Abstract
Introduction: While morphine has been used for treatment-resistant dyspnea in patients with end-stage heart failure, its information on in vivo cardiovascular profile remains limited.
Methods: Morphine was intravenously administered to the halothane-anesthetized dogs (n=4) in escalating doses of 0.1 followed by 1 mg/kg/10 min with respective 20 min observation periods under the monitoring of cardiohemodynamic and electrophysiological variables.
Results: The low dose hardly altered cardiovascular variables. The high dose reduced preload and afterload to the left ventricle for 5-15 min after the start of infusion, then decreased the left ventricular contractility along with the mean blood pressure for 10-30 min, and next suppressed the heart rate for 15-30 min. Morphine slowed the atrioventricular conduction and ventricular late repolarization, and prolonged the ventricular effective refractory period without altering the intraventricular conduction or ventricular early repolarization. A reverse-frequency-dependent delay of ventricular repolarization was confirmed.
Conclusion: Morphine could directly dilate the resistance and capacitance vessels, whereas it would attenuate the adrenergic tone followed by an increase of vagal tone. The reverse-frequency-dependent delay of ventricular repolarization by morphine along with the prolongation of late repolarization suggests hERG K+ channel inhibition in vivo in spite of its large IC50 value for hERG K+ channel in vitro (>1 mM), indicating the presence of indirect mechanisms for its inhibition.
