SUMMARY The acute effects of felodipine on left ventricular function and haemodynamics were studied in 11 patients with coronary artery disease. To block reflex sympathetic activation due to peripheral vasodilatation and to avoid effects secondary to changes in heart rate all patients received a standard regimen of beta adrenoceptor blockade and all measurements were made during sinus rhythm and right atrial pacing. At 30 minutes after an oral dose (0.075 mg/kg in solution) felodipine plasma concentration were 16-4 (3-5) nmol/l. A significant fall in systemic vascular resistance (30%) and increase in cardiac index (30%) occurred, whereas pulmonary vascular resistance was unchanged. Felodipine increased left ventricular ejection fraction and mean velocity of circumferential fibre shortening but had no effect on derivates of left ventricular pressure (dP/dt or dP/dt P-1) during sinus rhythm or pacing. Thus at the dosage used felodipine was a potent dilator of systemic arterioles but had no direct effect on left ventricular function.Felodipine is a new dihydropyridine compound, which has been claimed (in vitro) to be a potent vasodilator with less cardiodepressive effect than other calcium antagonists.' Its mechanism of action in relaxing vascular smooth muscle is unclear, although it has been suggested that it inhibits the activation, by calcium ions, of intracellular calmodulin2 and only at high concentration does it act as a slow calcium channel blocker. A non-invasive study3 of young healthy men confirmed its action as a vasodilator in man; there are, however, no direct measurements available of its effect on left ventricular function. In this study therefore we measured the systemic and left ventricular haemodynamic effects of felodipine in patients undergoing cardiac catheterisation for investigation of chest pain. We and others45 have previously shown that control of heart rate and blockade of reflex sympathetic activation is essential to avoid masking direct negative inotropic actions of peripheral vasodilators.6-8 For this reason measurements were carried out at rest and during atrial pacing in patients receiving beta blocking agents.Requests for reprints to:
A 31 year old white man was referred for investigation of a persistent sinus tachycardia. His only significant past medical history was of chronic schizophrenia for which he had been taking clozapine for six years. An electrocardiogram demonstrated sinus tachycardia, voltage criteria for left ventricular hypertrophy, and a prolonged QTc. Echocardiographic findings were consistent with a dilated cardiomyopathy. Serious cardiac complications of clozapine use are rare but have been reported previously. It is important to note that sinus tachycardia may be the only obvious clinical sign, and that complications can manifest months or even years (as in this case) after starting the drug. Patients on clozapine should be informed of potential cardiac symptoms and doctors should maintain a high degree of clinical suspicion throughout the duration of treatment.A 31 year old white man was referred by his general practitioner to the cardiology outpatient department for investigation of a persistent sinus tachycardia. In general he felt well, with no recent history of fever, chest pain, cough, or symptoms suggestive of thyrotoxicosis. On direct questioning there was a history of gradually worsening exertional dyspnoea over several months. His only past medical history of note was chronic schizophrenia which was well controlled on clozapine 400 mg daily. This was prescribed six years previously when flupenthixol had failed to control psychotic symptoms. He was on no other regular medications and did not consume alcohol. He also denied any recreational drug use. His only significant coronary risk factor was a smoking habit of 10 cigarettes daily. There was no family history of either premature coronary disease or cardiomyopathy.On examination he was afebrile. There was a resting sinus tachycardia of 110 beats/min and blood pressure of 110/75 mm Hg. His jugular venous pressure was raised at 6 cm, but heart sounds were normal with no added sounds or murmurs. The rest of the physical examination was entirely normal.A resting electrocardiogram (ECG) confirmed sinus tachycardia and changes consistent with left ventricular hypertrophy. The corrected QT interval (QTc) was prolonged at 479 ms (380-460 ms). Chest radiography demonstrated an enlarged cardiothoracic ratio with clear lung fields.He proceeded to echocardiography which demonstrated a grossly dilated heart with a left ventricular diastolic dimension of 7.3 cm (3.5-5.6 cm). There was very poor global function with an estimated ejection fraction of 9% (>50%). There were no significant valvular abnormalities. Full blood count, urea and electrolytes, liver function tests, ferritin, C-reactive protein, erythrocyte sedimentation rate, thyroid function tests, and troponin I were all normal.In the absence of any other likely aetiology a presumptive diagnosis of clozapine-induced cardiomyopathy was made and he was admitted for further management. The Committee on Safety of Medicines (CSM) was informed via the yellow card reporting scheme. His clozapine was converted to olanzapine 10 ...
The effect of myocardial catecholamine depletion on cellular electrophysiology and arrhythmias was assessed in Langendorff perfused guinea pig hearts during ischaemia and reperfusion. Myocardial noradrenaline was reduced to 0.17 +/- 0.04 microgram X g-1 by intracardiac injection of 6-hydroxydopamine (450 mg X kg-1 in six doses over 20 days) compared with 1.5 +/- 0.2 microgram X g-1 in vehicle injected controls. Myocardial catecholamine depletion significantly reduced the incidence of ventricular tachycardia and fibrillation during 30 min of global ischaemia and subsequent reperfusion. Myocardial catecholamine depletion prolonged action potential duration and refractory period during control perfusion and blunted ischaemia induced reduction in action potential amplitude, Vmax, and duration, but accentuated the prolongation in conduction time and QRS width. Catecholamine depletion abolished or attenuated reperfusion induced shortening of action potential duration and refractory period. Catecholamine depletion increased myocardial glycogen levels from 2.47 +/- 0.3 mg X g-1 wet weight to 4.39 +/- 0.3 mg X g-1; fasting animals for 48 h prior to study reversed this with no attenuation of the electrophysiological or antiarrhythmic action. These results provide further evidence that release of endogenous myocardial catecholamines contributes to the electrophysiological changes and arrhythmias associated with myocardial ischaemia and reperfusion.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.