Fluvastatin attenuates diabetes-induced cardiac sympathetic neuropathy in association with a decrease in oxidative stress.

Background: Increased oxidative stress might contribute to diabetic (DM) neuropathy, so the effects of long-term treatment with fluvastatin (FL) on myocardial oxidative stress and cardiac sympathetic neural function were investigated in diabetic rats.

Methods And Results: FL (10 mg . kg(-1) .

Atorvastatin-induced changes in plasma coenzyme q10 and brain natriuretic peptide in patients with coronary artery disease.

The beneficial effects of statins in patients with coronary artery disease (CAD) may be balanced by concerns that statins can depress production of ubiquinone (CoQ10), which serves as a component of mitochondrial energy production and an antioxidant. Accordingly, the effects of atorvastatin (ATO)-induced changes in plasma CoQ10 on BNP and oxidative stress were investigated. In 29 patients with CAD, the plasma levels of CoQ10 and BNP and urinary excretion of 8-iso-prostaglandin F2alpha (8-iso-PGF) were determined before and after 3-month treatment with ATO.

Ischemic preconditioning accelerates the fatty acid oxidation of rat hearts.

Background: Ischemic preconditioning (IPC) reduced myocardial ATP depletion during sustained ischemia and has a powerful protective effect on the myocardium. The purpose of the present study was to clarify the effects of IPC on myocardial accumulation of fatty acid (FA) tracer and its intracellular metabolism.

Methods: Myocardial ischemia-reperfusion (MI-R) injury was induced by the left coronary artery ligation for 15 min followed by reperfusion in Wistar rats.

Early administration of fluvastatin, but not at the onset of ischemia or reperfusion, attenuates myocardial ischemia-reperfusion injury through the nitric oxide pathway rather than its antioxidant property.

Background: Three-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) are known to attenuate myocardial ischemia-reperfusion (IR) injury. Fluvastatin (FV) has a potent free radical scavenging action, but it is unclear whether the timing of FV administration could affect its cardioprotective effect or if the antioxidant property of FV might attenuate IR injury.

Methods And Results: IR was induced in rats by left coronary artery occlusion for 30 min followed by 24-h reperfusion.

Influence of beta-adrenoceptor blockade on the myocardial accumulation of fatty acid tracer and its intracellular metabolism in the heart after ischemia-reperfusion injury.

Background: Increases in sympathetic nerve activity during ischemia may increase intracellular fatty acid (FA) accumulation via enhanced FA uptake and inhibition of beta-oxidation. Therefore, the beneficial effects of beta-adrenoceptor blockade on myocardial ischemic injury might result from the suppression of FA accumulation.

Methods And Results: Carvedilol (1 mg/kg) or propranolol (1 mg/kg) was injected 10 min before 15-min occlusion of coronary artery in rats.

Brief episode of myocardial ischemia before prolonged ischemia attenuates cardiac sympathetic nerve injury.

Background: The aim of this study was to investigate the effects of brief ischemia before prolonged ischemia on cardiac sympathetic neural function. Brief ischemia inhibits the sympathetic neural release of norepinephrine (NE) during subsequent sustained ischemia. However, whether it can attenuate the neural function after sustained ischemia remains unknown.

Influence of CYP2D6 genotype on metoprolol plasma concentration and beta-adrenergic inhibition during long-term treatment: a comparison with bisoprolol.

In patients routinely treated with metoprolol, influences of CYP2D6 genotype on the response of heart rate to isoproterenol (IP) were studied at its peak and trough concentrations and were compared with those of bisoprolol. In 72 patients treated with metoprolol or bisoprolol, CYP2D6 genotype (ie, CYP2D6*1, *2, *4, *5, *10, and *14) was determined. No patients except one who was heterozygous for CYP2D6*5 carried the null alleles of CYP2D6.

Effect of CYP2D6*10 on the pharmacokinetics of R- and S-carvedilol in healthy Japanese volunteers.

This study was performed to investigate the effect of CYP2D6*10 on the pharmacokinetics of R- and S-carvedilol in healthy Japanese volunteers. Five or 10 mg of carvedilol was orally administered to 23 subjects (22-44 years old), and blood samples were taken at 2 and 6 h after dosing. We determined the polymorphic alleles of CYP2D6 in each subject.

Ischemia-induced norepinephrine release, but not norepinephrine-derived free radicals, contributes to myocardial ischemia-reperfusion injury.

Background: Norepinephrine (NE)-derived free radicals may contribute to myocyte injury after ischemia -reperfusion, so the influence of sympathetic denervation on myocardial ischemia - reperfusion injury was investigated in the present study.

Methods And Results: Cardiac sympathetic denervation was produced in Wistar rats by a solution of 10% phenol 1 week before ischemia. Atenolol (0.

Evaluation of fatty acid metabolism in hearts after ischemia-reperfusion injury using a dual-isotope autoradiographic approach and tissue assay for metabolites of tracer.

Unlabelled: We investigated whether changes in myocardial uptake of fatty acid tracer after reperfusion following transient myocardial ischemia were closely related to alterations in intracellular fatty acid oxidation.

Methods: Using a fatty acid tracer of (131)I- and (125)I-labeled 15-(p-iodophenyl)-9-methylpentadecanoic acid (9MPA), the myocardial uptake and metabolites were determined by dual-tracer autoradiography and thin-layer chromatography in rats 3 or 14 d after reperfusion following 5 or 15 min of ischemia induced by coronary artery ligation.

Results: 9MPA metabolites processed via beta-oxidation were lower in the ischemic region (IR) than in non-IR 3 d after 5 min of ischemia, despite no reduction of tracer uptake in IR.

Discrepant recovery course of sympathetic neuronal function and beta-adrenoceptors in rat hearts after reperfusion following transient ischemia.

Unlabelled: Cardiac sympathetic neuronal function is closely coupled with beta-adrenoceptors and adrenergic signaling. However, the recovery process of sympathetic neuronal function and beta-adrenoceptors after reperfusion following transient ischemia is not fully understood. Accordingly, this study was performed to investigate serial changes in sympathetic neuronal function and beta-adrenoceptors after transient myocardial ischemia.

Saturated glucose uptake capacity and impaired fatty acid oxidation in hypertensive hearts before development of heart failure.

Abnormalities in energy metabolism may play an important role in the development of hypertensive heart failure. However, the transition from compensated hypertrophy to heart failure is not fully understood in terms of energy metabolism. In Dahl salt-sensitive (DS) and salt-resistant (DR) rats, myocardial fatty acid and glucose uptake values were determined using (131)I- or (125)I-labeled 9-methylpentadecanoic acid ((131)I- or (125)I-9MPA), and [(14)C]deoxyglucose ([(14)C]DG), fatty acid beta-oxidation was identified using thin-layer chromatography, and insulin-stimulated glucose-uptake was observed using a euglycemic hyperinsulinemic glucose clamp.

Supersensitive response to isoproterenol in patients with marked global reduction of cardiac metaiodobenzylguanidine uptake.

It is unknown whether the non-transplanted, denervated human heart is supersensitive to beta-adrenergic agonist in terms of inotropism and chronotropism. In the present study, 36 patients with normal left ventricular (LV) wall motion were divided into 3 groups according to the cardiac metaiodobenzylguanidine (MIBG) scintigrams: group I with normal MIBG uptake, group II with regionally reduced MIBG uptake, and group III with globally reduced MIBG uptake (heart-to-mediastinum ratio <1.6).