Bupivacaine Attenuates Contractility by Decreasing Sensitivity of Myofilaments to Ca2+, in Rat Ventricular Muscle |
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Authors: | Mio, Yasushi M.D. Fukuda, Norio Ph.D. Kusakari, Yoichiro M.D. Tanifuji, Yasumasa M.D. Kurihara, Satoshi M.D., Ph.D.
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Affiliation: | Mio, Yasushi M.D.*; Fukuda, Norio Ph.D.†; Kusakari, Yoichiro M.D.†; Tanifuji, Yasumasa M.D.‡; Kurihara, Satoshi M.D., Ph.D.§ |
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Abstract: | Background: Bupivacaine exhibits a cardiodepressant effect, the molecular mechanism(s) of which have yet to be fully understood. Bupivacaine may directly act on contractile proteins and thereby decrease myofibrillar Ca2+ sensitivity. Methods: Rat ventricular muscle was used. First, the effect of bupivacaine was examined on tetanic contractions in isolated intact myocytes. Next, Triton X-100-treated ventricular trabeculae were used to investigate the effect of bupivacaine on the pCa (= -log [Ca2+])-tension relation as well as on maximal Ca2+-activated tension. Furthermore, to test whether bupivacaine inhibits the pathway downstream from Ca2+ binding to troponin C, tension was elicited in the skinned preparations by lowering the Mg-adenosine triphosphate (MgATP) concentration in the absence of Ca2+. The effect of bupivacaine on the pMgATP (= -log [MgATP])-tension relation was examined. Results: In myocytes, 3 [mu]m bupivacaine significantly (P < 0.01) increased intracellular Ca2+ concentration required for 5% cell shortening from the resting cell length. In skinned preparations, bupivacaine shifted the pCa-tension relation to the lower pCa side; the midpoint of the pCa curve (pCa50) was significantly (P < 0.05) changed by 10 and 100 [mu]m bupivacaine. A highly correlated linear relation (R = 0.81;P < 0.0005) was present between pCa50 and maximal Ca2+-activated tension. Bupivacaine (10 and 100 [mu]m) significantly (P < 0.05) shifted the midpoint of the pMgATP-tension relation to the higher pMgATP side. |
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