Hostname: page-component-cd9895bd7-jn8rn Total loading time: 0 Render date: 2024-12-24T12:41:15.987Z Has data issue: false hasContentIssue false
  • English
  • Français

Insulin effects on myocardial function and bioenergetics in l-bupivacaine toxicity in the isolated rat heart

Published online by Cambridge University Press:  01 April 2007

S. N. Stehr ,
A. Pexa ,
S. Hannack ,
A. Heintz ,
A. R. Heller ,
A. Deussen ,
T. Koch  and
M. Hübler
S. N. Stehr
Affiliation:
Medical Faculty Carl Gustav Carus, Department of Anaesthesiology and Intensive Care Medicine
A. Pexa
Affiliation:
Institute of Physiology, Dresden, Germany
S. Hannack
Affiliation:
Medical Faculty Carl Gustav Carus, Department of Anaesthesiology and Intensive Care Medicine
A. Heintz
Affiliation:
Medical Faculty Carl Gustav Carus, Department of Anaesthesiology and Intensive Care Medicine
A. R. Heller
Affiliation:
Medical Faculty Carl Gustav Carus, Department of Anaesthesiology and Intensive Care Medicine
A. Deussen
Affiliation:
Institute of Physiology, Dresden, Germany
T. Koch
Affiliation:
Medical Faculty Carl Gustav Carus, Department of Anaesthesiology and Intensive Care Medicine
M. Hübler
Affiliation:
Medical Faculty Carl Gustav Carus, Department of Anaesthesiology and Intensive Care Medicine
Get access

Summary

Background and objectives

A positive effect of insulin–glucose–potassium infusion in severe bupivacaine-induced cardiovascular collapse has been described in vivo. It has been speculated that an antagonistic influence of insulin on sodium channel inhibition, transient outward potassium current, calcium-dependent adenosine triphosphatase or even improved myocardial energetics may be responsible for this effect. Using an isolated heart model, we therefore sought to further elucidate insulin effects in l-bupivacaine-induced myocardial depression.

Methods

An isolated rat heart constant-pressure perfused, non-recirculating Langendorff preparation was used. Hearts were exposed to l-bupivacaine 5 μg mL−1 and insulin 10 mIU mL−1. Heart rate, systolic pressure, the first derivative of left ventricular pressure (+dP/dt), coronary flow, double product, PR and QRS intervals were recorded. Hearts were freeze-clamped and high-performance liquid chromatography measurement of the total adenine nucleotide pool was performed.

Results

l-Bupivacaine led to a significant decrease in heart rate, +dP/dt, systolic pressure, coronary flow and double product, and to an increase in PR and QRS. Insulin exerted a positive inotropic effect, significantly augmenting +dP/dt and systolic pressure in both l-bupivacaine-treated and control hearts. Heart rate, coronary flow, total adenine nucleotides, PR and QRS were not significantly changed by the insulin intervention.

Conclusion

Insulin did not have a significant effect on total adenine nucleotides in controls and in l-bupivacaine-treated hearts. However, it does exert a positive inotropic action in bupivacaine-induced myocardial depression. We conclude that the positive effect of insulin application lies in positive inotropic action and not in changes in total adenine nucleotides.

