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The measurement of praecordial ST segment elevation after myocardial infarction is of value in assessing the natural history of ischaemic injury and the effectiveness of intervention. Hand analysis is, however, time consuming and inaccurate. A technique for continuous recording from 35 praecordial leads and subsequent computer analysis is presented, together with illustrative case studies. Changes in body posture and in heart rate are of importance in subsequent data interpretation.

Summary The effects of a β-adrenoceptor antagonist with partial agonist activity (pindolol) were assessed in the open-chest anaesthetised dog during 12-minute periods of left anterior descending coronary artery (LAD) occlusion and reperfusion before and after sympathetic stimulation. Regional myocardial catecholamine efflux, blood flow, and epicardial activation abnormalities were assessed in three groups. In a control group (n = 8). two periods of ischacmia resulted in reproducible intraexperimental changes in catecholamine responses, blood flow, conduction abnormalities, and arrhythmias. Intravenous (i.v.) pindolol (0.45 mg/kg before the second occlusion) reduced nerve-stimulated norepinephrine (NE) overflow from nonischaemic (NI) myocardium but did not modify overflow from ischaemic (I) myocardium either during ischaemia or reperfusion. At constant heart rate (atrial pacing, n = 8), pindolol reduced absolute blood flow to 1 and NI but had no effect on the ratio of endocardial/epicardial blood flow, arrhythmias, or activation abnormalities during occlusion. Following a reduction in heart rate of 32 ± 6 beats/min (no pacing, n = 8). pindolol resulted in similar reduction in blood flow to I and NI but also increased the ratio of endocardial/epicardial flow and reduced both spontaneous arrhythmias and activation delay during occlusion. The acute effects of pindolol on conduction abnormalities, arrhythmias, and blood How distribution in I are thus dependent on reduction in heart rate.

We studied the effects of yohimbine, and alpha-adrenoceptor blocker with selectivity for the alpha 2-subtype, on myocardial norepinephrine (NE) overflow, regional myocardial blood flow (RMBF), and patterns of epicardial conduction abnormalities during occlusion of the proximal left anterior coronary artery in an open-chest anaesthetised dog model. With a 12-min period of coronary occlusion (n = 9), spontaneous overflow of NE into ischaemic venous effluent was not observed either before or after yohimbine (1 mg/kg i.v.), but the drug significantly potentiated the enhanced NE overflow during supramaximal stimulation of the left stellate ganglion at low (1 Hz) and high (10 Hz) frequency [peak NE 4.3 +/- 0.4 pmol/ml control; 11.8 +/- 5.4 pmol/ml yohimbine (p less than 0.005)] with a delayed return towards prestimulation levels. Myocardial NE overflow on coronary reperfusion was also enhanced. Yohimbine increased arterial epinephrine two- to threefold but did not substantially alter myocardial lactate overflow during coronary occlusion. RMBF was reduced 24 and 36% to ischaemic endocardium and epicardium, respectively (p less than 0.01, compared with control occlusion). This contrasted with a 9 and 6% decrease in flow to the respective nonischaemic areas (p = NS, compared with control occlusion. Spontaneous ventricular fibrillation and the area and magnitude of epicardial conduction abnormalities in the ischaemic myocardium were both increased compared with the control occlusion. Thus, alpha-blockers with selectivity for the alpha 2-adrenoceptor may be detrimental to acutely ischaemic myocardium, presumably through increased local catecholamine release at the nerve terminal.

A double-blind cross-over study was performed on 12 men sith stable angina pectoris in order to determine the effect of antilipolytic treatment on exercise tolerance and exercise-induced electrocardiographic changes. The men were exercised to the onset of anginal pain using a reproducible and standardized ergometric load. A nicotinic acid analogue was used to reduce plasma free fatty acids and free glycerol before and during exercise testing and to eliminate their post-exercise rise. This was associated with significant reduction of exercise-induced ST segment depression (p less than 0-005), though there was no significant difference in the duration of exercise before the oneset of pain. A change in the prportions of lipid and carbohydrate for oxidation by the ischaemic myocardium, making relatively more glucose available, is a likely explanation.

