Introduction: Growing evidence points to sympathetic hyperactivity as one critical trigger for life-threatening arrhythmias among postmyocardial infarction patients.Methods and Results: We have evaluated, in a placebo-controlled multicenter study, the efficacy of a /3-adrenergic blocking agent (oxprenolol 160 mg) and of a selective left cardiac sympathetic denervation in preventing sudden death in patients with a first and anterior myocardial infarction. Two patient groups were studied. The high-risk group included 144 patients who survived a myocardial infarction complicated by either ventricular tachycardia or fibrillation. The relatively low-risk group included 869 patients whose myocardial infarction did not have these complications; they were allocated only to placebo or oxprenolol. Randomization took place 30 days postmyocardial infarction; mean follow-up was 22 months. In the high-risk group the sudden cardiac death (crude rate) in the placebo subgroup was indeed high (21.3%), and was strikingly reduced to 2.7% and to 3.6% by oxprenolol and by left cardiac sympathetic denervation, respectively (P < 0.05). In the low-risk group the sudden cardiac death (crude rate) in the placebo subgroup was 5.2% and was still reduced by oxprenolol to 1.6% (P < 0.05). The results for total mortality were quite similar to those for sudden death iu both groups.Conclusion: This study, unique for the populations studied and for one of the treatments used, demonstrates that pharmacologic and surgical antiadrenergic interventions significantly reduce sudden cardiac death in postmyocardial infarction patients at high and at low risk. With due consideration to the relatively small size of the high-risk group, it seems reasonable to suggest that left cardiac sympathetic denervatiou may be considered as a possible alternative for high-risk patients with contraindications to beta hlockers. (

SUMMARY Hemodynamic monitoring after a single dose (10 mg) of nifedipine in 27 primary hypertensive subjects (diastolic pressure > 110 mm Hg) documented that this calcium antagonistic agent exerts a potent arteriolar vasodilating action, which results in prompt (-21% of control at 30 minutes) and persistent (-16% of control at 120 minutes) fall in mean arterial pressure associated with a rise in cardiac output and pulse rate.The same patients received oral treatment for 3 weeks. Hourly pressure readings showed that 1) the antihypertensive response to each dose lasts 8-12 hours; and 2) nifedipine every 6 hours significantly reduced blood pressure throughout the 24 hours, without postural hypotension.Side effects were short-lasting (headache in five patients, palpitation without arrhythmias in eight patients, burning sensation in the face and legs in five patients and sporadic extrasystoles in five patients) and tended to disappear with continued treatment.Development of drug resistance, sodium retention, plasma volume expansion, renin release or angina pectoris were not observed during the study. Although these findings seem to differentiate nifedipine from other vasodilators currently used in the treatment of hypertension, broader experience and more prolonged trials with nifedipine as an antihypertensive agent will be needed before conclusions can be drawn on these particular aspects.HIGH VASCULAR RESISTANCE is the proximate cause of elevated arterial pressure in most patients with chronic hypertension. Blood pressure can be normalized either by decreasing cardiac output or by lowering vascular resistance. The former, however, makes circulation doubly abnormal, since vascular resistance remains excessive and cardiac output becomes abnormally low. This situation may be associated-with tissue hypoperfusion, involving kidneys, heart and brain. The desired hemodynamic effect in antihypertensive therapy is dilatation of constricted arterioles by a compound that acts directly on the smooth muscle, relaxes arterioles independently of the vasoconstrictor mechanism, and does not affect the heart or decrease the venous return.Hydralazine, diazoxide, minoxidil and guancydine act directly on vascular smooth muscle to produce vasodilatation, and were introduced with variable degrees of success in the chronic treatment of hypertension. These agents share several common side effects, including an exaggeration of cardiac action that may precipitate angina pectoris in patients with coronary disease and the promotion of renin release, sodium retention and plasma volume expansion. In most circumstances ,B-blockers and diuretics should be added to counteract these effects.' 3

