Long-term saturated fat supplementation in the rat causes an increase in PGI2/TXB2 ratio of platelet and vessel wall compared to n-3 and n-6 dietary fatty acids

The effect of long-term manipulation of dietary lipid intake on platelet and vessel wall lipid composition and eicosanoid synthesis was investigated. Rats were fed a standard diet (REF diet) supplemented (12% w/w) with either sheep fat (SF), sunflower seed oil (SSO) or tuna fish oil (TFO) for a period of 15 months. Significant compositional changes both in the aorta and platelets were observed following dietary lipid treatment and differences between these tissues were particularly apparent with regard to the incorporation and conversion of n-3 fatty acids. For example, platelets displayed a selective accumulation of eicosapentaenoic acid (EPA, 20:5 n-3) over docosahexaenoic acid (DHA, 22:6, n-3), but in the aorta the proportion of DHA was considerably higher than that of EPA. In both tissues, compared to REF diet, n-3 dietary fatty acids replaced the n-6 unsaturates 20:4 and 22:4, but did not affect the proportion of linoleic acid. In contrast to aorta, the unsaturation index for platelet membrane varied significantly between dietary groups. The capacity of aorta and platelets to generate PGI2-like activity and thromboxane was unaltered by the SSO diet. However, changes were seen following SF and TFO supplementation. Rats fed the SF diet displayed a greater synthetic capacity whilst in animals maintained on TFO diet the synthesis of these two eicosanoids was considerably suppressed. The SF group displayed the highest value for PGI2/TXB2 ratio whereas TFO diet fed rats showed the lowest which may partly be due to synthesis of TXA3. The reduction in eicosanoids following the tuna fish oil supplementation can be explained on the basis of concurrent compositional changes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dietary fish oil prevents ventricular fibrillation following coronary artery occlusion and reperfusion

Coronary artery occlusion and reperfusion in the anesthetized rat was used as a whole animal model of arrhythmia and sudden cardiac death to examine the influence of long-term dietary lipid modulation of myocardial membrane fatty acids on the development of cardiac arrhythmias. Feeding rats a diet supplemented with tuna fish oil significantly reduced the incidence and severity of arrhythmias, preventing ventricular fibrillation during both occlusion and reperfusion. Dietary sunflower seed oil reduced arrhythmias during occlusion but not in reperfusion. Dietary fat can modify the vulnerability of the myocardium to arrhythmic stimuli. The efficacy of tuna fish oil in reducing vulnerability to both ischemic and reperfusion arrhythmias suggests a potential beneficial effect of dietary n-3 fatty acids in addition to their influence on hemostasis, plasma lipids, and atherosclerosis that may contribute to their proposed role in lowering cardiovascular disease mortality and morbidity.     

The influence of dietary fats on plasma lipids, blood pressure and coagulation indices in the rat

Male Hooded Wistar rats were fed a commercial rat diet supplemented 12% by weight with sheep fat, sunflower seed oil and fish oil (tuna) over a period of 8 months. The influence of these diets on plasma fatty acids, triglycerides and cholesterol, blood pressure, body weight and coagulation indices was assessed. The sheep fat (SF)-fed rats showed a significant increase in body weight over the reference group (C) of 18%, and systolic blood pressure increased by 9.4%, whereas other dietary groups were not significantly affected. The fish oil (TFO)-fed rats showed a significant lowering of plasma cholesterol (-16.6%) and triglyceride (-47%) relative to the reference group, while the sunflower seed oil (SSO) group showed only a lowered plasma triglyceride (-32%). Plasma fatty acids in general reflected closely the dietary fatty acids, with some exceptions. Coagulation indices provided a consistent picture of an increased tendency to thrombosis in SF-fed rats and a significantly reduced tendency in the TFO-fed rats relative to reference rats. Fish oil rich in 20:5 and 22:6 omega 3 long-chain polyunsaturated fatty acids and low in cholesterol appears to have advantages in terms of reducing those parameters identified as risk factors for coronary heart disease in man. Sheep fat supplements rich in saturated fatty acids produce the opposite trend.     

