Improvement of perfusion and function of ischaemic porcine myocardium after reduction of heart rate by alinidine.
We studied the effect of alinidine on myocardial perfusion and function in 10 open-chest pigs with left anterior descending coronary artery (LAD) stenosis. Following LAD stenosis the systolic myocardial wall thickening (ultrasound) was reduced to 30% of the base-line value and the transmural blood flow and the endocardial/epicardial (endo/epi) ratio (microsphere method) in the affected segment of myocardium decreased from 1.42 +/- 0.15 to 0.68 +/- 0.11 ml/min/g and from 1.05 +/- 0.08 to 0.59 +/- 0.10, respectively. Alinidine, in a dose (0.4--0.9 mg/kg) that decreased the heart rate by about 25%, caused a marked redistribution of ischaemic flow in favour of the endocardium: the endo/epi ratio increased to 1.08 +/- 0.12. Concomitantly, systolic myocardial wall thickening of the hypokinetic myocardial segment returned to half its base-line value. The flow to the control area was decreased transmurally by about 30%, so that despite the presence of the stenosis, the whole heart was nearly homogenously perfused after alinidine. Right atrial pacing to the predrug heart rate only partially reduced the effects of alinidine on the endo/epi ratio (0.86 +/- 0.09) of the ischaemic myocardium; wall thickness variables did not change. It is concluded that alinidine ameliorates the imbalance between oxygen supply and demand in the post-stenotic segment of the myocardium. Prolongation of the diastolic perfusion period through heart rate reduction plays an important role in the favourable redistribution of myocardial blood flow, but other factors, such as negative inotropic effects of alinidine, may also be involved.
D000818:Animals; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003327:Coronary Disease / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D009206:Myocardium / Q000473:pathology; D012039:Regional Blood Flow / Q000187:drug effects; D013552:Swine
C022192:alinidine; D003000:Clonidine