title: Does local anesthetic stereoselectivity or structure predict myocardial depression in anesthetized canines?
abstract: OBJECTIVE
  It is unclear whether the susceptibility to myocardial depression from an accidental intravascular local anesthetic (LA) administration is associated with LA stereoselectivity or structure. By using direct left ventricular pressure monitoring and echocardiographic indices of contractile function in anesthetized, ventilated dogs, we compared the cardiac depressant effects of bupivacaine, ropivacaine, levobupivacaine, and lidocaine.
  
  
  METHODS
  Open-chest dogs were randomized to receive escalating incremental infusions of the 4 local anesthetics until cardiovascular collapse. We assumed a concentration relationship for potency of 4:1 for lidocaine/bupivacaine, ropivacaine, and levobupivacaine.
  
  
  RESULTS
  All LAs produced concentration-dependent increases in left ventricular end diastolic pressure (LVEDP) and decreases in dP/dtmax, ejection fraction % (EF), fractional shortening (%) (FS), and cardiac output (CO). When comparing the long-acting agents, the effect was least for ropivacaine. The effective concentration estimates for ropivacaine that produced 35% reductions in dP/dtmax and FS were 4.0 micro g/mL (95% confidence intervals [CI(95)]: 3.1 to 5.2 micro g/mL) and 3.0 micro g/mL (CI (95): 2.1 to 4.2 micro g/mL), respectively. The concentrations of levobupivacaine that produced these same end points of contractile dysfunction were significantly less: 2.4 micro g/mL (CI(95): 1.9 to 3.1 micro g/mL) and 1.3 micro g/mL (CI(95): 0.9 to 1.8 micro g/mL), respectively, and these were not different from bupivacaine. As expected, the concentrations of lidocaine that produced 35% reductions in dP/dtmax and FS were significantly greater than the longer acting agents; 8.0 micro g/mL (CI(95): 5.7 to 11.0 micro g/mL) and 5.5 micro g/mL (CI(95): 3.5 to 8.7 micro g/mL), respectively.
  
  
  CONCLUSIONS
  This study suggests that smaller molecular size and possibly a piperidine-free structure as opposed to stereoselectivity may be the more important factor in reducing the risk of LA-induced myocardial depression.
authors.affiliation: Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. lgroban@wfubmc.edu
authors.forename: Leanne
authors.initials: L
authors.lastname: Groban
authors.forename: Dwight D
authors.initials: DD
authors.lastname: Deal
authors.forename: Jason C
authors.initials: JC
authors.lastname: Vernon
authors.forename: Robert L
authors.initials: RL
authors.lastname: James
authors.forename: John
authors.initials: J
authors.lastname: Butterworth
mesh_terms: D000758:Anesthesia; D000779:Anesthetics, Local / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography; D009200:Myocardial Contraction / Q000187:drug effects*; D012121:Respiration, Artificial; D013237:Stereoisomerism; D013318:Stroke Volume / Q000187:drug effects; D013329:Structure-Activity Relationship; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000779:Anesthetics, Local