Paolo Moruzzi

Nifedipine, a new antihypertensive with rapid action.

Oral (17 cases) or sublingual (9 cases) administration of nifedipine (10 mg), a new coronary dilator, induced a prompt and large pressure reduction in patients with severe primary hypertension. Pressure started to fall within 20 and 5 min after oral and sublingual administration, respectively, and reached the lowest levels in the next 10 min. Maximal mean arterial pressure reduction averaged 36 mm Hg; 120 min after the drug, mean arterial pressure was diminished by 19.5% of control. The hypotension was mediated through diminished peripheral resistance associated with rise of cardiac output and pulse rate. Nifedipine was also administered sublingually in 3 cases with hypertensive encephalopathy and acute left ventricular failure with average systemic and pulmonary arterial pressures from 307/164 and 91/55 mm Hg, respectively, which fell to 237/115 and 68/35 mm Hg 15 min after 10 mg of the drug, and were further reduced to 176189 and to 47/19 mm Hg by an additional 10 mg.

Medium-term effectiveness of L-thyroxine treatment in idiopathic dilated cardiomyopathy

BACKGROUND In dilated cardiomyopathy, short-term administration of L-thyroxine (100 micrograms/ day) improves cardiac and exercise performance without changing the hearts adrenergic sensitivity. The aim of this study was to test the medium-term (3 months) efficacy of L-thyroxine (10 patients) compared with placebo (10 patients) and to find out whether later effects are obtainable. METHODS Echocardiographic parameters in the control state and during acute changes of left ventricular afterload, cardiopulmonary exercise test, and hemodynamic parameters, including cardiac beta 1 responses to dobutamine, were obtained before and at the end of treatment. RESULTS Significant (P < 0.05) changes were observed only with the active drug. After L-thyroxine, patients did not show evidence of chemical hyperthyroidism, despite the increase in thyroxine and the reduction in thyroid-stimulating hormone plasma levels. Cardiac performance improved, as shown by the increase in the left ventricular ejection fraction and rightward shift of the slope of the relation left ventricular ejection fraction/end-systolic stress. Resting cardiac output increased, and the left ventricular diastolic dimensions and systemic vascular resistances decreased. The responses of cardiac output and heart rate to dobutamine infusion were also enhanced. Functional capacity markedly improved, together with an increase in peak exercise cardiac output. CONCLUSION L-thyroxine does not lose its beneficial effects on cardiac and exercise performance on medium-term administration and does not induce adverse effects. In addition to the short-term study, the left ventricular diastolic dimensions were decreased. An upregulation of beta 1 receptors might explain the cardiac response to dobutamine.

Usefulness of L-thyroxine to improve cardiac and exercise performance in idiopathic dilated cardiomyopathy

The short-term effects of L-thyroxine (100 micrograms/day, 10 patients) and placebo (10 patients) on idiopathic dilated cardiomyopathy were compared. Before and at the end of the treatment, a hemodynamic study was performed in the control state and during dobutamine infusion. A cardiopulmonary exercise test was also performed with hemodynamic monitoring. An echocardiogram was recorded in the control state and during acute changes of left ventricular afterload. Plasma levels of triiodothyronine, thyroxine, thyroid-stimulating hormone and norepinephrine were measured. Placebo was ineffective. After administration of L-thyroxine all patients had normal thyroid function. The increase in left ventricular ejection fraction and the rightward shift of the slope of left ventricular ejection fraction/end-systolic stress relation (p < 0.05) indicated an improvement in the cardiac inotropic state. This proved to be independent of adrenergic influences by the unchanged beta 1 response to dobutamine. A decrease in resting systemic vascular resistances and an increase in cardiac output (p < 0.05) were also observed. Cardiopulmonary effort parameters improved (p < 0.05) without hemodynamic changes at peak exercise. It is concluded that L-thyroxine short-term administration improves cardiac and exercise performance in patients with chronic heart failure, without modifying the adrenergic support to the heart and the circulatory parameters at peak exercise.