Comparative changes in the fatty-acid composition of rat cardiac phospholipids after long-term feeding of sunflower seed oil- or tuna fish oil-supplemented diets

The fatty-acid composition of rat heart phospholipids was examined after long-term, i.e. more than 12 months, feeding of diets supplemented with n-6 fatty acids as sunflower seed oil (SSO), or n-3 fatty acids as tuna fish oil (TFO) which is a particularly rich source of docosahexenoic acid (DHA). Although some small changes occurred in the relative proportions of palmitic and stearic acids and in the ratio of total saturates to total unsaturates, the most important changes were in the relative proportions of 18:2 n-6 and 20:4 n-6 to 20:5 n-3 and 22:6 n-3. In general, the n-6/n-3 ratio of phosphatidylcholine (PC), phosphatidylethanolamine (PE) and diphosphatidyl glycerol (DPG) was altered in favour of the family of fatty acids administered, although the proportions of the individual long-chain polyunsaturated fatty acids which contributed to this ratio varied from one class of phospholipids to another. In cardiac PC and PE, feeding TFO supplements reduced the proportions of arachidonic acid (AA) and significantly elevated (p less than 0.01) the proportions of DHA but produced relatively little change in those of eicosapentenoic acid (EPA). In DPG, feeding TFO led to a significant increase in the proportion of AA as well as an increase in DHA. The level of EPA was relatively low in PC, PE and DPG even after TFO feeding and never reached comparable levels with that of either AA or DHA. Nevertheless the n-6/n-3 ratio in all these classes of major cardiac phospholipids was significantly reduced by feeding TFO compared to the SSO diet or the commercial rat chow (CC) reference group. In contrast to the reports of other workers who have studied the fatty-acid composition of platelet membranes after feeding various fish oil supplements, in the rat heart the major effect of tuna fish oil is an increase in the proportion of DHA rather than EPA in the cardiac phospholipids.     

Dietary lipid modulation of ventricular fibrillation threshold in the marmoset monkey.

Programmed electrical stimulation was used to examine the ability of long-term dietary lipid modulation to influence myocardial vulnerability to the induction of ventricular fibrillation in adult marmoset monkeys (Callithrix jacchus). Marmosets fed diets supplemented (to a total of 28.5% of the energy as fat) with polyunsaturated fatty acid (PUFA)-rich tuna fish oil or sunflower seed oil had significantly elevated mean ventricular fibrillation threshold compared with those fed a saturated animal fat supplemented diet or a reference diet not supplemented with fat (11.2% of the energy as fat). Fibrillation threshold was reduced during acute myocardial ischemia induced by coronary artery occlusion but still remained higher in the PUFA-fed animals than either the control or the ischemic threshold in reference or saturated fat supplemented animals. Dietary tuna fish oil was associated with a low incidence of sustained fibrillation episodes and no fatalities. These results indicate that myocardial substrate vulnerability to arrhythmic stimuli is increased during ischemia in a nonhuman primate model but dietary PUFA can reduce vulnerability under both normal and ischemic conditions. Reduced dietary fat intake alone was without effect.     

Altered levels of n-6/n-3 fatty acids in rat heart and storage fat following variable dietary intake of linoleic acid

Fat-supplemented dies enriched with linoleic acid by the addition of 12% w/w sunflower seed oil or proportionally reduced in linoleic acid by addition of 12% mutton fat were fed to rats for 18 months before the fatty acid composition of perirenal storage fat and myocardial membranes (phospholipids) was determined. Although the fatty acid composition of perirenal fat generally reflected that of the diet, there was an inverse relationship between the consumption of n-6 and the deposition of n-9 fatty acids. In addition, enhanced deposition of oleic acid (18:1, n-9) appears to be related to the dietary intake of stearic acid (18:0). In contrast, in myocardial membranes the n-3 polyunsaturated fatty acids are found to be increased when the intake of n-6 polyunsaturated fatty acids is reduced. This is particularly evident for docosahexaenoic acid (22:6, n-3) which is significantly increased in phosphatidylcholine, phosphatidylethanolamine, and diphosphatidylglycerol fractions of myocardial membranes, when the mutton fat diet was fed. After feeding the sunflower seed oil diet, the increased consumption of linoleic acid produced only small changes in the 18:2, n-6 content of cardiac phosphatidylcholine and phosphatidylethanolamine. These major classes of membrane phospholipids also showed only small increases in 20:4, n-6. In diphosphatidylglycerol, increased 18:2, n-6 also followed increased dietary intake, but this was not accompanied by increased 20:4, n-6. These changes in myocardial phospholipid fatty acid composition are similar to those observed after short-term feeding reported previously and confirm that changes in dietary n-6/n-3 fatty acid intake affect the fatty acid composition of both myocardial membranes and storage fat. These changes persist for the duration of the feeding period.     

