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Effects of vasoactive stimuli on coronary vascular resistance in isolated perfused rabbit hearts: No vasospastic response to ergonovine with or without atherogenic diet

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Abstract

The mechanism of ergonovine-provoked coronary vasospasm is poorly understood. We tested the effect of ergonovine in perfused hearts from normal and cholesterol-fed (18 weeks, 2% cholesterol diet) rabbits in a constant-flow Langendorff perfusion. Aortic perfusion pressure was monitored to measure coronary vascular resistance, and left ventricular pressure was measured with an isovolumetric balloon in the left ventricle. Control coronary vascular resistance was 1.12±0.11 mm Hg/ml/min in hearts from normal rabbits and 1.53±0.16 mm Hg/ml/min in hearts from cholesterol-fed rabbits (n=9 each,\(\bar x\), p<0.05). The cholesterol content of aortae from cholesterol-fed rabbits was markedly increased (432±85 mg/g protein vs. 14.9±8.2 in controls, p<0.001; for coronaries: 396±136 mg/g protein vs. 125±25, p<0.05). In both groups, increases in coronary vascular resistance were observed with vasopressin (40 IU/1) and phenylephrine (30 μM) and decreases with adenosine (10 μM), isoprenaline (0.1 μM) and 30 sec stopflow (all p<0.05). Ergonovine maleate (10 μM) and serotonine (10 μM) did not increase coronary vascular resistance.

Although in whole heart perfusion small changes in the caliber of epicardial vessels may not be detectable, changes severe enough to produce measurable changes in total coronary resistance were not found. Therefore the absence in our model of an increase in coronary vascular resistance after ergonovine is not compatible with a local direct mechanism in epicardial arterial wall, even when sensitized by a high cholesterol diet.

Zusammenfassung

Der Mechanismus des durch Ergonovin provozierten koronaren Vasospasmus ist weitgehend unklar. Wir untersuchten die Wirkung von Ergonovin an Herzen von normalen und cholesterol-gefütterten Kaninchen (18 Wochen, 2% Cholesterol-Fütterung, deutliche Atheromatose) in einer Langendorff-Perfusion mit konstantem Fluß. Der aortale Perfusionsdruck diente als Maß des Koronarwiderstandes, der linksventrikuläre Druck wurde über einen Ballon im linken Ventrikel gemessen. Unter Kontrollbedingungen betrug der Koronarwiderstand 1,12±0,11 mm Hg/ml/min für Normalherzen und 1,53±0,16 mm Hg/ml/min für Herzen von cholesterolgefütterten Kaninchen (jeweils n=9,\(\bar x\), p<0,05). Nach Cholesterolfütterung war der Cholesterolgehalt der Aorten auf 432±85 mg/g Protein erhöht (Kontrolle 14,9±8,2, p<0,001) und in den Koronarien auf 396±136 mg/g Protein (Kontrolle 125±25, p<0,05). In beiden Gruppen wurde ein Anstieg des Koronarwiderstands mit Vasopressin (40 IU/1) und Phenylephrin (30 μM) und Absinken mit Adenosin (10 μM), Isoprenalin (0,1 μM) und 30 s Abklemmen beobachtet. Ergonovinmaleat und Serotonin (je 10 μM) führten zu keinem Anstieg des Koronarwiderstands.

Obwohl in unserem Modell kleine Veränderungen im Kaliber epikardialer Gefäße unentdeckt bleiben können, wurden meßbare Veränderungen des Koronarwiderstands — wie sie notwendig wären, um in vivo eine Ischämie auszulösen-unter Ergonovin nicht gefunden. Das Fehlen eines Anstiegs im Koronarwiderstand nach Ergonovin erscheint nicht vereinbar mit einem lokalen direkten Angriffspunkt an epikardialen Koronargefäßen, auch nicht nach Cholesterol-Fütterung.

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  1. Th. v. Arnim

    Present address: Medizinische Klinik I, Klinikum Großhadern, 8000, München 70, W. Germany

Authors and Affiliations

  1. Cardiovascular Research Unit and MRC Lipid Metabolism Research Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, (England)

    G. R. Thompson

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  1. Th. v. Arnim
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  2. F. Crea
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  3. S. Chierchia
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  4. G. R. Thompson
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  5. A. Maseri
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Supported in part by the Deutsche Forschungsgemeinschaft (Ar 139/2)

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v. Arnim, T., Crea, F., Chierchia, S. et al. Effects of vasoactive stimuli on coronary vascular resistance in isolated perfused rabbit hearts: No vasospastic response to ergonovine with or without atherogenic diet. Basic Res Cardiol 78, 415–422 (1983). https://doi.org/10.1007/BF02070165

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  • DOI: https://doi.org/10.1007/BF02070165

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