Lipid emulsion reverses bupivacaine-induced asystole in isolated rat hearts: concentration-response and time-response relationships.
BACKGROUND
The concentration-response and time-response relationships of lipid emulsions used to reverse bupivacaine-induced asystole are poorly defined.


METHODS
Concentration response across a range of lipid concentrations (0-16%) to reverse bupivacaine-induced asystole were observed using isolated rat heart Langendorff preparation. Cardiac function parameters were recorded during infusion. Concentrations of bupivacaine in myocardial tissue were measured by liquid chromatography and tandem mass spectrometry at the end of the experiment.


RESULTS
Although all lipid-treated hearts recovered (cardiac recovery was defined as a rate-pressure product more than 10% baseline), no nonlipid-treated hearts (control group) did so. The ratio of the maximum rate pressure product during recovery to baseline value demonstrated a concentration-dependent relationship among lipid groups, with 0.25, 0.5, 1, 2, 4, 8, and 16%. Mean ± SD values for each corresponding group were 22 ± 4, 24 ± 5, 29 ± 6, 52 ± 11, 73 ± 18, 119 ± 22, and 112 ± 10%, respectively (n = 6, P < 0.01). Rate-pressure product in lipid groups with 4-16% concentrations was lower at 15-40 min than at 1 min, showing a decreasing tendency during recovery phase (P < 0.01). The concentration of myocardial bupivacaine in all lipid-treated groups was significantly lower than in the control group (P < 0.01). It was also lower in lipid groups with 2-16% concentrations than in those with concentrations at 0.25-1% (P < 0.05), with the 16% group lower than groups with 2-8% concentrations (P < 0.001).


CONCLUSIONS
Lipid application in bupivacaine-induced asystole displays a concentration-dependent and time-response relationship in isolated rat hearts.
Department of Anesthesiology, First Affiliated Hospital, Wenzhou Medical College, Zhejiang, China.
Ying
Y
Chen
Yun
Y
Xia
Le
L
Liu
Tong
T
Shi
Kejian
K
Shi
Quanguang
Q
Wang
Limei
L
Chen
Thomas J
TJ
Papadimos
Xuzhong
X
Xu
D000465:Algorithms; D000779:Anesthetics, Local / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics / Q000633:toxicity; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002045:Bupivacaine / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006323:Heart Arrest / Q000139:chemically induced* / Q000188:drug therapy*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left / Q000187:drug effects
D000779:Anesthetics, Local; D005217:Fat Emulsions, Intravenous; D002045:Bupivacaine