Cardiac dysfunction in rats with dietary-induced insulin resistance associated with pharmacologically-induced dyslipidemia.

Metabolic disorders such as insulin resistance (IR) and dyslipidemia (DL) might contribute to the induction of diabetic cardiomyopathy (DCM). However, few relevant animal models are currently available for studying the time-course of DCM and evaluating experimental therapeutics. The present study proposes a rodent model of dietary-induced IR combined or not with DL in order to investigate the impact of chronic IR and DL on in vivo myocardial function. Male rats were fed a western-type diet (65% fat; 15% fructose; WD). DL was induced by combining the western diet with i.p. injections of a nonionic surface-active agent (P-407; 0.2 mg/kg, 3 times/wk; P-407). A chow diet was used as control. At 11 and 14 weeks, cardiac function was assessed by echocardiography. Fasting blood glucose increased in WD group while plasma lipids markedly accumulated in P-407 treated rats. Echocardiographic data showed no significant difference in cardiac geometry under basal conditions. Diastolic dysfunction was evidenced at 14 weeks by a significant decrease in E/A ratio in the P-407 group. Moreover, fractional shortening was significantly depressed under dobutamine stress in WD group at 14 weeks whereas systolic dysfunction appeared as early as 11 weeks and worsened at 14 weeks in P-407 animals. Finally, myocardial TNF-alpha tissue content increased in P-407 group. In conclusion, DL exacerbated cardiac lipotoxicity and functional complications associated with IR. This experimental model of combined IR and DL closely mimics the main clinical manifestations of DCM and might therefore constitute a useful tool for the evaluation of pharmacological treatments.

Impact of dietary selenium intake on cardiac health: experimental approaches and human studies.

Selenium, a dietary trace mineral, essential for humans and animals, exerts its effects mainly through its incorporation into selenoproteins. Adequate selenium intake is needed to maximize the activity of selenoproteins, among which glutathione peroxidases have been shown to play a major role in cellular defense against oxidative stress initiated by excess reactive oxygen species. In humans, a low selenium status has been linked to increased risk of various diseases, including heart disease. The main objective of this review is to present current knowledge on the role of selenium in cardiac health. Experimental studies have shown that selenium may exert protective effects on cardiac tissue in animal models involving oxidative stress. Because of the narrow safety margin of this mineral, most interventional studies in humans have reported inconsistent findings. Major determinants of selenium status in humans are not well understood and several nondietary factors might be associated with reduced selenium status. In this review, we discuss recent studies regarding the role of selenoproteins in the cardiovascular system, the effect of dietary intake on selenium status, the impact of selenium status on cardiac health, and the cellular mechanisms that can be involved in the physiological and toxic effects of selenium.

Dietary selenium intake influences Cx43 dephosphorylation, TNF-α expression and cardiac remodeling after reperfused infarction.

SCOPE: Post-infarct left ventricular dysfunction and cardiac remodeling are the primary causes of chronic heart failure in industrialized countries. In the present study, we examined the influence of dietary selenium intake on cardiac remodeling after reperfused myocardial infarction and explored one of the possible mechanisms. METHODS AND RESULTS: Rats were fed a diet containing either 0.05 mg/kg (Low-Se, group of rats receiving the low-selenium diet) or 1.50 mg/kg (group of rats receiving the high-selenium diet) selenium. At the end of the 5th week of the diet, rats were subjected to transient (1 h) coronary ligation followed by 8 days of reperfusion. Infarct size and cardiac passive compliance were increased in the Low-Se group compared with group of rats receiving the high-selenium diet. Similarly, indices of cardiac remodeling (thinning index and expansion index) were more altered in Low-Se hearts. These adverse effects of the Low-Se diet on cardiac remodeling were accompanied by an increase in cardiac TNF-α content, a decreased activity of antioxidant seleno-enzymes and an increase in connexin-43 dephosphorylation. CONCLUSION: Dietary selenium intake influences post-infarct cardiac remodeling even when provided within the range of physiological values. Our data suggest that the cardioprotective effect of selenium might be mediated by a reduced oxidative stress, a lower connexin-43 dephosphorylation, and a decreased TNF-α expression.

