Advances in Myocardiology pp 595-604 | Cite as
Antiischemic Effects of Molsidomine in an Experimental Model of Coronary Artery Stenosis
Abstract
The effect of molsidomine, a novel antianginal agent, on the epicardial electrographic changes induced by reduced perfusion of the left anterior descending coronary artery (LAD) was investigated in the anesthetized dog. The LAD was cannulated and perfused at a constant volume with blood taken from a carotid artery. The perfusion volume was than reduced by approximately 75%. The sum of the ST-segment changes obtained from six unipolar epicardial leads was taken as a measure of myocardial hypoxia. Simultaneously, heart rate, blood pressure, left ventricular end-diastolic pressure, pulmonary arterial pressure, and heart contractility were also recorded. In control animals, reduction of the perfusion volume of the LAD resulted in a dramatic elevation of the ST segments lasting more than 4 hr. Molsidomine administered after the induction of the ischemia at a dose of 0.05 mg/kg i.v. resulted within 40 min in a complete normalization of the electrographic changes. This effect was evident for over 4 hr in spite of the continuous reduced perfusion of the LAD. The beneficial effect of molsidomine on the electrical changes paralleled the reduction of the left ventricular end-diastolic pressure. It is suggested that the effect of molsidomine on the ischemic electrographic changes is brought about by a reduction of the preload, resulting in a better perfusion of the ischemic zones.
Keywords
Left Anterior Descend Pulmonary Arterial Pressure Isosorbide Dinitrate Ischemic Zone Antianginal AgentPreview
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References
- 1.Berdeaux, A., Tato, F., Ho, S., Boissier, J.-R., and Giudicelli, J.-F. 1978. Molsidomine, debit coronaires regionaux et segment ST au niveau du myocarde sain et/ou ischemique chez le chien. J. Pharmacol. (Paris) 9:219–234.Google Scholar
- 2.Blazek, G., Gaul, G., and Heeger, H. 1977. Zur Wirkung von Molsidomin auf das Pul-monalarteriendruckverhalten Koronarkranker im ergometrischen Arbeitsversuch. Herz Kreisl. 9:478–481.Google Scholar
- 3.Bussmann, W. D., Neidel, K., and Kaltenbach, M. 1979. Wirkung von Molsidomin auf Hamodynamik und Ischamie bei Patienten mit frischem Herzinfarkt. In: W. Lochner and F. Bender (eds.), Molsidomin, Neue Aspekte in der Therapie der Ischamischen Herzerkrankung, pp. 100–104. Urban & Schwarzenberg, Munich, Vienna.Google Scholar
- 4.Dirschinger, J., Fleck, E., Bierner, M., Redl, A., and Rudolph, W. 1978. Poststenotische Myocarddurchblutung und Linksventrikelfunktion unter Molsidomin. Z. Kardiol. 67(Suppl. 5):62.Google Scholar
- 5.Enke, K. U., Keller, W., and Wagner, J. 1978. Wirksamkeit einer parenteralen Molsidom-ingabe auf die Hamodynamik des großen und kleinen Kreislaufes in Ruhe und unter Belastung. Z. Kardiol. 67(Suppl. 5):63.Google Scholar
- 6.Fleck, E., Dirschinger, J., and Rudolph, W. 1979. Hamodynamische Wirkungen von Molsidomin bei koronarer Herzerkrankung. Herz 4:285–292.PubMedGoogle Scholar
- 7.Fiedler, V. B. 1978. Behaviour of heart dimensions and other hemodynamic parameters after molsidomine, isosorbide dinitrate, nitroglycerin and nifedipine in dogs. Trans. Eur. Soc. Cardiol. 1:85.Google Scholar
