Effects Of Dimethylamiloride On Cardiac Function And Myocardium Inotropism In Nomal Rat Isolated Hearts And Its Primary Mechanism

AIM:To study effects of DMA on cardiac function in normal rat isolated hearts and myocardial contractility in normal rat isolated papillary muscle of left ventricle, and search for its primary mechanism. METHODS:With Langendorff perfusion, we observe changes of the indexes reflecting cardiac function in normal rat isolated hearts；With isolated papillary muscle perfusion, developed tension and diastolic time were measured to estimate the positive inotropic action of DMA on cardiac tissue level.RESULTS:1,In Langendorff-perfused rat hearts, DMA(2-20 μmol·L-1) enhances cardiac function and exerts positive effects on LVSP-LVDP, +dp/dtmax, -dp/dtmax, while the effects of DMA on LVEDP are of no statistic meaning. 2,The effects of DMA on cardiac function in normal rat iosolated hearts are dose-independent, and difference between concentrations is inapparent. The extent of augment of 2 μmol·L-1 DMA on LVSP-LVDP, +dp/dtmax, -dp/dtmax is 8.35%±5.16, 6.94%±1.92, 7.42%±2.23; The extent of augment of 5 μmol·L-1 DMA is 7.93%±4.49, 5.17%±4.34, 6.39%±4.81; The extent of augment of 10 μmol·L-1 DMA is 10.06%±8.83, 5.01%±2.34, 5.03%±5.38; The extent of augment of 20 μmol·L-1DMA is 9.34%±7.29, 6.59%±6.12, 6.09%±7.09, respectively. 3,In normal rat isolated papillary muscle of left ventricle, DMA(2,5 μmol·L-1) can improve developed tension, shorten diastolic time. While 1 μmol·L-1 DMA only shortens diastolic time and has no effect on developed tension. 4,The effects on myocardium inotropism in normal rat isolated papillary muscle of left ventricle are also dose-independent. 1 μmol·L-1 DMA shortens diastolic time 13.60%±3.70; 2 μmol·L-1 DMA can improve developed tension 3.33%±2.10, shorten diastolic time 14.97%±10.25; 5 μmol·L-1 DMA can improve developed tension 4.74%±2.40, shorten diastolic time 12.23%±8.79. 5,In normal rat isolated hearts, the effects of DMA start to present at the fourth minute and maximize at the sixth minute, then descend gradually; While the effects of DMA appear earlier in rat isolated papillary muscle than hearts, they begin at the second minute and maximize at the fifth minute(seventh minute for 5 μmol·L-1), then descend gradually. 6,The effects of DMA on cardiac function in normal rat isolated hearts and myocardium inotropism in normal rat isolated papillary muscle of left ventricle cannot be blocked by nicardipine—one of calcium channel blockers. 7,The effects of DMA on cardiac function in normal rat isolated hearts and myocardium inotropism in normal rat isolated papillary muscle of left ventricle can be blocked by NiCl2—one of sodium calcium exchanger (NCX) blockers. 8,The effects of DMA and Isoprenaline (Iso) on cardiac function in normal rat isolated hearts and myocardium inotropism in normal rat isolated papillary muscle of left ventricle are similar. CONCLUSION:1,DMA(2-20 μmol·L-1) enhances cardiac function in normal rat isolated hearts and exerts positive inotropic action in normal rat isolated papillary muscle of left ventricle. 2,The effects of DMA(2-20 μmol·L-1) on cardiac function in normal rat isolated hearts and myocardium inotropism in normal rat isolated papillary muscle of left ventricle are dose-independent. 3,By agitating NCX, DMA enhances cardiac function in normal rat isolated hearts and exerts positive inotropic action in normal rat isolated papillary muscle of left ventricle, independent of L-calcium channel.