Absence of coronary or aortic atherosclerosis in rats having dietary lipid modified vulnerability to cardiac arrhythmias.

Laboratory studies have shown that saturated fats in the diet increase vulnerability to ventricular fibrillation and other cardiac arrhythmias while polyunsaturates, especially the n-3 fatty acids of fish oils, are antiarrhythmic. Similarly, dietary saturated fat has been implicated in the development of coronary atherosclerosis while polyunsaturated fatty acids are reported to provide protection. In the present study, dietary fat supplements known to influence arrhythmic vulnerability after long term feeding in the rat were tested for their propensity to induce or prevent changes in the aorta or coronary vasculature. It was found that dietary supplementation for 15 months with saturated fat (from sheep fat) or n-6 (sunflower seed oil) or n-3 (fish oil) polyunsaturated fatty acids made no difference to the development of vascular changes in coronary arteries or aorta of the rat despite some significant differences in plasma triglyceride and cholesterol levels. The vascular lesions observed were minimal even in non-supplemented age-matched reference animals. They consisted of focal intimal thickening and slight mucopolysaccharide accumulation with no evidence of progression to fibrotic lesions or calcium accumulation and there were no fatty deposits observed. It is concluded that significant atherosclerosis-induced chronic myocardial ischaemia in no way contributes to dietary lipid modulation of arrhythmic vulnerability in the rat.     

The impact of dietary fat composition on serum leptin concentrations in healthy nonobese men and women

The recently discovered hormone leptin is primarily secreted by adipose tissue and serves as an internal signal indicating the size of body fat stores. The aim of the present study was to investigate the impact of the dietary fatty acid composition on serum leptin concentrations. Therefore, serum leptin levels were measured by RIA in healthy nonobese men (n = 30) and women (n = 25). First, all participants received a baseline high-fat diet, rich in saturated fat, for 2 wk and were then randomly assigned to one of three high-fat dietary treatments, which contained refined olive oil (rich in monounsaturated fatty acids, n = 19), rapeseed oil [rich in monounsaturated fatty acids and alpha-linolenic acid (18:3n-3), n = 17], or sunflower oil (rich in n-6-polyunsaturated fatty acids, n = 19) as the principal source of fat for 4 wk. On the rapeseed oil diet, serum leptin concentrations increased slightly in men [+0.25 ng/ml, T(9) = -2.778, P = 0.021], but decreased distinctly in women [-4.70 ng/ml, T(6) = 5.083, P = 0.002]. Both the olive oil and the sunflower oil diet did not affect serum leptin concentrations. Thus, it is proposed that serum leptin levels were affected by the high amount of alpha-linolenic acid in rapeseed oil. However, questions remain as to why this diet differently affected serum leptin in men and women.     

Dissociation between reperfusion induced arrhythmias and increases in ventricular alpha 1 receptor density in the anaesthetised rat

