Diuretic induced long term hemodynamic changes in hypertension. A retrospective study in a MRFIT clinical center.

Retrospective analysis of hemodynamic factors was performed on hypertensive participants of our Multiple Risk Factor Intervention Trial (MRFIT) center to determine whether these may have a role in the higher mortality in a subgroup of special intervention (SI) participants with minor baseline electrocardiographic abnormalities. Stroke volume was estimated by a formula [SV = K(LVETxPP)x(1 + LVET/DP) where the K factor was determined using a separate group of individuals undergoing cardiac catheterization. The Pearson correlation between the two methods (dye dilution and above formula) was 0.7744 with a 95% confidence interval of 0.57-0.89 for the true correlation. In 222 SI and 186 usual care (UC) participants with no differences in stroke volume index (SVI) and cardiac output index (CI) at baseline, SVI and CI were systematically lower during the entire period of treatment in SI receiving higher average doses of thiazide diuretics. There was a moderate increase of SVI and CI in SI participants toward baseline after hydrochlorothiazide was replaced by other antihypertensive medication in the fourth year of the trial. We conclude that the lower SVI and CI could have been a contributing factor in the higher mortality in the SI group with ECG abnormalities resulting in decreased coronary flow reserve under stress conditions in these participants with probably pre-existing asymptomatic coronary artery disease.

Antihypertensive effect of tiapamil from ambulatory and clinic methods.

Tiapamil (T), a calcium antagonist, was studied in hypertensive patients by 1) automatic monitor of blood pressure (AMBP), and 2) cuff and stethoscope clinic blood pressure (CBP). Systolic (SBP), diastolic (DBP) pressures and heart rate were measured. Patients (n = 58) received four weeks of placebos given twice daily. Baseline 24 h AMBP (wk 4), 147 +/- 18 (SBP) and 91 +/- 8 (DBP) mmHg; and CBP (wk 3 and 4), 152 +/- 16 (SBP) and 102 +/- 9 (DBP) were established. Then, patients received double-blinded therapy (wk 5-10) of twice daily tablets of placebo (n = 9); Level I T, 150-300 mg (n = 24); or Level II T, 450-600 mg (n = 25): i.e. 0 to 1,200 mg T/d. Significant responses, measured by AMBP (wk 10), were noted only at Level II T: SBP (-10.5 +/- 12.4) and DBP (-5.6 +/- 7.8) mmHg. However, CBP (wk 9 and 10) responded at Level I T (SBP, -7.7 +/- 12.4/DBP, -5.8 +/- 6.4) and Level II T (SBP, -8.8 +/- 9.4/DBP, -9.7 +/- 7.8 mmHg). There was minimal correlation (r = 0.16) of pressure responses to T measured by 24-h AMBP versus CBP methods. Therefore, T effectively lowered SBP and DBP, but individual responses measured by AMBP did not predict those measured by CBP. There was no effect of T on heart rate. Dizziness was noted in 12 percent of patients on T.

Muscular, respiratory and cardiovascular responses of quadriplegic persons to an F. E. S. bicycle ergometer conditioning program.

Seven quadriplegic subjects participated in F. E. S. bicycle ergometry, three times per week, over an eight week period. Left thigh girth measured at 20 cm above the knee increased from 44.4 cm pre-training to 46.5 cm post-training (p less than 0.05), and right thigh girth increased from 44.3 cm to 46.2 cm (p less than 0.05). Forced vital capacity increased from 3.23 liters (pre-training) to 3.42 liters (post-training) and was significant at the p less than 0.05 level. Forced inspiratory capacity increased for 3.30 liters, pre-training, to 3.42 liters, post-training (p less than 0.05). FEV1 (liters) increased from 2.77, pre-training to 3.07 post-training (p less than 0.05). All three respiratory parameters were 55%-60% of that predicted for normals. Significant changes were also found in resting cardiovascular data. Mean resting heart rate, pre-training, was 51.4 beats per minute compared to 54.5 beats per minute, post-training, (p less than 0.05). Resting cardiac output, pre-training was 4.14 L/min. compared to 4.47 L/min., post-training (p less than 0.05). Further analysis of the cardiovascular data showed that the increased heart rate post-training was associated with a decrease in the P-R interval from 0.186 sec., pre-training to 0.170 sec., post-training (p less than 0.05). Also, the increase in cardiac output, post-training was matched by an increase in the cardiac index from 2.21 L/min./M, pre-training, to 2.36 L/min./M, post-training (p less than 0.05). A statistically significant difference in the heart rate response to the cold pressor test was demonstrated (p less than 0.05) and a similar difference in the amount of heart rate response was seen during the tilt table test (p = 0.05).

