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.

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).

Long-term treatment with low-dose, but not high-dose, guanethidine improves ventricular function and survival of rats with heart failure after myocardial infarction.

Objectives: We sought to evaluate the effects of various doses of guanethidine, a sympathoinhibitory drug, on ventricular function and survival in chronic heart failure (CHF) after myocardial infarction (MI) in rats.

Background: Direct inhibition of sympathetic outflow by a sympathoinhibitory drug might be an effective approach to therapy of CHF. However, recent clinical trials suggest that excessive suppression of sympathetic activity has an adverse effect on outcome.

Effects of the angiotensin-converting enzyme inhibitor enalapril on sympathetic neuronal function and beta-adrenergic desensitization in heart failure after myocardial infarction in rats.

One of the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors in the treatment of heart failure may derive from sympathoinhibition and the prevention of beta-adrenergic desensitization. However, the roles of these properties in the overall effects of ACE inhibitor are not clear. We studied the effects of chronic enalapril treatment (20 mg/L in drinking water for 12 weeks) on left ventricular (LV) function, cardiac norepinephrine (NE), sympathetic neuronal function assessed by 131I-metaiodobenzylguanidine (MIBG), beta-receptors, and isometric contraction of papillary muscle in rats with myocardial infarction (MI) induced by coronary artery ligation.

Effects of long-term renal sympathetic denervation on heart failure after myocardial infarction in rats.

The purpose of the present study was to investigate the effects of long-term renal denervation (RD) on heart failure due to myocardial infarction (MI). Wistar rats were anesthetized and the bilateral renal nerves were surgically denervated 2 days before MI was induced by coronary artery ligation. Four weeks later, left ventricular (LV) function and sodium excretion were determined.