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The electrophysiological properties of Mexiletine were investigated by endocavitary His Bundle recording and programmed electrical stimulation of the heart in 30 patients. Differing dosage (2, 2.7 and 3.4 mg/kg) were given intravenously in 3 groups of 10 patients. The effects on the length of the sinus cycle, conduction intervals and cardiac refractory periods were observed and the following results obtained : 1. Sinus rhythm increased at all dosages but this effect was much more pronounced with 3.4 mg/kg dosage (--12.8% +/- 2.81% : : % shortening of sinus cycle with respect to the basal cycle +/- SD, p less than 0.005); 2. Atrioventricular nodal conduction time (A-H interval) decreased, the effect being more marked with the larger dose regimes; 3.His-Pirkinje conduction time (H-V interval) unaltered except in 3 cases where it increased by 5 ms after injection of 2.7 mg/kg; 4. Relative refractory period of His-Parkinje system shortened, this effect also being more pronounced with the larger doses ( --3.75 +/- 0.25% :2.7 mg/kg, p less than 0,001; -- 7 +/- 1.46% 3.4 mg/kg, p less than 0.005). In conclusion, the changes observed in the His-Purkinje system after mexiletine were similar to those of Lignocaine and Diphenylhydantoin. The drug also appears to have a marked vagal inhibitory effect as shown by the acceleration of the sinus rhythm and reduced atrioventricular conduction times.

The effects of a single oral dose of enalapril (20 mg) on blood pressure (BP), heart rate (HR) plasma renin activity (PRA) aldosterone (PA), converting enzyme inhibition (CEI) and enalaprilat (E, active metabolite) were investigated during 96 h in 3 groups of 5 hypertensive patients with (1) normal renal function (creatinine clearance: Clcr greater than 80 ml.min-1); (2) moderate chronic renal failure: 80 greater than or equal to Clcr greater than 30 ml.min-1; (3) severe chronic renal failure: 30 greater than or equal to Clcr greater than 10 ml.min-1. Results are as follows (mean +/- SEM): (Table: see text) CEmax: maximal plasma concentration; TEmax: delay corresponding to CEmax; TE 1/2: plasma elimination half-life; AUCE: area under plasma level versus time curve. a: p less than 0.01; b: p less than 0.001; versus (1). In the 3 groups, CEI reached 87-94% as early as the 3rd h; however, at 96 h, CE1 was higher in (3) than in (1) and (2): 77.6 +/- 3.3% versus 6.0 +/- 1.6 and 17.7 +/- 4.8 (p less than 0.001 respectively). In (3). PRA increased at the 1st h and remained elevated: at 96 h, delta PRA was + 3.0 +/- 2.9 ng.ml-1 -.h-1 in (3) versus + 0.10 +/- 0.06 and + 0.25 +/- 0.17 ng.ml-1.h-1 .n (1) and (2) [(3) versus (1): p less than 0.01]; delta PA was lower in (3): -4.56 +/- 2.01 ng. 100 ml-1 versus -0.54 +/- 0.31 and -2.50 +/- 0.38 ng. 100 ml-1 [(3) versus (1): p less than 0.05].(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac output, cardiopulmonary (CPBV) and total (TBV) blood volumes, vascular reactivity to norepinephrine and dopamine B hydroxylase (DBH) were determined in 41 borderline hypertensives patients in comparison with 28 normal subjects. Cardiac output (P less than 0.001) and CPBV/TBV ratio (P less than 0.01) were significantly increased. The ratio was directly correlated to the pressor-response to norepinephrine (P less than 0.01) and the DBH level (P less than 0.005). The results suggest that sympathetic overactivity plays a dominant role in the cardiac output elevation of borderline hypertensive patients.