Effects of pimobendan (UD-CG 115) on the contractile function of the normal and "postischemic" canine myocardium.

Pimobendan (UD-CG 115) is a long-acting positive inotropic drug with arterio- and venodilator properties. To determine to what extent this new agent is able to affect contractile function in previously ischemic areas of the left ventricle (LV), the effects of pimobendan on global and regional LV function were studied in eight conscious dogs, 2 days after a 2-h coronary occlusion followed by reperfusion. Before pimobendan, percentage of systolic shortening and mean velocity of shortening were lower in reperfused segments than in control areas (0.41 +/- 0.17 vs. 0.93 +/- 0.07 s-1 and 7 +/- 3 vs. 15 +/- 1%, respectively; both p less than 0.05). Infusion of 1 mg of pimobendan significantly improved peak + dP/dt (3202 +/- 372 to 3848 +/- 498 mm Hg/s; p less than 0.05) and ejection time (166 +/- 13 to 156 +/- 15 ms; p less than 0.05). Cumulative infusion up to 2.5 mg further improved these indexes to 5199 +/- 934 mm Hg/s and to 125 +/- 11 ms, (respectively; both p less than 0.05) without affecting mean arterial pressure (91 +/- 14 to 93 +/- 22 mm Hg; NS). Mean velocity of shortening rose to 1.18 +/- 0.09 s-1 (p less than 0.05) in control segments and to 0.62 +/- 0.18 s-1 (p less than 0.05) in reperfused segments. The ratio between end-systolic pressure and length increased by 26 +/- 9% (p less than 0.05) in the reperfused segments and by 20 +/- 8% (p less than 0.05) in control areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparisons of the inotropic effects of the beta 1-adrenoceptor partial agonists SL 75.177.10 and ICI 118,587 with digoxin on the intact canine heart.

The effects of the beta 1-adrenoceptor partial agonists ICI 118,587 (xamoterol) and SL 75.177.10 on the left ventricular inotropic state and relaxation rate were compared with those of digoxin in open-chest dogs. These agents were administered to three separate groups of dogs (5, 6, and 7 dogs, respectively). In each animal, the inotropic effects were assessed at fixed heart rate (atrial pacing) and at similar end-diastolic left ventricular diameter. Under these controlled conditions, ICI 118,587 (200 micrograms/kg) increased peak (+) dP/dt by 3176 +/- 363 mm Hg/s (p less than 0.005) and the slope of the end-systolic pressure/end-systolic diameter relation rose by 190% above the control value (p less than 0.01). These changes were significantly greater than after digoxin (100 micrograms/kg) which increased these indexes, respectively, by 2132 +/- 248 mm Hg/s (p less than 0.003) and by 31 +/- 4% (p less than 0.05). SL 75.177.10 (200 micrograms/kg) also increased dP/dt, but significantly less than did digoxin or ICI 118,587 (+428 +/- 105 mm Hg/s; p less than 0.007); the increase in end-systolic pressure/diameter slope was not different from that observed after digoxin. In contrast to ICI 118,587 which accelerated isovolumic relaxation (-7.6 ms in time constant of isovolumic pressure fall; p less than 0.01), neither SL 75.177.10 nor digoxin modified this phase of the cardiac cycle. Finally, at the dose used in the study, digoxin induced ventricular arrhythmias in all animals, a side effect which was never observed after ICI 118,587 or SL 75.177.10.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of dobutamine and sulmazol (AR-L115 BS) on myocardial metabolism and coronary, femoral, and renal blood flows: a comparative study in normal dogs and in dogs with chronic volume overload.

We compared the hemodynamic and metabolic effects of dobutamine and sulmazol (AR-L115 BS) in normal dogs and in dogs with chronic volume overload. In both cases, the doses of dobutamine and sulmazol were adapted to produce comparable increases in two indices of inotropic state, peak (+) left ventricular dP/dt and dP/dt normalized by a developed pressure of 40 mm Hg. In normal dogs, both drugs had similar effects on myocardial oxygen consumption, myocardial high-energy phosphate stores, and renal or femoral blood flows; in addition, mean aortic pressure (129 +/- 8 to 114 +/- 10 mm Hg; p less than 0.002), the renal vascular resistance (--18%; p less than 0.005), and the coronary vascular resistance (--30%; p less than 0.05) were all decreased significantly during sulmazol administration. In chronic volume overload, the changes in renal and femoral blood flows and in myocardial high-energy phosphate stores induced by dobutamine or sulmazol were again similar. However, sulmazol still decreased mean aortic pressure (--20 +/- 5 mm Hg; p less than 0.002) and markedly reduced the left ventricular filling pressure (--40%; p less than 0.006), while these parameters were not significantly modified after dobutamine. Myocardial oxygen consumption was unchanged after sulmazol but increased slightly with dobutamine. Finally, the frequency of ventricular premature beat was unchanged by sulmazol but increased after dobutamine. In conclusion, sulmazol is likely to be superior to dobutamine to stimulate a failing left ventricle when clinical status is characterized by markedly elevated filling pressures. It might also be superior when the coronary vascular reserve is reduced or in the presence of ventricular arrhythmias.