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Biomedical subjects

E D Freis

Publications and source records attributed to E D Freis.

At least 73 records · Page 4Linked to original sources

BP and hypertension.

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Antihypertensive Agents↗

Veterans Administration cooperative study on nadolol as monotherapy and in combination with a diuretic.

A series of studies on various therapeutic aspects of beta-adrenergic-blocking drugs was carried out by the Veterans Administration Cooperative Study Group on Antihypertensive Agents. In one study the diastolic blood pressures of 49% of 132 men with mild to moderate hypertension were controlled (less than 90 mm Hg) with once-daily nadolol. In a similar group, 85% were controlled with nadolol plus bendroflumethiazide, both given once daily. Nadolol alone was as effective as diuretic alone, although in another study comparing propranolol and hydrochlorothiazide, the latter was somewhat more effective. In both trials black patients tended to respond better to the diuretic, whereas white patients responded better to the beta blocker. Although high-renin hypertensive patients tended to respond better to the beta blocker and low-renin patients to the diuretic, the relationships were not close enough to provide a dependable guide to treatment. Sixty percent of patients whose blood pressure was not controlled on the nadolol-containing regimens reached goal blood pressure (less than 90 mm Hg) with the addition of hydralazine, 25 to 100 mg twice daily.

Adolescent↗

Preload and afterload reduction in treating congestive heart failure.

The importance of changes in the resistance and capacitance vessels in the development of congestive heart failure was demonstrated over 30 years ago. The beneficial effects of reducing total peripheral resistance and increasing vascular capacitance were also demonstrated. These studies illustrate the old adage "there is nothing new under the sun."

Autonomic Nerve Block↗

Acute volume expansion in humans releases a factor which inhibits the vascular Na+-K+ pump.

The authors previously observed increased Na+-K+ pump inhibitory activity in the plasma of low renin essential hypertensive unselected with respect to renin status. The present experiments were done to determine the effect of acute volume expansion on plasma Na+-K+ pump inhibitory activity in normotensive subjects. The data show that acute volume expansion increases vascular Na+-K+ pump inhibitory activity in plasma, suggesting that the increased level of this inhibitory activity in low essential hypertensives is probably volume dependent. The unique feature of this study is the use of vascular tissue for the bioassay.

Adult↗

Diuretic-induced hypokalemia in uncomplicated systemic hypertension: effect of plasma potassium correction on cardiac arrhythmias.

Sixteen patients with diuretic-induced hypokalemia underwent 24-hour ambulatory electrocardiographic monitoring during and after correction of hypokalemia. Plasma potassium averaged 2.83 +/- 0.08 mEq/liter before and 3.73 +/- 0.06 mEq/liter after correction with potassium chloride, triamterene or both. Premature atrial contractions decreased in 6 patients, increased in 6 and remained unchanged in 4. There was no improvement in ventricular ectopic activity after plasma potassium correction. Ventricular ectopic activity improved in 5 patients, worsened in 10 and remained unchanged in 1. Ventricular tachycardia was not observed in either phase. Plasma magnesium remained normal throughout. The investigators conclude that in patients with uncomplicated hypertension, correction of diuretic-induced hypokalemia does not significantly reduce the occurrence of spontaneous atrial or ventricular ectopic activity.

Adult↗

Multicenter clinical evaluation of long-term efficacy and safety of labetalol in treatment of hypertension.

The long-term efficacy and safety of labetalol, an antihypertensive agent with combined beta- and alpha-blocking activity, were evaluated alone (number = 193) and in combination with a diuretic (number = 144) in an open-label multicenter trial of 337 hypertensive patients aged 21 to 75 years, including initially 205 (61 percent) men and 219 (65 percent) Caucasians. There were 219 (65 percent) mild, 85 (25 percent) moderate, and 33 (10 percent) severe hypertensive patients. Labetalol (100 to 1,200 mg twice a day) alone or in combination with a diuretic reduced the mean standing blood pressure by 13/11 and 25/16 mm Hg to 135/88 and 130/91 mm Hg, respectively (p less than 0.01), and supine blood pressure by 6/7 and 18/13 mm Hg to 141/86 and 138/90 mm Hg (p less than 0.01), respectively. Blood pressure reductions observed at one month were maintained after one year; 206 (62 percent) patients had 10 mm Hg or greater reductions and 184 (56 percent) patients were maintained at diastolic blood pressures less than 90 mm Hg. Most frequently reported drug-related side effects included fatigue (14 percent), dizziness (12 percent), nausea (11 percent), nasal stuffiness (8 percent), headache (4 percent), and male sexual dysfunction (14 percent). Side effects were generally of mild to moderate intensity and often transient. In addition, in 27 (8 percent) patients reversible asymptomatic transaminase elevations to greater than twice normal developed at some time during the study. In 13 (4 percent) patients these alterations resolved during continued labetalol therapy, but in five (2 percent) patients these marked elevations led to discontinuation of the drug. A total of 32 (9.5 percent) patients were terminated prematurely due to side effects (most commonly genitourinary or gastrointestinal) possibly attributable to the drug. These findings indicate that labetalol with or without a diuretic is a potentially effective, safe, and relatively well-tolerated long-term antihypertensive therapy.