Protective effect of dietary n-3 polyunsaturated fatty acids on myocardial resistance to ischemia-reperfusion injury in rats.

Dietary n-3 polyunsaturated fatty acids (PUFA) reduce coronary heart disease (CHD) complications, such as chronic arrhythmia and sudden cardiac death. Improved myocardial resistance to ischemia-reperfusion injury results in smaller myocardial infarction, which is a major factor in the occurrence of CHD complications. We hypothesized that a specific dietary fatty acid profile (low in saturated and n-6 PUFA but high in plant and marine n-3 PUFA) may improve myocardial resistance to ischemia-reperfusion injury and reduce infarct size. To test this assumption, we used a well-defined rat model of myocardial infarction. Based on our results, in comparison to a diet that is high in either saturated or n-6 PUFA but poor in plant and marine n-3 PUFA, a diet that is low in saturated fats and n-6 PUFA but rich in plant and marine n-3 PUFA results in smaller myocardial infarct size (P < .01). The effects of the 3 diets were also examined by analyzing the fatty acid composition of plasma, erythrocyte cell membranes, and the phospholipids of myocardial mitochondria. The results show a great accumulation of n-3 PUFA and a parallel decrease in arachidonic acid, the main n-6 PUFA, in plasma, cell membranes, and cardiac mitochondria (P < .0001). We conclude that improved myocardial resistance to ischemia-reperfusion may be one of the critical factors explaining the protective effects of dietary n-3 PUFA against CHD complications in humans. In addition to increasing n-3 PUFA intake, an optimal dietary pattern aimed at reducing cardiovascular mortality should include a reduction of the intake of both saturated and n-6 PUFA.

Fish oil and heart health.

Large controlled trials have shown that intake of fish oil (marine n-3 fatty acids, eicosapentaenoic acid, and docosahexaenoic acid), whether from dietary sources or fish oil supplements, may exhibit beneficial effects on total and cardiovascular disease mortality. Stabilization of cell membranes and suppression of cardiac arrhythmias have been identified as possible mechanisms. Moreover, n-3 fatty acids have anti-inflammatory effects, reduce blood pressure, and may also be antiatherogenic. Finally, high doses of n-3 fatty acids can lower elevated serum triglyceride levels. The n-3 index (erythrocyte eicosapentaenoic acid plus docosahexaenoic acid) may be considered as a potential risk marker for coronary heart disease mortality, especially sudden cardiac death. The balance of n-6 to n-3 fatty acids is an important determinant in decreasing the risk for coronary heart disease, both in the primary and in the secondary prevention of coronary heart disease. Patients with known coronary heart disease should be recommended to consume n-3 fatty acid supplements at 1 g per day, without raising concerns for interactions with other medications or side effects. On the other hand, fish in the diet (preferably oily fish, 1-2 meals/week) should be considered as part of a healthy diet low in saturated fat.

A single intravenous sTNFR-Fc administration at the time of reperfusion limits infarct size--implications in reperfusion strategies in man.

