Summary
The present study focuses on the sequential development of myocardial ultrastructural changes produced by oxygen radicals. Isolated rat hearts were perfused with oxygen radicals, generated by hypoxanthine and xanthine oxidase, for 5 and 10 min followed by a 35-min recovery period. The frequency of, and the association between, ultrastructural changes were examined by semiquantitative morphometry using the micrograph as unit. In each micrograph sarcolemmal, myocytic mitochondrial and myofilamental alterations were observed and graded as slight, moderate or severe. The myocytic nucleus and the endothelial cells were scored as normal or altered.Five min group: Among the cellular organelles examined, the myocytic mitochondria showed the highest frequency of alteration (in 15.3% of the micrographs). Among the grades of myocytic mitochondrial ultrastructural changes, slight alterations predominated (12.5%). Slight myocytic mitochondrial alterations were not significantly associated with the occurrence of ultrastructural changes of other cellular organelles. Endothelial ultrastructural alterations were sparse (1.5%).Ten min group: The frequency of altered organelles was greater when compared to the 5 min group. The myocytic mitochondria were still the most frequently altered component (61.7%), and myocytic mitochondrial ultrastructural alterations of all grades were strongly associated with the occurrence of other myocytic ultrastructural changes. In conclusion, the present study showed that myocytic mitochondrial changes predominated after both 5 and 10 min of oxygen radical exposure followed by recovery. In the 5 min group slight myocytic mitochondrial changes appeared independent of other myocardial changes, but in the 10 min group, however, myocytic mitochondrial changes were strongly associated with other myocardial ultrastructural changes. These results indicate that myocytic mitochondria are especially vulnerable to oxygen radicals, and further that myocytic mitochondrial ultrastructural changes may be a crucial step in the development of oxygen radical-induced myocardial damage.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
baddeley AJ, Gundersen HJ, Cruz-Orive LM (1986) Estimation of surface area from vertical sections. J Microsc 142:259–276
Bagchi M, Prasad MR, Engelman RM, Das DK (1989) Effect of free radicals on the fluidity of myocardial membranes. Free Radic Res Commun 7:375–380
Burton KP, McCord JM, Ghai G (1984) Myocardial alterations due to free-radical generation. Am J Physiol 246:H776-H783
Dean RT, Hunt JV, Grant AJ, Yamamoto Y, Niki E (1991) Free radical damage to proteins: the influence of the relative localization of radical generation, antioxidants, and target proteins. Free Radic Biol Med 11:161–168
Franson RC, Harris LK, Raghupathi R (1989) Fatty acid oxidation and myocardial phospholipase A2 activity. Mol Cell Biochem 88:155–159
Gupta M, Singal PK (1989) Time course of structure, function, and metabolic changes due to an exogenous source of oxygen metabolites in rat heart. Can J Physiol Pharmacol 67:1549–1559
Harris EJ, Booth R, Cooper MB (1982) The effect of superoxide generation on the ability of mitochondria to take up and retain Ca2+. FEBS Lett 146:267–272
Hearse DJ, Humphrey SM, Naylor WG, Slade A, Border D (1975) Ultrastructural damage associated with reoxygenation of the anoxic myocardium. J Mol Cell Cardiol 7:315–324
Jennings B, Ganote CE (1974) Structural changes in the myocardium during acute ischemia. Circ Res 35 Suppl 3:156–174
Kako KJ (1985) Membrane damage caused by lipid peroxidation in myocardial ischemia. Jikeikai Med J 32:609–639
Koyama T, Zhu MY, Kinjo M, Araiso T (1991) Protective effect of idebenone against alterations in dynamic microstructure induced by lipid peroxidation in rat cardiac mitochondria. Jpn Heart J 32:91–100
Mehrotra S, Kakkar P, Viswanathan PN (1991) Mitochondrial damage by active oxygen species in vitro. Free Radic Biol Med 10:277–285
Miki S, Ashraf M, Salka S, Sperelakis N (1988) Myocardial dysfunction and ultrastructural alterations mediated by oxygen metabolites. J Mol Cell Cardiol 20:1009–1024
Rubanyi GM (1988) Vascular effects of oxygen-derived free radicals. Free Radic Biol Med 4:107–120
Schaper J, Schaper W (1983) Reperfusion of ischemic myocardium: ultrastructural and histochemical aspects. J Am Coll Cardiol 1:1037–46
Steenbergen C, Hill ML, Jennings RB (1985) Volume regulation and plasma membrane injury in aerobic, anaerobic, and ischemic myocardium in vitro. Effect of cell swelling on plasma membrane integrity Circ Res 7:864–875
Thompson JA, Hess ML (1986) The oxygen radical system: a fundamental mechanism in production of myocardial necrosis. Prog Cardiovasc Dis 28:449–462
Vandeplassche G, Bernier M, Thome F, Borgers M, Kusama Y, Hearse DJ (1990) Singlet oxygen and myocardial injury: ultrastructural, cytochemical and electrocardiographic consequences of photoactivation of rose bengal. J Mol Cell Cardiol 22:287–301
Vlessis AA, Muller P, Bartos D, Trunkey D (1991) Mechanism of peroxide-induced cellular injury in cultured adult cardiac myocytes. FASEB J 5:2600–2605
Ytrehus K, Hegstad AC (1991). Lipid peroxidation and membrane damage of the heart. Acta Physiol Scand 142 (S599):81–91
Ytrehus K, Myklebust R, Mjøs OD (1986) Influence of oxygen radicals generated by xanthine oxidase in the isolated perfused rat heart. Cardiovasc Res 20:597–603
Ytrehus K, Myklebust R, Mjøs OD (1987) Ultrastructural changes induced in the isolated rat heart by enzymatically generated oxygen radicals. J Mol Cell Cardiol 19:379–389
Ytrehus K, Rotevatn S, Løvaas E, Sœtersdal T, Mjøs OD (1989) Mitochondrial calcium in hearts subjected to lipid peroxidation with contracture development. Basic Res Cardiol 84:646–652
Zar JH (1984) Biostatistical analysis. Prentice-Hall, Inc, Englewood Cliffs, New Jersey, pp 390–395
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hegstad, A.C., Ytrehus, K., Myklebust, R. et al. Ultrastructural changes in the myocardial myocytic mitochondria: crucial step in the development of oxygen radical-induced damage in isolated rat hearts?. Basic Res Cardiol 89, 128–138 (1994). https://doi.org/10.1007/BF00788732
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00788732