Altering CO2 during reperfusion of ischemic cardiomyocytes modifies mitochondrial oxidant injury

Romeen Lavani, Wei Tien Chang, Travis Anderson, Zuo Hui Shao, Kimberly R. Wojcik, Chang Qing Li, Robert Pietrowski, David G. Beiser, Ahamed H. Idris, Kimm J. Hamann, Lance B. Becker, Terry L. Vanden Hoek

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

OBJECTIVE: Acute changes in tissue CO2 and pH during reperfusion of the ischemic heart may affect ischemia/reperfusion injury. We tested whether gradual vs. acute decreases in CO2 after cardiomyocyte ischemia affect reperfusion oxidants and injury. DESIGN: Comparative laboratory investigation. SETTING: Institutional laboratory. SUBJECTS: Embryonic chick cardiomyocytes. INTERVENTIONS: Microscope fields of approximately 500 chick cardiomyocytes were monitored throughout 1 hr of simulated ischemia (Po2 of 3-5 torr, Pco2 of 144 torr, pH 6.8), followed by 3 hrs of reperfusion (Po2 of 149 torr, Pco2 of 36 torr, pH 7.4), and compared with cells reperfused with relative hypercarbia (Pco2 of 71 torr, pH 6.8) or hypocarbia (Pco2 of 7 torr, pH 7.9). MEASUREMENTS AND MAIN RESULTS: The measured outcomes included cell viability (via propidium iodide) and oxidant generation (reactive oxygen species via 2′,7′- dichlorofluorescin oxidation and nitric oxide [NO] via 4,5-diaminofluorescein diacetate oxidation). Compared with normocarbic reperfusion, hypercarbia significantly reduced cell death from 54.8% ± 4.0% to 26.3% ± 2.8% (p < .001), significantly decreased reperfusion reactive oxygen species (p < .05), and increased NO at a later phase of reperfusion (p < .01). The NO synthase inhibitor N-nitro-l-arginine methyl ester (200 μM) reversed this oxidant attenuation (p < .05), NO increase (p < .05), and the cardioprotection conferred by hypercarbic reperfusion (increasing death to 54.3% ± 6.0% [p < .05]). Conversely, hypocarbic reperfusion increased cell death to 80.4% ± 4.5% (p < .01). It also increased reactive oxygen species by almost two-fold (p = .052), without affecting the NO level thereafter. Increased reactive oxygen species was attenuated by the mitochondrial complex III inhibitor stigmatellin (20 nM) when given at reperfusion (p < .05). Cell death also decreased from 85.9% ± 4.5% to 52.2% ± 6.5% (p < .01). The nicotinamide adenine dinucleotide phosphate oxidase inhibitor apocynin (300 μM) had no effect on reperfusion reactive oxygen species. CONCLUSIONS: Altering CO2 content during reperfusion can significantly affect myocardial postresuscitation injury, in part by modifying mitochondrial oxidants and NO synthase-induced NO production.

Original languageEnglish (US)
Pages (from-to)1709-1716
Number of pages8
JournalCritical Care Medicine
Volume35
Issue number7
DOIs
StatePublished - Jul 2007

Fingerprint

Cardiac Myocytes
Oxidants
Reperfusion
Wounds and Injuries
Reactive Oxygen Species
Nitric Oxide
Cell Death
Hypercapnia
Reperfusion Injury
Nitric Oxide Synthase
Ischemia
Propidium
Electron Transport Complex III
NADP
Cell Survival
Oxidoreductases

Keywords

  • Hypercarbia
  • Hypocarbia
  • Mitochondria
  • Oxidants
  • Reperfusion injury

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Lavani, R., Chang, W. T., Anderson, T., Shao, Z. H., Wojcik, K. R., Li, C. Q., ... Vanden Hoek, T. L. (2007). Altering CO2 during reperfusion of ischemic cardiomyocytes modifies mitochondrial oxidant injury. Critical Care Medicine, 35(7), 1709-1716. https://doi.org/10.1097/01.CCM.0000269209.53450.EC

Altering CO2 during reperfusion of ischemic cardiomyocytes modifies mitochondrial oxidant injury. / Lavani, Romeen; Chang, Wei Tien; Anderson, Travis; Shao, Zuo Hui; Wojcik, Kimberly R.; Li, Chang Qing; Pietrowski, Robert; Beiser, David G.; Idris, Ahamed H.; Hamann, Kimm J.; Becker, Lance B.; Vanden Hoek, Terry L.

In: Critical Care Medicine, Vol. 35, No. 7, 07.2007, p. 1709-1716.