BACKGROUND: Reperfusion of the ischemic myocardium is associated with increased inflammatory processes that can exert deleterious effects and therefore contribute to cardiac dysfunction. The aim of the present study was to verify whether the administration of sTNFR-Fc, a scavenger of the pro-inflammatory cytokine TNF-alpha, at the time of reperfusion would protect against myocardial infarction and reduce the severity of early mechanical dysfunction. METHODS: Male Wistar rats were subjected to 60 min coronary occlusion followed by reperfusion. A bolus of sTNFR-Fc (10 microg/kg, i.v.) (MI + sTNFR-Fc group) or a placebo (MI group) was injected prior to reperfusion. Cardiac geometry was assessed by echocardiography 1, 3 and 7 days after reperfusion. Eight days after reperfusion, left ventricular (LV) function was evaluated under basal conditions and during an experimental challenge of volume overload. Finally, infarct size was measured after euthanasia. RESULTS: sTNFR-Fc administration markedly reduced infarct size (P < 0.01) and decreased LV dilation as assessed by the echocardiographic measurement of the LV end diastolic area, 7 days post-MI (P < 0.01). Moreover, LV end-diastolic pressure was significantly preserved by sTNFR-Fc 1 week after myocardial infarction, under basal conditions (P < 0.05) as well as during cardiac overload (P < 0.05). CONCLUSION: A single administration of sTNFR-Fc at the time of reperfusion after myocardial infarction is able to limit infarct size and to reduce early LV diastolic dysfunction in rats. These findings suggest that intravenous neutralization of TNF-alpha during surgical cardiac reperfusion might improve the outcome of myocardial infarction in humans.

Interactions of ethanol drinking with n-3 fatty acids in rats: potential consequences for the cardiovascular system.

Moderate ethanol drinking (ED) and n-3 fatty acids have both been associated with low cardiac mortality. However, there are few data evaluating the interactions of ED with n-3. We recently reported that moderate ED results in increased n-3 in cardiac patients. The main aim of the present study was, through a well-controlled experimental model, to confirm that chronic ED actually results in increased n-3. Secondary aims were to examine the effects of chronic ED on cardiac mitochondria, cardiac function and experimental myocardial infarction. We studied the fatty acid profiles of plasma, cell membranes and cardiac mitochondria phospholipids in a rat model of chronic ED. In plasma and cell membranes, ED actually resulted in higher n-3 (P = 0.005). In mitochondria phospholipids of ED rats, n-3 were also increased (P < 0.05) but quite modestly. Cardiac mitochondrial function and left ventricular function were not significantly different in ED and control rats, while infarct size after 30 min ischaemia and reperfusion was smaller (P < 0.0001) in ED rats. This is the first animal study confirming interaction of alcohol drinking with n-3. We found no harmful effect of chronic ED on the heart in that model but a significant cardioprotection. Further studies are warranted to investigate the mechanisms by which moderate ED alters the metabolism of n-3 and whether n-3 are the mediators of the ED-induced cardioprotection.

Chronic dietary intake of plant-derived anthocyanins protects the rat heart against ischemia-reperfusion injury.

Consumption of flavonoid-rich foods and beverages is thought to reduce the risk of cardiovascular diseases. Whereas the biological activities of flavonoids have been characterized in vitro, there are no clear experimental data demonstrating that chronic dietary intake and intestinal absorption of flavonoids actually protects the heart against ischemia-reperfusion injury. We tested whether long-term consumption of specific flavonoids (anthocyanins) included in normal food could render the heart of rats more resistant to myocardial infarction. Maize kernels that differed specifically in their accumulation of anthocyanins were used to prepare rodent food in which anthocyanins were either present or absent. Male Wistar rats were fed the anthocyanin-rich (ACN-rich) or the anthocyanin-free (ACN-free) diet for a period of 8 wk. Anthocyanins were significantly absorbed and detected in the blood and urine of only rats fed the ACN-rich diet. In Langendorff preparations, the hearts of rats fed the ACN-rich diet were more resistant to regional ischemia and reperfusion insult. Moreover, on an in vivo model of coronary occlusion and reperfusion, infarct size was reduced in rats that ate the ACN-rich diet than in those that consumed the ACN-free diet (P < 0.01). Cardioprotection was associated with increased myocardial glutathione levels, suggesting that dietary anthocyanins might modulate cardiac antioxidant defenses. Our findings suggest important potential health benefits of foods rich in anthocyanins and emphasize the need to develop anthocyanin-rich functional foods with protective activities for promoting human health.

Interactions of wine drinking with omega-3 fatty acids in patients with coronary heart disease: a fish-like effect of moderate wine drinking.

