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Myocardial oxidative stress changes during compensated right heart failure in rats

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Abstract

The suggested role of oxidative stress in the pathogenesis of heart failure is largely based on utilizing left heart failure models. The present study on rats evaluated changes in antioxidants as well as oxidative stress in relation to hemodynamic function subsequent to the right heart failure induced by monocrotaline (50 mg/kg, i.p.). During the post-injection period, monocrotaline (MCT)-treated rats demonstrated a persistent growth depression. Two to three weeks after the injection, MCT-treated rats showed signs of fatigue, peripheral cyanosis and dyspnea. In these rats, right heart hypertrophy was confirmed by a significant increase in right ventricular weight as well as right ventricle to body weight ratio. In MCT-treated rats, there was also a significant increase in right ventricular systolic as well as end diastolic pressures. No change in lung and liver wet/dry weight ratios between MCT-treated and control animals was observed. Based on the hemodynamic data as well as other clinical observations, the functional stage achieved was compensated heart failure. Myocardial antioxidant enzymes, catalase, glutathione peroxidase and superoxide dismutase, in the MCT-treated rats were not different compared to control rats. Vitamin E levels were significantly depressed in the RV and there was no change in retinol levels. There was a significant increase in lipid hydroperoxide concentrations in MCT-treated rats as compared to the control group. These data provide evidence that right heart failure is associated with an increase in oxidative stress.

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References

  1. Comini L, Angoletti G, Panzali A, Mantero G, Pasini E, Gaia G, Albertini A, Ferrari R: Activation of atrial natriuretic peptide synthesis during congestive heart failure in rats treated with monocrotaline. Am J Physiol 268: H391–H398, 1995

    Google Scholar 

  2. Kuchel O, Cantin M, Boo N, Debinski W, Jasmin G, Genest J: Catecholamine dopamine hydroxylase and atrial natriuretic factor content in separate heart chambers of cardiomyopathic hamster. Life Sci 41: 2333–2338, 1987

    Google Scholar 

  3. Kaul N, Siveski-Iliskovic N, Hill M, Slezak J, Singal PK: Free radicals and the heart. J Pharmacol Toxicol Meth 30: 55–67, 1993

    Google Scholar 

  4. Hill M, Singal PK: Antioxidant and oxidative stress changes during heart failure subsequent to myocardial infarction in rats. Am J Pathol 148: 291–403, 1996

    Google Scholar 

  5. Singal PK, Kirshenbaum LA: A relative diet deficit in antioxidant reserve may contribute in cardiac failure. Can J Cardiol 6: 47–49, 1990

    Google Scholar 

  6. Diaz-Velez CR, Gracia-Castineiras S, Mendoza-Ramos E, Hernandez-Lopez E: Increased malondialdehyde in peripheral blood of patients with congestive heart failure. Am Heart J 131: 146–152, 1996

    Google Scholar 

  7. Clairbome A: Catalase activity. In: RA Greenwald (ed). Handbook of Methods for Oxygen Radical Research. CRC Press, Boca Raton, 1985, pp 283–284.

    Google Scholar 

  8. Paglia DE, Valentine WN: Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70: 158–159, 1967

    Google Scholar 

  9. Marklund SL: Pyrrogallol autoxidation. In: RA Greenwald (ed). Handbook of Methods for Oxygen Radical Research. CRC Press, Boca Raton, 1985, pp 243–247

    Google Scholar 

  10. Palace VP, Brown SB: HPLC determination of tocopherol, retinol, dehydroretinol and retinyl palmitate in tissues of lake char (Salvelinus namaycush) exposed to coplanar 3,3′,4,4′,5–pentachlorobiphenyl. Env Tox Chem 13: 473–476, 1994

    Google Scholar 

  11. Valdivia E: Right ventricular hypertrophy in guinea pigs exposed to simulated high altitude. Circ Res 5: 612–616, 1957

    Google Scholar 

  12. Roberts JP Jr, Roberts CT, Jones RC, Zapol WM, Bloch KD: Continuous nitric oxide inhalation reduces pulmonary arterial structural changes, right ventricular hypertrophy and growth retardation in the hypoxic newborn rat. Circ Res 76: 215–222, 1995

