Factors influencing left ventricular hypertrophy in systemic hypertension.
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Biomedical subjects
Publications and source records attributed to L Corea.
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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.
The effects of a single intravenous infusion of prenalterol, a beta 1 selective agonist, on haemodynamics (echocardiography) and venous plasma catecholamine concentration were studied in 8 patients with severe congestive heart failure. In these patients, age-adjusted plasma norepinephrine (NE) and epinephrine (E) levels before prenalterol infusion were higher compared to values found in 10 control healthy subjects (both P less than 0.01). In heart failure patients, circulating NE levels were not dissimilar in 2 samples drawn 60 and 0 minutes before commencing prenalterol infusion (772.0 +/- 131 ng/l [mean +/- SD] and 775.5 +/- 130.0 ng/l respectively). Prenalterol induced a significant improvement in the cardiac index, stroke index, ejection fraction and velocity of circumferential fiber shortening, associated with a moderate but significant decrease in peripheral vascular resistance. All these changes persisted for 60 minutes after the end of infusion. Circulating NE levels were 604.0 +/- 125 ng/l at 60 min. after start of infusion (P less than 0.01 vs pre-infusion levels) and 526.1 +/- 108 ng/l at 60 min. after the end of infusion (P less than 0.01 vs pre-infusion levels). Plasma E showed a slight decrease, which did not attain statistical significance. Heart rate and diastolic blood pressure remained unchanged during and after infusion, while systolic blood pressure increased by 10-15 mmHg during and after infusion. We conclude that a single 1-hour prenalterol infusion in patients with severe congestive heart failure induces an haemodynamic improvement associated with a reduction of previously elevated circulating NE levels. This reduction could indicate a lowering in the intensity of the afferent stimulus for the reflex sympathetic overactivity.
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.
Cardiac anatomy and function, and some biohumoral parameters, have been examined in 11 long-distance olympic runners, and in 11 healthy untrained control subjects. Echocardiographic methods and computed reading of tracings were adopted. Long-distance runners were also studied within 2 minutes after the end of a 30 Km race. At rest, the athletes had thicker interventricular septa and, posterior walls, higher left ventricular mass index, larger end-diastolic dimensions, cardiac index and stroke index compared to the untrained subjects (all P less than 0.01). Resting heart rate was lower in runners (P less than 0.01). In runners, competitive exercise test induced significant haemodynamic changes (increases in cardiac index, heart rate, stroke index, ejection fraction [all P less than 0.01], decreases in end-systolic dimensions and peripheral vascular resistance [both P less than 0.01]). After exercise, runners showed massive increases both of norepinephrine and epinephrine serum levels (measured in 4 subjects), an increase, in haematocrit and plasma glucose concentration, and a decrease in plasma potassium concentration (all P less than 0.01). In conclusion, olympic long-distance runners have increased cardiac dimensions and wall thickness at rest as compared with healthy untrained subjects matched for age and resting blood pressure. In the former group, a competitive long-distance test results in marked haemodynamic changes, with massive increase in plasma catecholamine concentration and concomitant reduction in plasma potassium concentration. This combination is potentially hazardous, and warrants further investigation.
