Myocardial necrosis in rats

Effect of D-003 on isoproterenol-induced myocardial necrosis in rats. J... 

Nirmala, C., Anand, S., and Puvanakrishnan, R., Curcumin treatment modulates collagen metabolism in isoproterenol induced myocardial necrosis in rats, Mo/. Cell. Biochem., 197 (1-2), 31-37,1999. 

The problem of myocardial necrosis in rats has received the greatest attention in attempts to correlate myocardial necrosis to myocardial lipid changes. Myocardial necrosis has been observed in male rats irrespective of the dietary oil or fat, provided a sufficient number of heart sections (Vies et al., 1976 and 1978) or a sufficient number of rats (Hulan et a/., 1977d) are examined. Dietary fats high in saturated fatty acids (Hulan et a/., 1976 Kramer et a/., 1981 Farnworth et a/., 1982) and linoleic acid (Vies et a/., 1978) are associated with a low incidence of heart lesions, whereas diets which contain linolenic acid (McCutcheon eta/., 1976 Hulan eta/., 1977a Vies et a/., 1978) and erucic acid (Abdellatif and Vies, 1973) are associated with a high incidence of heart lesions. A statistical analysis of much of the heart lesion data clearly showed this correlation of dietary fatty acids to heart lesions (see Chapter 17, Table XXV). 

Myocardial Necrosis in Male Rats Fed Decreasing Levels of Fat in the Form of High Erucic Acid Rapeseed (HEAR) Oils... 

Myocardial Necrosis in Male Rats Reproduced by Erucic Acid... 

A comparison between Sprague-Dawley and Wistar rats in myocardial lesion response to the feeding of high fat diets has shown very little difference in the incidence of lesions (Table IV, see also Vies et a/., 1978). However, there is convincing evidence to indicate that the severity of myocardial necrosis in the Wistar male rat is significantly lower than in the... 

A statistical analysis of much of the published data on myocardial necrosis in male rats fed fats and oils for at least 16 weeks indicated that the heart lesions were negatively correlated to dietary saturated fatty acids (16 0 and 18 0) and linoleic acid (18 2), and positively correlated to dietary linolenic (18 3), oleic (18 1), eicosenoic (20 1), and docosenoic (22 1) acids (Table XXV). Most of the variation in lesion incidence between experiments could be explained by the concentration of 16 0 and 18 3. A plot of the observed incidence of heart lesion versus the lesion incidence predicted based on the concentration of 18 3 and 16 0 in the dietary oil of 23 experiments with over 2000 rats is shown in Fig. 8. Figure 8 shows a continuum of points representing a broad spectrum of fats, oils, and fat-oil mixtures. The more satu-... 

Again, by reference to Fig. 8, it is noted that linolenic acid increases lesion incidence. This has also been shown directly by experiments where 18 3 was removed from synthetic fat rnixtures high in 22 1 (Table XXIX). With the removal of 18 3 the lesion incidence did not change but the severity of the lesions decreased markedly (McCutcheon et al., 1976). In agreement with this. Vies et al. (1978) was able to show that the severity of myocardial necrosis in Sprague-Dawley rats fed linseed oil rich in 18 3 for 53 weeks was significantly increased over that obtained by feeding sunflower oil, but still below that obtained with a LEAR oil cv. Primor (Fig. 1). 

Focal myocardial lesions are sometimes found incidentally in human hearts. These have some histological features that are similar to those seen in the rat. However, the etiology of these lesions is different. A low grade infectious myocarditis may be involved in some cases (Kline et al., 1963 Pomerantz and Davies, 1975). A number of drugs, poisons, and clinical conditions are known to cause diffuse or multifocal myocardial necrosis in humans but there is no hard evidence indicating dietary fat consumption as a factor in this respect (McKinney, 1974). 

Following short-term inhalation exposure to 160 ppm [620 mg/m ] methyl bromide (6 h per day on five days per week for up to six weeks), B6C3F, mice were found to be more sensitive than Fischer 344/N rats 50% of male mice died after eight exposures and 50% of female mice after six exposures, while similar mortality was observed in male rats only after 14 exposures. Neuronal necrosis and testicular degeneration were observed in both species nephrosis was observed in nearly all mice, while necrosis of the olfactory epithelium was more marked in rats. Myocardial degeneration occurred in rats and to a lesser degree in male mice. In the adrenal cortex, there was cytoplasmic vacuolation in rats and inner zone atrophy in female mice (Eustis et al., 1988). 

The observation that the agent accumulated in necrotic tissue and not specifically or preferentially into viable tumors led to the investigation of the agent as a marker for necrosis [110]. Acute myocardial infarctions were induced in rats... 

Several studies have shown that carbon disulfide causes vascular changes in various organs of experimentally exposed animals. Acute inhalation (2 days) of 1,285 ppm in phenobarbitone-pretreated rats resulted in myocardial lesions characterized by necrosis, interstitial edema, and cellular infiltrate (Chandra et al. 1972). This effect was not observed in rats treated with carbon disulfide alone. 

Chrostek-Maj and Czeczotko 1995a Drexler et al. 1995b). A transient decrease in blood pressure was reported in rats administered 506 mg/kg carbon disulfide once by gavage (Hoffmann and Klapperstuck 1990). ECG changes were seen at 373 and 506 mg/kg, while heart rate decreased at 632 mg/kg. The other studies on animals attest to the adverse effects of carbon disulfide on the cardiovascular system (Antov et al. 1985 Chandra et al. 1972 Wronska-Nofer et al. 1980). These effects included lipid droplet infiltration in the coronary arteries, metabolic and structural changes in the myocardium and the aorta, and myocardial lesions characterized by necrosis, interstitial edema, and cellular infiltrate. 

Fig. 1). It is, however, interesting to observe that whereas with lard/corn oil control diets there was a zero incidence of heart lesions, when sunflower oil diets were used as controls, the heart lesion incidence was 29%. This suggests that myocardial necrosis can be reduced quite effectively by saturated fatty acids, while a mixture of polyunsaturated fatty acids, as in sunflower oil, is not as effective. It must be kept in mind, however, that in these two experiments both the rat strain and the experimental feeding period were different. Wistar rats were fed the sunflower oil mixtures for 32 weeks, while the Sprague-Dawley rats were fed the lard/corn oil mixtures for only 16 weeks. 

It is quite evident from the results in Table III that male rats fed diets containing high levels of HEAR oil will develop myocardial necrosis. These heart lesions can also be produced by feeding an equal mixture of trierucin and sunflower oil at 60 calorie % (Abdellatif and Vies, 1973) with a level of 22 1 in the oil of about 42% (Table V). Subsequently, this finding was confirmed when rats were fed olive oil interesterified with erucic acid to give a mixture which contained 30% 22 1 (Beare-Rogers, 1975). 

Comparison of Myocardial Necrosis Induced by Different Positional Isomers of Docosenoic Fatty Acids in Male Rats... 

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