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The aim of this study was to evaluate the involvement of mitochondria in the mechanism of the anti-arrhythmic lidocaine. Rats were fed with a diet containing either n-6 polyunsaturated fatty acids (PUFAs, SSO group) or an equimolecular mixture of n-3 and n-6 PUFAs (FO group) for 8 weeks. The hearts were perfused according to the working mode using a medium with or without lidocaine 5 μM. They were then subjected to local ischemia (20 min) and reperfusion (30 min). Dietary n-3 PUFAs triggered the expected decrease in the n-6/n-3 PUFA ratio of cardiac phospholipids. Reperfusing the ischemic area favored the incidence of severe arrhythmias. Lidocaine treatment abolished almost completely reperfusion arrhythmias in the FO group, but did not display anti-arrhythmic properties in the SSO group. As it was indicated by measurements of the mitochondrial function, lidocaine seemed to favor mitochondrial calcium retention in the FO group, which might prevent cytosolic calcium spikes and reperfusion arrhythmias. In the SSO group, the resistance to lidocaine was associated with an aggravation of cellular damages. The mitochondrial calcium retention capacities were saturated, and lidocaine was unable to increase them, making the drug inefficient in preventing reperfusion arrhythmias.

Brain-derived neurotrophic factor (BDNF) and TrK receptors play an important role in vascular development and response to injury. In this study, we investigated the participation of the BDNF/TrK pathway and oxidative stress during the development of hypertension in spontaneously hypertensive rats (SHR). In SHR and normotensive rats (WKY) at 6 and 13 weeks of age, we studied (i) plasma antioxidant capacity, (ii) production of superoxide and NAD(P)H oxidase activity in aorta (iii) plasma BDNF and vascular expression of BDNF, TrKB, NAD(P)H oxidase subunits, AT1 receptor, and MCP-1. In 6- and 13-week-old SHR aorta, superoxide level was twice than in WKY aorta. At 13 weeks, when blood pressure in SHR was 60 mmHg higher in SHR than in WKY, an enhancement of NAD(P)H oxidase activity in SHR was associated with an increase in p47phox, AT1, and BDNF expression in vessels. MCP-1 expression increased with blood pressure. Our study demonstrated that in SHR rats, an increase in levels of vascular oxidative stress and in aortic BDNF and TrKB expression occurs prior to the rise in blood pressure, while a reinforcement of vascular and circulating oxidative stress markers is brought about later by hypertension.

Little is known about the role of neurotrophins (NT) under adult vascular homeostasis in normal and pathological conditions. The NT family, including nerve growth factor and brain-derived neurotrophic factor (BDNF) are expressed in atherosclerotic vessels. Previous studies demonstrated that plasma BDNF levels were increased in the coronary circulation in patients with unstable angina. However, the role of BDNF during the onset and evolution of unstable angina remains to be elucidated. The objective of this study was to evaluate the relationship between BDNF, functional parameters and biological markers associated with inflammatory processes and platelet activation. BDNF serum levels were assessed in patients with acute myocardial infarction (MI) (n = 20) or stable angina pectoris (SAP) (n = 20) who underwent coronary angiography. Serum levels of IL-6, MCP1, sVCAM, soluble CD-40-ligand (sCD40L) and soluble P-selectin (sP-selectin) were measured simultaneously by flux cytometry. Median BDNF levels were higher in the MI than in the SAP group (1730 vs. 877 pg/mL, respectively; P = 0.025). In MI patients, we observed a significant correlation between BDNF and sP-selectin (r = 0.58, P = 0.023), although we found a non-significant trend between BDNF and sCD40L (r = +0.35, P = 0.144). By contrast, no such correlation was observed in SAP patients (r = -0.22, P = 0.425). No difference was observed between the two groups regarding baseline demographics, risk factors, biological data and angiographic findings. The study suggests that BDNF serum levels in MI patients could be related to platelet activation and the inflammatory response. Further studies are needed to investigate the role of NT in the setting of acute MI.

