RESUMO
The effects of diltiazem (2.2 X 10(-7) and 2.2 X 10(-6) M) on isometric contraction and K+-induced contracture (Pc) were determined for right ventricular muscles from normal cats and cats with right ventricular systolic hypertension (RVSH) monitored 4-15 days after partial pulmonary artery obstruction. Muscles obtained from cats with RVSH had significantly decreased maximum isometric force (Po) and maximum rate of force development (dF/dt). Diltiazem (2.2 x 10(-7) and 2.2 x 10(-6) M) significantly reduced Pc of both normal and pressure-overloaded muscle. Po of normal muscle was decreased only by 2.2 X 10(-6) M, while Po of pressure-overloaded muscle was significantly reduced at a lower concentration (2.2 X 10(-7) M0. The effect of diltiazem was reversed by increases to [Ca2+]0. These results demonstrate that contractile function of pressure-overloaded ventricular myocardium is more sensitive to diltiazem.
Assuntos
Benzazepinas/farmacologia , Diltiazem/farmacologia , Hipertensão/fisiopatologia , Contração Miocárdica/efeitos dos fármacos , Animais , Cálcio/metabolismo , Gatos , Miocárdio/metabolismoRESUMO
The effects of amrinone (5.3 X 10(-4) M) on isometric contraction and K+-induced contracture force of right ventricular muscle isolated from normal cats (n = 6) and cats in right ventricular failure (RVF, n = 6), 3-14 days after partial pulmonary artery ligation, were studied. Peak isometric contractile force (Po) and maximal rate of force development (dP/dt) of RVF muscles (1.38 +/- 0.21 g/mm2; means +/- SEM, and 11 +/- 1 g/s/mm2, respectively) were significantly lower than normal muscles (2.46 +/- 0.41 g/mm2, p less than 0.025, and 24 +/- 3 g/s/mm2, p less than 0.005, respectively). Duration of contraction (DC) was significantly longer in RVF muscles (442 +/- 32 ms) than in normal muscles (361 +/- 11 ms, p less than 0.025). Times to peak twitch force (TTP) and peak K+-induced contracture force (Pc) of RVF and normal muscles were not different. Amrinone increased Po and dP/dt significantly in normal muscles (+78 +/- 24%; means +/- SEM; p less than 0.01, and +53 +/- 17%, p less than 0.025, respectively), but not RVF muscles (+11 +/- 16% and +8 +/- 19%, respectively). TTP and DC of normal muscle were unchanged by amrinone, whereas TTP was unchanged while DC was shortened (-12 +/- 3%, p less than 0.025) in RVF muscle. Amrinone relaxed Pc similarly and significantly in normal (-28 +/- 7%, p less than 0.005) and RVF (-26 +/- 4%, p less than 0.025) muscles. These results suggest that part of amrinone's salutary action in the failing heart occurs through modification of myocardial relaxation.
Assuntos
Aminopiridinas/farmacologia , Cardiotônicos/farmacologia , Insuficiência Cardíaca/fisiopatologia , Contração Miocárdica/efeitos dos fármacos , Potássio/farmacologia , Amrinona , Animais , Gatos , Glucagon/farmacologia , Técnicas In VitroRESUMO
The positive inotropic action of phenylephrine in cardiac muscle is mediated by alpha- and beta-adrenoceptors. Data suggest the responsiveness of myocardium to inotropic agents is altered in cardiac disease. We evaluated the actions of phenylephrine on isometric contraction and K+-induced contracture in isolated cat right ventricular muscle from normal hearts and hearts with partial pulmonary artery ligation-induced pressure overload of 5-11 days in duration. Peak contractile force (Po) and rate of force development (dP/dt) were lower (p less than or equal to 0.005) in pressure-overloaded (0.59 +/- 0.2 g/mm2 and 4.6 +/- 1.7 g/s/mm2, respectively) than in normal (1.33 +/- 0.2 g/mm2 and 10.5 +/- 1.6 g/s/mm2, respectively) muscle. Phenylephrine (10(-6), 5 X 10(-6), and 10(-5) M) significantly (p less than or equal to 0.01) increased Po and dP/dt in normal but not in pressure-overloaded muscle. Phenylephrine (5 X 10(-6) M) reduced peak K+-induced contracture force (Pc) similarly in normal (-30 +/- 8%) and pressure-overloaded (-36 +/- 11%) muscles. beta-Adrenergic blockade (nadolol, 10(-4) M) reduced, but did not abolish, the "relaxant" action of the drug on Pc in both muscle groups. The lack of a positive inotropic effect of phenylephrine in pressure-overloaded muscle suggests a derangement in both alpha- and beta-adrenoceptor function in this model of cardiac disease.