Keywords

ANAESTHETICS LOCAL, bupivacaine, toxicityDRUG TOXICITYHEARTINSULINADENOSINE TRIPHOSPHATE
Type
Research Article
Information
European Journal of Anaesthesiology , Volume 24 , Issue 4 , April 2007 , pp. 340 - 346
Copyright
Copyright © European Society of Anaesthesiology 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Albright, GA. Cardiac arrest following regional anesthesia with etidocaine or bupivacaine. Anesthesiology 1979; 51: 285–287.CrossRefGoogle ScholarPubMed
2.Weinberg, GL. Current concepts in resuscitation of patients with local anesthetic cardiac toxicity. Reg Anesth Pain Med 2002; 27: 568–575.CrossRefGoogle ScholarPubMed
3.Cho, HS, Lee, JJ, Chung, IS, Shin, BS, Kim, JA, Lee, KH. Insulin reverses bupivacaine-induced cardiac depression in dogs. Anesth Analg 2000; 91: 1096–1102.Google ScholarPubMed
4.Kim, JT, Jung, CW, Lee, KH. The effect of insulin on the resuscitation of bupivacaine-induced severe cardiovascular toxicity in dogs. Anesth Analg 2004; 99: 728–733.CrossRefGoogle ScholarPubMed
5.Weinberg, G, VadeBoncouer, T. Improved energetics may explain the favorable effect of insulin infusion on bupivacaine cardiotoxicity. Anesth Analg 2001; 92: 1075–1076.CrossRefGoogle ScholarPubMed
6.Mather, LE, Chang, DH. Cardiotoxicity with modern local anaesthetics: is there a safer choice? Drugs 2001; 61: 333–342.CrossRefGoogle Scholar
7.Grupp, IL, Subramaniam, A, Hewett, TE, Robbins, J, Grupp, G. Comparison of normal, hypodynamic, and hyperdynamic mouse hearts using isolated work-performing heart preparations. Am J Physiol 1993; 265: H1401–H1410.Google ScholarPubMed
8.Sutherland, FJ, Hearse, DJ. The isolated blood and perfusion fluid perfused heart. Pharmacol Res 2000; 41: 613–627.CrossRefGoogle ScholarPubMed
9.Haink, G, Deussen, A. Liquid chromatography method for the analysis of adenosine compounds. J Chromatogr B Analyt Technol Biomed Life Sci 2003; 784: 189–193.CrossRefGoogle ScholarPubMed
10.Himsworth, RL. Hypothalamic control of adrenaline secretion in response to insufficient glucose. J Physiol 1970; 206: 411–417.CrossRefGoogle ScholarPubMed
11.Burmester, MD, Schluter, KD, Daut, J, Hanley, PJ. Enantioselective actions of bupivacaine and ropivacaine on coronary vascular resistance at cardiotoxic concentrations. Anesth Analg 2005; 100: 707–712.CrossRefGoogle ScholarPubMed
12.Graf, BM, Martin, E, Bosnjak, ZJ, Stowe, DF. Stereospecific effect of bupivacaine isomers on atrioventricular conduction in the isolated perfused guinea pig heart. Anesthesiology 1997; 86: 410–419.CrossRefGoogle ScholarPubMed
13.Zapata-Sudo, G, Trachez, MM, Sudo, RT, Nelson, TE. Is comparative cardiotoxicity of S(−) and R(+) bupivacaine related to enantiomer-selective inhibition of L-type Ca(2+) channels? Anesth Analg 2001; 92: 496–501.Google Scholar
14.Scott, DB, Lee, A, Fagan, D, Bowler, GM, Bloomfield, P, Lundh, R. Acute toxicity of ropivacaine compared with that of bupivacaine. Anesth Analg 1989; 69: 563–569.CrossRefGoogle ScholarPubMed
15.Mather, LE, Long, GJ, Thomas, J. The intravenous toxicity and clearance of bupivacaine in man. Clin Pharmacol Ther 1971; 12: 935–943.CrossRefGoogle ScholarPubMed
16.Bardsley, H, Gristwood, R, Baker, H, Watson, N, Nimmo, W. A comparison of the cardiovascular effects of levobupivacaine and rac-bupivacaine following intravenous administration to healthy volunteers. Br J Clin Pharmacol 1998; 46: 245–249.CrossRefGoogle ScholarPubMed
17.Rieker, RP, Lee, JC, Downing, SE. Positive inotropic action of insulin on piglet heart. Yale J Biol Med 1975; 48: 353–359.Google ScholarPubMed
18.Airaksinen, J, Lahtela, JT, Ikaheimo, MJ, Sotaniemi, EA, Takkunen, JT. Intravenous insulin has no effect on myocardial contractility or heart rate in healthy subjects. Diabetologia 1985; 28: 649–652.CrossRefGoogle ScholarPubMed
19.Lee, JC, Downing, SE. Effects of insulin on cardiac muscle contraction and responsiveness to norepinephrine. Am J Physiol 1976; 230: 1360–1365.CrossRefGoogle ScholarPubMed
20.Tune, JD, Mallet, RT, Downey, HF. Insulin improves cardiac contractile function and oxygen utilization efficiency during moderate ischemia without compromising myocardial energetics. J Mol Cell Cardiol 1998; 30: 2025–2035.CrossRefGoogle ScholarPubMed
21.Gupta, MP, Lee, SL, Dhalla, NS. Activation of heart sarcoplasmic reticulum Ca++-stimulated adenosine triphosphatase by insulin. J Pharmacol Exp Ther 1989; 249: 623–630.Google ScholarPubMed
22.Gupta, MP, Makino, N, Khatter, K, Dhalla, NS. Stimulation of Na+-Ca2+ exchange in heart sarcolemma by insulin. Life Sci 1986; 39: 1077–1083.CrossRefGoogle ScholarPubMed
23.Ballard, C, Mozaffari, M, Schaffer, S. Signal transduction mechanism for the stimulation of the sarcolemmal Na(+)-Ca2+ exchanger by insulin. Mol Cell Biochem 1994; 135: 113–119.CrossRefGoogle ScholarPubMed
24.Schmidt, HD, Koch, M. Influence of perfusate calcium concentration on the inotropic insulin effect in isolated guinea pig and rat hearts. Basic Res Cardiol 2002; 97: 305–311.CrossRefGoogle ScholarPubMed
25.Tanz, RD, Heskett, T, Loehning, RW, Fairfax, CA. Comparative cardiotoxicity of bupivacaine and lidocaine in the isolated perfused mammalian heart. Anesth Analg 1984; 63: 549–556.Google ScholarPubMed
26.Butterworth, JF, Brownlow, RC, Leith, JP, Prielipp, RC, Cole, LR. Bupivacaine inhibits cyclic-3′,5′-adenosine monophosphate production. A possible contributing factor to cardiovascular toxicity. Anesthesiology 1993; 79: 88–95.CrossRefGoogle ScholarPubMed
27.Rossner, KL, Freese, KJ. Bupivacaine inhibition of L-type calcium current in ventricular cardiomyocytes of hamster. Anesthesiology 1997; 87: 926–934.CrossRefGoogle ScholarPubMed
28.Mio, Y, Fukuda, N, Kusakari, Y, Tanifuji, Y, Kurihara, S. Bupivacaine attenuates contractility by decreasing sensitivity of myofilaments to Ca2+ in rat ventricular muscle. Anesthesiology 2002; 97: 1168–1177.CrossRefGoogle ScholarPubMed