Response to mental and physical stress before and during adrenoreceptor blocker and angiotensin-converting enzyme inhibitor treatment in essential hypertension.

The effects of mental, static and dynamic stresses on physiologic parameters before and after beta-blocker (n = 24) and angiotensin-converting enzyme inhibitor (n = 29) treatment were examined. Mental stress induced similar elevation in systolic and diastolic blood pressures (BPs) with and without beta-blocker treatment. During angiotensin-converting enzyme inhibitor treatment, the change in systolic BP was significantly greater (p less than 0.05). Heart rate response was attenuated by beta blockers and unchanged by the angiotensin-converting enzyme inhibitor. Skin temperature and galvanic skin resistance significantly decreased (p less than 0.05) with mental stress. Beta blockers did not change the response pattern, whereas the angiotensin-converting enzyme inhibitor attenuated the stress-induced reduction of both skin temperature and galvanic skin response. After handgrip exercise, increases in systolic and diastolic BPs and heart rate were similar before and after beta-blocker treatment, whereas the angiotensin-converting enzyme inhibitor induced small but significantly fewer (p less than 0.05) changes in diastolic BP and heart rate. Treadmill exercise induced similar changes in systolic and diastolic BPs with both treatments compared with no treatment. The angiotensin-converting enzyme inhibitor appears to provide additional protection to that seen with beta blockers during mental and static stressors by blunted changes in skin temperature and galvanic skin resistance.

Atrial fibrillation developing in the acute phase of myocardial infarction. Prognostic implications.

Atrial fibrillation was observed in 39 (11 percent) of 350 instances of acute myocardial infarction. The mortality among these patients was 41 percent (16/39). Atrial fibrillation was more common in patients with undetermined infarctions and in older people. As opposed to death rates close to 50 percent among patients with anterior, combined, and undetermined infarctions, the presence of atrial fibrillation did not affect the mortality among patients with inferior infarctions (10 percent, 1/10). Ventricular rates higher than 120 beats per minute and duration of the arrhythmia longer than six hours were not associated with increased mortality. Hemodynamic failure was present in almost all of the cases and preceded the arrhythmia in most of them. It is concluded that different mechanisms are responsible for the production of atrial fibrillation in the setting of acute myocardial infarction, and the prognosis of the patient is related to the mechanism of production and not to the arrhythmia itself.

Serum dopamine beta-hydroxylase activity in acute cardiac disease.

The activity of dopamine beta-hydroxylase in the serum was measured in patients with acute cardiac disorders who were admitted to a coronary care unit. The activity of the enzyme on admission was similar in patients with acute myocardial infarction and in those with other conditions; on discharge, the activity was reduced significantly. Patients with myocardial infarction had the greatest fall in the activity of dopamine beta-hydroxylase. Patients with multiple signs of sympathetic hyperactivity had significantly higher values for the activity of dopamine beta-hydroxylase on admission. Pain was found to significantly increase the activity of the enzyme. These data confirm findings that the activity of dopamine beta-hydroxylase in the serum reflects the intensity of sympathetic activity. The factors contributing to the elevated sympathetic activity in some patients with acute myocardial infarction seem to be nonspecific, but because of the ominous nature of increased sympathetic tone in this condition, it could be advantageous to identify these patients.

A multicenter, double-blind, randomized, placebo-controlled study of isradipine and methyldopa as monotherapy or in combination with captopril in the treatment of hypertension. The LOMIR-MCT-IH Research Group.

This multicenter, double-blind, randomized trial of 1 year's duration compared the safety and efficacy of isradipine, methyldopa, and placebo in 368 men, aged 40 to 65 years, with mild-to-moderate essential hypertension. Initial treatment with isradipine (1.25 mg twice daily), methyldopa (250 mg twice daily), or placebo was started after a wash-out and single-blind placebo period. If normotension [diastolic blood pressure (DBP) < 95 mm Hg] was not achieved, doses were doubled. If the maximum dose as monotherapy did not result in normotension, captopril (25 mg or, if necessary, 50 mg, once daily) was added to the treatments of the three patient groups. Despite the marked placebo effect during the first 2 weeks of treatment, monotherapy with isradipine resulted in a higher rate of normalization (more than 64%) compared with 50% in the methyldopa group and 36% in the placebo group. Adding captopril to the treatments of non-responders increased the rate of normalization to 90% in the isradipine group, 84% in the methyldopa group, and 75% in the placebo group. Twenty-one patients dropped-out and 70 patients discontinued the study, the majority because of a lack of efficacy and adverse reactions. The most common adverse reactions reported were cardiovascular and gastrointestinal complaints, headaches, and sleep and sexual disorders, mostly by patients taking methyldopa. Isradipine was well tolerated and the side-effects were minimal. These results indicate that isradipine is superior to methyldopa and, whether as monotherapy or in combination with captopril, highly effective and well tolerated in the treatment of mild-to-moderate hypertension.

Effect of isradipine on factors affecting blood viscosity.