Using anaesthetised rats we have assessed (1) whether the density of alpha 1 adrenergic receptors increases during coronary artery occlusion, (2) whether any change in density can be associated with the onset of reperfusion induced ventricular fibrillation, and (3) whether alpha 1 blockade with prazosin modifies the incidence of reperfusion induced ventricular fibrillation. The incidence of fibrillation upon reperfusion after 3, 5, 10, 20 and 30 min occlusion was 20, 75, 50, 16 and 10% (n = 10-12 in each group) respectively. alpha 1 Receptor density was measured using [3H]-prazosin in non-ischaemic and ischaemic tissue obtained after 0, 5 and 30 min ischaemia. Receptor density was not significantly altered at the time of maximum incidence of reperfusion induced ventricular fibrillation (5 min occlusion) but did significantly increase in both non-ischaemic and ischaemic tissue after 30 min occlusion, when the incidence of fibrillation upon reperfusion was very low (8%). At this time the values were 17.0(SEM 2.3) and 18.4(0.6)fmol.mg-1 protein in non-ischaemic and ischaemic zones as compared to 10.7(0.6) and 12.8(1.0)fmol.mg-1 protein in sham operated control animals (p less than 0.05 in both cases). Prazosin (0.1 or 1.0 mg.kg-1 body wt intravenously, 5 min prior to coronary occlusion) did not alter the incidence of ventricular fibrillation, ventricular tachycardia or total number of premature ventricular complexes upon reperfusion. We conclude that ischaemia induced changes in alpha 1 receptor density do not parallel changes in vulnerability to reperfusion induced arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of the type of dietary fatty acid on the insulin receptor function in rat epididymal fat cells

Feeding young rats diets containing sunflowerseed oil (SSO) or palm oil (PO) induced several differences in the properties of the isolated epididymal fat cells: insulin stimulated deoxyglucose uptake 127% over the basal value in cells of the SSO group but only 47% in those of the PO group; the insulin concentration giving half maximal stimulation differing only slightly; insulin binding to the cells was higher in the SSO group; Scatchard analysis revealed that this was due to a significantly higher number of low-affinity binding sites, and the epididymal fat pad showed a concomitant change in the fatty acid pattern of the phospholipids, reflecting to a limited extent the differences in the composition of the diets. Neither the average diameters of the isolated fat cells, nor the serum insulin level at the time of sacrifice of the rats differed for the two types of dietary fat. These results indicate that a diet high in linoleic acid (SSO) induces a better response of fat cells to insulin than a diet high in saturated fatty acids (PO).     

Dietary fish oil protects against stretch-induced vulnerability to atrial fibrillation in a rabbit model

INTRODUCTION: Dietary fish oil is thought to reduce sudden cardiac death by suppressing ventricular arrhythmias but little is known about its impact on atrial arrhythmias. We examined the effect of dietary fish oil on the rabbit model of stretch-induced vulnerability to atrial fibrillation (AF). METHODS AND RESULTS: Six-week-old rabbits were fed standard rabbit pellets supplemented with 5% tuna fish oil (n = 6) or supplemented with 5% sunflower oil (n = 6) for 12 weeks. Six rabbits raised on the standard diet were used as controls. In Langendorff-perfused hearts intraatrial pressures were increased in a stepwise manner and rapid burst pacing applied to induce AF at increasing intraatrial pressures until AF was sustained (>1 minute). Atrial refractory periods were recorded at each pressure. Increased atrial pressure resulted in a reduction in atrial refractory period and a propensity for induction of sustained AF. Higher pressures were needed to induce and sustain AF in the fish oil group compared with the sunflower oil and control groups. The stretch-induced drop in refractory period was also less marked in the fish oil group. Red blood cell, atrial, and ventricular omega-3 fatty acid levels were significantly higher in the fish oil group. The ratio of atrial n-6/n-3 polyunsaturated fatty acids was 13 +/- 0.9 with sunflower oil and 1.5 +/- 0.01 with fish oil (P < 0.001). CONCLUSIONS: Incorporation of dietary omega-3 fatty acids into atrial tissue reduces stretch-induced susceptibility to AF.     

Silymarin and Vitamin E do not Attenuate and Vitamin E Might Even Enhance the Antiarrhythmic Activity of Amiodarone in a Rat Reperfusion Arrhythmia Model

