Acute hemodynamic effects of nisoldipine and pimobendan in conscious pigs with chronic heart failure.
The acute systemic hemodynamic effects of the calcium antagonist nisoldipine and the pyridazinone-derivative pimobendan, a phosphodiesterase inhibitor with vasodilating as well as positive inotropic properties, were studied in conscious pigs with chronic heart failure. Left ventricular (LV) dysfunction, manifested by a 25% decrease in cardiac output (CO), a 35% increase in systemic vascular resistance (SVR), and a doubling of the left ventricular filling pressure, was induced by a proximal ligation of the left circumflex coronary artery. Two to three weeks after myocardial infarction, cumulative 10-min infusions of either nisoldipine (0.05, 0.1, 0.25, and 0.5 micrograms/kg/min), pimobendan (2.5, 5, 12.5, and 25 micrograms/kg/min) or the solvents were administered. Infusion of the solvents did not affect any of the hemodynamic variables. Both nisoldipine and pimobendan normalized CO and exhibited a similar cardiac profile [systemic vasodilatation, reduction in left ventricular filling pressure, and an increase in heart rate (HR)] except for the significantly (p less than 0.05) larger increase in LVdP/dtmax with pimobendan (85%) than with nisoldipine (45%). In animals with heart failure, lower doses of both nisoldipine (twice) and pimobendan (four times) were needed to elicit a 30% reduction in SVR than in animals with normal pump function. For both drugs, the slope of the line describing the vasodilatory and positive inotropic properties shifted more in favor of the vasodilatory actions during heart failure (p less than 0.05). We conclude that in swine with chronic LV dysfunction nisoldipine, despite its lack of inotropic properties, appeared to improve ventricular function to the same extent as the primary positive inotropic agent pimobendan.
van der Giessen
W J
WJ
Department of Cardiology, Thoraxcenter, Erasmus University Rotterdam, The Netherlands.
van Woerkens
L J
LJ
Duncker
D J
DJ
Roelandt
J R
JR
Verdouw
P D
PD
D000136:Acid-Base Equilibrium / Q000187:drug effects; D000818:Animals; D001784:Blood Gas Analysis; D002908:Chronic Disease; D006333:Heart Failure / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects*; D015737:Nisoldipine / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology*; D013552:Swine; D014665:Vasodilator Agents / Q000494:pharmacology*
D011724:Pyridazines; D014665:Vasodilator Agents; C041648:pimobendan; D015737:Nisoldipine