Adult↗

Intravenous labetalol in the treatment of severe hypertension and hypertensive emergencies.

The antihypertensive effects of intravenous labetalol were evaluated in 59 patients with hypertensive crises or severe hypertension in need of rapid lowering of blood pressure in a multicenter study. Patients appearing with a supine diastolic blood pressure 125 mm Hg or greater, or a supine systolic blood pressure of more than 200 mm Hg received an initial mini-bolus injection (20 mg) of labetalol. This was followed by repeated incremental doses of 20 to 80 mg given at 10 minute intervals to achieve a supine diastolic blood pressure of less than 95 mm Hg or decrease 30 mm Hg or greater, or a satisfactory decrease in systolic blood pressure. Patients were stratified into those who had taken antihypertensive medication within 24 hours and those who had not. The initial mini-bolus injection caused rapid but not abrupt reduction in blood pressure; the baseline mean blood pressure decreased 23/14 mm Hg. Further injections were needed in the majority of patients (mean: 197 mg). The blood pressure reduction after the last dose of labetalol was 55/33 mm Hg. In pretreated patients and in those who had no medication for 24 hours prior to the intravenous labetalol, the response was similar. Heart rate decreased 10 beats per minute in the total population. In patients pretreated with beta-adrenergic blockers, blood pressure response was similar to that in the total group (59/35 versus 55/33 mm Hg), but heart rate remained essentially unchanged. The dose required to achieve the therapeutic effect was less in pretreated patients than in untreated patients, but the duration of action was shorter. No serious adverse effects were encountered even in patients with concomitant diagnoses of acute left ventricular failure, myocardial infarction, stable congestive heart failure, atrial fibrillation, angina pectoris, acute stroke, transient ischemic attack or encephalopathy. Labetalol is a safe and effective treatment for a rapid blood pressure reduction in hypertensive emergencies.

Adrenergic beta-Antagonists↗

Electrocardiographic changes in the course of antihypertensive treatment.

Since the early trials of antihypertensive drug treatment, regression of electrocardiographic evidence of left ventricular hypertrophy has been demonstrated. The first multiclinic trial in which these effects were reported was the Veterans Administration trial. In this study the development of abnormal QRS voltage, S-T segment depression or T-wave flattening or inversion in the treated patients was only one-fourth that found in the control group. In those patients with electrocardiographic evidence of left ventricular hypertrophy prior to randomization, reversal of the abnormalities occurred two and a half times more frequently in the treated patients then in the control patients. Other controlled trials have shown similar results with antihypertensive treatment. It is concluded that following antihypertensive drug treatment the electrocardiographic evidence of left ventricular hypertrophy in hypertensive patients is markedly reduced. However, the electrocardiographic signs associated with coronary heart disease did not seem to be altered.

Adult↗

A new microcomputer-based ECG analysis system.

A new automated ECG system using advances in microprocessor technology and computerized electrocardiography is described. This microcomputer-based system is self-contained and mobile. It acquires both the 12-lead and orthogonal lead (Frank) electrocardiograms and analyzes the latter within minutes. Software includes the program developed in the Veterans Administration which uses advanced statistical classification techniques and a large well-documented patient data base. Diagnostic probabilities are computed using a Bayesian approach. Diagnostic performance has been tested using independent clinical criteria and found to be quite accurate. This system enables the clinician to immediately review the computer's identifications, measurements, and diagnostic classifications and quickly use these results in clinical decision making. Serial comparisons are readily made since all previous recordings are stored on floppy diskettes. The use of microprocessors in this system makes it economically feasible for practicing physicians.

Cardiovascular Diseases↗

How diuretics lower blood pressure.

