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The sustained haemodynamic effects of prazosin (20-30 mg) and metoprolol (400-800 mg) alone and combined (half-dose) were evaluated in five patients with hypertension, left ventricular hypertrophy, and radiological cardiac enlargement. Measurements were made at rest and during isometric handgrip exercise. Blood pressure at rest was equally well controlled on each regimen. The heart rate and cardiac output (thermodilution) were reduced by metoprolol, even when combined with prazosin. Systolic ejection time was prolonged by metoprolol, but there were no changes in left ventricular dimensions at rest. During isometric handgrip the pressure increments were similar on each of the three regimens, although absolute diastolic pressure was lower on combined therapy. The arterial pressure increment on prazosin therapy was predominantly due to a rapid rise in heart rate and cardiac output, whereas with metoprolol and combined therapy the major contribution to the response was by peripheral vasoconstriction. Moreover, with the latter regimens there was a rapid rise in pulmonary artery occluded pressure, which did not occur with prazosin therapy. In conclusion, metoprolol alone, or combined with prazosin, caused significant depression of cardiac function, which was apparent only when the patients were subjected to the haemodynamic stress of isometric exercise.

The antiarrhythmic effect of intravenous disopyramide phosphate was assessed in a multicentre open study of 141 patients admitted to coronary care units. Disopyramide was administered in a bolus dose of 2 mg/kg over 10 min with an optional second bolus of 1 mg/kg and infusion of 0.4 mg/kg hour. Atrial fibrillation was terminated in 57% of 56 patients, supraventricular tachycardia in 82% of 11 patients, ventricular tachycardia in 88% of 17 patients and premature ventricular contractions were controlled in 85% of 55 patients. Atrial flutter was terminated in only 2 of 17 patients (12%). Side effects occurred in 38% of the patients, the most frequent being those relating to anticholinergic properties of the drug (15%) or systemic hypotension (13%). Occasionally worsening of the arrhythmia (4%), QRS widening (3) or apparent hypertension (2%) were noted. It was concluded that intravenous disopyramide is an effective antiarrhythmic agent in the coronary care unit setting, but that side effects require close monitoring of dosage.

Twelve control dogs receiving a single intravenous injection of mercuric chloride, 3.0 mg. per kg., all died within 4 to 11 days afterwards with marked nitrogen retention and extensive necrosis and calcification of the epithelium lining the proximal convoluted tubules. Three dogs of comparable age and weight were reduced to a standard hypoproteinemic state by repeated plasmapheresis. Each dog then received the same dose of mercuric chloride as the controls. None of these dogs became sick, none showed any elevation of non-protein nitrogen, and the kidneys- both in the gross and histologically-appeared normal when they were examined 8 to 45 days later. As tested thus far intensive plasmapheresis following the injection of mercuric chloride has been without effect in preventing the classical changes of mercuric chloride injury observed in the control dogs. The simplest explanation for these phenomena is that mercuric chloride acts on a more or less specific substance (presumably fabricated or concentrated in the renal cortex) which is depleted in the standard hypoproteinemic state. Other possibilities are mentioned. These findings are in sharp contrast to the results of similar experiments with uranium nitrate. The hypoproteinemic state appears to render the animals more susceptible to uranium injury (3). This probably indicates that the mode of action of the two heavy metals is different.