We wondered if Zucker obese (ZO) rats would be a good experimental model to evaluate cardiovascular complications of metabolic syndrome (MS). ZO rats were compared with both their littermate controls, Zucker lean (ZL) rats and to Wistar rats (reference strain). We designed this work:(i) to measure certain physical and biochemical characteristics of MS; (ii) to evaluate coronary and cardiac function in isolated conditions and after ischemia; and (iii) to study plasma and heart tissue oxidative stress markers. In vivo, ZO rats had higher levels of plasma glucose, cholesterol and triglycerides than their ZL littermates, but there was no difference between the groups for systolic arterial blood pressure and heart rate. In vitro, coronary endothelial function was notably impaired in ZO and ZL rats. After global ischemia, the worse ventricular recovery in ZO and ZL rats was associated with arrhythmias during reperfusion. We detected similar levels of plasma ascorbyle free radical, oxygen radical absorbance capacity and vitamin C concentrations in the three groups. Dihydroethidium staining showed higher superoxide production in the coronary vessels of ZO rats than in ZL and Wistar rats. Our results show that ZO might only correspond to early-stage cardiovascular complications associated with MS.

Heart transplant is considered to be an extremely severe ischemia-reperfusion sequence. Post-ischemic dysfunction triggers multiple processes especially oxidative stress, but the mechanisms remain unclear. Free radical interactions lead to peroxynitrite generation, which seems to be involved in early post-transplant heart failure. The aim of this study was to evaluate the potential impact of a peroxynitrite decomposition catalyst: FeTPPS (5,10,15,20-tetrakis-[4-sulfonatophenyl]-porphyrinato-fer[III]) and pyruvate on myocardial functional recovery after cardioplegic arrest using an experimental protocol in rat hearts. Isolated working rat hearts were subjected to ischemia (4 h at 4 degrees C in cardioplegic solutions), followed by 45 min of reperfusion. Four groups were constituted: control, pyruvate: (2 mm) added to cardioplegic and Ringer-lactate solutions, FeTPPS: (10 microm) perfused during the reperfusion, and a combination of both treatments. Lactate dehydrogenase (LDH) activity was assessed during the reperfusion to evaluate the level of cardiac injury. Oxidative stress was evaluated on heart slices using a fluorescent probe: dihydroethidium, and the collagen content was assessed using picro-Sirius coloration. Global post-ischemic recovery in the control group was about 35% of pre-ischemic values. Results showed that addition of pyruvate led to an increase in myocardial function and to a decrease in LDH activity released during the reperfusion. FeTPPS protected against injury after cardioplegic arrest during reperfusion. No additive effect of the two treatments (pyruvate + FeTPPS) was observed. The collagen content was better preserved in the FeTPPS group than in the control and pyruvate groups. In conclusion, this study shows that peroxynitrite plays an important role in the functional and cellular alterations associated with cardiac ischemia-reperfusion sequences and confirms that pyruvate helped to preserve myocardial function. The use of the peroxynitrite decomposition catalyst (FeTPPS) may help to improve myocardial preservation during a prolonged ischemia sequence.

Glyceryl trinitrate (GTN) is commonly delivered by a patch for the treatment of angina pectoris. The idea is now generally accepted that GTN requires a biotransformation process that activates the drug, in particular through nitric oxide (NO) generation. However, the pharmacokinetics of NO delivery from GTN still remains obscure. The objective of this study was to assess GTN-derived NO formation in vascular tissues and organs in rabbit given GTN patches. NO levels were evaluated in rabbits after 3 h of treatment with a 10 mg GTN patch (GTN group; n = 7) or a placebo patch (CTL; n = 7). Nitrosylhaemoglobin (HbNO) was evaluated by electron spin resonance (ESR) spectroscopy in red cell suspension. In vivo spin trapping technique using FeMGD as a spin trap, associated with ESR was used to quantify NO in tissues. The NO-spin trap complex, which is a relatively stable product, has been measured in several tissues. The ESR spectrum corresponding to HbNO was not found in red cell of GTN or CTL rabbits. The spectrum corresponding to the NO-spin trap complex was observed in all analysed tissues of CTL rabbits. The signal was significantly increased in liver, renal medulla, heart left ventricle and spleen of GTN-treated rabbits, and to a lesser extent in right ventricle and lung. No difference was shown between NO-spin trap levels measured in aorta or inferior vena cava from GTN or CTL rabbits. These data suggest that GTN patch treatment induced NO release, and that tissue-specific differences in transdermal GTN-derived NO exist. The GTN-NO pathway appears to be largely involved in organs such as the liver, kidney and heart.