Thiazides produce an average loss of 2 L of extracellular fluid volume, of which about 300 ml is plasma volume, during the first 48 hours of administration, and this reduction is maintained without further loss for as long as the drug is given. Do thiazides lower blood pressure by volume depletion or by direct vasodilator action? As evidence against the vasodilator theory, these facts may be adduced: (1) thiazides do not lower blood pressure in patients (with renal disease) who cannot obtain a diuresis, and (2) other diuretics and diets very low in sodium also reduce blood pressure and volume to a similar degree. A related hypothesis is that thiazides reduce total peripheral vascular resistance (TPR) by "dehydrating" vascular walls. However, direct measurements in small arteries failed to confirm such changes. There is, however, a fall in TPR after long-term treatment, although initially cardiac output falls and TPR remains unchanged. How these long-term readjustments occur remains unknown, although several hypotheses have been advanced.

Benzothiadiazines↗

Comparison of propranolol or hydrochlorothiazide alone for treatment of hypertension. III. Evaluation of the renin-angiotensin system.

In this study, the relation between renin activity and therapeutic response to hydrochlorothiazide or propranolol was studied. Patients with a diastolic blood pressure of 95 to 114 mm Hg were treated with propranolol (40 to 320 mg twice daily) or hydrochlorothiazide (25 to 100 mg twice daily). The initial renin profiles were: low, 56 percent (n = 300); normal, 33 percent (n = 174); high, 11 percent (n = 60). A greater incidence of low and fewer high renin profiles (p less than 0.001) were observed in blacks. After furosemide administration (40 mg intravenously), 55 percent of patients (n = 291) had a low renin response and 45 percent (n = 240) had a normal renin response. No correlation between renin profile and renin response was observed, although low renin response and low renin profile occurred more frequently in older patients. Hydrochlorothiazide administration resulted in a greater decrement in diastolic blood pressure (p less than 0.05) in the total group. Irrespective of renin activity, both hydrochlorothiazide and propranolol reduced diastolic blood pressure. When renin profile was considered, no significant variation in response to hydrochlorothiazide therapy was observed, and there was a greater reduction in diastolic blood pressure in the patients with a high renin profile receiving propranolol. In comparing therapeutic response, patients with a low renin profile had a better response to hydrochlorothiazide, and propranolol was more effective in patients with a high renin profile. The anticipated effect of therapy on plasma renin activity was observed. Although these results are consistent with a volume-vasoconstrictor analysis of hypertension, the results of therapy could not have been prejudged from renin profile or responsivity. The slight differences observed do not warrant the expense of renin determinations when a simple determination of therapeutic response is sufficient.

Blood Pressure↗

Mild hypertension.

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Clinical Trials as Topic↗

Persistence of normal BP after withdrawal of drug treatment in mild hypertension.

Antihypertensive therapy was discontinued in 24 patients with mild hypertension whose BPs had been well controlled with diuretics alone. Eleven patients (46%) maintained normal diastolic BPs (less than or equal to 90 mm Hg) for six months after stopping treatment and five patients (21%) for 12 months. All patients who remained normotensive for six to 12 months had mean diastolic BPs of 82 mm Hg or less during treatment. There was no significant correlation between maintenance of normotension and any of the following: pretreatment BP, presence of target-organ damage, duration of known hypertension, family history of hypertension, heart rate, body weight, weight gain after stopping diuretic therapy, 24-hour urinary sodium and potassium excretion, serum electrolyte values or renin profile. This study demonstrates that hypertension may be favorably modified, sometimes for many months, by effective antihypertensive treatment.

Blood Pressure↗

Treatment of severe hypertension with intravenous labetalol.

The effectiveness of repeated intravenous injections of labetalol in reducing blood pressure (BP) was evaluated in patients with severe hypertension. The subjects were 10 patients who were 29 to 61 yr old and who had diastolic blood pressure (DBP) of 125 mm Hg or higher. Repeated injections titrated from 20 to 80 mg were given at 15-min intervals until there was a reduction in DBP of 30 mm Hg or until 300 mg had been administered. The average reduction of BP ranged from 201 +/- 5/132 +/- 1 to 157 +/- 6/108 +/- 4 mm Hg (mean +/- SEM). Four patients responded with a reduction in DBP of 30 mm Hg or more with total doses of 60 to 220 mg. Of the remaining six who received the full dose, in four there was a 20 to 29 mm Hg reduction in DBP, in one there was a 10 mm Hg fall, and in one there was no reduction. There was a positive correlation between age and response to intravenous labetalol. No severe side effects were encountered. Intravenous labetalol is useful and well tolerated in patients with severe hypertension.

Adult↗