- 8.Fiedler, V. B., and Scholtholt, J. 1978. Haemodynamic effects of molsidomine. Arzneim. Forsch. 28:1605–1612.Google Scholar
- 9.Fiedler, V. B., Scholtholt, J., and Gobel, H. 1978. Molsidomin: Wirkungen auf den my-ocardialen Sauerstoffverbrauch (MVO2) des Hundes. Verh. Dtsch. Ges. Kreislaufforsch. 44:184.CrossRefGoogle Scholar
- 10.Fozzard, H. A., and Dasgupta, D. S. 1976. ST-segment potentials and mapping. Circulation 54:533–537.PubMedCrossRefGoogle Scholar
- 11.Grund, E., Muller-Rucholtz, E.-R., Lapp, E. R., Losch, H.-M., and Lochner, W. 1978. Comparative study of nitroglycerin and molsidomine. Effects on the integrated systemic venous bed and the arterial pressure in the dog. Arzneim. Forsch. 28:1624–1628.Google Scholar
- 12.Guerchicoff, S., Vasquez, A., Kunik, H., Drajer, S., and Diaz, F. 1978. Acute double blind trial of a new anti-anginal drug: Molsidomine. Eur. J. Clin. Pharmacol. 23:247–250.CrossRefGoogle Scholar
- 13.Hashimoto, K., Taira, N., Hirata, M., and Kokubun, M. 1971. The mode of hypotensive action of newly synthetized sydnonimine derivatives. Arzneim. Forsch. 21:1329–1332.Google Scholar
- 14.Hirata, M., and Kikushi, K. 1970. Coronary collateral vasodilatator action of N-ethoxy-carbonal-3-morpholino-sydnonimine (SIN-10) in heart with chronic coronary insufficiency in dogs. Jpn. J. Pharmacol. 20:187–193.PubMedCrossRefGoogle Scholar
- 15.Holland, R. P., and Brooks, H. 1975. ST-segment mapping: Fact and fallacy. Circulation 52(Suppl. II):6.Google Scholar
- 16.Holland, R. P., and Brooks, H. 1975. Precordial and epicardial surface potentials during myocardial ischemia in the pig. A theoretical and experimental analysis of the TQ and ST segments. Circ. Res. 73:471–480.CrossRefGoogle Scholar
- 17.Holland, R., Pashkow, F., and Brooks, H. 1974. Atraumatic epicardial electrode and rapid sampling switch for cardiac surface mapping. J. Appl. Physiol. 37:424–427.PubMedGoogle Scholar
- 18.Holtz, J., Bassenge, E., and Kolin, A. 1978. Hemodynamic and myocardial effects of long-lasting venodilation in the conscious dog: Analysis of molsidomine in comparison with nitrates. Basic Res. Cardiol. 73:469–481.PubMedCrossRefGoogle Scholar
- 19.Jansen, E., and Klepzig, H. 1978. Zum Einfluß von Molsidomin in verschiedener Dosierung auf die Belastungskoronarinsuffizienz. Med. Klin. 73:983–986.PubMedGoogle Scholar
- 20.Karsch, K. R., Rentrop, K. P., Blanke, H., and Kreuzer, H. 1978. Haemodynamic effects of molsidomine. Eur. J. Clin. Pharmacol. 13:241–245.PubMedCrossRefGoogle Scholar
- 21.Kikuchi, H., Hirata, M., and Nagaoka, A. 1970. Hypotensive action of N-ethoxycarbonyl-3-morpholinosydnonimine, SIN-10. Jpn. J. Pharmacol. 20:102–115.PubMedCrossRefGoogle Scholar
- 22.Kikuchi, K., Hirata, M., Nagaoka, A., and Aramaki, Y. 1970. Cardiovascular action of mesionic compounds, 3-substituted sydnonimines. Jpn. J. Pharmacol. 20:23–42.PubMedCrossRefGoogle Scholar
- 23.Lochner, W., Muller-Rucholtz, E.-R., Grund, E., Hauer, F., and Lapp, E. 1978. Integrated systemic venous volume as influenced by antianginal drugs: Effects of beta-blockers, nitroglycerin and molsidomine. In: Abstracts, VIII World Congress of Cardiology (Tokyo), p. 192.Google Scholar
- 24.Majid, P. A., DeFeyter, P. J. F., van der Wall, E. E., Warden, R., and Roos, J. P. 1980. Molsidomine in the treatment of patients with angina pectoris. Acute hemodynamic effects and clinical efficacy. N. Engl. J. Med. 302:1–6.PubMedCrossRefGoogle Scholar