Oxidative stress and lysosomal phospholipoidosis, which also might be partly attributed to free radicals induced by amiodarone (AM), may be involved in AM toxicity, which can be prevented by antioxidants. Our aim was to study if vitamin E (E) or silymarin (S), a lipid and a water-soluble antioxidant, modified the antiarrhythmic efficacy of AM in a rat reperfusion arrhythmia test. The following groups of male Sprague-Dawley rats (15 rats/group) were treated by gavage once a day for 4 weeks: 1. methylcellulose (MC, 0.4%), 2. sunflower seed oil (SSO), 3. AM, suspended in MC (30 mg/kg), 4. E, dissolved in SSO (100 mg/kg), 5. AM + E, 6. S, suspended in MC (80 mg/kg), 7. AM + S. The mean duration of ventricular tachycardia + fibrillation (MDVT + VF) and sinus rhythm (MDSR) the incidence of ventricular fibrillation (VF) and ventricular tachycardia (VT) and mortality were measured during a 10-min reperfusion after a 5-min coronary artery occlusion in anaesthetized rats. An arrhythmia score, representing the combined incidence and duration of different types of ventricular arrhythmia, was calculated. Compared with the MC group, MDSR was longer and MDVT + VF was shorter in all drug treated groups and in the SSO group. In the AM + E treated group MDSR was prolonged more and MDVT + VF was shortened more than in the AM, E or SSO groups. Compared with the MC group, the incidence of VF and mortality was similarly decreased in the SSO group and in most drug treated groups. No significant difference in the incidence of VT was found among all groups. The arrhythmia score was reduced by all drug treatments. Combined treatment with AM + E decreased arrhythmia score more than treatment with AM or SSO alone, but arrhythmia score was similar in the AM + E and E groups. In conclusion, both AM and antioxidant treatments alone or together resulted in a marked reduction of reperfusion arrhythmias in this model. SSO also exerted a moderate antiarrhythmic effect. Antioxidants administered together with AM did not attenuate and E might have even enhanced the antiarrhythmic effect of AM, therefore the combination of antioxidants with AM may be advantageous to reduce AM toxicity.     

Lipid peroxidation in normoxic and ischaemic-reperfused hearts of fish oil and lard fat fed pigs

The in situ and in vitro rate of lipid peroxidation of hearts were determined in two groups of pigs which had been fed diets which differed only in fatty acid composition for 8 weeks. During the dietary period venous plasma levels of malondialdehyde and lipofuscin were not higher in pigs receiving the highly unsaturated fatty acid-containing mackerel oil than those receiving lard fat. Malondialdehyde was produced in the coronary system of the mackerel oil fed animals. After the heart was subjected to a sequence of short periods of ischaemia (5 min) and reperfusion (10 min), myocardial malondialdehyde production in the mackerel oil fed pigs did not increase. Contribution of prostaglandin synthesis products to myocardial malondialdehyde formation is probably of minor importance. Recovery of regional heart function after the ischaemic periods was similar for both dietary groups. In the phospholipids of sarcolemmal preparations isolated from the left ventricle of mackerel oil fed animals 18:2 n-6 and 20:4 n-6 were partially replaced by 20:5 n-3 and 22:6 n-3. Ischaemia-reperfusion did not alter sarcolemmal fatty acid composition and Ca2+ pumping ATPase activity. Sarcolemmal membrane from mackerel oil fed pigs exposed in vitro to a free radical generating system showed a higher malondialdehyde production than that from lard fat fed pigs. Thus, in spite of the increased susceptibility of heart membranes to free radical generated peroxidation in mackerel oil fed animals, recovery of left ventricular function was similar following multiple short-term periods of ischaemia.     

Diet and cardiac arrhythmia: effects of lipids on age-related changes in myocardial function in the rat

Male rats were fed for 3-4 months (short-term) or 12-15 months (long-term) on a standard laboratory diet alone (control) or supplemented with sunflower seed oil (SSO, 12% w/w) or sheep kidney fat (SKF, 12% w/w). Papillary muscles were electrically driven (1 Hz, 5 ms, supramaximal voltage) at 37 degrees C in Krebs-Henseleit solution, and contractions were measured isometrically. Both the positive inotropic responses to CA++ and the incidence of spontaneous tachyarrhythmias under catecholamine stress were increased by short-term SKF feeding and with age in control and SKF groups, whereas SSO prevented these changes. The results show a marked effect of age upon ventricular myocardial function in the rat, which appears to be accelerated by the consumption of animal (saturated) fat while polyunsaturated vegetable oil provides some degree of protection. It is suggested that changes in membrane lipid composition can alter the Ca++ handling characteristics of myocardial cells.     

