Factors influencing left ventricular hypertrophy in systemic hypertension.
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Biomedical subjects
Publications and source records attributed to M Motolese.
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The aim of this study was to examine the interrelationships between age, plasma catecholamines, plasma renin activity (PRA) and blood pressure in essential hypertensive (EH) patients. PRA, plasma noradrenaline (NA) and adrenaline (A) were measured in 76 consecutive EH patients (WHO stages 1-2, aged 24-66 years) and in 28 normotensive subjects (aged 25-64 years) studied at rest in supine position after 5 days of normal fixed sodium and potassium intake. Both plasma NA and A were slightly but significantly higher in EH patients (p less than 0.05). While no relationship was found between the various parameters in normotensive subjects, in EH patients, particularly those at WHO stage 2, plasma NA was directly related to mean blood pressure (MBP) (p less than 0.001) and PRA (p less than 0.01). Plasma A was weakly related to MBP (p less than 0.05); PRA was inversely related to age (p less than 0.01) but no relationship was found between NA or A and age. Partial correlation analysis confirmed all these relationships. In fact, NA was related to MBP also considering constant PRA (p less than 0.001) or age (p less than 0.001), and NA was related to PRA also considering constant MBP (p less than 0.01) or age (p less than 0.001). Acute pharmacological alpha- and beta-blockade, with labetalol 100 mg i.v., induced a reduction of MBP which was directly related to basal plasma NA (p less than 0.001). These results support the view that in EH the sympathetic nervous system might be in part responsible for PRA levels and for the severity of hypertension.
By using echocardiography it is possible to quantify accurately and repeatedly the degree of left ventricular hypertrophy (LVH) in patients with arterial hypertension. It therefore appears to be a valuable tool for investigating the mechanisms that may be involved in the pathogenesis of this condition in hypertensive patients. The role of increased afterload in LVH induction is well established, and results of several independent laboratories concord in indicating blood pressure as a major independent factor in the pathogenesis of LVH in hypertensive patients. The role of factors other than blood pressure has not yet been fully established, however, in this setting. Animal and human studies from different laboratories are providing conflicting results on the possible role of factors such as the catecholamines or the renin-angiotensin system as additional stimuli facilitating LVH development. Clinical pharmacology could be a useful tool in seeking to clarify this important question. Drugs that lower blood pressure without consistently affecting the humoral factors possibly responsible for LVH might be expected to induce a lesser degree of LVH reversal than drugs that lower blood pressure while at the same time reducing or inhibiting the factors responsible for LVH. This experimental approach raises several methodological and technical points which are crucial in the trial planning stages. The question whether borderline hypertensive patients should be considered separately from stable hypertensive patients in the search for relationships between LVH and possible pathogenic factors is also discussed.
In order to assess the adrenergic contribution to hypoglycemic glucose counterregulation in type I diabetes mellitus and to determine whether the adrenergic contribution is mediated through beta 1- or beta 2-adrenergic receptors, hypoglycemia was induced by an i.v. insulin infusion (30 mU/m2 x min) for 60 min in 11 insulin-dependent diabetic patients (IDDM), 5 with normal plasma glucagon responses and 6 with blunted responses, and also in 7 age-weight-matched nondiabetic subjects. Rates of plasma glucose decrease and postnadir increase, as well as plasma concentrations of free insulin and of counterregulatory hormones, were measured when insulin was infused alone, and when insulin was infused along with propranolol (a beta 1- and beta 2-adrenergic receptor antagonist) or metoprolol (a selective beta 1-antagonist). Postnadir plasma glucose recovery was decreased in IDDM with blunted plasma glucagon responses (21 +/- 0.8 mumol x L-1 x min-1, P less than 0.001), but was normal in patients with normal plasma glucagon responses (30 +/- 0.4 versus 33 +/- 0.5 mumol x L-1 x min-1 in nondiabetic subjects, P = NS). Postnadir plasma glucose recovery was not affected by either propranolol or metoprolol in normal subjects and in IDDM with normal glucagon responses. However, in IDDM with blunted plasma glucagon responses, postnadir plasma glucose recovery was further decreased by propranolol (14 +/- 0.6 mumol x L-1 x min-1, P less than 0.01), but was unaffected by metoprolol (22 +/- 0.9 mumol x L-1 x min-1, P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)
Exercise testing in myocardial infarction before discharge has been used for treatment and exercise prescription in the post-hospital phase. Aim of this study was to investigate the prognostic significance, within one year after the infarction, of submaximal exercise testing before discharge. 428 patients performed the test 14.5 days after the acute episode and were followed for 12 months. The following variables were examined: heart rate, blood pressure, rate-pressure product at maximum exercise, total work and reasons for stopping the test (fatigue, submaximal HR, BP greater than or equal to 200/110, hypotension, ischemic or arrhythmic response). Two events were considered: 1) non fatal reinfarction; 2) cardiac death. Two methods of multivariate analysis (Cox's model regression analysis and discriminant analysis) were used. None of the considered variables was found to be predictive of non fatal reinfarction. According to Cox's model total performed work and hypertensive response were found to be predictive of cardiac death, while using discriminant analysis only total work had a predictive value (discriminant function: L = 0.00094 X total work performed + 1.48643; p less than 0.01). In detail, the higher the total work, the better the probabilities of survival, while in patients who stopped the test because of hypertension, the probabilities of cardiac death were lower. Exercise testing performed in uncomplicated myocardial infarction before hospital discharge provides, the basis for a more rational management of patients in the post-infarction phase, and contributes to identify a subset of high-risk patients.