BACKGROUND: Moderate alcohol drinking and marine omega-3 fatty acids (omega3) have both been associated with low mortality from coronary heart disease (CHD). However, there is little data evaluating the interactions of wine ethanol drinking with omega3 in CHD patients. METHODS: The relationships between wine drinking and marine omega3 were evaluated in a cross-sectional study in patients with CHD participating in a randomized trial testing the effect of a high alpha-linolenic acid (ALA, the main plant omega3) diet. Daily ethanol intake was calculated as energy and expressed as a percentage of total energy. Plant and marine omega3 in the diet were carefully evaluated in each patient in both groups. RESULTS: Patients were classified according to their habitual consumption of ethanol. Patients in the "high ALA group" and controls ("low ALA group") were analyzed separately. Within each group, there was a progressive increase in marine omega3 levels with increased alcohol intake, with a level of eicosapentanoic acid (EPA) that increased by 50% (P < .005) and 37% (P < .05) in the low and high ALA groups, respectively. After controlling for potential confounders (including dietary EPA) in a multivariate linear model, the association between wine ethanol and EPA remained significant in the low (P < .001) and high (P < .05) ALA groups. CONCLUSION: In these patients with CHD, moderate wine drinking was associated with higher marine omega3 concentrations than no alcohol use. Although the data have to be confirmed in large groups, this effect of wine comparable to that of fish may partly explain the protective effects of wine drinking against CHD.

Delayed expression of cytokines after reperfused myocardial infarction: possible trigger for cardiac dysfunction and ventricular remodeling.

Previous studies have shown that 1 wk after permanent coronary artery ligation in rats, some cellular mechanisms involving TNF-alpha occur and contribute to the development of cardiac dysfunction and subsequent heart failure. The aim of the present study was to determine whether similar phenomena also occur after ischemia-reperfusion and whether cytokines other than TNF-alpha can also be involved. Anesthetized male Wistar rats were subjected to 1 h coronary occlusion followed by reperfusion. Cardiac geometry and function were assessed by echocardiography at days 5, 7, 8, and 10 postligation. Before death, heart function was assessed in vivo under basal conditions, as well as after volume overload. Finally, hearts were frozen for histoenzymologic assessment of infarct size and remodeling. The profile of cardiac cytokines was determined by ELISA and ChemiArray on heart tissue extracts. As expected, ischemia-reperfusion induced a progressive remodeling of the heart, characterized by left ventricular free-wall thinning and cavity dilation. Heart function was also decreased in ischemic rats during the first week after surgery. Interestingly, a transient and marked increase in TNF-alpha, IL-1beta, IL-6, cytokine-induced neutrophil chemoattractant (CINC) 2, CINC3, and macrophage inflammatory protein-3alpha was also observed in the myocardium of myocardial ischemia (MI) animals at day 8, whereas the expression of anti-inflammatory interleukins IL-4 and IL-10 remained unchanged. These results suggest that overexpression of proinflammatory cytokines occurring during the first week after ischemia-reperfusion may play a role in the adaptative process in the myocardium and contribute to early dysfunction and remodeling.

Does nitric oxide contribute to progressive cardiac tissue damage and dysfunction after infarction?

Myocardial infarction induces contractile dysfunction and remodeling that can lead to heart failure. Nitric oxide has been proposed as one of the major actors of this pathophysiologic process. We note that N (G)-nitro-L-arginine methyl ester (L-NAME) administration from day 2 to day 7 after myocardial infarction in rats improves stroke volume, preserves cardiac compliance, and reduces infarct expansion. Our observations lead to the hypothesis that the mechanisms by which cytokines contribute to myocardial remodeling and dysfunction in the days after infarction might involve *NO signalling pathways.

Cardioprotective mechanisms of Prunus cerasus (sour cherry) seed extract against ischemia-reperfusion-induced damage in isolated rat hearts.

