The present study was undertaken to test the hypothesis that the human RR-QT relationship during dynamic exercise differs markedly from that during the recovery phase. Fourteen subjects from the age of 16 to 71 years exercised on a treadmill according to the Bruce protocol. Electrocardiograms were recorded continuously on a magnetic tape, from 1 minute before exercise to 10 minutes into recovery. An exponential formula, proposed by us earlier, closely represented the exercise RR-QT data. However, it was not appropriate for the often S-shaped recovery curves which invariably deviated from the exercise curves, exhibiting hysteresis. Initially, all recovery QT intervals were shorter than the exercise values, but later in the recovery, some crossed the exercise curves from below, resulting in longer QT intervals. The recovery data were fitted by a third degree polynomial, and the hysteresis was calculated as the area between the exercise and recovery curves within a 150 ms range of the RR interval starting from its minimum value. The mechanisms for the occurrence of hysteresis are likely to involve the sympatho-adrenal activity in the early post-exercise period and the time course of QT interval adaptation to rapid changes in the RR interval.

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sumARY A new method was used to study the effect of a single dose of propranolol on the QT intervals during exercise in 11 normal volunteers. They exercised maximally on a bicycle ergometer and repeated the test after taking propranolol (40 mg) by mouth two hours before. Electrocardiograms were continuously recorded on magnetic tape and the cardiac cycle length (RR interval) and the QT interval were measured every five seconds by a computer aided method. The RR-QT data from each test during the exercise phase were analysed by an exponential formula, QT = A -B x exp (-k x RR) and by Bazett's formula, QT = K x (RR). Three reference QT intervals, QTcI, QT,2, and QTc3, estimnated at RR = 400, 700, and 1000 ms respectively from the regression curves of both formulas were compared. The exponential formula, which consistently gave a better fit with the data, showed that propranolol had a biphasic action on the QT intervals during exercise. It significantly prolonged the mean (SD) interval at longer cycle lengths (from 287 (27)

SUMMARY The effects of the calcium antagonist diltiazem on diastolic blood pressure and various parameters of erythrocyte membrane cation transport were evaluated in hypertensive patients with diastolic blood pressure between 95 and 110 mm Hg in a placebo-controlled, double-blind parallel study. Twenty-one patients completed the study; 13 received placebo, while 8 received diltiazem. Diastolic blood pressure, intracellular sodium and calcium concentrations, ouabain-sensitive Na + ,K + -adenosine triphosphatase (ATPase) activity, and net sodium efflux and potassium influx across red blood cell membranes were examined in both groups at the end of placebo run-in, at the end of the titration phase, and at the completion of study. In the placebo group, none of the parameters changed significantly. In the drug-treated group, diastolic blood pressure declined by approximately 10% (placebo, 95.1 ± 8.9; drug-treated, 86.9 ± 4.9 mm Hg; p<0.03) at the end of the study. There were also reductions in intracellular sodium (placebo, 7.9 ± 1.8; drug-treated, 5.2 ± 0.4 mmol/L cells; p<0.002) and calcium (placebo, 13.5 ± 1.6; drug-treated 10.8 ± 3.3 Mmol/L cells; p<0.03) concentrations, accompanied by a simultaneous rise in the activity of the ouabain-sensitive Na+ ,K + -ATPase of erythrocyte membranes (placebo, 7.1 ± 1.1 x 10-J ; drug-treated, 9.0 ± 0.6 x 10-2 fiM inorganic pbosphate/hr/mg; p < 0.001) at the end of the study. However, no significant change in the ouabaininsensitive moiety of the ATPase pump was found. Diltiazem treatment increased net sodium efflux and potassium influx. It is concluded that diltiazem reduces diastolic blood pressure of hypertensive subjects. Erythrocyte studies indicate that diltiazem not only blocks entrance of calcium into the cells but may also stimulate Na+,K+-ATPase activity, resulting in reduction in intracellular sodium concentration, thus suggesting a possible dual mechanism for its antihypertensive effects. 18In the present investigation, we studied the changes that occur in the erythrocytes of hypertensive persons treated with diltiazem to test the hypothesis that the abnormalities in the red blood cell cation concentrations and various pump activities are reversed in those who respond to the drug treatment. These studies were conducted in a placebo-controlled, double-blind, parallel fashion. Patients and Methods Selection of Study PatientsThe protocol was approved by the institutional review board, and written informed consent was obtained from each subject. Twenty-one patients, 12 men (average age, 51 ± 15 years) and 9 women (average age, 57 ± 13 years), completed the protocol. Inclusion criteria were 1) a stable resting supine diastolic blood pressure (DBP) between 95 and 110 mm Hg at least 2 weeks after cessation of antihypertensive medications and 2) a stable DBP with variation of 7 mm Hg or less 19between two consecutive weekly measurements starting with days 7 through 10 of the placebo run-in.After a 2-week placebo run-in phase, the eligible patients were randomized to placebo...