Mechanisms underlying greater sensitivity of neonatal cardiac muscle to volatile anesthetics

Y.s. Prakash, Inanc Seckin, Larry W. Hunter, Gary C Sieck

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background: In neonatal heart, plasma membrane Na +-Ca 2+ exchange (NCX) and Ca 2+ channels play greater roles in intracellular Ca 2+ concentration [Ca 2+] i regulation compared with the sarcoplasmic reticulum (SR). In neonatal (aged 0-3 days) and adult (aged 84 days) rat cardiac myocytes, we determined the mechanisms underlying greater sensitivity of the neonatal myocardium to inhibition by volatile anesthetics. Methods: The effects of 1 and 2 minimum alveolar concentration halothane and sevoflurane on Ca 2+ influx during electrical stimulation in the presence or blockade of NCX and the Ca 2+ channel agonist BayK8644 were examined. [Ca 2+] i responses to caffeine were used to examine anesthetic effects on SR Ca 2+ release (via ryanodine receptor channels) and reuptake (via SR Ca 2+ adenosine triphosphatase). Ca 2+ influx via NCX was examined during rapid activation in the presence of the reversible SR Ca 2+ adenosine triphosphatase inhibitor cyclopiazonic acid and ryanodine to inhibit the SR. Efflux mode NCX was examined during activation by extracellular Na + in the absence of SR reuptake. Results: Intracellular Ca 2+ concentration transients during electrical stimulation were inhibited to a greater extent in neonates by halothane (80%) and sevoflurane (50%). Potentiation of [Ca 2+] i responses by BayK8644 (160 and 120% control in neonates and adults, respectively) was also blunted by anesthetics to a greater extent in neonates. [Ca 2+] i responses to caffeine in neonates (∼30% adult responses) were inhibited to a lesser extent compared with adults (35 vs. 60% by halothane). Both anesthetics inhibited Ca 2+ reuptake at 2 minimum alveolar concentration, again to a greater extent in adults. Reduction in NCX-mediated influx was more pronounced in neonates (90%) compared with adults (65%) but was comparable between anesthetics. Both anesthetics also reduced NCX-mediated efflux to a greater extent in neonates. Potentiation of NCX-mediated Ca 2+ efflux by extracellular Na + and NCX-mediated Ca 2+ influx by intracellular Na + were both prevented by halothane, especially in neonates. Conclusions: These data indicate that greater myocardial depression in neonates induced by volatile anesthetics may be mediated by inhibition of NCX and Ca 2+ influx channels rather than inhibition of SR Ca 2+ release.

Original languageEnglish (US)
Pages (from-to)893-906
Number of pages14
JournalAnesthesiology
Volume96
Issue number4
DOIs
StatePublished - 2002

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Sarcoplasmic Reticulum
Anesthetics
Myocardium
Halothane
Caffeine
Electric Stimulation
Adenosine Triphosphatases
Ryanodine
Ryanodine Receptor Calcium Release Channel
Cardiac Myocytes
Cell Membrane

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Mechanisms underlying greater sensitivity of neonatal cardiac muscle to volatile anesthetics. / Prakash, Y.s.; Seckin, Inanc; Hunter, Larry W.; Sieck, Gary C.

In: Anesthesiology, Vol. 96, No. 4, 2002, p. 893-906.

Research output: Contribution to journalArticle

Prakash, Y.s. ; Seckin, Inanc ; Hunter, Larry W. ; Sieck, Gary C. / Mechanisms underlying greater sensitivity of neonatal cardiac muscle to volatile anesthetics. In: Anesthesiology. 2002 ; Vol. 96, No. 4. pp. 893-906.
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abstract = "Background: In neonatal heart, plasma membrane Na +-Ca 2+ exchange (NCX) and Ca 2+ channels play greater roles in intracellular Ca 2+ concentration [Ca 2+] i regulation compared with the sarcoplasmic reticulum (SR). In neonatal (aged 0-3 days) and adult (aged 84 days) rat cardiac myocytes, we determined the mechanisms underlying greater sensitivity of the neonatal myocardium to inhibition by volatile anesthetics. Methods: The effects of 1 and 2 minimum alveolar concentration halothane and sevoflurane on Ca 2+ influx during electrical stimulation in the presence or blockade of NCX and the Ca 2+ channel agonist BayK8644 were examined. [Ca 2+] i responses to caffeine were used to examine anesthetic effects on SR Ca 2+ release (via ryanodine receptor channels) and reuptake (via SR Ca 2+ adenosine triphosphatase). Ca 2+ influx via NCX was examined during rapid activation in the presence of the reversible SR Ca 2+ adenosine triphosphatase inhibitor cyclopiazonic acid and ryanodine to inhibit the SR. Efflux mode NCX was examined during activation by extracellular Na + in the absence of SR reuptake. Results: Intracellular Ca 2+ concentration transients during electrical stimulation were inhibited to a greater extent in neonates by halothane (80{\%}) and sevoflurane (50{\%}). Potentiation of [Ca 2+] i responses by BayK8644 (160 and 120{\%} control in neonates and adults, respectively) was also blunted by anesthetics to a greater extent in neonates. [Ca 2+] i responses to caffeine in neonates (∼30{\%} adult responses) were inhibited to a lesser extent compared with adults (35 vs. 60{\%} by halothane). Both anesthetics inhibited Ca 2+ reuptake at 2 minimum alveolar concentration, again to a greater extent in adults. Reduction in NCX-mediated influx was more pronounced in neonates (90{\%}) compared with adults (65{\%}) but was comparable between anesthetics. Both anesthetics also reduced NCX-mediated efflux to a greater extent in neonates. Potentiation of NCX-mediated Ca 2+ efflux by extracellular Na + and NCX-mediated Ca 2+ influx by intracellular Na + were both prevented by halothane, especially in neonates. Conclusions: These data indicate that greater myocardial depression in neonates induced by volatile anesthetics may be mediated by inhibition of NCX and Ca 2+ influx channels rather than inhibition of SR Ca 2+ release.",
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T1 - Mechanisms underlying greater sensitivity of neonatal cardiac muscle to volatile anesthetics

AU - Prakash, Y.s.