The effects of kernel extract obtained from sour cherry (Prunus cerasus) seed on the postischemic cardiac recovery were studied in isolated working rat hearts. Rats were treated with various daily doses of the extract for 14 days, and hearts were then isolated and subjected to 30 min of global ischemia followed by 120 min of reperfusion. The incidence of ventricular fibrillation (VF) and tachycardia (VT) fell from their control values of 92% and 100% to 50% (not significant) and 58% (not significant), 17% (P<0.05), and 25% (P<0.05) with the doses of 10 mg/kg and 30 mg/kg of the extract, respectively. Lower concentrations of the extract (1 and 5 mg/kg) failed to significantly reduce the incidence of VF and VT during reperfusion. Sour cherry seed kernel extract (10 and 30 mg/kg) significantly improved the postischemic recovery of cardiac function (coronary flow, aortic flow, and left ventricular developed pressure) during reperfusion. We have also demonstrated that the extract-induced protection in cardiac function significantly reflected in a reduction of infarct size. Immunohistochemistry indicates that a reduction in caspase-3 activity and apoptotic cells by the extract, beside other potential action mechanisms of proanthocyanidin, trans-resveratrol, and flavonoid components of the extract, could be responsible for the cardioprotection in ischemic-reperfused myocardium.

Protection of endothelial-derived vasorelaxation with cariporide, a sodium-proton exchanger inhibitor, after prolonged hypoxia and hypoxia-reoxygenation: effect of age.

Calcium overload during hypoxia and reoxygenation exerts deleterious effects in endothelial and smooth muscle cells but potential effects of sodium-proton exchanger (NHE) inhibitors have never been investigated in both adult and senescent vessels. Isolated aortic rings from adult and senescent rats were submitted to hypoxia (50 min) or to hypoxia/reoxygenation (20/30 min) without or with cariporide (10(-6) M) and aortic vasoreactivity was recorded. After hypoxia, relaxation to acetylcholine was preserved in adult rings treated with cariporide (-22.3% vs. -9.3% of baseline value in control and treated groups respectively, P<0.05) but not in senescents. Cariporide treatment restored relaxation to acetylcholine after hypoxia-reoxygenation in adult rings (-32.04% vs. -0.03% of baseline value in control and treated groups respectively, P<0.01) and to a lesser extent, in senescent rings (-30.8% vs. -24.4% of baseline value in control and treated groups respectively, P<0.01). These results suggested that hypoxia induced lower acidosis and/or involved other mechanisms of proton extrusion than NHE in senescent aorta. Improvement of endothelial function with cariporide after reoxygenation in senescent aorta, but in a lesser extent than in adult aorta, suggests a lower role of NHE in pH regulation and subsequent calcium overload during aging.

Selenium status as determinant of connexin-43 dephosphorylation in ex vivo ischemic/reperfused rat myocardium.

Recent studies have demonstrated that electrical uncoupling at gap junctions during ischemia is associated with cardiac Connexin-43 (Cx43) dephosphorylation. Whether oxidative stress is involved in this phenomenon still remains unclear. In the present study, we examined the influence of selenium intake on reperfusion-induced Cx43 dephosphorylation. Male Wistar rats were fed a diet containing either 0.05 mg/kg (Low-Se, n = 13) or 1.5 mg/kg (High-Se, n = 11) selenium for 8 weeks. At the end of this diet, hearts were isolated and subjected to 10 min regional ischemia followed by 10 min reperfusion. The level of dephosphorylated Cx43 was determined in tissue samples from ischemic/reperfused and non-ischemic regions of the hearts. At the end of the experiemental diet, the activity of the antioxidant enzyme glutathione peroxidase (GSH-Px) was increased in high-Se hearts compared with low-Se hearts (+ 13%; p < 0.05). After ischemia/reperfusion, in low-Se hearts, Cx43 dephosphorylation appeared significantly increased in the left ventricle compared to the non-ischemic right ventricle (+ 149%; p < 0.05). The high-Se diet significantly reduced Cx43 dephosphorylation in the left ventricle (p < 0.05 vs. low-Se diet). In conclusion, our results suggest that oxidative stress may be involved in Cx43 dephosphorylation during myocardial ischemia/reperfusion, thereby contributing to arrhythmogenesis.