Twenty hypertensive outpatients WHO stage I or II, with supine diastolic blood pressure greater than or equal to 95 mmHg at the end of a 4-week treatment period with atenolol (Tenormin) 100 mg daily, continued atenolol in free association with half a tablet of Moduretic (i.e., hydrochlorothiazide 25 mg + amiloride 2.5 mg) for a further 4 weeks. Atenolol monotherapy induced a drop of systolic blood pressure from 175.0 +/- 11 (mean +/- s.d.) mmHg to 158.7 +/- 6 mmHg (p less than 0.01), and of diastolic blood pressure from 113.5 +/- 8 mmHg to 102.7 +/- 5 mmHg (p less than 0.01). After 4 weeks with atenolol in association with half a tablet of Moduretic, systolic blood pressure further decreased to 145.7 +/- 8 mmHg (p less than 0.01), and diastolic blood pressure to 90.2 +/- 10 mmHg (p less than 0.01). Seven out of 20 patients remained with diastolic blood pressure greater than or equal to 95 mmHg despite the above combination therapy. In these patients, the doubling of diuretic dose (hydrochlorothiazide 50 mg + amiloride 5 mg) in combination with atenolol resulted in a further drop in systolic pressure (to 142.1 +/- 9 mmHg) and diastolic (to 92.1 +/- 6 mmHg) (both p less than 0.01). Plasma potassium concentration showed a slight and non-significant increase during atenolol monotherapy (from 4.4 +/- 0.5 mEq/l to 4.6 +/- 0.7 mEq/l; n.s.).(ABSTRACT TRUNCATED AT 250 WORDS)
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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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The aim of this study was to investigate and compare the effects of two calcium antagonist drugs, verapamil (VER) and nifedipine (NIF), on blood pressure (BP), heart rate (HR), plasma catecholamines (pCA), renin (PRA), plasma aldosterone (pALD), and plasma volume (PV) in a group of patients with mild to moderate essential hypertension. In 12 hypertensive patients on a fixed normal sodium and potassium intake, VER (80 mg t.i.d., per os) first and then NIF (10 mg, t.i.d. per os), or vice versa according to a random sequence, were each given for 8 days, with an interval of 5 days between the two treatments. Both NIF and VER significantly reduced BP (p less than 0.001); this reduction was quantitatively similar in both treatment schedules. Supine and standing PRA, pALD, and PV were not significantly affected by VER or NIF. HR and pCA were unchanged after VER, whereas they were significantly increased (p less than 0.05, at least) mainly in standing position after NIF treatment. The antihypertensive and metabolic effects of VER (80 mg t.i.d.) and NIF (10 mg t.i.d.) were maintained after chronic treatment (4 months with VER in 10 patients and 2 months with NIF in 12 patients). After 2 months of treatment with VER (160 mg t.i.d.) in 18 patients, BP was further reduced, while pCA were slightly increased. In conclusion, VER and NIF are effective and equipotent antihypertensive agents that do not induce significant renin stimulation or fluid retention; adrenergic stimulation seems to be greater with NIF, which should be taken into account in the clinical use of these drugs.
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The report describes a case of Kearns syndrome in which cardiac involvement occurred more than 15 years after the appearance of the myopathic disorder. The surface electrocardiogram showed a left axis deviation and Q-waves in D3 and aVF leads, and appeared against a background of general systemic worsening of the condition of the muscular system. In the eye, despite a slightly increased salt-and-pepper macular pigmentary disturbance, retinal fluorescein angiography did not show significant differences in comparison with previous examinations. Some observations are made on the possible evolution of the Kearns syndrome.
1. Nifedipine, a calcium antagonist drug, was given sublingually (10 mg) to seven normal subjects and 19 patients with essential hypertension. In addition, 12 of the hypertensive subjects then received nifedipine (10 mg thrice daily) for 3 weeks. 2. Sublingual administration of nifedipine in hypertensive patients induced a prompt and sustained reduction of blood pressure, without a significant increase of heart rate; in normotensive subjects blood pressure did not change, and heart rate was significantly increased. After chronic treatment, blood pressure remained reduced and heart rate did not rise. 3. Plasma catecholamines and plasma renin activity increased significantly in normotensive subjects after acute administration. 4. After both acute and chronic administration, only plasma noradrenaline was significantly increased in hypertensive patients; in long-term treatment, it was increased in both the lying and standing positions. 5. Nifedipine is an active antihypertensive drug, which may induce some degree of sympathetic activation.
Tienilic acid (TA) is a common new diuretic agent with a potent uricosuric action. In a double-blind cross-over study its antihypertensive effect was compared to that of hydrochlorothiazide (HCT). 20 patients with essential hypertension were studied: after I weeks of placebo wash-out 10 patients received TA (dose range 250-750 mg/die) and 10 HCT (dose range 50-150 mg/die), for 5 weeks. Systolic and diastolic blood pressures were significantly and equally reduced (p < 0.001) after the first week of treatment in both groups. While serum uric acid concentration increased after HCT, it was significantly reduced (p < 0.001) after TA treatment. Serum potassium was slightly reduced with both treatments. Serum tryglicerides, unchanged after HCT, showed a slight tendency to reduction on TA treatment. Ten patients with congestive heart failure, on full digitalis treatment, were given TA (dose range 250-1000 mg/die): in each patient a prompt diuretic effect was observed, associated to a significant reduction of body weight and to a marked improvement of the clinical signs of heart failure. Therefore, TA is an effective diuretic agent which may be conveniently used in the treatment of arterial hypertension and congestive heart failure, as it induces a diuretic effect comparable to that obtained with HCT, reducing at the same time, serum uric acid levels.
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