Background and objective: In spite of the widespread clinical use of articaine and ropivacaine there is little information available on the effects of these drugs on myocardial Ca handling. In the present study, therefore, the concentration-dependent effects of articaine and ropivacaine on the components of intracellular Ca handling were studied and compared in canine ventricular myocardium.
Methods: Contractility was measured in ventricular trabeculae, [Ca]i transients were recorded from electrically stimulated isolated ventricular myocytes loaded with the calcium-sensitive dye fura-2, L-type Ca current was recorded under whole cell patch clamp conditions, and the release and reuptake of Ca was monitored in sarcoplasmic reticulum vesicles.
Results: Articaine and ropivacaine caused a reversible and concentration-dependent decrease in amplitude of the [Ca]i transient (EC50 = 87.4 +/- 12 and 99.3 +/- 17 micromol l, respectively), which was congruent with the reduction obtained for contractility (EC50 = 73.7 +/- 10 and 72.8 +/- 14 micromol l, respectively). No significant change in diastolic [Ca]i was found. L-type Ca current was significantly reduced by articaine and ropivacaine with EC50 values of 327 +/- 56 and 263 +/- 67 micromol l, respectively. Neither Ca release and Ca uptake nor the ATPase activity of the sarcoplasmic reticulum vesicles was altered by articaine or ropivacaine at concentrations less than 200 micromol l. In summary, articaine and ropivacaine caused no significant changes at the therapeutically relevant concentrations of the micromolar range. No significant differences between the effects of articaine and ropivacaine on contractility, [Ca]i transients, L-type Ca current, and sarcoplasmic reticulum Ca release and uptake were observed.
Conclusions: Under conditions of normal application both articaine and ropivacaine are free of cardiodepressant effects; however, a negative inotropic action can be anticipated in cases of accidental intravenous injection or overdose. The observed negative inotropic actions of articaine and ropivacaine are similar in magnitude, and can be mainly attributed to a reduction in net trans-sarcolemmal Ca influx.