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The ischaemic vulnerability of the heart of spontaneously hypertensive rats (SHR) is enhanced after feeding an alpha-linolenic acid (LNA) enriched diet. Because oxygen radical-induced reactions (e.g. lipid peroxidation) are involved in the ischaemic damage, an increased susceptibility of the SHR heart to such damaging reactions might be the reason. As a sign of the enhanced susceptibility to lipid peroxidation of LNA-fed SHR, we found (measured as TBARS) higher plasma and heart lipid peroxide levels (3.84 +/- 0.50 micromol/l vs 2.98 +/- 0.78 micromol/l and 507 +/- 127 nmol/g prot. vs 215 +/- 80 nmol/g prot., respectively) after feeding LNA. Using Fe2+/Vit. C to induce lipid peroxidation in myocardial tissue homogenates, we demonstrated the enhanced susceptibility to lipid peroxidation of the LNA-fed SHR heart (68 +/- 12 nmol/min x g prot. vs 40 +/- 8 nmol/min x g prot.) also in vitro. The myocardial enrichment of n-3 polyunsaturated fatty acids (PUFA) resulting in a higher peroxidation index (PI 227 vs. 170) and the loss in myocardial activities of the antioxidative enzymes (SOD: 76 +/- 24 U x 10(3)/g prot. vs 235 +/- 150 U x 10(3)/g prot.; GSH-Px: 32 +/- 5 U/g prot. vs 110 +/- 30 U/g prot.) by feeding LNA could be the cause of the increase in myocardial susceptibility to lipid peroxidation of PUFA supplemented SHR.

The effect of prenatal hypoxia on the development of the beta-adrenoceptor during the ontogenesis of rats was investigated. It was shown that the offspring from hypoxic dams, in comparison with normoxic control animals, exhibited alterations of the density (Bmax) of the myocardial beta-receptors and of the catecholamine levels in heart tissue during development. The results suggest that the beta-adrenoceptor changes might be involved in the phenomenon of enhanced sensitivity of prenatal hypoxic animals to catecholamines in adult age.

The present study utilized a cultured adult myocardial cell model to examine the arachidonic acid metabolism under different cell-damaging and normoxic conditions. Cell injury was caused by short-time hypoxia, calcium ionophore A 23187-triggered cell-damage under hypoxia and cell disruption by freezing and thawing. The current study demonstrates that under the cell-damaging conditions cultured adult heart myocytes resemble myocardial cells under normoxic conditions in metabolizing arachidonic acid into triacylglycerols and phospholipids as the major route (a), in formation of ETYA-inhibitable indomethacin-resistant lipid metabolites in minor amounts (b) and in being independent of calcium overload in the metabolic pathways of arachidonic acid metabolism (c). The ETYA-inhibitable components were resolved by HPLC. There was no evidence in formation of lipoxygenase products. The results were supported by negative hybridisation experiments of the total mRNA isolated from adult myocardial cells with a cDNA probe of a red-cell-specific lipoxygenase mRNA. We conclude from these observations that cell injury does not result in expression of lipoxygenase activities in heart myocytes.

The purine oxidation via XOD formed from XDH in ischemia in an oxidative or proteolytic way is regarded as a source of reactive O2- species. Usually the XOD/XDH ratio is measured to determine the capacity of tissues to form these important inducers of cell damage. But we found that it is difficult to fix the in vivo XOD/XDH ratio, because preparation and measurement time and conditions (absence or presence of SH-protecting agent, of cations) influenced this ratio. A supposed additional proteolytic increase of XOD during the killing procedure could not confirmed.

Lipid peroxidation as well as enzyme and isoenzyme activities in heart and blood plasma were investigated in 8- and 20-week-old SHR after administration of 40 mg/kg body weight isoproterenol in comparison to WKY rats in order to examine the susceptibility of the hearts of hypertensive animals towards catecholamine-induced damage. The mortality of SHR after isoproterenol application was distinctly higher as compared with WKY rats. SHR showed significantly higher concentrations of lipid peroxides in the myocardium after isoproterenol. Distinctly higher plasma activities of CK, isoenzymes of LDH and ASAT as well as markedly lower CK activities in the myocardium point to an enhanced sensitivity of SHR to catecholamine-induced damage. The results obtained in this study favour the suggestion that an exaggerated nonenzymatic and perhaps enzymatic formation of peroxidized lipids in the myocardium might contribute to this increased sensitivity.

In vitro studies have demonstrated that free radicals generated by Fe2+/Vit. C alter the beta-RAS function. SH-oxidation, peroxidation of sarcolemmal lipids and reaction of aldehydes (formed by lipid peroxidation) with the beta-RAS may contribute to this effect. In order to clarify the role of these reactions in respect to their ability to alter the beta-RAS function the time course of SH-oxidation, lipid peroxidation and formation of aldehyde reaction products has been studied. As result it is shown that SH-oxidation is nearly completed within 5 minutes and lipid peroxidation within 30 minutes after exposure to Fe2+/Vit. C. During this time period there was only a very small amount of aldehyde reaction products detectable. Therefore SH-oxidation and/or lipid peroxidation should be responsible for the activity loss of the beta-RAS.

It is demonstrated on the heart tissue of rats that the extent of lipid peroxidation following induction of radical-forming mechanisms is correlated with the Vit. E concentration of the heart. When incubated with Fe2+/Vit.C, the heart tissue of normotensive (WKY) and hypertensive rats receiving Vit. E supplementation (SHR + Vit. E), consistently with their higher Vit. E concentration, reacted with a lower lipid peroxidation than the heart tissue of SHR. Considering the importance of lipid peroxidation as a damaging mechanism at ischemia, the lower Vit. E concentration in the hearts of SHR should be responsible for the lower tolerance to ischemia in comparison to WKY.

In endomyocardial biopsies from 67 patients with various chronic heart diseases (small vessel disease, cardiomyopathies and hypertensive heart disease) the isoenzymes of Lactate Dehydrogenase (LDH) and Aspartate Aminotransferase (ASAT) and Glycogen Phosphorylase (GP) were investigated and compared with a reference group without actual morphological and functional evidence of chronic heart disease. The analyzed parameters showed characteristical alterations dependent on the degree of hypertrophy of the heart muscle cells and the stage of the disease as assessed by left ventricular enddiastolic pressure (LVEDP), ventricular kinetics, left ventricular heart mass (LVHM) and exercise electrocardiogram. The biochemical alterations found reflect different metabolic situations in the myocardium and could be useful as additional information for assessing the severity of the disease.

Methods have been developed for measuring several biochemical parameters (isoenzymes of LDH and ASAT, glycogen phosphorylase, lipid peroxides) in extremely small tissue samples (0.2-1.8 mg) taken using a left ventricular biopsy technique. Endomyocardial biopsies from patients with dilative and hypertrophic cardiomyopathy (CMP) and with myocarditis were investigated and compared with a reference group without actual functional and morphological evidence of chronic heart disease. Patients with myocarditis showed the highest activities of LDH and its isoenzymes, ASAT, ASATm and glycogen phosphorylase and the highest concentration of lipid peroxides. In patients with hypertrophic CMP increased activities of glycogen phosphorylase and decreased activities of ASAT and ASATm have been found. In patients with dilative CMP slightly elevated ASAT and ASATm activities have been observed. The results obtained in this study suggest that the parameters investigated could be useful in differentiating between cardiomyopathies and myocarditis.