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ANESTHETIC PHARMACOLOGY

The Effects of Alfentanil on Cytosolic Ca²⁺ and Contraction in Rat Ventricular Myocytes

Mark D. Graham, BSc^*, Philip M. Hopkins, MD, and Simon M. Harrison, PhD^*

*School of Biomedical Sciences and Academic Unit of Anaesthesia, University of Leeds, Leeds, United Kingdom

Address correspondence and reprint requests to Simon M. Harrison, PhD, School of Biomedical Sciences, University of Leeds, Leeds, LS2 9JT, UK. Address e-mail to S.M.Harrison{at}Leeds.ac.uk

Previous investigations of the effects of potent opioid analgesics on the heart have concentrated on effects on contraction magnitude and time course, but little is known about their effects on cytosolic Ca²⁺ regulation in cardiac tissue. In this study, we sought to assess the effects of alfentanil on contractility and the cytosolic Ca²⁺ transient in ventricular myocytes isolated from the rat ventricle by enzymatic dispersion. Cells were loaded with fura-2 and electrically stimulated at 1 Hz, and Ca²⁺ transients and contractions were recorded optically at 30°C. Alfentanil 10^-8 and 10^-7 M had no effect on the magnitude or time course of contraction or the cytosolic Ca²⁺ transient. In contrast, 10^-6 M alfentanil induced a significant (P < 0.001) positive inotropic effect, increasing the mean (±SEM) unloaded shortening from 7.3 ± 1.3 µm to 8.7 ± 1.4 µm (an increase of 20%), with no change in the cytosolic Ca²⁺ transient. Myofilament Ca²⁺ sensitivity was significantly (P = 0.027) increased by 10^-6 M alfentanil but unaffected at 10^-7 M alfentanil. These data show that 10^-6 M alfentanil, a concentration close to the maximum clinical free plasma concentration, induced a positive inotropic effect due to sensitization of the myofilaments to Ca²⁺ rather than to modified cytosolic Ca²⁺ regulation.

IMPLICATIONS: Alfentanil, at concentrations achieved in clinical practice, increased contraction in ventricular cells by a mechanism involving an increase in the sensitivity of the contractile apparatus to Ca²⁺.