Carboxyhemoglobin Particle Infusion, but not Carbon Monoxide Inhalation ameliorates Myocardial Infarction via Attenuated Oxidative Stress and In Situ Inflammation in a Rat Model
Main Article Content
Abstract
ABSTRACT
Objective: Effects of PEGylated-carboxyhemoglobin bovine (SG) infusion and carbon monoxide (CO) inhalation were compared in a rat model of myocardial infarction (MI).
Methods: Lewis rats with induced MI received either 10 mL/kg of SG or of saline (SL), or 400 ppm CO inhalation (CO) daily for 3 days, 4 doses in total. On the fourth day, all animals had left ventricular (LV) functions studied by pressure-volume relationship analyses or in-situ myocardial gene expression by polymerase-chain reaction (PCR).
Results: Both SG infusion and CO inhalation increased the arterial carboxyhemoglobin fraction to 10%, which decreased the total O2 content by 10% for 3 hours before returning to control level, except for the plasma hemoglobin (Hb) over 200 mg/dL 24 hours later, in SG rats. Four days after MI, the SL and CO rats had enhanced cardiac contraction and relaxation, while the SG rats had LV end-systolic pressure, and the isovolumic contraction as well as relaxation remained suppressed at the post-MI levels. PCR showed significant reductions in in-situ antioxidant transcriptional master regulator (Nrf2), its down-stream antioxidant response genes (Nqo-1), hypoxic signal transduction in SG compared to SL or CO rats with enhanced pro-inflammatory, pro-apoptotic genes, and myocardial damage. These cardiac indices were reversed 4 weeks after MI, when SG had less LV dilatation, dysfunction, and myoglobin loss than those with SL or CO.
Conclusion: The results suggest that repeated SG infusion, but not CO inhalation, generates less oxidative stress, reduces hypoxic responses, supports early hemodynamics, and alleviates cardiac compensation early after MI, resulting in attenuated LV dilatation, dysfunction, and myoglobin loss late after MI in this rat model.
Keywords: Artificial Oxygen Carrier, Myocardial Infarction, HBOCs, Carbon Monoxide, Oxidative Stress, Antioxidant Response genes, Cardiac Function
Article Details
How to Cite
KAWAGUCHI, Akira T et al.
Carboxyhemoglobin Particle Infusion, but not Carbon Monoxide Inhalation ameliorates Myocardial Infarction via Attenuated Oxidative Stress and In Situ Inflammation in a Rat Model.
Medical Research Archives, [S.l.], v. 11, n. 11, nov. 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/4810>. Date accessed: 16 may 2024.
doi: https://doi.org/10.18103/mra.v11i11.4810.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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2. Abuchowski A. Sanguinate (PEGylated Carboxyhemoglobin Bovine): Mechanism of action and clinical update. Artif Organs 2017:41:346-350.
3. Sakai H, Horinouchi H, Tsuchida E, Kobayashi K. Hemoglobin vesicles and red blood cells as carriers of carbon monoxide prior to oxygen for resuscitation after hemorrhagic shock in a rat model. Shock 2009;31:507-14.
4. Vandegriff KD, Young MA, Lohman J, et al. CO-MP4, a polyethylene glycol-conjugated haemoglobin derivative and carbon monoxide carrier that reduces myocardial infarct size in rats. Br J Pharmacol 2008;154:1649-61.
5. Natanson C, Kern SJ, Lurie P, Banks SM, Wolfe SM. Cell-free hemoglobin-based blood substitutes and risk of myocardial infarction and death: a meta-analysis. JAMA 2008;299: 2304-12.
6. Foresti R, Bani-Hani MG, Motterlini R. Use of carbon monoxide as a therapeutic agent: promises and challenges. Intensive Care Med. 2008;34:649-58. Doi 10.1007/s00134-008-1011-1.
7. Bauer I, Pannan BHJ. Bench-to-bedside review: Carbon monoxide-from mitochondrial poisoning to therapeutic use. Crit Care 2009;13:220 Doi:10.1186/cc7887.
8. Motterlini R, Otterbein LE. The therapeutic potential of CO. Nature Medicine 2010;10: Doi:10.1038/nrd3228.
9. Zeynalov E, Dore S. Low dose of carbon monoxide protect against experimental focal brain ischemia Neurotox Res 2009;15;133-137. Doi:10.1007/s12640-009-9014-4.
10. Ruan Y, Wang L, Zhao, Yao Y, Chen S, Li J, et al. Carbon monoxide potently prevents ischemia-induced high-mobility group box 1 translocation and release and protects against lethal renal ischemia-reperfusion injury. Kidney international. 2014;86:525-37.
11. Kim SK, Joe Y, Chen Y, et al. Carbon monoxide decreases interleukin-1β levels in the lung through the induction of pyrin. Cellular & Molecular Immunol. 2017;14:349-59.
12. Ning W, Choi AMK, Li C. Carbon monoxide inhibits IL-17-induced IL-6 production through the MAPK pathway in human pulmonary epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2005;289:L268-L273.