Effects of thiazide on erythrocyte sodium and potassium concentrations and Na+K+ATPase in hypertensive patients.

The mechanism of thiazide induced sodium and potassium transport across the cell membranes of humans has not been extensively studied. To assess the effects of thiazide diuretics on erythrocyte sodium transport and potassium distribution we measured intracellular sodium and potassium, sodium-potassium ATPase activity (with and without ouabain) and total body potassium in normokalemic and mildly hypokalemic hypertensive patients. We also measured serum and urine sodium, potassium, calcium and magnesium, plasma renin activity and serum aldosterone levels. The study patients, on long-term thiazide, had measurements obtained during, one month after cessation and one month after resumption of thiazide. In this study of normokalemic and mildly hypokalemic hypertensives there were no significant measurement changes, in contrast to previous studies of severely hypokalemic hypertensives. These results suggested that thiazide did not routinely affect erythrocyte active membrane transport and potassium distribution in the absence of severe hypokalemia.

Mechanism of diuretic-induced hypopotassemia in human hypertension.

Diuretic treatment (hydrochlorothiazide) induced a marked decrease of red cell membrane Na+K+ ATPase activity in excessive potassium loser hypertensive patients. The decreased activity occurred within 2-4 weeks of treatment and returned to baseline in 4-6 weeks after cessation of treatment. Simultaneously, red cell sodium increased, potassium decreased together with increased 24-h urinary excretion. The persistent low serum potassium may be due to impaired absorption of potassium from the gut as a result of suppressed enzyme activity since total body potassium appears also to decrease. The decreased Na+K+ ATPase activity may be due to a direct effect of the diuretic on cell membrane.

Blood pressure, electrolytes, and body size: their relationships in young relatives of men with essential hypertension.

In 154 white chldren aged 8 to 18 years from four large kindreds, relationships among blood pressure (BP), age, sex, body size, and electrolyte excretion were studied. Each kindred was ascertained through one male aged 35-58 years with essential hypertension, namely, a diastolic blood pressure (DBP) over 95 mm Hg. Weight, relative weight (relative to NCHS median for age, sex, and stature), subcutaneous fatfolds, various indices of obesity, and other measures of body size were significantly correlated with systolic blood pressure (SBP) and DBP in each sex (r = 0.3 to 0.7). Sodium and potassium excretion in 24-hour urine was also positively correlated with some measures of body size, and tended to increase with body size at a slightly more rapid rate in boys than in girls. In addition, there was a strong correlation between electrolyte excretion and BP in boys (r = 0.2 to 0.6); however, when the effects of age, body size and fatness were statistically removed, the correlations between BP and electrolyte excretion were not significant, except for 4th phase diastolic pressure (DBP4). These data, therefore, while not strongly supporting a relationship between sodium excretion and BP in children, do not rule out such a relationship, especially in families with a history of hypertension. In addition, these data provide further evidence of a very strong association between BP and body size and fatness in boys and girls.

Cardiovascular response to cooling of limbs determined by noninvasive methods.

Cold, even local exposure to a limited portion of the body, is a stress to man which elevates arterial pressure, thereby intensifying cardiac workload. The sequence of cardiac events following local cooling was noninvasively studied by observation of changes in cardiac interval, left ventricular ejection time, time from A wave of electrocardiogram to the peak of the dD/dt of the carotid pulse wave (which includes pre-ejection period), and amplitude of the pulse wave from a photoelectric cell on the earlobe, along with arterial pressures. Twelve subjects, aged 22--41 years, exposed a hand or foot to cold water for 1 min while seated and while supine (four experiements each). Results indicate that arterial pressure is monotonically elevated throughout the minute of exposure. Cardiac intervals are initially abbreviated, then return towards control. This may include an initial response to the cold, followed by a baroreflex at the heart. Subject posture and limb exposed also affect cardiac responses.

Cardiac reflexes conducted by vagal afferents in normotensive and renal hypertensive dogs.

1. The renal sympathetic reflex responses to transient balloon occlusion of the descending aorta (systemic baroreceptor activation) and the ascending aorta (cardiac stretch-receptor activation) have been studied together with blood pressure increases after successive cutting of carotid sinus, aortic and vagus nerves in acute experiments in the dog. 2. Results from these experiments provide evidence for cardiac vagal afferent participation in the tonic regulation of systemic blood pressure. 3. In other experiments the reflex pressure-response curve of the isolated gracilis muscle at constant flow to transient ascending aorta occlusion was measured. This curve was moved to the right in renal hypertensive dogs as compared with normotensive dogs. The threshold response of left ventricular vagal afferent nerves was shifted to higher left ventricular pressure in the former. 3. These findings indicate resetting of ventricular receptors in hypertensive animals.