The objective of the study was to investigate the effect of isradipine on red blood cell filtrability in 20 men with mild-to-moderate hypertension. In this prospective, double-blind study, parallel groups of hypertensive male patients were randomized to receive either isradipine (n = 11) or placebo (n = 9). An additional group of nine normotensive age-matched volunteers served as controls. Tests were performed before and after patients were treated with either isradipine or placebo. The hypertensive patients differed from the normotensive controls in having a higher level of fibrinogen (P less than .04), a higher hematocrit (P less than .001), a higher filtration rate (P less than .05; impaired red blood cell deformability), and a higher mean corpuscular volume (MCV; P less than .005). Treatment with isradipine lowered blood pressure and improved red blood cell filterability (P less than .05) compared with placebo.

Serum amyloid A concentrations during the course of acute ischaemic heart disease.

Serum amyloid A concentrations were determined in serial serum samples of 41 patients with confirmed acute myocardial infarction (10 with acute ischaemia and two with myocarditis). A sharp increase in serum amyloid A concentration was observed early at onset of infarct; it peaked on the third day (up to 2200 fold of normal values) and declined towards normal during the following days, if no complications occurred. Different patterns were observed in patients with acute ischaemia or myocarditis. Although serum amyloid A is not a specific marker, it may, because of its high sensitivity and characteristic patterns of change, represent an additional useful biochemical variable in the diagnosis, follow up, and prognosis of acute ischaemic heart disease.

Quality of life in normotensives compared to hypertensive men treated with isradipine or methyldopa as monotherapy or in combination with captopril: the LOMIR-MCT-IL study.

Quality of life (QOL) measures were assessed in a multi-center, double-blind, case-controlled trial of 1 year's duration. A total of 368 hypertensive male patients were randomly assigned to monotherapies of either isradipine, methyldopa or placebo. If normotension was not achieved, captopril was added. QOL assessments in the hypertensives and in 155 normotensives included a self-structured scale to measure the subjective perception of QOL, the severity, desirability and controllability of recent critical life events, semantic memory, physical dysfunction, sleep disorders, sexual difficulties, depression and work-related stress. The overall withdrawal rate during the trial was 19%, mainly due to lack of efficacy and adverse experiences. At baseline, and at the end of the trial, the normotensives as compared to hypertensive patients, had significantly better scores in most QOL measures. Patients treated with the combination of isradipine and captopril reported more favorable changes in the subjective measure of QOL (P < 0.03) and in semantic memory (P < 0.001) than patients treated with any of the monotherapies or with methyldopa in combination with captopril. There were no statistically significant differences among treatments for changes of other indices of QOL. In most QOL measurements, normotensives rated better then hypertensives. Patients treated on long-term therapy with the combination of isradipine and captopril showed improvement in self-structured QOL measures and semantic memory, compared to patients treated either with methyldopa or placebo.

Cardiovascular drugs and exercise interactions.

An appreciation of the hemodynamic and biochemical changes induced by drugs is critical for a logical diagnostic interpretation of graded stress tests and the evaluation of the projected exercise prescription and exercise programs that a patient is asked to follow. Drug therapy is clearly not a contraindication to acute or chronic exercise as long as the potential benefits and complications of exercise and drug interaction are considered.

The use of transdermal clonidine in the hypertensive patient with chronic renal failure.

The efficacy of transdermally administered clonidine was evaluated in twenty-four patients with mild-to-moderate hypertension (seated diastolic blood pressure 95-115 mmHg) and renal impairment. Patients were initially treated with oral clonidine; the dose was titrated until the seated diastolic pressure fell below 90 mmHg or a minimum 10% reduction in baseline was achieved. Oral clonidine produced a significant decrease in both systolic and diastolic blood pressure; mean seated diastolic blood pressure decreased 16.9 mmHg from baseline. When transdermal clonidine was substituted for twice daily dosage of oral clonidine, blood pressure decreases were fully maintained. Sixteen patients completed three months of stable-dose transdermal therapy. The results suggest that, in mild-to-moderate hypertensive patients with chronic renal impairment, blood pressure can be controlled with a once-weekly application of transdermal clonidine as effectively as with oral clonidine. Mean diastolic blood pressure was decreased approximately 17% during clonidine therapy independent of the severity of renal dysfunction or route of clonidine administration.

Plasma fibrinogen levels and the clinical course of acute myocardial infarction.

Plasma fibrinogen levels were followed from admission to the coronary care unit up to 3 months after an acute myocardial infarction (AMI) (51 patients at entry--49 patients at follow-up). Mean initial value as determined with 24 hours of onset of symptoms was 522 mg% +/- 205 S.D. Peak value 845 mg% +/- 215 S.D. was reached 3-5 days after onset of symptoms. Mean fibrinogen level on a later follow-up was similar to the initial value (521 mg% +/- 145 S.D.). Our data confirm that a rise in the plasma fibrinogen level is common after myocardial necrosis. No correlation was found between the maximum peak value and the clinical course of the disease. However, death, reinfarction and cardiogenic shock were more frequent among patients with an initial plasma fibrinogen level higher than 400 mg%. Our findings suggest that the acute increase in fibrinogen following necrosis is less significant to the clinical course than a chronically high plasma fibrinogen level.