Attacks of Prinzmetal's variant form of angina pectoris are spontaneous, recur cyclically, and present unequivocal electrocardiographic alterations: they are idealfor a detailed haemodynamic study.Four patients with this form of angina were investigated. As the electrocardiogram started reverting to the pre-attack aspect, cardiac performance rapidly improved and, after a 'supernormal' phase, returned in about 2 minutes to basal levels. It is possible that this phase is dependent on a temporary sympathetic compensatory mechanism.No significant qualitative differences were detected between the circulatory pattern of various anginal episodes. The difference was mainly quantitative and the magnitude of the haemodynamic changes correlated well with the degree of the electrocardiographic abnormalities. Pain, when present, seemed just a concomitant symptom not significantly interfering with the circulatory changes associated with the episodes of this form of angina pectoris.The circulatory changes associated with exertion or drug-induced angina pectoris have been the subject of several reports. The available haemodynamic data concerning spontaneous angina pectoris are more often the result of occasional observations than of a systematic study. The latter has been beset by technical problems: the rapidity of the circulatory changes associated with the onset, presence, and disappearance of the anginal attacks necessitates continuous recording of the electrocardiogram and of the circulatory parameters. In addition, finding patients with

Thefunction of both right and left sides of the heart was studied during spontaneous attacks of angina pectoris at rest in 7 patients showing ST depression (type I) and 4 showing ST elevation (type II) during the attack.In none of the 44 type I attacks and 29 type II attacks which were recorded did circulatory changes precede the cardiographic changes; the latter were invariably the initiating events. The subsequent haemodynamic changes were different in the two groups.Type I attacks showed: a) a brieffall in arterial pressure, accompanied by b) a rise of right atrial and pulmonary wedge pressures and c) a decrease ofcardiac output, right and left stroke work, the mean rate ofsystolic ejection, and indirect left ventricular pre-ejection dP/dt. In the course of the attack a hypertensive phase followed, which was paralleled by an increase of heart rate, cardiac output, left and right stroke work, and mean systolic ejection rate, left dP/dt; right atrial pressure and wedge pressure remained raised. All of the circulatory functions started to revert towards the pre-attack levels coincident with the waning phase of the electrocardiographic alteration, the latter occurring either spontaneously or after nitroglycerin.Type II attacks for the entire duration of the electrocardiographic changes showed : a) a reduction of arterial pressure, cardiac output, right and left stroke work, mean systolic ejection rate, and left dP/dt, b) a rise of right atrial and wedge pressures, and c) quite small changes of heart rate. When the electrocardiogram started to revert to the pre-attack aspect, the cardiac function rapidly improved and, after a supernormal phase, returned to the basal levels in about 2 minutes.It is concluded: I) that no circulatory factor interfering with the mechanical effort of the heart is responsible for eliciting spontaneous angina: 2) that in type I attacks right and left ventricular impairment occurs which recovers rapidly, possibly through a sympathetic compensation; 3) that in type II attacks dysfunction of both sides of the heart occurs and persists throughout the episode of electrocardiographic alteration; 4) that the dynamic impairment is probably more severe in type I than in type II angina.

Diazoxide, a new compound of the benzo-thiadiazine group, has been shown to decrease both systolic and diastolic arterial pressure in mild or moderate hypertensive patients, even though it lacks the saluretic properties characteristic of the other known compounds of the group. Instead of promoting sodium excretion, diazoxide appears to be a powerful sodium- and chloride-retaining agent, its prolonged use leading to important increases in plasma volume and body weight, and probably to some redistribution between extracellular and intracellular fluid. Glomerular filtration rate and renal plasma flow are often increased during treatment with the drug. Although diazoxide was in several respects a useful hypotensive agent, at least in hypertensive patients without heart failure, it may share with other benzothiadiazine compounds some pancreatic toxicity, a side effect that should be carefully considered during benzothiadiazine treatment.