Importance of myocardial blood flow changes in the protective action of diltiazem in a new model of myocardial ischaemia

Abstract

1The effect ofdiltiazem was studied in a new model ofmyocardial ischaemia in which in addition to a critical constriction of the left circumflex branch (LCX), the left anterior descending coronary artery (LAD) was suddenly occluded. This model is probably more relevant to the clinical situation in which multivessel coronary artery disease is common. 2 In this model diltiazem exerted a beneficial effect, manifested by an increase in myocardial blood flow (MBF) within the stenosed area of the LCX; by a marked reduction of the enhanced preload (LVEDP); by a diminution of the inhomogeneity of electrical activation and by a decrease in STsegment elevation. Diltiazem also caused a significant reduction both in the number of extrasystoles and in the incidence of ventricular fibrillation. 3 Increased MBF within the stenosed area was associated with enhanced blood flow to the ischaemic myocardium, i.e. diltiazem directed flow to the ischaemic zone by improvement of the collateral circulation. 4 The beneficial electrophysiological changes caused by diltiazem are probably at least partly due to the drug-induced improvement of myocardial blood supply to the ischaemic area.

Nifedipine effects in severe myocardial ischaemia in the dog due to left anterior descending coronary occlusion with left circumflex coronary artery constriction

“…As described earlier (Szekeres et al, 1985) the harmful consequences of myocardial ischaemia due to LAD occlusion were aggravated by simultaneous constriction of the LCX. This results in the compensatory increase in blood flow being absent in the area supplied by the LCX.…”

“…Mean arterial blood pressure (MAP) The experimental arrangements were similar to those already described (Szekeres et al, 1985). Thoracotomy was performed in the fifth intercostal space, the LAD and LCX coronary arteries were dissected free and silk threads loosely placed around them.…”

“…Inhomogeneity of activation was expressed as the greatest delay in activation (in ms) between the first and the last burst (for the method in detail see: Szekeres et al, 1985). Changes in the epicardial ST- Szekeres et al, 1985). The MBF from each site was registered continuously on a Kipp & Zonen BD6 recorder.…”

“…Widening and fractionation of this summarized picture of R waves following occlusion indicated that adjacent fibres were not simultaneously activated because of an inhomogeneous conduction of impulses. Inhomogeneity of activation was expressed as the greatest delay in activation (in ms) between the first and the last burst (for the method in detail see: Szekeres et al, 1985). Changes in the epicardial ST- Szekeres et al, 1985).…”

“…In earlier experiments (Szekeres et al, 1985) we described a new model of local myocardial ischaemia in dogs more closely related to the clinical situation in ischaemic heart disease. Here the single vessel disease is a rarity and usually more than one vessel is involved in the sclerotic narrowing.…”