AU - Seckin, Inanc

AU - Hunter, Larry W.

AU - Sieck, Gary C

PY - 2002

Y1 - 2002

N2 - Background: In neonatal heart, plasma membrane Na +-Ca 2+ exchange (NCX) and Ca 2+ channels play greater roles in intracellular Ca 2+ concentration [Ca 2+] i regulation compared with the sarcoplasmic reticulum (SR). In neonatal (aged 0-3 days) and adult (aged 84 days) rat cardiac myocytes, we determined the mechanisms underlying greater sensitivity of the neonatal myocardium to inhibition by volatile anesthetics. Methods: The effects of 1 and 2 minimum alveolar concentration halothane and sevoflurane on Ca 2+ influx during electrical stimulation in the presence or blockade of NCX and the Ca 2+ channel agonist BayK8644 were examined. [Ca 2+] i responses to caffeine were used to examine anesthetic effects on SR Ca 2+ release (via ryanodine receptor channels) and reuptake (via SR Ca 2+ adenosine triphosphatase). Ca 2+ influx via NCX was examined during rapid activation in the presence of the reversible SR Ca 2+ adenosine triphosphatase inhibitor cyclopiazonic acid and ryanodine to inhibit the SR. Efflux mode NCX was examined during activation by extracellular Na + in the absence of SR reuptake. Results: Intracellular Ca 2+ concentration transients during electrical stimulation were inhibited to a greater extent in neonates by halothane (80%) and sevoflurane (50%). Potentiation of [Ca 2+] i responses by BayK8644 (160 and 120% control in neonates and adults, respectively) was also blunted by anesthetics to a greater extent in neonates. [Ca 2+] i responses to caffeine in neonates (∼30% adult responses) were inhibited to a lesser extent compared with adults (35 vs. 60% by halothane). Both anesthetics inhibited Ca 2+ reuptake at 2 minimum alveolar concentration, again to a greater extent in adults. Reduction in NCX-mediated influx was more pronounced in neonates (90%) compared with adults (65%) but was comparable between anesthetics. Both anesthetics also reduced NCX-mediated efflux to a greater extent in neonates. Potentiation of NCX-mediated Ca 2+ efflux by extracellular Na + and NCX-mediated Ca 2+ influx by intracellular Na + were both prevented by halothane, especially in neonates. Conclusions: These data indicate that greater myocardial depression in neonates induced by volatile anesthetics may be mediated by inhibition of NCX and Ca 2+ influx channels rather than inhibition of SR Ca 2+ release.

AB - Background: In neonatal heart, plasma membrane Na +-Ca 2+ exchange (NCX) and Ca 2+ channels play greater roles in intracellular Ca 2+ concentration [Ca 2+] i regulation compared with the sarcoplasmic reticulum (SR). In neonatal (aged 0-3 days) and adult (aged 84 days) rat cardiac myocytes, we determined the mechanisms underlying greater sensitivity of the neonatal myocardium to inhibition by volatile anesthetics. Methods: The effects of 1 and 2 minimum alveolar concentration halothane and sevoflurane on Ca 2+ influx during electrical stimulation in the presence or blockade of NCX and the Ca 2+ channel agonist BayK8644 were examined. [Ca 2+] i responses to caffeine were used to examine anesthetic effects on SR Ca 2+ release (via ryanodine receptor channels) and reuptake (via SR Ca 2+ adenosine triphosphatase). Ca 2+ influx via NCX was examined during rapid activation in the presence of the reversible SR Ca 2+ adenosine triphosphatase inhibitor cyclopiazonic acid and ryanodine to inhibit the SR. Efflux mode NCX was examined during activation by extracellular Na + in the absence of SR reuptake. Results: Intracellular Ca 2+ concentration transients during electrical stimulation were inhibited to a greater extent in neonates by halothane (80%) and sevoflurane (50%). Potentiation of [Ca 2+] i responses by BayK8644 (160 and 120% control in neonates and adults, respectively) was also blunted by anesthetics to a greater extent in neonates. [Ca 2+] i responses to caffeine in neonates (∼30% adult responses) were inhibited to a lesser extent compared with adults (35 vs. 60% by halothane). Both anesthetics inhibited Ca 2+ reuptake at 2 minimum alveolar concentration, again to a greater extent in adults. Reduction in NCX-mediated influx was more pronounced in neonates (90%) compared with adults (65%) but was comparable between anesthetics. Both anesthetics also reduced NCX-mediated efflux to a greater extent in neonates. Potentiation of NCX-mediated Ca 2+ efflux by extracellular Na + and NCX-mediated Ca 2+ influx by intracellular Na + were both prevented by halothane, especially in neonates. Conclusions: These data indicate that greater myocardial depression in neonates induced by volatile anesthetics may be mediated by inhibition of NCX and Ca 2+ influx channels rather than inhibition of SR Ca 2+ release.

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