Influence of alpha- and beta-adrenergic blockade on systemic and pulmonary hemodynamics during intravenous administration of local anesthetics.
The effects of alpha- and beta-adrenergic blockade on the systemic and pulmonary circulation during i.v. bolus injection of sub-seizure doses of lidocaine and bupivacaine were studied in dogs anesthetized with nitrous oxide. Pretreatment with hexamethonium or propranolol produced a marked decrease in cardiac output (CO), although pretreatment with phenoxybenzamine inhibited the decrease in CO during i.v. administration of lidocaine. Pretreatment with hexamethonium or phenoxybenzamine attenuated the increase in total peripheral resistance (TPR) following lidocaine 10 mg/kg i.v. In contrast, the propranolol-treated dogs developed a marked increase in TPR. The increases in mean pulmonary arterial pressure and pulmonary vascular resistance (PVR) following lidocaine 10 mg/kg i.v. were blocked by pretreatment with hexamethonium. Furthermore, PVR increased markedly with pretreatment with propranolol, although pretreatment with phenoxybenzamine prevented the large increase in PVR. These findings indicate that lidocaine has both a direct depressant effect and an indirect beta adrenergic stimulant effect on the heart. Systemic or pulmonary vasoconstriction following intravenous administration of lidocaine 10 mg/kg is associated primarily with an indirect stimulant effect mediated by alpha-adrenergic mechanisms. Bupivacaine, as well as lidocaine, has an indirect stimulant effect mediated by the autonomic nervous system.
D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage*; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects*; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007275:Injections, Intravenous; D008012:Lidocaine / Q000008:administration & dosage*; D010643:Phenoxybenzamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects; D013565:Sympatholytics / Q000494:pharmacology*
D006584:Hexamethonium Compounds; D013565:Sympatholytics; D010643:Phenoxybenzamine; D018738:Hexamethonium; D008012:Lidocaine; D011433:Propranolol; D002045:Bupivacaine