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The protective effect against reperfusion arrhythmias of a 3-month oral pretreatment with a dried extract of Crataegus oxyacantha (LI 132)(standardized to 2.2% flavonoids) was studied with the Langendorff heart of the rat after global no-flow ischemia. The heart was perfused with a modified Krebs-Henseleit solution in which the K+ content was reduced to 3.4 mmol/l in order to lower the fibrillation threshold. According to pilot experiments which considered various durations of global no-flow ischemia ranging from 10 to 20 minutes, two durations were chosen for the present study: 20 minutes (group 20) in which ventricular fibrillation (VF) was the predominant form of arrhythmias, and 18 minutes (group 18) in which the prevalence of VF was markedly lower despite the small difference in the duration of ischemia. Crataegus pretreatment significantly (p = 0.02) reduced the average prevalence of malignant arrhythmias (VF + Flutter) as observed during the 20-min-period of reperfusion as follows: group 20: from 89% (control, n = 9) to 51% (LI 132, n = 7), group 18: from 48% (control, n = 8) to 8% (LI 132, n = 8). In group 20, ventricular tachycardia (VT) could be observed only in the treated group, because of the predominance of VF in the control group. LI 132 pretreatment reduced the average prevalence of VT in group 18 in spite of the identical percentage of occurrence (6 out of 8 rats, with and without treatment) due to a shorter duration of the VT episodes. Thus, under the conditions of our experiments, effective prevention against reperfusion arrhythmias by Crataegus pretreatment was evident.

It was the aim of this study to investigate (1) whether preconditioning modifies the fatty acid (FA) composition of myocardial phospholipids (PL), (2) whether a previous modification of membrane PL composition by the administration of coconut oil or fish oil influences the preconditioning, and (3) to compare the protective effects of preconditioning to those of dietary fish oil. To this end, three groups of rats were given during 10 weeks either a standard diet, or a standard diet + 10% coconut oil, or a standard diet + 10% fish oil. The preconditioning was performed in situ in the anesthetized open-chest rats by 2 cycles of 3 min left anterior descending coronary artery occlusion and 10 min reperfusion. It was followed by a 40 min ischemia and a 60 min reperfusion. ECG was recorded and used for the continuous count of the salves of extrasystoles, ventricular flutter and fibrillation. These rhythm disturbances were subsequently added and evaluated as total arrhythmias. The FA of tissue PL were analyzed in a sample of the ischemic zone the size of which was determined by means of malachite green. Coconut oil diet (rich in saturated FA) modified slightly the myocardial PL by increasing oleic acid and decreasing linoleic acid and resulted in the highest incidence of arrhythmias. Fish oil diet had the opposite effect in modifying drastically the PLFA (replacement of the n-6 FA by the n-3 FA) and minimizing significantly the arrhythmias in comparison with the standard diet group.(ABSTRACT TRUNCATED AT 250 WORDS)

1 Monochloroacetic acid (MCAA) and its sodium salt, sodium monochloroacetate (SMCA) are widely used in chemical industries as intermediates in the synthesis of carboxymethylcellulose, phenoxyacetic acid, thio-glycolic acid, glycine, indigoid dyes and others. More-over, MCAA has been found as a by-product of the chlorination disinfection of drinking water and as an environmental contaminant of the atmosphere from the photodechlorination reactions of chlorinated hydrocarbons. Little is known about the mode of action of both compounds on the cellular level. From cases of accidental poisoning of man it is known that MCAA accumulates in liver and kidney. 2 In this study, the cytotoxicity of SMCA on cultured liver (Chang liver cells) and kidney epithelial cells of the proximal tubule (Opossum kidney cells) was investigated and its effect on metabolism, ultrastruc-ture and organization of cytoskeleton was examined. 3 Independent from the growth state of the cells (proliferating or quiescent), the results clearly show that SMCA causes a dose-dependent decrease in cell viability after an exposure period of 24 h. In all experiments, proliferating cells were more sensitive than quiescent and confluent cells. Liver cells were less sensitive against SMCA treatment than kidney epithe-lial cells. In contrast to liver cells, kidney cells exhibited a dose-dependent decrease in cell volume. The decrease in cell viability was accompanied by an increase of lactate and pyruvate concentrations released into the culture medium. In the case of Opossum kidney cells, lactate and pyruvate levels increased 5-6-fold, whereas in the case of Chang liver cells the increase was approximately twofold. While the ultrastructure of liver cells remained unaltered after drug treatment, kidney cells exhibited cytoplas-mic vacuolization, membraneous disruption and especially mitochondrial alterations. In accordance with the changes in the ultrastructure of Opossum cells, was the reorganization of cytoskeletal elements with an increased stress fiber network at the basolat-eral surface as well as a partial depolymerization of microtubules and vimentin filaments. A cytoskeletal reorganization was not observed for Chang liver cells after SMCA treatment. 4 The results demonstrate that SMCA causes a dose-dependent cytotoxicity which is accompanied by metabolic, mitochondrial and cytoskeletal alterations in the cells.

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