A double-blind, cross-over study in 16 patients with essential hypertension was carried out, to evaluate any possible interference by indomethacin, a known prostaglandin-synthetase inhibitor, with the antihypertensive effect of oxprenolol, a non-selective beta-adrenoceptor blocking agent. Both indomethacin and oxprenolol, as well as the two drugs combined, inhibited plasma renin activity; no change was found in urinary sodium excretion or body weight. Oxprenolol alone caused a highly significant decrease in the systolic ( - 10.4 mmHg, p less than 0.001), diastolic ( - 7.4 mmHg, p less than 0.001) and mean ( - 7.7 mmHg, p less than 0.01) blood pressures, whereas indomethacin did not influence blood pressure. When the two drugs were given in combination, blood pressure decreased (systolic: - 5.9 mmHg; diastolic: - 4.0 mmHg; mean: - 4.6 mmHg), but the changes induced in blood pressure were reduced by about 50% when compared with those in the oxprenolol alone period. The data show that indomethacin seems to interfere with the antihypertensive effect of oxprenolol, by an action which may be due to the inhibition of prostaglandin synthesis.
In a multicentre, double-blind (DB), within-patient study, the antihypertensive effectiveness and tolerability of two oral administration schedules of metoprolol (M) 100 mg b.i.d. versus 200 mg once daily (o.d.), were investigated in 103 outpatients with mild to moderate essential hypertension. The study lasted 14 weeks and was divided into 3 periods: a) a weeks of single-blind (SB) placebo wash-out; b) 4 weeks of SB administration of M 100 mg b.i.d.; at the end of the second week of this period, chlorthalidone (C) 25 mg was added in patients with a recumbent diastolic blood pressure (BP) still greater than 95 mmHg and was continued throughout the following period; and c) DB cross-over administration of M 200 mg/d for 4 weeks on a b.i.d. schedule and 4 weeks on a once daily schedule. In comparison with pretreatment values, heart rate and systolic and diastolic BP were reduced (p less than 0.001) by both M administration schedules; there was no differences between the once and twice daily treatment regimens. During M once daily, betablockade was still maintained over 24 hours or longer, as the heart rate remained significantly lower than the basal value. In 57 patients, C was added at the end of the second week of SB M administration, and a further decrease in BP was observed; again, there was no significant change during once and twice daily M administration. Unwanted effects during M treatment were of minor severity, and the majority occurred when C, too, was added.
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In a multicenter, single-blind, interpatient study, 103 outpatients with mild to moderate hypertension were given, after 2 weeks of placebo wash-out, 160 mg oxprenolol slow-release in fixed combination with chlorthalidone (20 mg per tablet) (SROC 160) once daily or conventional oxprenolol (80 mg) in fixed combination with chlorthalidone (10 mg per tablet) (COC 80) twice daily for 8 weeks. Throughout the study 22 of 51 patients on SROC 160 and 24 of 51 on COC 80 received 1 tablet once daily and, respectively, 1 tablet twice daily. The remaining patients of both groups double the corresponding dosage after the first 4 weeks. Systolic and diastolic blood pressure decreased on both treatments without and difference observed between the groups. Diastolic blood pressure normalization was achieved in both groups in the same number of patients (35). Minor side effects occurred on both treatments: only one patient on SROC 160 interrupted the study due to severe dizziness and fatigue. The advantages are discussed as regards patient's compliance with administration of fixed combination SROC 160 once daily in treatment of mild to moderate hypertension.
