Acute effects of intravenous nisoldipine on left ventricular function and coronary hemodynamics

Abstract

The hemodynamic effects of nisoldipine were investigated in 16 patients with suspected coronary artery disease who underwent routine cardiac catheterization. Nisoldipine was given intravenously in a dose of 6 pg/kg over 3 minutes and measurements made before and after drug administration during spontaneous and matched atrial paced heart rate. During sinus rhythm, nisoldipine produced a significant increase in heart rate (19%, p <10m5). Left ventricular systolic pressure decreased 28 % (p <10W6) and left ventricular end-diastolic pressure did not change significantly (5%, difference not significant). Coronary sinus and great cardiac vein blood flow increased by 21% (p <O-02) and 25 % (p <O.OOS), respectively, after nisoldipine administratlon. Simultaneously, mean aortic pressure decreased 33% (p <10V6); consequently, the global and regional coronary vascular resistances decreased by 50 % (p <10P4). The decreases In global (-8%) and regional (-4%) myocardial oxygen consumption did not reach statistical significance. A 6% (not significant) increase in enddiastolic volume and an 11% (p <0.002) decrease in end-systolic volume resulted in an increase of 21% in stroke volume (p <10m4) with a consistent increase in ejection fraction (-I-16 %, p <10m5). Total systemic vascular resistance was reduced by 30% (p <0.0002). During spontaneous heart rate and matched atrial pacing, the time constant of isovolumic relaxation as assessed by a biexponential model, was significantly shortened. The maximal velocity of isovolumic contraction after nisoldipine was admlnistered remained higher (+I2 %, p <0.02) at an identical paced heart rate. Thus, nisoldipine is a potent coronary and peripheral vasodilator. No negative inotropic effects were observed in the dosage used.( Am J Cardiol 1985;56:140-146) Nisoldipine is a new dihydropyridine derivative, chemically similar to nifedipine and other related dihydropyridines.1-4Despite its chemical similarity, its pharmacologic properties differ substantially from nifedipine. Although less potent in the inhibition of contraction of isolated heart muscle, nisoldipine is 4 to 10 times more potent in the inhibition of vascular smooth muscle contraction5The main in vivo pharmacologic action of nisoldipine appears to be its inhibitory effect on vascular smooth muscle, particularly that of the coronary vasculature.5 The electrophysiologic effects

Effect of Nisoldipine on De-Endothelialized Large Coronary Artery in Isolated Working Rabbit Hearts

“…Our findings are in agreement with those of Perez et al [10], who found that in open chest dogs, intravenous infusion of nisoldipine abolished the vasoconstriction of large coronary arteries induced by topical application of potassium ion; Drexler et al [9] also reported that intravenous infusion of nisoldipine in rats induced a significant va sodilatation of coronary arteries during rest and exercise. Nisoldipine also increases col lateral blood flow to the ischemic zone in acutely occluded left anterior descending coronary arteries of dogs [27], The effect of nisoldipine was recently studied in patients with coronary artery diseases at rest and dur ing exercise [5,28], It induced coronary and peripheral vasodilatation without negative inotropic effect.…”

“…Nisoldipine is one of the newer dihydro pyridine derivatives (l,4-dihydro-2,6-dimethyl-4 [2-nitrophenyl]-3,5-pridinecarbonic acid isobutyl methyl ester) which acts as powerful vasodilator by inhibiting slow channel transmembrane calcium influx [1], It reduces cardiac afterload and is a potent coronary and peripheral vasodilator [2,3], Nisoldipine is 4-10 times more potent than nifedipine in inhibiting K+-induced contrac tions of isolated vascular preparation [4], Nisoldipine may have a preferential effect on the coronary vasculature in vivo [5], For this reason, nisoldipine is useful in the treat ment of ischemic heart disease [2,6], Most of the previous studies [7][8][9] have dealt with the effect of nisoldipine on total coronary vascular resistance and coronary flow. Little is known about its effect on large coronary arteries in beating hearts.…”

Pharmacokinetics and pharmacodynamics of nifedipine infusion in normal volunteers.

“…Newer dihydropyridine calcium antagonists have also been studied using this route (Serruys et al, 1985;Campbell et al, 1985). For reasons of solubility, these drugs are often administered in a vehicle of 15% ethanol, 15% polyethylene glycol and 70% water.…”

Effect of Nisoldipine on Large Coronary Arteries in situ: Inhibition of Vasoconstriction Induced by Vasopressin

“…However, the sec ond generation of calcium antagonists such as the dihydropyridine derivative nisoldi pine (isobutylmethyl-l,4-dihydro-2,6-dimethyl-4-(o-nitrophenyl)-3,5-pyridinc dicarbox-ylate) offers high selectivity to vascular smooth muscle [7], It also has been recently shown that nisoldipine inhibits both phasic and tonic vascular contractions induced by potassium and acetylcholine [8]. Nisoldipine induces coronary and peripheral vasodila tion in patients with coronary artery disease without major negative inotropic effect [9].…”