Ethanol Inhalation and Dietary N-6, N-3, and N-9 Fatty Acids in the Rat: Effect on Platelet and Aortic Fatty Acid Composition

The effects of 18-carbon n-6, n-3, and n-9 fatty acid diets and ethanol exposure on the fatty acyl composition of platelets and vascular tissue were examined. An experimental design was devised to control the dietary content of 18-carbon fatty acids. The levels of 18:3n6, 18:3n3 and 18:1n9 were varied by a formulation of dietary oils which contained similar proportions of 18:2n6. Male Sprague-Dawley rats were fed a purified diet containing 11% by weight of either borage oil (BOR) rich in 18:3n6, linseed/safflower oil (LSO) rich in 18:3n3, or sesame oil (SES) rich in 18:1n9 for 7 weeks and exposed to ethanol vapors by means of inhalation for the final 6 days of the dietary regimen. Moderate blood ethanol levels of 118 +/- 6.6 mg/dl were obtained. Total lipids were extracted from platelets and aortae, and the fatty acid distributions were analyzed by gas chromatography. BOR feeding resulted in increases in the proportion of n-6 fatty acids (18:3n6, 20:3n6, 20:4n6) in platelets and aorta. Animals fed the LSO diet had increased levels of n-3 fatty acids (18:3n3, 20:5n3, 22:6n3). The SES-based diet resulted in an increase in 18:1n9 in both aorta and platelets. Following ethanol exposure alone, the most marked change in the fatty acid profile was a decrease in 20:4n6 in the platelet. This effect was not observed in rats supplemented with BOR. No significant changes were observed in the aortic fatty acid content at this level of ethanol exposure. The results suggested that, in the rat, a diet enriched with BOR effectively prevented ethanol-induced alterations in platelet fatty acid composition.     

Compared effect of n-3 and n-6 dietary fatty acids on rat intestinal acyl-CoA:cholesterol acyltransferase activity

Polyunsaturated fatty acids are known to lower plasma cholesterol concentrations. We studied their effect on intestinal acyl-CoA:cholesterol acyltransferase (ACAT) activity in rats fed either salmon oil or corn oil (17% fat) with or without 1% cholesterol. After an 8-week feeding period we confirmed the hypolipidemic effect of salmon oil and we established its ability to stimulate ACAT activity in rats fed low-cholesterol diets. The most striking effect of 1% dietary cholesterol on ACAT activity was obtained in the control group (34% enhancement), whereas cholesterol supplementation had no effect on ACAT activity in the salmon oil group. The results enable us to suggest that n-3 fatty acids have an effect per se on ACAT activity; the regulation of enzyme activity by dietary cholesterol probably involves independent processes.     

Effects of different paced heart rates on canine coronary occlusion and reperfusion arrhythmias

Little information exists regarding the effect of heart rate on arrhythmias induced by coronary reperfusion. We therefore evaluated the effects of different heart rates on arrhythmias following canine coronary artery occlusion and reperfusion. Dogs were paced at either 350 msec cycle length (171 bpm; n = 30) or 480 msec cycle length (125 bpm; n = 30). They were then subjected to a 20-minute occlusion of the proximal left anterior descending coronary artery, followed by sudden reperfusion. Ligated vessel perfusion bed size (myocardial "at risk") was measured with monastral blue and red dyes. The incidence of both occlusion and reperfusion arrhythmias correlated with the myocardium at risk. Dogs paced at 171 bpm had more ventricular ectopic depolarizations (37/1000 beats vs 8/1000 beats, p less than 0.01) and a higher incidence of ventricular tachycardia during occlusion than those paced at 125 bpm (67% vs 33%, p less than 0.05). Dogs paced at the faster rate also had a higher incidence of ventricular tachycardia (83% vs 60%, p = 0.08) and ventricular fibrillation (70% vs 40%, p less than 0.05) after reperfusion. Thus, heart rate can have a substantial effect on occlusion and reperfusion arrhythmias and should be considered when making therapeutic interventions and risk assessments in this setting.     