There is a non-linear discontinuos relationship between serum cholesterol, and LDL cholesterol, with IHD. There is no sound evidence that reduction of serum cholesterol below 200–210 mg/dl will reduce IHD incidence. It has not yet been shown that regression of advanced lesions in middle-aged men can occur, but regression of cholesterol-induced atheromatous lesions has been achieved in juvenile monkeys by discontinuing atherogenic diets. While the three major primary prevention trials of lowering raised serum cholesterol were all associated with reduction in non-fatal mortality from IHD - thereby supporting the lipid hypothesis - all also showed an increase in non-cardiovascular mortality. It is legitimate to raise doubts about the consequences on normal biological function of ageing cells of reducing cholesterol concentrations over many years. It is probably of little value to reduce raised serum cholesterol concentrations in patients with overt IHD, since their prognosis is largely determined by the extent of myocardial damage sustained and of coexisting thrombogenic tendency. Patients with familial hypercholesterolemia should be vigorously treated with a diet with a PIS ratio 1–5, cholestyramine and perhaps nicotinic acid also. The general population should be advised to reduce fat calories to below 30 per cent of total energy with no more than one-third from saturated fat.

Publisher Summary The severity of an acute myocardial ischemic injury is determined by factors that alter the oxygen requirement of the heart relative to oxygen supply. Plasma fatty acid concentration is an important determinant of myocardial oxygen consumption. This chapter describes an investigation to study whether the induction of myocardial ischemia per se might stimulate myocardial lipolytic activity with breakdown of endogenous triglycerides in the in vivo situation. If the induction of myocardial ischemia per se might stimulate myocardial lipolytic activity with breakdown of endogenous triglycerides in the in vivo situation, then a part of the beneficial effect of antilipolytic agents on the severity of myocardial ischemia might be because of the inhibition of myocardial lipolysis with reduced local free fatty acid (FFA) release to the ischemic myocardium in addition to reduced extraction of FFA from plasma. Another purpose of the investigation was to study the possible mechanisms of action of the antilipolytic agents, namely, nicotinic acid and sodium salicylate, both of which have shown to reduce an acute myocardial ischemic injury.

There is a moderately good correlation between dietary saturated fatty acids and coronary heart disease (CHD) when populations in different parts of the world are compared but not within the same cultural community or for individuals. Total energy, essential fatty acids (EFA), dietary fibre, alcohol and salt also contribute to the relationship of diet to CHD. Saturated fatty acids exert their pathogenic role mostly through altering the homoeostasis of lipoprotein metabolism, leading to an increase in cholesterol-rich low-density lipoproteins, and influencing adversely the balance between the accumulation in and clearance of cholesterol esters from the arterial wall. Polyunsaturated fatty acids (PUFA) alter lipoprotein metabolism directly by decreasing synthesis and increasing catabolism and excretion and indirectly by being substitutes for saturated fatty acids, which are therefore consumed in smaller quantities. PUFA have an important additional role, because of their EFA content. A deficiency of the EFA, linoleic and arachidonic acids, relative to the saturated fatty acid intake, can be correlated with CHD mortality. The pathogenic pathways of a relative EFA deficiency leading to CHD are as likely to be related to intravascular coagulation and myocardial metabolism as to lipoprotein metabolism. EFA requirements may not be met in communities having a high intake of saturated fatty acids if there is also a dietary deficiency of antioxidants particularly vitamin E. Two large primary prevention trials of diets enriched with PUFA showed, under institutional circumstances, that it is possible to reduce serum cholesterol by 10-15 per cent. There was in each a reduction in the total incidence of cardiovascular diseases, and the greatest effect was on the incidence of non-fatal myocardial infarction. In both trials there was an increase in non-cardiovascular mortality. The significance of this finding is evaluated in conjunction with a similar finding derived from the only long-term primary prevention trial using a drug. The possibility that gradual depletion of membrane cholesterol over many years might have an adverse effect on the function of ageing cells cannot be dismissed. In communities where there is a high incidence of CHD, the aim should be to reduce plasma cholesterol concentrations to the region of 210 mg/dl. The evidence that it is necessary, practicable or even desirable to reduce plasma cholesterol to lower levels in order to reduce CHD incidence further is not impressive. To achieve this aim by dietary measures there should be a reduction of energy from fats to a level of 35 per cent or below and reduction of the contributions from saturated fats to about 10 per cent. In addition, there is a sound basis for recommending reduction of total energy intake to that actually needed, an increase in dietary cereal fibre and a reduction in alcohol.