Differential effects of short- and long-term bupivacaine treatment on α1-adrenoceptor-mediated contraction of isolated rat aorta rings and the reversal effect of lipid emulsion

Abstract

Aim: Arterial function is significantly influenced by bupivacaine at both clinically relevant concentrations and toxic concentrations, but the underlying mechanisms are not fully understood. In the present study we investigated the role of α 1 -adrenoceptors in bupivacaine effects on isolated rat aortas. Methods: Isolated aortic rings were prepared from rats and suspended in an organ bath. Phenylephrine (Phe)-induced vasoconstriction and acetylcholine (ACh)-induced vasodilation were recorded through an isometric force transducer connected to a data acquisition system. Results: Administration of bupivacaine (30-300 μmol/L) produced mild vasoconstriction, and this response declined with repeated administrations. Treatment of the aortic rings with bupivacaine (3-30 μmol/L) for 20 min enhanced Phe-induced vasoconstriction, while treatment for 40 min suppressed Phe-induced vasoconstriction. Both the short-and long-term bupivacaine treatment suppressed ACh-induced vasodilation. Incubation of the aortic rings with 0.2%-0.6% lipid emulsion (LE) for 100 min significantly increased the pD 2 and E max values of Phe-induced vasoconstriction, and incubation with 0.4% LE for 100 min reversed the inhibition of bupivacaine on vasoconstriction induced by Phe (30 μmol/L). In contrast, incubation with LE suppressed ACh-induced vasodilation, even at a lower concentration and with a 5-min incubation. Conclusion: Bupivacaine exerts dual effects on α 1 -adrenoceptor-mediated vasoconstriction of isolated rat aortic rings: short-term treatment enhances the response, while long-term treatment inhibits it; the inhibition may be reversed via long-term incubation with LE.

Effects of Solvents, Emulsions, Cosolvents, and Complexions on Ex Vivo Mouse Myometrial Contractility

“…In the present study, we investigated the potential of emulsion-based formulations as a delivery system for insoluble compounds in organ bath experiments. There are published reports on emulsions tested in organ baths on rat aortic tissue [ 45 , 46 ]; however, this is the first report of emulsions being used as a solubilization method for poorly soluble compounds in an organ bath assay using mouse myometrial tissue. Importantly, we found that the base emulsion without drug was not different to that of water or KBS.…”

Epinephrine Deteriorates Pulmonary Gas Exchange in a Rat Model of Bupivacaine-Induced Cardiotoxicity

“…These results are consistent with the finding of Hiller et al 11 We also found that compared with a normal saline bolus, administration of epinephrine led to a dramatic elevation of systolic left atrial pressure that gradually declined after reaching peak at approximately 90 seconds. We speculate that α-adrenoceptormediated peripheral vasoconstriction 10 (bupivacaine enhanced the α-adrenergic effect as well 19 ) elevated the afterload of the left ventricle (elevation of left ventricular wall stress), whereas β-adrenoceptor stimulation increased cardiac output 10 (increasing pulmonary inflow) and HR (shortening of ventricular diastolic period). Thus, epinephrine increased pulmonary blood flow while impairing left ventricular diastolic function (elevation of left .…”