H. Ikram

DOUBLE-BLIND TRIAL OF CHRONIC ORAL BETA BLOCKADE IN CONGESTIVE CARDIOMYOPATHY

Abstract Acebutolol or placebo was given for one month, in a double-blind, cross-over trial, to 15 patients with congestive cardiomyopathy. Acebutolol significantly reduced maximum exercise tolerance and also ventricular function, as shown by an increase in cardiothoracic ratio. These results argue against routine administration of beta adrenoceptor blockers in congestive cardiomyopathy.

Diurnal Patterns of Blood Pressure, Heart Rate and Vasoactive Hormones in Normal Man

In order to determine arterial pressure and vasoactive hormone relationships in normotensive man, we measured intra-arterial pressure continuously along with hourly venous hormone levels (renin, angiotensin II, aldosterone and catecholamines) for 24 hours in 5 healthy volunteers under standardized conditions. Mean 24-hour levels of intra-arterial pressure 106/63 +/- 5.4/4.9 mmHg were much lower than in patients with mild essential hypertension studied earlier. A common diurnal pattern was seen for plasma renin, angiotensin II, and catecholamines, with higher levels in the day time and lower levels at night. Aldosterone levels however, paralleled those of cortisol at night. Plasma norepinephrine levels showed close, positive correlations with arterial pressure in all volunteers. We conclude that the level of blood pressure as measured continuously over 24 hours is lower than might be expected from regular clinic recordings; that aldosterone regulation is contributed to by ACTH in the nocturnal hours; and that fluctuations in arterial pressure and sympathetic activity over 24 hours are closely coupled.

Effects of alpha-human atrial natriuretic peptide in essential hypertension.

Because there is little published information on the effects of atrial peptides in hypertensive humans, 100 micrograms of alpha-human atrial natriuretic peptide was injected intravenously into six patients with essential hypertension in a double-blind, placebo-controlled study under standardized conditions of body posture and dietary sodium and potassium intake. The peptide increased urine sodium excretion sixfold in the first 30 minutes. Smaller increments occurred in urine volume and in calcium, magnesium, and phosphorus excretion; the rise in urine potassium concentration was not statistically significant. Most of these indices returned to time-matched placebo values within 1 hour, but urine sodium excretion remained high for 2 1/2 hours. Arterial pressure fell within 2 minutes of alpha-human atrial natriuretic peptide injection, then returned to matching placebo levels by 10 minutes. Conversely, heart rate increased rapidly and remained elevated for 3 hours. The peptide induced a prompt, brief rise in plasma norepinephrine concentration and a more sustained fall in epinephrine and aldosterone levels, but it did not affect plasma renin activity or cortisol concentration. Compared with normotensive volunteers studied previously under the same conditions, the hypertensive subjects had a greater response in urine volume and sodium, calcium, and magnesium excretion but a less sustained fall in arterial pressure.

HAEMODYNAMIC, HORMONAL, AND ELECTROLYTE RESPONSES TO CAPTOPRIL IN RESISTANT HEART FAILURE

In five patients with resistant heart failure treated with the oral converting-enzyme inhibitor, captopril, standardised and intensive haemodynamic, hormone, and electrolyte monitoring showed significantly raised cardiac output and reduced arterial, pulmonary-wedge, and pulmonary-artery pressures which correlated closely with concomitant alterations in the activity of the renin-angiotensin system. These changes occurred in the absence of a natriuresis or diuresis. Clinical improvement was dramatic and paralleled the objective haemodynamic changes. Hyponatraemia and a rise in plasma-potassium were noted. Captopril is a major advance in the treatment of resistant heart failure, and its beneficial haemodynamic effects relate primarily to a blockade of the renin-angiotensin system, the activity of which is increased by conventional drug therapy.

Left atrial function after electrical conversion to sinus rhythm.

Atrial fibrillation is undesirable because it reduces the efficiency of the heart, particularly the diseased heart (Kory and Meneely, 1951) and gives rise to systemic or pulmonary embolism in about one-third of the cases (Goldman, 1960). The recent introduction of the use of the synchronized directcurrent shock (Lown, Amarasingham, and Neuman, 1962) has simplified the restoration of sinus rhythm, but little is known about the return of the mechanical activity to the atrium. Bramwell and Jones (1944) have suggested that an effective left atrial contraction may be absent in sinus rhythm, and cardiac catheterization studies have shown that the return of a P wave to the electrocardiogram may not be accompanied by the restoration of detectable mechanical activity to the left atrium (Braunwald, 1964; Logan et al., 1965). It is important to know if or when mechanical activity returns to the atrium; its failure to return may be a cause of continuing disability, and its delayed return may be associated with late embolism. Left heart catheterization is not a technique that is suitable for repeated use after conversion. This paper describes a study of the left atrial contraction, by a simple bedside technique, in patients recently converted to sinus rhythm.

