Molsidomine in the Treatment of Patients with Angina Pectoris

Majid, P A; deFeyter, Pim J.; Wall, Ernst E. van der; Wardeh, R; Roos, J. P.

doi:10.1056/nejm198001033020101

Cited by 91 publications

(42 citation statements)

References 25 publications

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“…27,28 In additional experiments with the selective ET B agonist IRL 1620, we demonstrated that the ET B receptor might provide evidence for ET-induced positive inotropy. 19 The present study examined whether the NO donor molsidomine, used clinically as a coronary dilating drug, 20 might unmask the positive inotropy of ET-1 by attenuating ETinduced myocardial ischemia without affecting the hemodynamics as adenosine does. Furthermore, we tested how effectively selective blockade of ET A receptors by BQ 610 21 is able to prevent ET-induced myocardial ischemia with subsequent depression of ventricular function.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, the effect of ET-1 was studied after pretreatment with the nitric oxide (NO) donor molsidomine, which is used clinically for treatment of myocardial ischemia. 20 The second part of the study examined the effect of ET-1 after selective blockade of the ET A receptors by the ET A receptor antagonist BQ 610. 21 Additionally, the effect of ET-1 on coronary flow and on myocardial energy metabolism under different conditions was investigated by colored microsphere technique and by determination of the myocardial high-energy phosphates.…”

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confidence: 99%

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Inotropic Effects of Endothelin-1

et al. 1999

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Abstract-In vivo studies could not detect a positive inotropy of endothelin (ET)-1 as described in in vitro experiments.ET-induced direct positive inotropy, which seems to be mediated by ET B receptors, may be antagonized in vivo by an indirect cardiodepressive effect owing to an ET-induced coronary vasoconstriction via ET A receptors. This study compares the effects of a dose of 1 nmol/kg ET-1 alone on myocardial contractility and myocardial energy metabolism with the effects of 1 nmol/kg ET-1 after pretreatment with 5 mg/kg molsidomine or with 100 g/kg of the ET A receptor antagonist BQ 610. We investigated the effects of ET-1 versus saline controls in open-chest rats. In addition to measurements in the intact circulation, myocardial function was examined by isovolumic registrations independent of peripheral vascular effects. We also studied the effect of ET-1 on myocardial high-energy phosphates. Pretreatment with molsidomine and BQ 610 attenuated the ET-induced reduction of cardiac output (ET-1: Ϫ62%; molsidomineϩET-1: Ϫ47%; BQ 610ϩET-1: Ϫ27% different from controls). After a transient initial vasodilation, ET-1 raised total peripheral resistance (ET-1: ϩ190%; molsidomineϩET-1: ϩ171%; BQ 610ϩET-1: ϩ89%). BQ 610 was more effective in preventing ET-induced vasoconstriction. The increase of isovolumic peak first derivative of left ventricular pressure (ET-1: Ϫ2%; molsidomineϩET-1: ϩ16%; BQ 610ϩET-1: ϩ19%) after pretreatment with molsidomine or BQ 610 indicates that these drugs unmask the positive inotropy of ET-1. ET-induced myocardial ischemia was abolished by molsidomine and BQ 610. Key Words: endothelin Ⅲ BQ 610 Ⅲ molsidomine Ⅲ contractility Ⅲ phosphates, high-energy Ⅲ rats T he peptide endothelin (ET)-1 is the most potent vasoconstrictor known to date, 1 and it is involved in the development of several diseases. Increased ET plasma concentrations have been reported in patients with angina, 2,3 myocardial infarction, 4,5 or heart failure. 6 Drugs that antagonize or block the effects of ET-1 may consequently be of importance in the treatment of these diseases. Two different ET receptors have been characterized (the ET A 7 and the ET B 8 receptors), and many selective and nonselective ET receptor antagonists have been synthesized. Nevertheless, until now it has been unclear whether selective or nonselective ET receptor antagonists should be used in therapy. In addition to its important vascular effects, several experiments with isolated cardiac tissues demonstrated a positive inotropic effect of ET-1. 9 -12 In isolated hearts 13,14 and in in vivo studies, 15,16 ET-1 showed a controversial effect on myocardial contractility. In a previous in vivo study with rats, we could not detect the described positive inotropy of ET-1. 17 We supposed that the potent vasoconstrictive effect of ET-1 might cause myocardial ischemia with consecutive cardiodepression, thereby masking the described direct positive inotropic effect of ET-1 in vivo. Our hypothesis was confirmed by the fact that the combination of ET-1 with high do...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Inotropic Effects of Endothelin-1

et al. 1999

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“…To treat reeunent spontaneous angina, we administered several drugs, mainly oral Ca antagonist (diltiazem [Kawai et al, 1981;Kimura and Kishida' 1981;Nakamura and Koiwaya, 1979;Rosenthal et al, 1980;Yasue et al, 1978Yasue et al, , 1979a or nifedipine [Autman et aI., 1980;Endo et al, 1976;Kawai et al, 1981;Kimura and Kishida 1981;Muller and Gunther 1977]) and/or nitrates (isosorbide dinitrate [ISDN) or molsidomine [Majid et al, 1980;Takeshita et al, 1977)). Propranolol was given to one patient (patient 15).…”

Section: Methodsmentioning

confidence: 99%

Clinical characteristics and prognosis of patients with postinfarction angina caused by coronary artery spasm

Koiwaya

Nakagaki

Takeshita

et al. 1984

Clinical Cardiology

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“…2). The final prescrip- tion was 16 mg of molisidomine (Majid et al, 1980) and 80 mg of nifedipine per day, and the patient experienced no form of chest pain for 22 months under medication.…”

Section: Patientmentioning

confidence: 99%

Elimination of unstable angina by diltiazem under temporary pacing

Ishikawa

Imamura

Koiwaya

et al. 1984

Clinical Cardiology

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Summary: We describe two patients in whom spontaneous angina following acute myocardial infarction (postinfarction angina caused by coronary artery spasm) and worsening angina were successfully eliminated after clinical dosage of oral diltiazem, while marked sinus node suppression developed and temporary pacing was performed. The patients were females (one was 67 years and one was 64 years old), and had no history of sinus node dysfunction. The occurrence of the adverse effect was not during angina, and the intervals between the initiation of diltiazem and the Occurrence were 6 days after 120 mg/day in one patient, and 4 h after a single administration of 60 mg in the other. Diltiazem is also efficacious in the elimination of unstable angina, however one should note that diltiazem may remarkably suppress not only atrioventricular node activity but also sinus node activity in some patients.

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Molsidomine in the Treatment of Patients with Angina Pectoris

Cited by 91 publications

References 25 publications

Inotropic Effects of Endothelin-1

Inotropic Effects of Endothelin-1

Clinical characteristics and prognosis of patients with postinfarction angina caused by coronary artery spasm

Elimination of unstable angina by diltiazem under temporary pacing

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