Cardiac Effects of Amrinone on Rabbit Papillary Muscle and Guinea Pig Langendorff Heart Preparations

Onuaguluchi, G; Tanz, Ralph D.

doi:10.1097/00005344-198111000-00022

Cited by 21 publications

(15 citation statements)

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“…The concentrations of amrinone used in the present experiments were similar to the effective concentrations on the contractile force of cardiac muscles (Onuaguluchi & Tanz, 1981;Honerjaiger et al, 1981;Kondo etal., 1983). Therefore, it is reasonable that the high doses of amrinone should have both a positive inotropic and positive chronotropic effect on the heart.…”

Section: Influence Ofpindololsupporting

confidence: 75%

“…In addition, no meaningful change in the heart rate was demonstrated in patients receiving reasonably high doses of amrinone (Le Jemtel, Keung, Sonnenblick, Ribner, Matsumoto, Davis, Schwartz, Alousi & Davolos, 1979;Benotti, Grossman, Braunwald & Carabello, 1980), yet all of these patients were also receiving cardiac glycosides. On the other hand, amrinone was shown to have a positive chronotropic effect on guinea-pig Langendorff perfused heart (Onuaguluchi & Tanz, 1981). Also, in a series of 20 normal male volunteers, amrinone increased the heart rate significantly (de Guzman, Munoz, Palmer, Davolos & Alousi, 1978).…”

Section: Introductionmentioning

confidence: 96%

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Effects of amrinone on the transmembrane action potential of rabbit sinus node pacemaker cells

Kodama

Kondo

Shibata

1983

British J Pharmacology

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Effects of amrinone on the membrane action potential and spontaneous activity were investigated in sinus node pacemaker cells of rabbit heart by use of microelectrode techniques. Amrinone (1 × 10−4m to 6 × 106m) caused a shortening of cycle length of spontaneous firing (SPCL) accompanied by an increase in the maximum upstroke velocity at phase 0 () and amplitude of action potential (AAP), while it did not affect the maximum diastolic potential (MDP). All the effects of amrinone on sinus node pacemaker cells were markedly attenuated or abolished in a low calcium medium (Ca+0.1 mm or 0.3 mm) or in the presence of the slow channel blocking agent, verapamil (5 × 10−7m, 2 × 106m). The effects of amrinone were not antagonized by the β‐adrenoceptor blocking agent, pindolol (2 × 10−7m). These results indicate that amrinone has an intrinsic effect on sinus node pacemaker cells, increasing their spontaneous firing activity. It is also assumed that the effects of amrinone on sinus node cells are probably mediated by an augmentation of the slow calcium and/or sodium inward current through the cell membrane.

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Section: Influence Ofpindololsupporting

confidence: 75%

Section: Introductionmentioning

confidence: 96%

Effects of amrinone on the transmembrane action potential of rabbit sinus node pacemaker cells

Kodama

Kondo

Shibata

1983

British J Pharmacology

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“…Although the precise mechanisms of the dysrhythmogenic effects are not clear from these experiments, the occurrence of dysrhythmias is of interest since studies in other mammalian species have shown that milrinone, piroximone and related drugs are not arrhythmogenic (Rosenthal & Ferrier, 1982;Piwonka et al, 1983;Roebel et al, 1983). However, amrinone-induced arrhythmias have been observed in rabbit papillary muscle (Onuaguluchi & Tanz, 1981).…”

Section: Toxic Effects Ofmilrinone Andpiroximonementioning

confidence: 98%

The effects of milrinone and piroximone on intracellular calcium handling in working myocardium from the ferret

Gwathmey

Morgan

1985

British J Pharmacology

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1 The effects of milrinone and piroximone were compared to those of isoprenaline, dibutyryl adenosine 3':5'-cyclic monophosphate (dibutyryl cyclic AMP), forskolin, isobutylmethylxanthine, increased extracellular calcium ([Ca2"10) and caffeine in ferret right ventricular papillary muscles that were loaded intracellularly with aequorin, a bioluminescent calcium indicator that emits light when it combines with calcium. 2 The positive inotropic action of each drug, except caffeine, was associated with an increase in the peak amplitude of the aequorin light signal (i.e. intracellular Ca2" transient) reflecting an increased amount of calcium available for excitation-contraction coupling; the positive inotropic effect of caffeine appears to occur by other mechanisms. 3 The time courses of the aequorin light signal and corresponding tension response were shortened by isoprenaline, forskolin, isobutylmethylxanthine, dibutyryl cyclic AMP, milrinone and piroximone; unchanged by increased [Ca2+] and prolonged by caffeine, suggesting that the rates of Ca2+ release and uptake by the sarcoplasmic reticulum were respectively increased, unchanged or decreased by these groups of drugs.4 Relative to changes in [Ca2+1L, the ratio of the peak of the aequorin light signal to the peak of the tension response was increased by isoprenaline, milrinone and piroximone, and decreased by caffeine, indicating that the Ca2+-sensitivity of the myofilaments was respectively decreased, and increased by these drugs. 5 The effects of milrinone and piroximone on the amplitude and time course of the aequorin light signal, as they relate to changes in uptake and release of calcium from the sarcoplasmic reticulum and to changes in the sensitivity of the myofilaments to Ca2+, are consistent with the findings that positive inotropic doses of these agents act by increasing intracellular concentrations of cyclic AMP. 6 Higher doses of milrinone and piroximone produced negative inotropic effects that were characterized by diminution of developed tension but no change or an increase in the amplitude of the aequorin light signal, suggesting a decrease in the sensitivity of the contractile elements to Ca2 . 7 Toxic doses of milrinone, piroximone and isoprenaline were associated with development of a Ca2+-overload state characterized by the presence of after-glimmers, after-contractions and dysrhythmias, and by decreased amplitude of both the aequorin light signal and tension response.8 The negative inotropic and toxic effects of milrinone and piroximone can be explained only in part by increased intracellular concentrations of cyclic AMP; we suggest that these drugs may have other cardiac actions.

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“…Several recent reports indicate that the actions of this substance are exerted preferentially on the myocardial contractility; the chronotropic and vasodilatatory effects on the coronary and other peripheral vascular beds are thought to be rather limited both in vivo and in vitro (1,2), although there are papers maintaining that the substance is a preferential vasodilator (3)(4)(5)(6). However, quantitative comparison of the effects of amrinone on the heart and the coronary vasculature has not been adequately conducted yet.…”

Section: Pharmaceuticalmentioning

confidence: 99%

Cardiotonic and Coronary Vasodilatatory Effects of Amrinone in the Canine Heart-Lung Preparation with a Support Dog as Compared with Those of Dobutamine

Takeda

Matsui

Nakazawa

et al. 1986

Japanese Journal of Pharmacology

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Cardiac Effects of Amrinone on Rabbit Papillary Muscle and Guinea Pig Langendorff Heart Preparations

Cited by 21 publications

References 0 publications

Effects of amrinone on the transmembrane action potential of rabbit sinus node pacemaker cells

Effects of amrinone on the transmembrane action potential of rabbit sinus node pacemaker cells

The effects of milrinone and piroximone on intracellular calcium handling in working myocardium from the ferret

Cardiotonic and Coronary Vasodilatatory Effects of Amrinone in the Canine Heart-Lung Preparation with a Support Dog as Compared with Those of Dobutamine

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