Endopeptidase 24.11 inhibition by SCH 42495 in essential hypertension.

The detailed integrated renal, hormonal, and hemodynamic effects of acute (first dose) and established (4 days) inhibition of endopeptidase 24.11 by SCH 42495 (200 mg, every 12 hours) were documented in eight patients with essential hypertension in a double-blind, balanced random-order, crossover study. SCH 42495 suppressed plasma endopeptidase activity (> 90%, P < .001) for the duration of the dosing period. Initially, plasma atrial natriuretic factor levels increased markedly (+123%, P < .01) and remained elevated, although to a lesser extent (+34%, P < .01), with established enzyme inhibition. Cyclic guanosine monophosphate in both plasma and urine remained elevated throughout the treatment period. Significant augmentation of sodium excretion in excess of placebo values (96 +/- 27 mmol sodium, P < .001) was established in the initial 24 hours of dosing but later became attenuated, with a mild antinatriuresis (P < .01) in the latter 3 days of treatment. Blood pressure, heart rate, the renin-angiotensin-aldosterone system, and plasma norepinephrine levels were all initially (first dose) unchanged. With established enzyme inhibition (day 4), however, blood pressure was significantly lower (mean 24-hour values, 9.3 +/- 3/-3.8 +/- 1 mm Hg, P < .05 for both systolic and diastolic pressures) than matched placebo values, whereas heart rate was higher (2.7 +/- 1 beats per minute, P < .01). Mean 24-hour values of plasma renin activity (+33%, P < .05), aldosterone (+36%, P < .05), and norepinephrine (+40%, P < .001) were all clearly increased above placebo values with established enzyme inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Propranolol in persistent ventricular fibrillation complicating acute myocardial infarction

Abstract Four cases of persistent ventricular fibrillation complicating acute myocardial infarction are described. In each case, control of the arrhythmia was achieved by the intravenous administration of 1 mg. of propranolol. In this dose, this drug can be used with reasonable safety in controlling a lethal arrhythmia in patients suffering from extensive fresh myocardial infarctions.

Hormone and Blood Pressure Relationships in Primary Aldosteronism

We used continuous intra-arterial pressure monitoring and hourly venous hormone sampling over 24 hours in 5 patients with primary aldosteronism to study blood pressure and hormone regulation. Three patients were restudied under identical conditions of controlled diet electrolyte intake and body posture 3-7 months after removal of the aldosterone-secreting adrenal tumor. Prior to surgery there was no positive relationship of arterial pressure to renin or to aldosterone. Norepinephrine fluctuations showed positive correlations with arterial pressure but these 2 indices were more closely related after surgery. Plasma aldosterone levels paralleled those of cortisol both before and after cure of primary aldosteronism. Aldosterone/cortisol regression lines were steeper before surgery, and norepinephrine/renin regression lines were steepened in the post-operation studies. Our findings indicate that in established primary aldosteronism, fluctuations in arterial pressure are regulated in part by the sympathetic nervous system: the pattern of aldosterone secretion is controlled mainly by ACTH: aldosterone responsiveness to endogenous ACTH is enhanced: and sympathetic modulation of renin release in inhibited.

Cardiogenic shock treated with infusion of dextrose solution

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Mechanisms in human renovascular hypertension.

To clarify the pathophysiology of renovascular hypertension, we monitored intraarterial pressure continuously and measured hourly hormone levels for 24 hours under carefully controlled conditions in two hypertensive patients with unilateral renal artery occlusion. Comparison of the results with those obtained when the patients were normotensive 3 months after uninephrectomy indicated that, while the renin-angiotensin system played a central role in maintaining the hypertension, the sympathetic nervous system also contributed and, in addition, modulated short-term arterial pressure fluctuations. In the untreated state, the sympathetic regulation of renin secretion was heightened, and angiotensin II/aldosterone dose-responsiveness was augmented. It is suggested that these adaptive changes might serve to offset the tendency to severe sodium depletion and thence exacerbation of the hypertension.