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Therapeutische Optionen zur Verbesserung der Myokardperfusion bei koronarer Atherosklerose

Therapeutic options to improve myocardial perfusion in coronary atherosclerosis

  • Koronare Atherosklerose — Funktionelle Konsequenzen
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Zusammenfassung

Die Kombination aus morphologischen arteriosklerotischen Veränderungen der Koronargefäße und einer Störung der Tonusregulation in den Epikard- und Widerstandsgefäßen ist entscheidend für die Limitation des myokardialen Sauerstoffangebotes. Das Endothel spielt dabei eine zentrale Rolle für die funktionelle Beeinträchtigung der Koronararterien bei Patienten mit koronarer Arteriosklerose oder Risikofaktoren. Eine Therapie, welche darauf abzielt, die endotheliale Dilatationsfähigkeit zu steigern, verbessert die myokardiale Perfusion bei Patienten mit einer koronaren Herzkrankheit. Auch bei Patienten mit angiographisch normalen Koronararterien oder geringen Wandveränderungen, bei denen aufgrund einer Mikrozirkulationsstörung eine Myokardischämie auftritt, kann eine Therapie aus symptomatischen Gründen indiziert sein.

Die koronare Tonusregulation und Gefäßproliferationsprozesse werden beide durch das Redoxgleichgewicht in der Gefäßwand zwischen Stickstoffmonoxid (NO) und Angiotensin II/Sauerstoffradiakalen gesteuert und sind somit eng miteinander verknüpft. Ziel einer therapeutischen Intervention, um die endotheliale Dysfunktion zu verbessern, ist es demnach, zum einen die NO-Bioaktivität in der Gefäßwand zu erhöhen, zum anderen den oxidativen Streß zu reduzieren. Die NO-Bioaktivität kann durch ACE-Hemmer, Steigerung der Scherkräfte am Endothel durch Sport, Östrogene oder L-Arginin verbessert werden. Bei diesen Therapien konnte daher auch klinisch eine Verbesserung der endothelabhängigen Dilatationsfähigkeit nachgewiesen werden. Ebenfalls mit einer Besserung der endothelialen Vasoreaktivität gehen Behandlungen einher, welche den oxidativen Streß reduzieren, wie Antioxidanzien und insbesondere Lipidsenker. Endothelinantagonisten und Angiotensin-II-Rezeptor-Blocker stellen vielversprechende Therapieansätze dar, welche jedoch noch validiert werden müssen.

Viele Therapiestrategien, welche auf eine Verbesserung der endothelialen Dysfunktion abzielen, konnten bisher nachweisen, daß sie auch die Prognose günstig beeinflussen. Ob eine Endotheldysfunktion allein — ohne Hinweis auf eine manifeste koronare Herzkrankheit—aus prognostischer Indikation ausreicht, cine medikamentöse Langzeittherapie zu rechtfertigen, muß jedoch noch geklärt werden.

Summary

The combination of morphological atherosclerotic alterations of coronary vessels and disturbance of coronary vasomotor control of epicardial and resistance vessels determines the amount of myocardial oxygen supply. The endothelium plays a crucial role for functional alterations of the coronary vessels in patients with early atherosclerosis or risk factors for coronary artery disease. A therapy which aims to ameliorate endothelium-dependent vasodilator capacity improves myocardial perfusion in patients with coronary artery disease. Thereby, even in patients with angiographically normal or minimally diseased coronary vessels who develop myocardial ischemia due to microvascular disease, symptomatic improvement might be achieved.

Control of coronary vasomotor tone and proliferation processes within the vessel wall are both determined by the redox equilibrium of nitri oxide (NO) and superoxide radicals (O −2 ), induced by angiotensin II. Thus, vasomotor control and vessel wall proliferation is closely related to each other. Aim of a therapeutic intervention to enhance NO bioactivity is either to increase NO production in the endothelium or to decrease O −2 production, which rapidly inactivates NO. NO bioactivity can be ameliorated by ACE-inhibitors, increase of shear stress on the endothelium by physical exercise, estrogens or L-arginine. For these therapies clinically an improvement of endothelial vasodilator function could be shown. In addition, improvement of endothelial vasodilator function can be achieved by a treatment which reduced oxidative stress in the vascular wall such as antioxidants and, especially, lipid lowering drugs. Endothelin-antagonists and angiotensin II receptor-blockers are promising to improve endothelial dysfunction. However, these therapies have to be validated.

Most therapy strategies, which have shown to ameliorate endothelial dysfunction, are also able to improve prognosis of the patients. Whether endothelial dysfunction alone—without evidence of overt coronary atherosclerosis — is sufficient to justify a long-term therapy to improve prognosis, still has to be clarified.

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  1. Medizinische Klinik IV, Abteilung Kardiologie, Klinikum der J. W. Goethe-Universität, Theodor-Stern-Kai 7, D-60590, Frankfurt/Main

    Volker Schächinger

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Schächinger, V. Therapeutische Optionen zur Verbesserung der Myokardperfusion bei koronarer Atherosklerose. Herz 23, 116–129 (1998). https://doi.org/10.1007/BF03044542

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