James Conway

Hemodynamic and Hypotensive Effects of Long-term Therapy with Chlorothiazide

Long-term treatment of hypertension with chlorothiazide alone produces mioderate reduction in blood pressure in 66 per cent of patients with hypertension. This fall in pressure is due to a reduction in total peripheral resistance rather than a fall in cardiac output.

Influence of Age on the Hemodynamic Response to Exercise

Respiratory and hemodynamic measurements were made on 54 sedentary subjects during progressive exercise on a bicycle ergometer up to the point of maximal voluntary effort. The age range of the group was from 18 to 68 years.The maximum tolerated exercise, as indicated by the highest achieved level of oxygen consumption (Vo2), diminished with age. Older subjects had a lower resting cardiac output (Q) than normal subjects, but an identical increase in Q with Vo2. There was no evidence of flattening of this curve as the older subjects approached highest exercise loads. Consequently, the arteriovenous oxygen difference did not increase abnormally on high loads, and the cardiac response to exercise in older subjects appeared to be adequate. The relationship between inspired air volume and heart rate with Vo2 at submaximal loads was not influenced by age.Systolic pressure increased progressively with exercise and showed a greater change in older subjects. Total peripheral resistance at rest increased with age; but with increasing exercise, this difference progressively diminished.

Hemodynamic Studies in Patients with Borderline Blood Pressure Elevation

Ninety-four patients with occasionally elevated (borderline) blood pressure, 61 patients with asymptomatic established hypertension, and 63 normal subjects have been studied at rest and during a progressive exercise test on a cycle ergometer. Subjects with borderline blood pressure had increased cardiac output in the resting recumbent position, but this was not maintained in the sitting position or during exercise. In the resting recumbent position there was overlap in the total peripheral resistance of normal subjects and patients with borderline blood pressure, but when analyzed in relation to the cardiac output, the total peripheral resistance of patients with borderline blood pressure was significantly elevated. In the sitting position the peripheral resistance of the patients with borderline blood pressure was elevated and remained elevated during light exercise, but fell into the normal range at higher loads. In this respect patients with borderline blood pressure differed from hypertensive patients who maintain a higher peripheral resistance than the normal subjects do at all levels of exercise. In conclusion, patients with occasional elevation of blood pressure have an abnormal peripheral resistance in relation to cardiac output both at rest and at low levels of exercise. This observation may indicate a prehypertensive state.

A vascular abnormality in hypertension. A study of blood flow in the forearm.

Forearm blood flow measurements have been made at rest and after 8 to 10 minutes arterial occlusion in 50 normal and 131 untreated hypertensive subjects. The latter group comprised 91 with essential hypertension; 11 with chronic renal disease (nephritis or pyelonephritis); 21 with renovascular disease; and eight with primary aldosteronism.The resting blood flow increased with the rising pressure in patients with mild hypertension but there was a significant increase in the resting resistance in the more severe cases. The average minimal resistance obtained during reactive hyperemia was greater in hypertensive (3.1 SE 1.0 units) than in normal subjects (2.0 SE 0.07 units). This abnormality was related to the level of blood pressure but not to the duration of the disease.Patients with renovascular disease or aldosteronism presented the same vascular fault as the more common causes of hypertension.Evidence is presented to show that the reactive hyperemia produced maximal dilatation of the forearm vasculature, and acute elevation in pressure in normotensive or acute depression of pressure in hypertensive subjects did not influence the level of resistance achieved by reactive hyperemia.It is concluded that the blood vessels themselves are abnormal in hypertension and that this abnormality may not be related to the activity of vascular smooth muscle.

Influence of Hypertension on the Hemodynamic Response to Exercise

Sixty-one asymptomatic hypertensive patients from 19 to 68 years of age were subjected to a progressive exercise test on a cycle ergometer. A decline in maximal oxygen consumption and cardiac output and an increase in systolic blood pressure were observed with age. These findings were similar to those observed in normal subjects. In the middle-aged (35 to 49 years) and older subjects (50 to 60 years), the systolic pressure showed a greater increase with exercise than in normals of their age, but this did not apply to subjects aged 19 to 34 years. The cardiac response to exercise was normal at rest and at all levels of exercise in the middle-aged group, but the oldest group showed a reduced maximum cardiac output. In the youngest age group, cardiac output was normal at rest but fell below normal at all levels of exercise.Maximal voluntary oxygen consumption and cardiac output were significantly reduced with increasing severity of hypertension.

