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

Abstract

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.

The effect of β‐adrenoceptor blocking agents, with differing ancillary properties, on the arrhythmias resulting from acute coronary artery ligation in anaesthetized rats

“…Certainly, it has been argued that this is a useful property rather later in the progression of ischaemia. Thus, Marshall & Parratt (1976;1977) compared, in anaesthetized greyhounds, the ability of several 3-adrenoceptor blocking drugs to maintain myocardial blood flow in developing infarcts and to reverse lactate production in the ischaemic region. They found that it was only those drugs (practolol, H 87/07 and oxprenolol) with some degree of intrinsic sympathomimetic activity that maintained blood flow.…”

Intrinsic sympathomimetic activity and coronary blood flow.

“…Although these beneficial effects are thought to be related to a more favourable balance between myocardial oxygen supply and demand within the ischaemic region, the present study outlined important differences between these drugs as to their effects on ischaemic areas flow (see Figure 2). Such differences have previously been described by Marshall & Parratt (1976) and Parratt et al (1980) who demonstrated that for a similar degree of myocardial 1l-adrenoceptor blockade, cardioselective blocking drugs, e.g., practolol, metoprolol or H 87/07, reduce ischaemic flow to a lesser extent than non-cardioselective ones, e.g., propranolol and oxprenolol. These authors suggested that the noncardioselective P-adrenoceptor blocking drugs unmask a-adrenoceptors (mediating coronary vasoconstriction) which would be activated by endogenous noradrenaline and adrenaline within the ischaemic area.…”

“…From another point of view, it is now well established that some P-adrenoceptor blocking agents can alterate the transmural distribution of CBF between the different myocardial layers and/or between the non-ischaemic and ischaemic areas within the myocardium (Gross & Winbury, 1973;Becker et al, 1975;Warltier et al, 1976;Berdeaux et al, 1978) and hence reduce the severity of ischaemic injury. However, differences also exist among the P-adrenoceptor blocking agents regarding this so-called redistribution phenomenon (Marshall & Parratt, 1976;Berdeaux et al, 1978;Buck et al, 1979), differences which once again could be due to the existence or the absence of properties such as ISA or cardioselectivity.…”

Cardiovascular Effects of Acebutolol Following Coronary Artery Occlusion and Reperfusion in Anaesthetized Dog

“…Practorto-coronary lol, a cardio-selective ,B-adrenoceptor blocking agent in patients without any membrane stabilizing activity, has been n the expecshown to suppress arrhythmias (Dunlop & Shanks, le, ischaemic 1968;Jewitt, Mercer & Shillingford, 1969) and reduce imbalance abnormalities of ST segment (Libby et al, 1973;Mar-,mands and shall & Parratt, 1976) and cardiac lactate extraction ,perfusion is (Marshall & Parratt, 1976) Snow, 1966; ischaemic myocardium (Marshall & Parratt, 1976). It luring posthas however been shown to reduce the myocardial and during necrosis that develops after temporary coronary r to correct occlusion (Reimer et al, 1973).…”

“…Several previous studies have demonstrated that propranolol and practolol cause a reduction in the extent of myocardial ischaemic injury and infarct size after experimental coronary artery occlusion in dogs (Maroko, Burnstein, Libby, De Laria, Covell, Ross & Braunwald, 1972a; Libby, Maroko, Covell, Malloch, Ross & Braunwald, 1973;Theroux, Franklin, Ross & Kemper, 1974; Lekven, 1975;Marshall & Parratt, 1976;Shatney, Maccarter & Lillehei, 1976;Reimer, Rasmussen & Jennings, 1976). In patients, propranolol appears to protect the myocardium during anoxic arrest (Reul, Romagnoli, Sandiford, Wukasch, Cooley & Norman, 1974), and if administered in early hours of myocardial infarction, it can significantly reduce the signs of myocardial ischaemic injury (Gold, Leinbach & Maroko, 1976).…”