title: The myocardial and vascular effects of bupivacaine, levobupivacaine, and ropivacaine using pressure volume loops.
abstract: Ropivacaine and levobupivacaine were developed to reduce the risk of fatal accidental overdose reported with bupivacaine. The myocardial depressant potential of these drugs in sublethal dosage is unknown. Pressure volume loops can be used to separate myocardial from vascular effects. We acquired dose-response curves to incremental infusions in seven anesthetized, open-chest New Zealand white rabbits in each of bupivacaine, levobupivacaine, ropivacaine, and saline control groups. Simultaneous high-fidelity left ventricular pressure and volume data were acquired during caval occlusion with a combined conductance-pressure catheter inserted via an apical stab. Measurements of contractility (V(100)), diastolic function (tau and end-diastolic pressure volume relation), and vascular resistance were performed after each dose increase. Drugs were infused at a ratio of 0.125:0.2 for levobupivacaine and bupivacaine/ropivacaine to simulate clinical usage, with a log(2) (8 step) dose escalation protocol. Over 40 min, the accumulated doses were 2.66/4.25 mg/kg. Levobupivacaine (P = 0.013) and bupivacaine (P = 0.019) significantly impaired contractility at doses exceeding 1.32 mg/kg, whereas ropivacaine was not different from control at 4.25 mg/kg. Bupivacaine reduced ejection fraction (EF) and cardiac index, and increased vascular resistance. Levobupivacaine reduced EF and cardiac index and demonstrated a biphasic vascular response, increasing vascular resistance at larger dosage. Ropivacaine increased vascular resistance and reduced EF without effect on contractility. Mean arterial blood pressure and diastolic function were unchanged for all drugs. Significant decline in contractility from control occurs with bupivacaine and levobupivacaine, but not with ropivacaine, at doses achievable in routine clinical practice.
authors.affiliation: Cardiovascular Therapeutics Unit, Department of Pharmacology, University of Melbourne, Victoria, Australia.
authors.forename: Colin F
authors.initials: CF
authors.lastname: Royse
authors.forename: Alistair G
authors.initials: AG
authors.lastname: Royse
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001810:Blood Volume / Q000187:drug effects*; D002045:Bupivacaine / Q000031:analogs & derivatives / Q000494:pharmacology; D003971:Diastole; D004305:Dose-Response Relationship, Drug; D017097:Electric Impedance; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D000077554:Levobupivacaine; D009200:Myocardial Contraction / Q000187:drug effects*; D011817:Rabbits; D000077212:Ropivacaine; D013599:Systole; D014655:Vascular Resistance / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000577:Amides; D000777:Anesthetics; D000077212:Ropivacaine; D000077554:Levobupivacaine; D002045:Bupivacaine