13. Zhang X, Ding M, Zhu P, Nalley CM, et al. New insights into the Nrf-2/HO-1 signaling axis and its application in pediatric respiratory diseases. Oxidative Med Cellular Longevity 2019; Article ID3214196. Doi org/10.1155/2019/3214196
14. Coceani F. Carbon monoxide in vasoregulation. The promise and the challenge. Circ Res 2000;86:1184-6.
15. Liu XM, Chapman GB, Peyton KJ, Schafer AI, Durante W. Carbon monoxide inhibits apoptosis in vascular smooth muscle cells. Cardiovasc Res 2002;55:396-405.
16. Motterlini R, Foresti R, Vandegriff K, Intaglietta M, Winslow RM. Oxidative-stress response in vascular endothelial cells exposed to acellular hemoglobin solutions. Am J Physiol 1995;269: (Heart Circ Physiol 38):H648-H655.
17. Suliman HB, Carraway MS, Ali AS, Raynolds CM, Welty-Wolf KE, Piantadosi CA. The CO/HO system reverses inhibition of mitochondrial biogenesis and prevents murine doxorubicin cardiomyopathy. J Clin Investig. 2007;117:3730-41.
18. Kawaguchi AT, Tamaki T. Artificial Oxygen carrier improves fatigue resistance in slow muscle but not in fast muscle in a rat in situ model. Artif Organs. 2019.
19. Nakao A, Toyokawa H, Abe M, et al. Heart allograft protection with low-dose carbon monoxide inhalation: effects on inflammatory mediators and alloreactive T-cell responses. Transplantation 2006;81220-230.
20. Lavitrano M, Smolenski RT, Musumeci A, et al. Carbon monoxide improves cardiac energetics and safeguards the heart during reperfusion after cardiopulmonary bypass in pigs. FASEB J 2004 Doi: 10.1096/fj.03-0996fje.
21. Gilbert TC, Leite-Moreira AF, De Hert SG. Relaxation-systolic pressure relation. Circulation 1997;95:745-52.
22. Hartupee J and Mann DL. Neurohumoral activation in heart failure with reduced ejection fraction. Nat Rev Cardiol 2017; 14:30-38.
23. Parrish DC, Gritman K, Van Winkle DM, Woodward WR, Barder M, Habecker BA. Postinfarct sympathetic hyperactivity differentially stimulates expression of tyrosine hydroxylase and norepinephrine transporter. Am J Physiol Heart Circ Physiol 2008; 294: H99-H106.
24. Henning RJ, Levy MN. Effects of autonomic nerve stimulation, asynchrony, and load on dP/dtmax and dP/dtmin. Am J Physiol 1991;260 (Heart Circ Physiol 29):H1290-H1298.
25. Jardine DL, Charles CJ, Ashton RK, et al. Increased cardiac sympathetic nerve activity following acute myocardial infarction in a sheep model. J Physiol 2005;565:325-33.
26. Burwash IG, Morgan DE, Koilpillai CJ, Blackmore GL, Johnstone DE, Armour JA. Sympathetic stimulation alters left ventricular relaxation and chamber size. Am J Physiol 1993; 264(Regulatory Integrative Comp Physiol 33): R1-R7.
27. Zhang DY, Anderson AS. The sympathetic nervous system and heart failure. Cardiol Clin 2014;32:33-vii. Doi:10.1016/j.ccl.2013.09.010.
28. Klaus JA, Kibler KK, Abuchowski A, Koehler RC. Early treatment of transient focal cerebral ischemia with bovine PEGylated carboxy hemoglobin transfusion. Artif Cell Blood Substit Biotechnol 2010; 38:223-9.
29. Ananthakrishnan R, Li Q, Karen M, et al. Carbon monoxide form of PEGylated hemoglobin protects myocardium against ischemia/reperfusion injury in diabetic and normal mice. Artif Cell Nanomed Biotechnol 2013; Early Online: 1-9.
30. Kawaguchi AT, Salybekov AA, Yamano M, Kitagishi H, Sekine K, Tamaki T. PEGylated carboxyhemoglobin bovine (SANGUINATE) ameliorates myocardial infarction in a rat model. Artif Organs 2018;42:1174-84. doi: 10.1111/aor.13384
31. Sagawa K, Maugahan L, Suga H, Sunagawa K. Cardiac contraction and the pressure-volume relationship. Sagawa K, Maugahan L, Suga H, Sunagawa K, eds. 1988 by Oxford University Press, Inc. 200 Madison Avenue, NY, NY 10016
32. Luomanmaki K, Coburn RF. Effects of metabolism and distribution of carbon monoxide on blood and body stores. Am J Physiol 1969;217:354-363.
