Clinically relevant concentrations of bupivacaine inhibit rat aortic baroreceptors.
Bupivacaine is clinically associated with cardiovascular toxicity. To examine the possible role of drug actions at arterial baroreceptors, we studied discharge properties of baroreceptors in an in vitro aortic nerve-aortic arch preparation from rats. We measured single fiber discharge, pressure, and aortic diameter simultaneously during perfusion of the aortic arch with bupivacaine. Perfusion mean arterial pressure was held at 80 mm Hg. Only regularly discharging, presumably myelinated, baroreceptors were studied. To assess pressure threshold, threshold frequency, and maximum discharge rate, nerve activity was evoked by slow ramps of increasing pressure (< 2 mm Hg/s) beginning at 20 mm Hg and ranging up to 150-170 mm Hg. Following replicate control measurements, test ramps were repeated in the presence of sodium nitroprusside (1 microM) and phentolamine (1 microM) to eliminate potential smooth muscle and alpha 1-adrenoceptor effects, respectively. Bupivacaine was then added to the perfusate in increasing concentrations from 0.1 to 50 microM for 15 min to construct a full concentration-response curve at each level. Individual baroreceptors showed substantial depression of maximum discharge frequency and/or increases in pressure threshold at 1-5 microM bupivacaine. In overall population averages (n = 7), 5-10 microM bupivacaine clearly reduced maximum discharge and shifted the pressure threshold to higher values (P < 0.01). The net result was a general depression of discharge. Concentrations as low as 10 microM bupivacaine completely blocked discharge in some baroreceptors. Inasmuch as the pressure-diameter relations were not changed, discharge relations plotted against diameter showed equivalent changes. Bupivacaine-free solution reversed the block in all cases.(ABSTRACT TRUNCATED AT 250 WORDS)
Chang
K S
KS
Department of Anesthesiology, Oregon Health Sciences University, Portland 97201.
Yang
M
M
Andresen
M C
MC
D000818:Animals; D001013:Aorta, Thoracic / Q000294:innervation*; D002045:Bupivacaine / Q000008:administration & dosage / Q000633:toxicity*; D066298:In Vitro Techniques; D008297:Male; D011311:Pressoreceptors / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002045:Bupivacaine