Research output: Contribution to journalArticle

Lavani, R, Chang, WT, Anderson, T, Shao, ZH, Wojcik, KR, Li, CQ, Pietrowski, R, Beiser, DG, Idris, AH, Hamann, KJ, Becker, LB & Vanden Hoek, TL 2007, 'Altering CO2 during reperfusion of ischemic cardiomyocytes modifies mitochondrial oxidant injury', Critical Care Medicine, vol. 35, no. 7, pp. 1709-1716. https://doi.org/10.1097/01.CCM.0000269209.53450.EC
Lavani, Romeen ; Chang, Wei Tien ; Anderson, Travis ; Shao, Zuo Hui ; Wojcik, Kimberly R. ; Li, Chang Qing ; Pietrowski, Robert ; Beiser, David G. ; Idris, Ahamed H. ; Hamann, Kimm J. ; Becker, Lance B. ; Vanden Hoek, Terry L. / Altering CO2 during reperfusion of ischemic cardiomyocytes modifies mitochondrial oxidant injury. In: Critical Care Medicine. 2007 ; Vol. 35, No. 7. pp. 1709-1716.
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abstract = "OBJECTIVE: Acute changes in tissue CO2 and pH during reperfusion of the ischemic heart may affect ischemia/reperfusion injury. We tested whether gradual vs. acute decreases in CO2 after cardiomyocyte ischemia affect reperfusion oxidants and injury. DESIGN: Comparative laboratory investigation. SETTING: Institutional laboratory. SUBJECTS: Embryonic chick cardiomyocytes. INTERVENTIONS: Microscope fields of approximately 500 chick cardiomyocytes were monitored throughout 1 hr of simulated ischemia (Po2 of 3-5 torr, Pco2 of 144 torr, pH 6.8), followed by 3 hrs of reperfusion (Po2 of 149 torr, Pco2 of 36 torr, pH 7.4), and compared with cells reperfused with relative hypercarbia (Pco2 of 71 torr, pH 6.8) or hypocarbia (Pco2 of 7 torr, pH 7.9). MEASUREMENTS AND MAIN RESULTS: The measured outcomes included cell viability (via propidium iodide) and oxidant generation (reactive oxygen species via 2′,7′- dichlorofluorescin oxidation and nitric oxide [NO] via 4,5-diaminofluorescein diacetate oxidation). Compared with normocarbic reperfusion, hypercarbia significantly reduced cell death from 54.8{\%} ± 4.0{\%} to 26.3{\%} ± 2.8{\%} (p < .001), significantly decreased reperfusion reactive oxygen species (p < .05), and increased NO at a later phase of reperfusion (p < .01). The NO synthase inhibitor N-nitro-l-arginine methyl ester (200 μM) reversed this oxidant attenuation (p < .05), NO increase (p < .05), and the cardioprotection conferred by hypercarbic reperfusion (increasing death to 54.3{\%} ± 6.0{\%} [p < .05]). Conversely, hypocarbic reperfusion increased cell death to 80.4{\%} ± 4.5{\%} (p < .01). It also increased reactive oxygen species by almost two-fold (p = .052), without affecting the NO level thereafter. Increased reactive oxygen species was attenuated by the mitochondrial complex III inhibitor stigmatellin (20 nM) when given at reperfusion (p < .05). Cell death also decreased from 85.9{\%} ± 4.5{\%} to 52.2{\%} ± 6.5{\%} (p < .01). The nicotinamide adenine dinucleotide phosphate oxidase inhibitor apocynin (300 μM) had no effect on reperfusion reactive oxygen species. CONCLUSIONS: Altering CO2 content during reperfusion can significantly affect myocardial postresuscitation injury, in part by modifying mitochondrial oxidants and NO synthase-induced NO production.",
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T1 - Altering CO2 during reperfusion of ischemic cardiomyocytes modifies mitochondrial oxidant injury

AU - Lavani, Romeen

AU - Chang, Wei Tien

AU - Anderson, Travis

AU - Shao, Zuo Hui

AU - Wojcik, Kimberly R.

AU - Li, Chang Qing

AU - Pietrowski, Robert

AU - Beiser, David G.

AU - Idris, Ahamed H.

AU - Hamann, Kimm J.

AU - Becker, Lance B.

AU - Vanden Hoek, Terry L.

