTn that likely involves augmented phosphorylation of cTnI. left ventricle; troponin; phosphorylation; cardiac disease