The antihypertensive effect and the tolerability of the cardioselective beta-blocking drug metoprolol, in comparison to methyldopa, were assessed in 119 hypertensive patients (73 WHO stage 1 and 46 WHO stage 2). After 2 weeks of placebo wash-out, the patients were randomly allocated to treatment with either of the two drugs: metoprolol up to 200 mg bid, and methyldopa up to 500 mg bid, for 6 weeks. Periodical clinical, biochemical, haematological, radiological and electrocardiographical measurements were performed. In respect to pre-treatment values, heart rate, both in lying and standing position, was significantly reduced (P less than 0.01) only in the metoprolol group, while systolic and diastolic blood pressures were significantly reduced (P less than 0.01) with both drugs in both positions. Asymptotic regression analysis showed that velocity of blood pressure reduction was comparable with both drugs. In the lying position, the diastolic blood pressure reduction obtained with metoprolol was significantly greater (P less than 0.05) in respect to that obtained with methyldopa. In general, side effects were few and of mild severity: mainly bradycardia in the metoprolol group and dizziness and fatigue in the methyldopa group. After the formal end of the double-blind trial, 36 patients, 14 in the metoprolol group and 22 in the methyldopa group, were treated in open conditions with metoprolol alone; after an average period of 6.5 weeks, diastolic blood pressure was significantly reduced (P less than 0.05) only in the group previously treated with methyldopa. In conclusion, metoprolol is a well tolerated and effective antihypertensive agent, which may be safely used in patients with mild to moderate hypertension.
In a multicentre double-blind study, 92 out-patients with mild to moderate hypertension who had a resting blood pressure greater than or equal to 160/100 mmHg after a two-weeks' placebo wash-out were treated for 6 weeks with a fixed combination of oxprenolol 80 mg + chlorthalidone 10 mg per tablet or chlorthalidone alone (1 tablet = 10 mg). Five patients were drop-outs, 19 out of 44 patients on fixed combination and 7 out of 43 on chlorthalidone were given only 1 tablet b.i.d. throughout the study; the remaining doubled the corresponding dosage after the first 2 weeks. Resting and standing systolic and diastolic blood pressure decreased on both treatments, the reductions being significantly more marked on fixed combination in comparison to chlorthalidone alone (p < 0.01 and p < 0.05). The systolic blood pressure decrease was significantly greater on fixed combination from the first week of treatment (p < 0.05). Normalization of diastolic blood pressure was reached more frequently on fixed combination (73%) than on chlorthalidone (49%) (p < 0.05). Side-effects were recorded in 14 out of 44 patients treated with fixed combination and in 14 out of 43 treated with chlorthalidone. The advantages of treating patients with mild to moderate hypertension with a fixed combination of beta-blocker and diuretics are discussed.
In a multicentre, single-blind, within-patient study, the effectiveness and tolerability of the fixed combination oxprenolol 80 mg + chlorthalidone 10 mg per tablet given once daily, compared to the well established b.i.d. schedule, has been investigated in forty out-patients with mild to moderate hypertension. After a two-weeks placebo wash-out, twenty patients were given 1 tablet b.i.d. of the fixed combination for 4 weeks and thereafter 2 tablets once-daily for a further 4 weeks; the remaining twenty patients were given the fixed combination in the reverse order. There was no significant difference in clinical response between the two treatment regimes, which were equally effective and well tolerated. However, patient compliance might be considerably improved with the once-daily dosage schedule of the fixed combination.
The study investigated the acute hemodynamic changes induced in patients with angiographically confirmed coronary artery disease by 3 beta-blockers: metoprolol, cardioselective without intrinsic sympathomimetic activity (ISA), group I, 11 patients; bunitrolol, noncardioselective with ISA, group II, 11 patients; oxprenolol, noncardioselective with ISA, group III, 11 patients. Hemodynamic variables were obtained at rest and during exercise, before and 45 min after 10 mg i.v. of the drug. Changes in LVEDP and cardiac indexes were such as LV function was improved in 1 patient of group I, 7 patients of group II and 5 patients of group III; impaired in 4 patients of group I and in 1 patient of group III; unchanged in the others. Contractility indexes were less influenced by bunitrolol and oxprenolol. During exercise there was a significant difference between groups for LVEDP which was lower in group II (P less than 0.01). The data seem to indicate that the choice of the beta-blocker may be of importance when it is desirable that an already compromised cardiac function be not further impaired by pharmacological intervention.
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