PY - 2007/7

Y1 - 2007/7

N2 - OBJECTIVE: Acute changes in tissue CO2 and pH during reperfusion of the ischemic heart may affect ischemia/reperfusion injury. We tested whether gradual vs. acute decreases in CO2 after cardiomyocyte ischemia affect reperfusion oxidants and injury. DESIGN: Comparative laboratory investigation. SETTING: Institutional laboratory. SUBJECTS: Embryonic chick cardiomyocytes. INTERVENTIONS: Microscope fields of approximately 500 chick cardiomyocytes were monitored throughout 1 hr of simulated ischemia (Po2 of 3-5 torr, Pco2 of 144 torr, pH 6.8), followed by 3 hrs of reperfusion (Po2 of 149 torr, Pco2 of 36 torr, pH 7.4), and compared with cells reperfused with relative hypercarbia (Pco2 of 71 torr, pH 6.8) or hypocarbia (Pco2 of 7 torr, pH 7.9). MEASUREMENTS AND MAIN RESULTS: The measured outcomes included cell viability (via propidium iodide) and oxidant generation (reactive oxygen species via 2′,7′- dichlorofluorescin oxidation and nitric oxide [NO] via 4,5-diaminofluorescein diacetate oxidation). Compared with normocarbic reperfusion, hypercarbia significantly reduced cell death from 54.8% ± 4.0% to 26.3% ± 2.8% (p < .001), significantly decreased reperfusion reactive oxygen species (p < .05), and increased NO at a later phase of reperfusion (p < .01). The NO synthase inhibitor N-nitro-l-arginine methyl ester (200 μM) reversed this oxidant attenuation (p < .05), NO increase (p < .05), and the cardioprotection conferred by hypercarbic reperfusion (increasing death to 54.3% ± 6.0% [p < .05]). Conversely, hypocarbic reperfusion increased cell death to 80.4% ± 4.5% (p < .01). It also increased reactive oxygen species by almost two-fold (p = .052), without affecting the NO level thereafter. Increased reactive oxygen species was attenuated by the mitochondrial complex III inhibitor stigmatellin (20 nM) when given at reperfusion (p < .05). Cell death also decreased from 85.9% ± 4.5% to 52.2% ± 6.5% (p < .01). The nicotinamide adenine dinucleotide phosphate oxidase inhibitor apocynin (300 μM) had no effect on reperfusion reactive oxygen species. CONCLUSIONS: Altering CO2 content during reperfusion can significantly affect myocardial postresuscitation injury, in part by modifying mitochondrial oxidants and NO synthase-induced NO production.

AB - OBJECTIVE: Acute changes in tissue CO2 and pH during reperfusion of the ischemic heart may affect ischemia/reperfusion injury. We tested whether gradual vs. acute decreases in CO2 after cardiomyocyte ischemia affect reperfusion oxidants and injury. DESIGN: Comparative laboratory investigation. SETTING: Institutional laboratory. SUBJECTS: Embryonic chick cardiomyocytes. INTERVENTIONS: Microscope fields of approximately 500 chick cardiomyocytes were monitored throughout 1 hr of simulated ischemia (Po2 of 3-5 torr, Pco2 of 144 torr, pH 6.8), followed by 3 hrs of reperfusion (Po2 of 149 torr, Pco2 of 36 torr, pH 7.4), and compared with cells reperfused with relative hypercarbia (Pco2 of 71 torr, pH 6.8) or hypocarbia (Pco2 of 7 torr, pH 7.9). MEASUREMENTS AND MAIN RESULTS: The measured outcomes included cell viability (via propidium iodide) and oxidant generation (reactive oxygen species via 2′,7′- dichlorofluorescin oxidation and nitric oxide [NO] via 4,5-diaminofluorescein diacetate oxidation). Compared with normocarbic reperfusion, hypercarbia significantly reduced cell death from 54.8% ± 4.0% to 26.3% ± 2.8% (p < .001), significantly decreased reperfusion reactive oxygen species (p < .05), and increased NO at a later phase of reperfusion (p < .01). The NO synthase inhibitor N-nitro-l-arginine methyl ester (200 μM) reversed this oxidant attenuation (p < .05), NO increase (p < .05), and the cardioprotection conferred by hypercarbic reperfusion (increasing death to 54.3% ± 6.0% [p < .05]). Conversely, hypocarbic reperfusion increased cell death to 80.4% ± 4.5% (p < .01). It also increased reactive oxygen species by almost two-fold (p = .052), without affecting the NO level thereafter. Increased reactive oxygen species was attenuated by the mitochondrial complex III inhibitor stigmatellin (20 nM) when given at reperfusion (p < .05). Cell death also decreased from 85.9% ± 4.5% to 52.2% ± 6.5% (p < .01). The nicotinamide adenine dinucleotide phosphate oxidase inhibitor apocynin (300 μM) had no effect on reperfusion reactive oxygen species. CONCLUSIONS: Altering CO2 content during reperfusion can significantly affect myocardial postresuscitation injury, in part by modifying mitochondrial oxidants and NO synthase-induced NO production.

KW - Hypercarbia

KW - Hypocarbia

KW - Mitochondria

KW - Oxidants

KW - Reperfusion injury

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