Dose-dependent effects of bupivacaine on rat muscle arterioles

The dose-dependent actions of bupivacaine on the microvasculature were evaluated by television microscopy in an in vivo rat cremaster muscle preparation. Animals were anesthetized with chloralose and urethane. Mean arterial pressure was measured via a carotid artery cannula; heart rate was calculated from the phasic pressure trace. The cremaster muscle was suffused with a balanced electrolyte solution that was controlled for temperature, pH, PO2, PCO2, and osmolarity to provide a physiologic environment. Internal diameters of fourth-order arterioles were measured with an electronic vernier displayed on the video monitor. Arteriolar diameters were measured every 30 s during a 10-min control period, a 10-min period of topical application of bupivacaine hydrochloride, and a 30-min recovery period. Bupivacaine 10(-1), 10(0), 10(1), and 10(2) micrograms X ml-1 produced progressive vasoconstriction to 82.7 +/- 2.9%, 75.0 +/- 5.6%, 71.0 +/- 7.0%, and 65.7 +/- 9.4% of control (P less than 0.05 for each), respectively. Bupivacaine, 10(3) and 2.5 X 10(3) micrograms X ml-1, did not alter arteriolar diameters significantly, although there was a tendency for vasodilation. In a second group of animals, arteriolar diameters were measured during intravenous bupivacaine infusion that produced stable plasma concentrations of 2.3 +/- 0.2 micrograms X ml-1. Vasoconstriction of 91.4 +/- 2.2%, of control (P less than 0.01) was observed. These results demonstrate that dose-dependent arteriolar constriction occurs even with blood bupivacaine levels that are at the upper limits of those expected to occur during regional anesthesia.