Effect of a new alpha 2-adrenoceptor antagonist on poststenotic coronary resistance and myocardial function

Abstract

The effect of the alpha 2-adrenoceptor antagonist 4-fluoro-2-(imidazoline-2-ylamino)-isoindoline maleate (BDF 8933) on poststenotic end-diastolic distal coronary resistance and poststenotic myocardial function (sonomicrometry) was investigated under control conditions and during cardiac sympathetic nerve stimulation (CSNS = electrical stimulation of the left ventrolateral cervical cardiac nerve). In 7 vagotomized, open-chest dogs end-diastolic distal coronary resistance was determined. This variable was essentially unchanged after administration of the agent. In additional 6 dogs regional myocardial function was measured as systolic wall thickening (SWT). CSNS increased SWT of the posterior circumflex-perfused myocardium from 12.7 +/- 4.6% to 21.9 +/- 8.4% (p less than 0.05) under control conditions. With a severe stenosis on the left circumflex coronary artery, SWT was reduced to 5.4 +/- 4.0% and further decreased to 2.1 +/- 5.1% (p less than 0.05) during CSNS. After i.v. injection of 150 micrograms/kg BDF 8933, poststenotic myocardial function at rest was 4.2 +/- 4.2%, and 5.6 +/- 3.6% during CSNS. Regarding to the systemic effects BDF 8933 significantly increased peak left ventricular pressure in all 13 dogs. Thus, the new alpha 2-adrenoceptor antagonist BDF 8933 at the chosen dosage prevents sympathetically induced myocardial ischemia, but increases left ventricular afterload resistance.