Drug-induced changes in blood flow in the acutely ischaemic canine myocardium; relationship to subendocardial driving pressure

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.

Section: Discussionmentioning

confidence: 86%

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

Szekeres

Udvary

Végh

1985

“…(a) We have previously shown (Ledingham, Marshall & Parratt, 1973;Marshall & Parratt, 1974b) that one of the main factors influencing blood flow in the acutely ischaemic myocardium is the transventricular driving pressure, i.e., the difference during diastole between coronary artery pressure distal to the occlusion and left ventricular pressure. It was therefore of interest to see whether the differing effects of propranolol and practolol on infarct flow were related to changes in this parameter.…”

Section: Discussionmentioning

confidence: 99%

Comparative Effects of Propranolol and Practolol in the Early Stages of Experimental Canine Myocardial Infarction

Marshall

Parratt

1976

I The effects of propranolol and practolol, at equivalent myocardial P-adrenoceptor blocking doses, (as assessed by the degree of shift of isoprenaline dose-response curves) were investigated in anaesthetized greyhounds before and after acute coronary artery ligation. 2 When administered intravenously to the intact closed-chest dog, propranolol (0.1 mg/kg) and practolol (0.5 mg/kg) caused similar decreases in heart rate, left ventricular dP/dt max, myocardial blood flow and cardiac output. Only propranolol increased peripheral vascular resistance. 3 When administered 2-3 h after acute coronary artery ligation, propranolol (0.1 mg/kg) significantly decreased blood flow in both normally perfused and ischaemic regions of the heart. There was also electrocardiographic evidence of further deterioration after propranolol; two out of seven animals died following this treatment. 4 Practolol (0.5 mg/kg) when administered after coronary artery ligation also decreased normal myocardial blood flow but flow in the ischaemic area remained unchanged. Evidence was obtained from electrocardiographic, myocardial temperature, myocardial 02 consumption and lactate measurements that the administration of practolol, in contrast to propranolol, benefited the ischaemic myocardium. SAnalysis of the results suggests that this beneficial action of practolol may be related to at least two mechanisms. Firstly the ability of practolol to increase the period during diastole when perfusion of the subendocardium is possible, without decrteing the transventricular pressure during this period. Secondly that practolol does not unnu;k a-adrenoceptor vasoconstriction in the ischaemic region.

“…Left ventricular end-diastolic pressure (LVEDP) was recorded from the LV pressure trace using a higher amplifier gain. of 2.5 mm internal diameter, tapered at the coronary end to 1.5 mm connecting the left femoral artery to the left descending coronary artery (see Figure 1) and subendocardial driving pressure was calculated from the difference between LVEDP and the coronary (diastolic) perfusion pressure (Marshall & Parratt, 1974). Inflow through the autoperfused LAD coronary artery was measured using a Nycotron 376 flowmeter.…”

Section: Methodsmentioning

confidence: 99%

Haemodynamic factors influencing myocardial ischaemia in a canine model of coronary artery stenosis: the effects of nitroglycerine

Szekeres¹,

Udvary²

1983

1At a critical degree of coronary stenosis (allowing a just adequate blood supply to the poststenotic area only at the expense of maximal hypoxic coronary vasodilatation), an additional loading of the heart induced marked local myocardial ischaemia, as indicated by appropriate biochemical, electrophysiological and haemodynamic changes. 2 In this model myocardial oxygen demand was increased in three different ways: (i) increasing heart rate by atrial pacing; (ii) increasing afterload by aortic occlusion and (iii) increasing preload by blood infusion. These procedures were compared in their ability to produce local myocardial ischaemia and characterized by ST-segment elevation recorded from the endocardium and epicardium. 3 Increasing afterload evoked the mildest degree of ischaemia since the resulting increase in coronary perfusion pressure and coronary flow almost met the augmented myocardial oxygen demand evoked by the elevated peripheral resistance and by the simultaneously increased preload. A rather more pronounced ischaemia was produced by increasing the preload. The most serious ischaemia of all was induced by atrial pacing. This reduced coronary flow and perfusion pressure and increased left ventricular end diastolic pressure (LVEDP). 4 Nitroglycerine transiently reduced blood pressure and coronary blood flow and increased epicardial and endocardial ST-segment elevation; the changes had disappeared 10 min after terminating the infusion. However, at this time a prolonged protective action against pacing-induced ST-segment elevation was observed. This protection was also seen after intracoronary injections of nitroglycerine. This indicated that part of the beneficial effect of nitroglycerine in ischaemia is due to direct coronary and/or myocardial actions.