Control of pulmonary vasomotility in congestive heart failure

Although enhanced sympathetic tone is a well-known component of the autonomic imbalance of heart failure, its influence on pulmonary vasomotility is undefined. We investigated the pulmonary circulation in 12 patients with congestive heart failure in NYHA functional class III and in a control group of 10 normal subjects. Sympathetic influence on pulmonary vessels was studied through adrenergic activation by the arithmetic test and the cold pressor test. A rubber balloon was distended in the inferior vena cava to reduce transpulmonary flow and its influence on vascular tone. In normal individuals the arithmetic test caused pulmonary vasodilation, probably because of the mechanical effect of a largely enhanced flow: in fact, caval obstruction unmasked a neurogenic vasoconstrictor response to the arithmetic test by simply reducing the amount of cardiac output increase. In patients with heart failure, cardiac output and pulmonary arteriolar resistance remained steady during the arithmetic test, no matter what the condition of the venous return was. The cold pressor test was always a vasoconstrictor stimulus, but only in normal subjects was vasoconstriction potentiated by reducing, with caval obstruction, transpulmonary flow and its vasodilatory influence. From these data an attenuation of the sympathetic influence on pulmonary vessels in congestive heart failure seems to be likely. This might be explained as the result of modifications of pulmonary vessels rather than of reduced sympathetic excitability since circulating catecholamine levels varied to similar extents in the two groups during the tests. In congestive heart failure interstitial edema and vascular wall imbibition might increase pulmonary vessel tone and decrease vascular receptor availability. Lower reactivity to sympathetic stimuli, particularly to the vasoconstrictor ones, would ensue.

Long-term follow-up of the primary hyperkinetic heart syndrome: An echocardiographic and hemodynamic study

Abstract Anxiety, cardiac overactivity and hypercontractility, favorable response to beta-blockade characterize the primary hyperkinetic heart syndrome. Its natural history is unknown; evolution toward obstructive cardiomyopathy has been postulated. We undertook this study to evaluate the following: (1) the existence of a mutual potential between anxiety and cardiac overactivity and its contribution to the perpetuation of the disorder; (2) the development of hypertrophic subaortic stenosis and whether it represents a complication of the syndrome; and (3) the very prolonged normalization of the circulatory regimen by beta-blockade and whether it promotes an irreversible circulatory adjustment. Fourteen hyperkinetic patients were investigated by intravascular and ultrasound methods at their first admission and at yearly intervals in the subsequent five years. During this period seven of them were maintained untreated (group I) and seven received propranolol (group II). Interventricular septal and left ventricular posterior wall thickness (ultrasounds) and the ratio between the two were within normal limits in the control state and remained so for the duration of the follow-up, both in the treated (persistent circulatory normalization was documented) and in the untreated patients (cardiac hyperkinesis was unchanged or somewhat increased). Substitution of placebo for the active propranolol in group II, at the end of the follow-up, caused a prompt recurrence of the overactivity of the heart. It is concluded that (1) transition toward hypertrophic cardiomyopathy probably is not a feature of the syndrome; (2) propranolol does not produce an irreversible circulatory adjustment; (3) it is unlikely that a reciprocal potentiation between anxiety and cardiac overactivity perpetuate the disorder; if it did, then prolonged circulatory normalization could be expected to extinguish the syndrome.

Neural influences on the human pulmonary circulation as a defence reaction to volume depletion

The role of the autonomic nervous system in the regulation of pulmonary vasomotility in man is unsettled and great emphasis is usually given to changes in flow as the main regulating mechanism. In order to simulate hypovolemia, which might reduce the mechanical influence of flow and disclose a neural mechanism, we decreased venous return through balloon distention in the inferior vena cava in 12 normal subjects, during right heart catheterization performed for diagnostic purposes. Caval obstruction was graduated to reduce cardiac output, right atrial and pulmonary arterial pressures, without altering systemic arterial pressure and heart rate. The sympathetic nervous system was activated by arithmetic and cold pressor tests. During the former, the increase in cardiac output was more than halved by venous return restraint, as compared to the unrestrained condition, and clear pulmonary vasoconstriction, instead of vasodilatation, was observed. During the cold test, cardiac output remained almost steady, in the absence as in the presence of balloon expansion. In both conditions pulmonary arteriolar resistance rose, but in the latter this increase was more than doubled. This study suggests that the autonomic nervous system is involved in the regulation of pulmonary vasomotility in man, its role being unveiled when the mechanical influence of flow is reduced by mimicking a hypovolemic state.

Echocardiographic and hemodynamic correlates in Prinzmetal angina pectoris: A case report

In a patient suffering from Prinzmetal angina pectoris, ischemic attacks of the anterior left ventricular wall were associated with the following changes: fall in cardiac output; increased left ventricular diastolic pressure (LVDP) and volume; flattening of the septal motion; marked reduction of the mitral valve early diastolic amplitude and rate of opening; and marked reduction of the systolic closure velocity. It is suggested that LVDP rise depends, at least in part, on variations in left ventricular diastolic volume and segmental wall motion, and that disruption of the mitral valve motion derives from changes in LVDP and flow through the mitral orifice.