    Google Scholar 

  13. Jett GK, Applebaum RE, Clark RE: Right ventricular assistance for experimental right ventricular dysfunction. J Thorac Cardiovasc Surg 92: 272–278, 1986

    Google Scholar 

  14. Ng CV, Angus PW, Chabrial H, Chou ST, Arnolada L, Morgan DJ, Smallwood RA: Right heart failure impairs hepatic oxygenation and theophylline clearance in rats. J Pharmacol Exp Ther 273: 1332–1336, 1995

    Google Scholar 

  15. Liang CS, Fan TH, Sullebarger JT, Sakamoto S: Decreased adrenergic neuronal uptake activity in experimental right heart failure. A chamber-specific contributor to beta adrenoceptor downregulation. J Clin Invest 84: 1267–1275, 1989

    Google Scholar 

  16. Pan LC, Wilson DW, Lame MW, Jones AD, Segall HJ: Cor Pulmonale is caused by monocrotaline and dehydromonocrotaline, but not by glutathione or cysteine conjugates of dihydropyrrolizine. Toxicol Appl Pharmacol 118: 87–97, 1993

    Google Scholar 

  17. Okumura K, Yamada Y, Matsui H, Shinoda M, Naruse K, Toke Y, Hashimoto H, Ito T: Altered myocardial neurotransmitter and 1,2–diacylglycerol concentrations in right ventricular hypertrophy and failure in rats. In: PK Singal, IMC Dixon, RE Beamish, NS Dhalla (eds). Mechanisms of Heart Failure. Kluwer Academic Publishers, Boston, 1995, pp 51–62.

    Google Scholar 

  18. Ceconi C, Condorelli E, Quinzanini M, Rodella A, Ferrari R, Harris P: Noradrenaline, atrial natriuretic peptide, bombesin and neurotensin in myocardium and blood of rats in congestive heart failure. Cardiovasc Res 23: 674–682, 1980

    Google Scholar 

  19. Todorovich-Hunter L, Dodo H, Ye C, McCready L, Keeley FW, Rabinovitch M: Increased pulmonary artery elastolytic activity in adult rats with monocrotaline-induced progressive hypertensive pulmonary vascular disease compared with infant rats with nonprogressive disease. Am Rev Respir Dis 146: 213–223, 1992

    Google Scholar 

  20. Wilson DW, Segall HJ, Pan LCW, Dunston SK: Progressive inflammatory and structural changes in the pulmonary vasculature of monocrotaline-treated rats. Microvasc Res 38: 57, 1989

    Google Scholar 

  21. Huxtable RJ: Activation and pulmonary toxicity of pyrrolizidine alkaloids. Pharmacol Ther 47: 371–389, 1990

    Google Scholar 

  22. Randhawa AK, Singal PK: Pressure overload-induced cardiac hypertrophy with and without dilation. J Am Coll Cardiol 20: 1569–1575, 1992

    Google Scholar 

  23. Khaper N, Singal PK: Effects of afterload-reducing drugs on pathogenesis of antioxidant changes and congestive heart failure in rats. J Am Coll Cardiol 29: 856–861, 1997

    Google Scholar 

  24. Dhalla AK, Singal PK: Antioxidant changes in hypertrophied and failing guinea pig hearts. Am J Physiol 266: H1280–HI285, 1994

    Google Scholar 

  25. Siveski-Iliskovic N, Kaul N, Singal PK: Probucol promotes endogenous antioxidants and provides protection against adriamycininduced cardiomyopathy in rats. Circulation 89: 2829–2835, 1994

    Google Scholar 

  26. Lemoyne BF, Van Gossum A, Kurian R, Ostro M, Axler J, JeeJeebhoy KN: Breath pentane analysis as an index of lipid peroxidation: A functional test of vitamin E status. Am J Clin Nutr 46: 267–272, 1987

    Google Scholar 

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Pichardo, J., Palace, V., Farahmand, F. et al. Myocardial oxidative stress changes during compensated right heart failure in rats. Mol Cell Biochem 196, 51–57 (1999). https://doi.org/10.1023/A:1006914111957

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