AT1 receptor blockade prevents cardiac dysfunction after myocardial infarction in rats.

Myocardial infarction (MI) can induce severe alterations of contractile function that can, in turn, lead to heart failure. In a previous study, we have demonstrated that TNF-alpha was involved in cardiac contractile dysfunction 7 days after coronary artery ligation in rats. Since Angiotensin II type 1 (AT1) receptor can be involved in TNF-alpha production, we have investigated whether early short-term treatment with irbesartan, an AT1 receptor blocker, is able to limit TNF-alpha production within the heart and to improve cardiac function and geometry following MI in rats. Male Wistar rats were subjected to permanent coronary artery ligation and received either a placebo or irbesartan (50 mg/kg/day) per os daily from day 3 to day 6 after surgery. On day 7, cardiac TNF-alpha was significantly reduced in MI rats receiving irbesartan (p < 0.05). Moreover, irbesartan improved residual LV end-diastolic pressure under both basal conditions and after volume overload (p < 0.01). In addition, a significant leftward shift of the pressure-volume curve in the irbesartan-treated group was found versus placebo. Finally, infarct expansion index was also significantly improved by irbesartan (p < 0.01). In conclusion, early, short-term AT1 receptor blockade limits post-infarct cardiac TNF-alpha production and diminishes myocardial alterations observed 7 days after MI in the rat.

Early pre-diabetic state alters adaptation of myocardial glucose metabolism during ischemia in rats.

Pre-diabetic subjects with high insulin secretory capacity have double risk of cardiovascular disease compared with subjects who do not develop insulin-resistance. It is well established that the ability of the myocardium to increase its glycolytic ATP production plays a crucial role in determining cell survival under conditions of ischemia. Up to now, whether the pre-diabetic state reduces the tolerance of the heart to ischemia by affecting its ability to increase its energy production through glycolysis remains unknown. The aim of the present study was to assess whether insulin resistance affects the ability of the myocardium to increase glycolysis under ischemic conditions. Male Wistar rats were fed for 8 weeks a fructose-enriched (33%) diet to induce a pre-diabetic state. Hearts were isolated and subjected to ex-vivo low-flow (2%) ischemia for 30 min. The fructose diet increased sarcolemmal GLUT4 localisation in myocardial cells under basal conditions compared with controls. This effect was not accompanied by increased glucose utilisation. Ischemia induced the translocation of GLUT4 to the plasma membrane in controls but did not significantly modify the distribution of these transporters in pre-diabetic hearts. Glycolytic flux under ischemic conditions was significantly lower in fructose-fed rat hearts compared with controls. The reduction of glycolytic flux during ischemia in fructose-fed rat hearts was not due to metabolic inhibition downstream hexokinase II since no cardiac accumulation of glucose-6-phosphate was detected. In conclusion, our results suggest that the pre-diabetic state reduces the tolerance of the myocardium to ischemia by decreasing glycolytic flux adaptation.

Lipid-lowering drugs and essential omega-6 and omega-3 fatty acids in patients with coronary heart disease.

BACKGROUND AND AIM: There are only little data about the effects of lipid-lowering drugs (LLDs) on the metabolism of essential n-6 and n-3 fatty acids in patients with established coronary heart disease (CHD). METHODS AND RESULTS: Male patients with CHD and high cholesterol levels (>6.2 mmol/L) were randomized (double-blind protocol) to receive either simvastatin 20mg (S) or fenofibrate 200mg daily (F) for 3 months. Dietary habits and plasma fatty acids were not different in the two groups at baseline. After treatment, there were significant changes in both the groups for the main n-6 fatty acids, with an increase in arachidonate (from 6.5+/-1.7% of total fatty acids to 7.5+/-2.1, p<0.001 in S and from 6.2+/-1.4 to 6.8+/-1.4, p<0.005 in F) and a decrease in linoleate (from 26.9+/-3.9 to 24.2+/-3.6, p<0.001, and from 27.8+/-3.4 to 26.1+/-4.2, p<0.05, in S and F, respectively). In addition, there was a decrease in two major n-3 fatty acids (alpha-linolenate and docosahexanoate, both p<0.05), but only in F. CONCLUSIONS: For the first time in a double-blind randomized study in CHD patients, we report that LLDs significantly alter the metabolism of essential fatty acids that are critically important for the pathogenesis and prevention of CHD. Further studies are urgently needed to examine the effects of higher dosages of statins (as currently proposed to reduce more cholesterol) on these essential fatty acids in the clinical setting and the crucial questions of whether specific dietary intervention (combining low intake of n-6 fatty acids and high intake of n-3 fatty acids) may improve the effectiveness of these drugs.