33. Mao Q, Kawaguchi AT, Mizobata S, Mottelini R, Foresti R, Kitagishi H. Sensitive quantification of carbon monoxide in vivo reveals a protective role of circulating hemoglobin in CO intoxication. Communication Biology 2021;4:425
34. Mao Q, Zhao X, Kiriyama A, et al. A synthetic porphyrin as an effective dual antidote against carbon monoxide and cyanide poisoning. PNAS 2023;120:e2209924120
35. Kitagishi H, Minegishi S, Yumura A, et al. Feedback response to selective depletion of endogenous carbon monoxide in the blood. J Am Chem Soc 2016;138:5417-25.
36. Cronenberger C, Mould DR, Roethig HJ, Sarkar M. Population pharmacokinetic analysis of carboxy-hemoglobin concentration in adult cigarette smokers. Br J Clin Pharmacol 2008;65:30-9.
37. Morse D, Pischke SE, Zhou Z, et al. Suppression on inflammatory cytokine production by carbon monoxide involves the JNK pathway and AP-1. J Biol Chem 2003;278:36993-8.
38. Cabrales P, Tsai AG, Integrietta M. Hemorrhagic shock resuscitation with carbon monoxide saturated blood. Resuscitation 2007;72:306-18.
39. Cooper CE, Silkstone GGA, Simons M, et al. Engineering hemoglobin to enable homogenous PEGylation without modifying protein functionality. Biomater Sci 2020;8:3896. Doi:10.1039/c9bm01773a
40. Pamplona A, Ferreira A, Balla J, et al. Heme oxygenase-1 and carbon monoxide suppresses the pathogenesis of experimental cerebral malaria. Nature Med. 2007;13:703-10.
41. Nalley CM, Abucowski A, Hsu S, Lanzkron S. Successful use of carboxyhemoglobin bovine as an emergency treatment for severe anemia in a patient with sickle cell disease and hyperhemolysis: A case report. Blood 2014;124:4928.
42. Fujimoto H, Ohno M, Ayabe S, et al. Carbon monoxide protects against cardiac ischemia-reperfusion injury in vivo via MAPK and Akt-eNOS pathways. Arterioscler Thromb Vasc Biol 2004;24:1848-53.
43. Chu LM, Shaefi S, Byrne JD, Alves de Souza RW, Otterbein LE. Carbon monoxide and a change of heart. Redox Biol 2021;48:102183 Doi.org/10.1016/j.redox. 2021102182
44. Delvau N, PenalozaA, Franssen V, Thys F, Roy PM, Hanson P. Unexpected carboxy-hemoglobin half-life during cardiopulmonary resuscitation: a case report. Intern J Emer Med 2023;16:22
45. Zhang J, Cao S, Kwansa H, Crafa D, Kibler KK, Koehler RC. Transfusion of hemoglobin-based oxygen carriers in the carboxy state is beneficial during transient focal cerebral ischemia. J Appl Physiol 2012;113:1709-17.
46. Wang Q, Hu L, Hu Y, et al. Carbon monoxide-saturated hemoglobin-based oxygen carriers attenuate high-altitude-induced cardiac injury by amelioration of the inflammation response and mitochondrial oxidative damage. Cardiology 2017;136:180-91.
47. Kawaguchi AT. Artificial oxygen carrier to regulate hypoxic signal transduction. Artif Organs 2014;38:617-20. Doi:10.1111/aor.12372
48. Fukui T, Kawaguchi AT, Takekoshi S, Miyasaka M, Sumiyoshi H, Tanaka R. Liposome-encapsulated hemoglobin accelerates skin wound healing in diabetic dB/dB mice. Artif Organs. 2017;41:319-326. Doi: 10.1111/aor.12864
49. Kawaguchi AT, Kurita D, Furuya H, Yamano M, Ogata Y, Haida M. Liposome-encapsulated hemoglobin alleviate brain edema after permanent occlusion of the middle cerebral artery. Artif Organs 209;33:153-8.
50. Fukuta T, Ishii T, Asai T, et al. Real-time trafficking of pegylated liposomes in the rodent focal brain ischemia analyzed by positron emission tomography. Artif Organs. 2014;38:662-6. Doi:10.1111/aor.12350.
51. Umar S, Laarse AVD. Nitric oxide and nitric oxide synthase isoforms in the normal, hypertrophic, and failing heart. Mol Cell Biochem 2010;333:191-201.
52. Janssen S, Pokreisz P, Schoonjans L, et al. Cardiomyocyte-specific overexpression of nitric oxide synthase 3 improves left ventricular performance and reduces compensatory hypertrophy after myocardial infarction. Circ Res 2004;94:1256-62.
53. Wu L, Wang R. Carbon monoxide: Endogenous production, physiological functions, and pharmacological applications. Pharmacol Rev. 2005;57:585-630.
54. Tsai AG, Cabrales P, Manjula BN, Acharya SA, Winslow RM, Intaglietta M. Dissociation of local nitric oxide concentration and vasoconstriction in the presence of cell-free hemoglobin oxygen carrier. Blood. 2006;108:3603-10.
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