The effects of alfentanil on cytosolic Ca(2+) and contraction in rat ventricular myocytes.
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 Ca(2+) regulation in cardiac tissue. In this study, we sought to assess the effects of alfentanil on contractility and the cytosolic Ca(2+) 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 Ca(2+) transients and contractions were recorded optically at 30 degrees C. Alfentanil 10(-8) and 10(-7) M had no effect on the magnitude or time course of contraction or the cytosolic Ca(2+) 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 microm to 8.7 +/- 1.4 microm (an increase of 20%), with no change in the cytosolic Ca(2+) transient. Myofilament Ca(2+) 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 Ca(2+) rather than to modified cytosolic Ca(2+) regulation.


CONCLUSIONS
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 Ca(2+).
Graham
Mark D
MD
*School of Biomedical Sciences and †Academic Unit of Anaesthesia, University of Leeds, Leeds, United Kingdom.
Hopkins
Philip M
PM
Harrison
Simon M
SM
D015760:Alfentanil / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism*; D004558:Electric Stimulation; D005456:Fluorescent Dyes; D016257:Fura-2; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D051381:Rats
D018686:Anesthetics, Intravenous; D005456:Fluorescent Dyes; D015760:Alfentanil; D002118:Calcium; D016257:Fura-2