Heme oxygenase-1-related carbon monoxide and flavonoids in ischemic/reperfused rat retina.

PURPOSE: There is increasing evidence to show cytoprotective effects of various flavonoid-rich extracts and the tissue-protective capacity of flavonoid-rich extract of sour cherry is due to flavonoid components of seeds. Sour cherry seed flavonoids were evaluated for their contribution to postischemic recovery related to endogenous carbon monoxide (CO) production in rat retinas subjected to ischemia/reperfusion. METHODS: Rats were orally treated with selected doses of flavonoid-rich extract of sour cherry seeds for 2 weeks. Animals were anesthetized, and a suture was placed behind the globe including the central retinal artery. Next, retinas were subjected to 90 minutes of ischemia followed by 24 hours of reperfusion. After this procedure, heme oxygenase-1 (HO-1)-related protein expression and enzyme activity, HO-1-related endogenous CO production, and ionic imbalance including tissue Na(+), K(+), and Ca(2+) in untreated and treated ischemic/reperfused retinas were measured. RESULTS: Retinal ischemia/reperfusion resulted in a significant reduction (to 10%) in HO-1 protein expression, enzyme activity, and HO-1-related endogenous CO production in the retina. These changes were accompanied by increases in retinal Na(+) and Ca(2+) gains and loss of K(+). In rats treated with 10 and 30 mg/kg of sour cherry flavonoid-rich extract, after 24 hours of reperfusion, tissue Na(+) and Ca(2+) accumulation and K(+) loss were prevented in comparison with the drug-free control. CONCLUSIONS: Sour cherry seed flavonoid-rich extract showed a protective effect against reperfusion-induced injury through its ability to reduce the changes in concentrations of retinal ions through HO-1-related endogenous CO production in the ischemic/reperfused retina.

Preischemic selenium status as a major determinant of myocardial infarct size in vivo in rats.

Prospective epidemiological studies have shown that the incidence of numerous cardiovascular pathologies is correlated with body selenium status. However, it remains unclear whether selenium status also influences the outcome of myocardial infarction. The aim of the present study was to test whether dietary selenium intake affects myocardial necrosis induced by transient regional ischemia in vivo in rats. For this purpose, male Wistar rats received either a high-selenium (High-Se: 1.5 mg of Se/kg) or a low-selenium (Low-Se: 0.05 mg of Se/kg) diet for 10 weeks. Animals were subjected to 30 min of myocardial ischemia induced by coronary artery ligation followed by 60 min of reperfusion. Pre- and postischemic blood samples were collected for glutathione (GSH and GSSG) determination and for glutathione peroxidase (GSH-Px) assessment. Our results show that high-selenium intake reduces myocardial infarct size (High-Se: 25.16 +/- 1.19% versus Low-Se: 36.51 +/- 4.14%, p < 0.05), preserves postischemic GSH/GSSG ratio (High-Se: 1.37 +/- 0.37 versus Low-Se: 0.47 +/- 0.10, p < 0.05), increases plasma GSH-Px activity, and improves postischemic mean arterial pressure. In conclusion, preischemic body selenium status is a major determinant of the outcome of myocardial ischemia in vivo in rats probably because it influences the cellular redox status.