Cytoskeletal Role in the Contractile Dysfunction of Hypertrophied Myocardium

Abstract

Cardiac hypertrophy in response to systolic pressure loading frequently results in contractile dysfunction of unknown cause. In the present study, pressure loading increased the microtubule component of the cardiac muscle cell cytoskeleton, which was responsible for the cellular contractile dysfunction observed. The linked microtubule and contractile abnormalities were persistent and thus may have significance for the deterioration of initially compensatory cardiac hypertrophy into congestive heart failure.

Mechanisms associated with the negative inotropic effect of deuterium oxide in single rat ventricular myocytes

“…In another series of experiments (not shown for brevity), 50% DµO had very similar qualitative and quantitative effects on isometric contractions of isolated ferret papillary muscles at 30°C, suggesting that our observations were not uniquely dependent upon of our experimental conditions. Single myocytes were exposed to colchicine (245 ìÒ for at least 30 min) in order to test for a possible role for microtubules (Tsutsui et al 1993(Tsutsui et al , 1994Ishibashi, et al 1996;Howarth et al 1999;Cicogna, et al 1999) in the negative inotropic effect of DµO. This agent has been reported to disrupt microtubles following a 1 h exposure at 10 ìÒ and to reverse microtubule-induced negative inotropic effects (Tsutsui et al 1993(Tsutsui et al , 1994Ishibashi et al 1996).…”

“…Single myocytes were exposed to colchicine (245 ìÒ for at least 30 min) in order to test for a possible role for microtubules (Tsutsui et al 1993(Tsutsui et al , 1994Ishibashi, et al 1996;Howarth et al 1999;Cicogna, et al 1999) in the negative inotropic effect of DµO. This agent has been reported to disrupt microtubles following a 1 h exposure at 10 ìÒ and to reverse microtubule-induced negative inotropic effects (Tsutsui et al 1993(Tsutsui et al , 1994Ishibashi et al 1996). Prior incubation with colchicine had no significant effects on either the amplitude or time course of contraction of single rat myocytes (in agreement with previous findings on control animals from Tsutsui et al 1993Tsutsui et al , 1994Ishibashi et al 1996;Cicogna, et al 1999).…”

“…This agent has been reported to disrupt microtubles following a 1 h exposure at 10 ìÒ and to reverse microtubule-induced negative inotropic effects (Tsutsui et al 1993(Tsutsui et al , 1994Ishibashi et al 1996). Prior incubation with colchicine had no significant effects on either the amplitude or time course of contraction of single rat myocytes (in agreement with previous findings on control animals from Tsutsui et al 1993Tsutsui et al , 1994Ishibashi et al 1996;Cicogna, et al 1999). Upon exposure to 50% DµO, in the continued presence of colchicine, cell shortening was reduced from 7.4 ± 1.1 to 2.7 ± 0.5% of resting cell length (n = 13, P < 0.05; Fig.…”

“…Proliferation of microtubules during hypertrophy (e.g. Tsutsui et al 1993Tsutsui et al , 1994 or by use of agents such as Taxol (Tsutsui et al 1994;Howarth et al 1999) have been shown to reduce myocyte contraction. DµO is used to modulate microtubules in cardiac muscle (e.g.…”

“…DµO is used to modulate microtubules in cardiac muscle (e.g. Takahashi et al 1998) and it has been suggested that acute proliferation of microtubules by DµO can explain its reduction of the contraction of cardiac myocytes (Tsutsui et al 1993(Tsutsui et al , 1994. If DµO were to rapidly polymerize microtubules, in the absence of other effects, in cardiac muscle, it would not only explain the contractile effects of DµO but, perhaps more importantly, it would identify DµO as the agent of choice for microtubule proliferation, as agents such as Taxol require several hours for their effects on microtubules to develop (Tsutsui et al 1994;Howarth et al 1999).…”