Ketamine-induced cardiac depression is associated with increase in [Mg2+]i and activation of p38 MAP kinase and ERK 1/2 in guinea pig

Kim, Shang-Jin; Kang, Hyung-Sub; Lee, Mun-Young; Lee, Sei‐Jin; Seol, Jea-Won; Park, Sang-Yeol; Kim, In-Shik; Kim, Namsoo; Kim, Sung-Zoo; Kwak, Yong-Geun; Kim, Jin-Shang

doi:10.1016/j.bbrc.2006.08.082

Cited by 14 publications

(18 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In order to determine the relevant signaling pathways that participate in ketamine-induced changes in heart rate, we focused on the p38 kinase that has been shown to be activated in perfused guinea pig hearts upon ketamine treatment [18]. A member of the SAPK family, p38 kinase activity is inhibited by a synthetic inhibitor, SB203580.…”

Section: Effect Of the Sapk/p38 Kinase Inhibitor Sb203580 On Zebrafimentioning

confidence: 99%

“…In guinea pig hearts, ketamine has been shown to activate ERK (MAPK) [18]. In our study, we first sought to determine whether the synthetic ERK inhibitor, PD 98059 affects heart rate in zebrafish.…”

Section: Effect Of the Mapk/erk Inhibitor Pd 98059 On Zebrafish Embrymentioning

confidence: 99%

“…However, a different effect of ketamine on heart rate has been documented in several mammalian species. Ketamine reduces heart rates in rats [17] and guinea pigs [18]. In rhesus monkeys, extended intravenous infusions of ketamine result in decreased heart rates in pregnant females and in PND (post natal day) 5 and PND 35 infants [19] but in older humans (50-60 years of age); intravenous ketamine (1 mg/kg) does not affect heart rate [20].…”

Section: Introductionmentioning

confidence: 99%

“…P38 MAPK is a subfamily of the stress-activated MAPKs (SAPKs) [40][41][42]. In isolated rat hearts, drugs like ketamine and imipramine have been shown to activate the MAPK/ERK (extracellular signal-regulated kinase), which is accompanied by an increase in Mg 2+ that results in decreased heart rate [18,43]. Here, we explored the role of SAPK (stress-activated protein kinase)/p38 kinase since ketamine activation of the p38 kinase in isolated guinea pig hearts has also been linked to cardiac depression [18].…”

Section: Introductionmentioning

confidence: 99%

“…In isolated rat hearts, drugs like ketamine and imipramine have been shown to activate the MAPK/ERK (extracellular signal-regulated kinase), which is accompanied by an increase in Mg 2+ that results in decreased heart rate [18,43]. Here, we explored the role of SAPK (stress-activated protein kinase)/p38 kinase since ketamine activation of the p38 kinase in isolated guinea pig hearts has also been linked to cardiac depression [18]. Additionally, we examined whether ketamine affected heart rate and ERK activation in zebrafish embryos and whether L-carnitine interfered with ketamine's effects.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

l-Carnitine rescues ketamine-induced attenuated heart rate and MAPK (ERK) activity in zebrafish embryos

Kanungo

Cuevas

Ali

et al. 2012

Reproductive Toxicology

View full text Add to dashboard Cite

Ketamine, an antagonist of the N-methyl-D-aspartate (NMDA)-type glutamate receptors, is a pediatric anesthetic. Ketamine has been shown to be neurotoxic and cardiotoxic in mammals. Here, we show that after 2 h of exposure, 5 mM ketamine significantly reduced heart rate in 26 h old zebrafish embryos. In 52 h old embryos, 1 mM ketamine was effective after 2 h and 0.5 mM ketamine at 20 h of exposure. Ketamine also induced significant reductions in activated MAPK (ERK) levels. Treatment of the embryos with the ERK inhibitor, PD 98059, also significantly reduced heart rate whereas the p38/SAPK inhibitor, SB203580, was ineffective. Ketamine is known to inhibit lipolysis and a decrease of ATP content in the heart. Co-treatment with Lcarnitine that enhances fatty acid metabolism effectively rescued ketamine-induced attenuated heart rate and ERK activity. These findings demonstrate that L-carnitine counteracts ketamine's negative effects on heart rate and ERK activity in zebrafish embryos.

show abstract

Section: Effect Of the Sapk/p38 Kinase Inhibitor Sb203580 On Zebrafimentioning

confidence: 99%

Section: Effect Of the Mapk/erk Inhibitor Pd 98059 On Zebrafish Embrymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

l-Carnitine rescues ketamine-induced attenuated heart rate and MAPK (ERK) activity in zebrafish embryos

Kanungo

Cuevas

Ali

et al. 2012

Reproductive Toxicology

View full text Add to dashboard Cite

show abstract

Acetyl L‐carnitine targets adenosine triphosphate synthase in protecting zebrafish embryos from toxicities induced by verapamil and ketamine: An in vivo assessment

Guo

Dumas

Robinson

et al. 2016

J of Applied Toxicology

View full text Add to dashboard Cite

Verapamil is a Ca2+ channel blocker and is highly prescribed as an anti-anginal, antiarrhythmic and antihypertensive drug. Ketamine, an antagonist of the Ca2+-permeable N-methyl-D-aspartate-type glutamate receptors, is a pediatric anesthetic. Previously we have shown that acetyl L-carnitine (ALCAR) reverses ketamine-induced attenuation of heart rate and neurotoxicity in zebrafish embryos. Here, we used 48 h post-fertilization zebrafish embryos that were exposed to relevant drugs for 2 or 4 h. Heart beat and overall development were monitored in vivo. In 48 h post-fertilization embryos, 2 mM ketamine reduced heart rate in a 2 or 4 h exposure and 0.5 mM ALCAR neutralized this effect. ALCAR could reverse ketamine’s effect, possibly through a compensatory mechanism involving extracellular Ca2+ entry through L-type Ca2+ channels that ALCAR is known to activate. Hence, we used verapamil to block the L-type Ca2+ channels. Verapamil was more potent in attenuating heart rate and inducing morphological defects in the embryos compared to ketamine at specific times of exposure. ALCAR reversed cardiotoxicity and developmental toxicity in the embryos exposed to verapamil or verapamil plus ketamine, even in the presence of 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester, an inhibitor of intracellular Ca2+ release suggesting that ALCAR acts via effectors downstream of Ca2+. In fact, ALCAR’s protective effect was blunted by oligomycin A, an inhibitor of adenosine triphosphate synthase that acts downstream of Ca2+ during adenosine triphosphate generation. We have identified, for the first time, using in vivo studies, a downstream effector of ALCAR that is critical in abrogating ketamine- and verapamil-induced developmental toxicities. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

show abstract

Cardiovascular Effects of Anesthetics, Sedatives, Postoperative Analgesic Agents, and Other Pharmaceuticals

Gross

2009

Animal Models in Cardiovascular Research

View full text Add to dashboard Cite

Ketamine-induced cardiac depression is associated with increase in [Mg2+]i and activation of p38 MAP kinase and ERK 1/2 in guinea pig

Cited by 14 publications

References 27 publications

l-Carnitine rescues ketamine-induced attenuated heart rate and MAPK (ERK) activity in zebrafish embryos

l-Carnitine rescues ketamine-induced attenuated heart rate and MAPK (ERK) activity in zebrafish embryos

Acetyl L‐carnitine targets adenosine triphosphate synthase in protecting zebrafish embryos from toxicities induced by verapamil and ketamine: An in vivo assessment

Cardiovascular Effects of Anesthetics, Sedatives, Postoperative Analgesic Agents, and Other Pharmaceuticals

Contact Info

Product

Resources

About