- 25.Mannes, G. A., Goebel, G., Kafka, W., and Rudolph, W. 1978. Behandlung der Angina pectoris mit Molsidomin. Herz 3:172–184.PubMedGoogle Scholar
- 26.Maroko, P. R., and Braunwald, W. 1976. Effects of metabolic and pharmacologic interventions on myocardial infarct size following coronary occlusion. Circulation 53:162.Google Scholar
- 27.Maroko, P. R., Kiekshus, R., Sobel, B. E., Watanabe, T., Cowell, J. W., Ross, J., and Braunwald, E. 1971. Factors influencing infarct size following coronary artery occlusion. Circulation 43:67–82.PubMedCrossRefGoogle Scholar
- 28.Mogilev, A. M., Gobel, H., and Nitz, R. E. 1980. Antiischemic effect of molsidomine on experimental left anterior descending coronary artery stenosis. Z. Kardiol. 69:205 (abstr.).Google Scholar
- 29.Nitz, R.-E. 1979. Zur Pharmakologie von Molsidomin. In: W. Lochner and F. Bender (eds.), Molsidomin, Neue Aspekte in der Therapie der Ischamischen Herzerkrankung pp. 6–13. Urban & Schwarzenberg, Munich.Google Scholar
- 30.Pirzada, A. M., DeFeyter, P. J. F., van der Wall, E. E., Wardeh, R., and Roos, J. P. 1980. Molsidomin in the treatment of patients with angina pectoris. N. Engl. J. Med. 302:1–6.CrossRefGoogle Scholar
- 31.Ross, J. 1976. Electrocardiographic ST-segment analysis in the characterization of myocardial ischemic and infarction. Circulation [Suppl.] 53:73–81.Google Scholar
- 32.Schaper, W. 1979. Zur Pathophysiologie der koronaren Herzkrankheit. 1. In: W. Lochner and F. Bender (eds.), Molsidomin, Neue Aspekte in der Therapie der Ischämischen Her-zerkrankung, pp. 2–5. Urban & Schwarzenberg, Munich.Google Scholar
- 33.Schaper, W., Flameng, W., Winckler, B., Wusten, B., Turschmann, W., Neugebauer, G., Carl, M., and Pasyk, S. 1976. Quantification of collateral resistance in acute and chronic experimental coronary occlusion in the dog. Cir. Res. 39:371–377.CrossRefGoogle Scholar
- 34.Scholtholt, J., Fiedler, V. B., and Keil, M. 1977. Molsidomine, effects on blood flow of normal and ischemic myocardium. In: Joint Meeting German and Italian Pharmacologists, Venice, p. 184. Fondazione Cini, Venice.Google Scholar
- 35.Scholtholt, J., Fiedler, V. B., and Keil, M. 1978. Die Wirkung von Molsidomin auf die regionale Verteilung des Herzminutenvolumens des narkotisierten Hundes. Arzneim. Forsch. 28:1612–1619.Google Scholar
- 36.Scholtholt, J., Fiedler, V. B., and Keil, M. 1978. Die Wirkung von Molsidomin und Nitroglycerin auf die regionale Durchblutung des normalen und akut-ischamischen Myokards. Arzneim. Forsch. 28:1619–1624.Google Scholar
- 37.Slany, J., Mosslacher, H., Schmoliner, R., and Kronik, G. 1976. Einfluß von Molsidomin auf Hamodynamik und Arbeitstoleranz bei Patienten mit Angina pectoris. Med. Welt 27:2369–2400.Google Scholar
- 38.Takenaka, F., Takeya, N., Ishihara, T., Inoue, S., Tsutsumi, E., Nakamura, R., Mitsufuji, Y., and Sumie, M. 1970. Effects of N-ethoxycarbonyl-3-morpholinosydnonimine (SIN-10) on the cardiovascular system. Jpn. J. Pharmacol. 20:253–263.PubMedCrossRefGoogle Scholar
- 39.Takeshita, A., Nakamura, M., Tajimi, T., Matsuguchi, H., Kuroiwa, A., Tanaka, S., and Kikuchi, Y. 1977. Long-lasting effect of oral molsidomine on exercise performance. A new antianginal agent. Circulation 55:401–407.PubMedCrossRefGoogle Scholar