Cardioprotective effect of combined use of coenzyme Q9 and cyclohexyladenosine in ischemia, reperfusion and acute myocardial infarction

Effects of coenzyme Q9 (25 mg/kg), N6-cyclohexyl adenosine (CHA, 100 micrograms/kg) and their combination were compared in rats with short-term or permanent ligation of the left coronary artery. The following parameters were evaluated in three series of experiments: 1) incidence and duration of ventricular fibrillation and tachycardia during coronary occlusion (10 min) and consecutive reperfusion (5 min); 2) contractility and electrical stability of the heart (ventricular fibrillation threshold) in animals with 2-day myocardial infarction; 3) ischemic myocardial mass after coronary occlusion (5 min) and necrotic tissue mass in 2-day myocardial infarction. The rats were given oral drugs 5 days and 2 hours before the study. All the experiments were performed in open-chest anesthetized (nembutal, 50 mg/kg) rats exposed to ventilation at room air. Both the coenzyme Q9 and CHA significantly reduced the incidence and duration of coronary occlusion and reperfusion arrhythmias, prevented cardiac contractile depression (heart rate.developed pressure) and increased ventricular fibrillation threshold). The effect of coenzyme Q9 was more marked than that of CHA. Coenzyme Q9 substantially reduced necrotic tissue mass while CHA diminished ischemic tissue mass. At the same time the total cardioprotective action of the Q9 + CHA combination was more pronounced than that of them used alone.     

Effects of glibenclamide on ventricular arrhythmias and cardiac function in ischaemia and reperfusion in isolated rat heart.

OBJECTIVE: The aim was to investigate the effects of glibenclamide, a specific blocker of the ATP sensitive potassium channel, on the incidence of ventricular arrhythmias and the functional changes occurring during myocardial ischaemia and reperfusion. METHODS: Hearts (n = 10 per group) were obtained from male Wistar rats, weight 250-300 g. The study was performed in isolated Langendorff perfused rat hearts subjected to ligation of the left coronary artery and reperfusion. Because of the occurrence of arrhythmias, cardiac function was not evaluated during reperfusion. Glibenclamide (1 or 10 microM) was added to the perfusion solution before the coronary artery occlusion, during ischaemia or after reperfusion. In some experiments the incidence of various durations of ischaemia (5, 10, 15, and 30 min) was evaluated. RESULTS: During the preischaemic period, glibenclamide induced a marked reduction in coronary flow, with a slight decrease in heart rate and left ventricular pressure. The ischaemia induced decrease in left ventricular pressure was markedly attenuated when glibenclamide was given before ischaemia. Thus the isovolumetric left ventricular pressure measured after 15 min ischaemia, which represents 59(SEM 6)% of the preischaemic value in the control group, was increased to 82(9) and 94(8)% in presence of glibenclamide (1 and 10 microM, p < 0.05 respectively). The effect was less pronounced when glibenclamide was added to the perfusion fluid during the ischaemic period. None of the hearts showed ventricular fibrillation during the ischaemic period. Glibenclamide (1 and 10 microM) did not reduce the incidence of reperfusion induced ventricular fibrillation. However, a defibrillatory action was observed since glibenclamide reduced the duration of ventricular fibrillation during reperfusion. CONCLUSIONS: Glibenclamide may increase the probability of spontaneous termination of ventricular fibrillation and facilitate the restoration of the myocardial function during regional ischaemia.     

Steatosis and Collagen Content in Experimental Liver Cirrhosis Are Affected by Dietary Monounsaturated and Polyunsaturated Fatty Acids

Background and Methods: We used thioacetamide administered orally to induce cirrhosis in rats, and after these had recovered for 1 and 2 weeks we examined the effects of dietary supplementation with monounsaturated and n-3 polyunsaturated fatty acids, or with a combination of n-3 and n-6 polyunsaturated fatty acids, on the extent of steatosis and collagen content in the liver. Results: Nodular cirrhosis, increased collagen content, and lipid accumulation were established after 4 months of treatment with thioacetamide. When the animals were fed a diet rich in oleic acid for 2 weeks, the steatosis and fibrosis decreased. Supplementation with n-3 polyunsaturated fatty acids favored reductions in collagen content but did not reduce the fat accumulation. With a diet supplemented with a mixture of n-3 and n-6 fatty acids we found no reduction in either lipid accumulation or collagen content. Conclusions: Fibrosis and steatosis may be influenced by dietary fat, and monounsaturated fat appears to influence favorably the histologic recovery of the damaged liver.