Hemodynamic Responses to Tilt and Beta-Adrenergic Blockade in Young Patients with Borderline Hypertension

Seventeen young patients with borderline hypertension (one female) and 18 normotensive paid volunteers (two females) were studied at rest and in the tilted position after 10 min of 45° head-up tilt. Cardiac output, heart rate, and intra-arterial pressure were recorded. The measurements at rest and during the tilt were repeated after betaadrenergic blockade with propranolol.By comparison with the normotensives, cardiac output and heart rate in those with borderline hypertension were elevated initially, after 50 min of rest, and during tilt. The change of the cardiac output and heart rate to tilt was of the same magnitude in patients and control subjects. Consequently, regulation of the rate and flow in borderline hypertensives appears to be normal but starts from a higher base line level.After blockade with propranolol, cardiac output in patients with borderline hypertension was still slightly elevated, but the difference from controls was not significant. The heart rate, however, remained significantly elevated at rest and during tilt. Elevation of the heart rate in borderline hypertensives is not mediated through the beta-adrenergic system and may result from decreased parasympathetic inhibition or from different intrinsic myocardial pacing.

Hemodynamic Consequences of Induced Changes in Blood Volume

The effects of transfusion or bleeding on cardiac output and blood pressure have been followed for periods of seven to ten hours in trained, conscious dogs. When blood volume is increased by transfusion of blood, supplemented by dextran to minimize the expected change in hematocrit, cardiac output and blood pressure increase initially. After one and one-half hours the cardiac output returns to the initial level but blood pressure remains elevated and calculated peripheral resistance increases. This state has been maintained for a period of ten hours by repeated transfusion. After bleeding, with replacement of packed cells, again to minimize the change in hematocrit, cardiac output decreases initially and peripheral resistance increases, but after three hours, output returns to its former level, and peripheral resistance falls below the control value. These changes become more prominent when a second hemorrhage is performed two hours after the first one. The reduction of resistance was then maintained for seven hours. These findings demonstrate that the effects of changes in blood volume are not limited to the acute changes in cardiac output and filling pressure. After periods of one to three hours, changes in peripheral resistance also become evident.

Changes in Sodium Balance and Hemodynamics during Development of Experimental Renal Hypertension in Dogs

After unilateral nephrectomy and application of a Goldblatt clamp to the remaining renal artery, there was sodium retention of approximately 123 mEq in 15 days. At this time, blood pressure increased from 95 to 142 mm Hg without demonstrable changes in plasma volume or cardiac output. When the accumulation of sodium was prevented and a negative balance induced by a low sodium diet and a single dose of a diuretic agent postoperatively, the blood pressure increased from 102 to 139 mm Hg, but it increased further, to 155 mm Hg, after a normal sodium diet had been restored and there had been a gain of 189 mEq of sodium above control. The accumulation of sodium after application of the Goldblatt clamp does not appear to be necessary for the emergence of hypertension, but it does appear to play some part in determining the magnitude of the rise in pressure.

The antihypertensive and diuretic effects of amiloride and of its combination with hydrochlorothiazide

The hypotensive effect as well as changes in serum electrolytes and uric acid of amiloride (AM) and of its combination with hydrochlorothiazide (HC) were studied. In five hypertensive patients over a five‐day period, AM and HC administered together produced more natriuresis than either alone. Potassium, chloride, and bicarbonate concentrations in the serum showed a smaller alteration from normal with the combination than with HC alone. Twelve additional outpatients with moderate hypertension were followed for twelve weeks with the use of randomized Latin squares in double‐blind fashion. A blood pressure‐lowering effect of AM by itself or when added to HC was not seen. AM had no discernible effect on serum glucose, uric acid, or chloride concentrations.

Hypotensive Effect of Ethacrynic Acid

Ethacrynic acid has been found to possess a similar antihypertensive action to the thiazide diuretics. The use of the two drugs together results in a greater fall in pressure than that obtained with either drug alone. When thiazide therapy is supplemented by ethacrynic acid and dietary restriction of sodium a substantial additional reduction in blood pressure averaging 48/18 mm. Hg was obtained.