1,721,059 research outputs found
Na+/H+-exchanger and Na+/Ca2+-exchanger activation determinate the delayed stretch induced inotropy in human myocardium
No full textSerotonin Syndrome with Severe Hyperthermia after Ingestion Of Tranylcypromine Combined with Serotonin Reuptake Inhibitors and Tyramine-Rich Food in a Case of Suicide
No full textInsulin causes [Ca2+](i)-dependent and [Ca2+](i)-independent positive inotropic effects in failing human myocardium
No full textBackground - Insulin has been shown to exert positive inotropic effects in several in vitro and in vivo models, but signal transduction and substrate dependency remain unclear. We examined inotropic responses and signal transduction mechanisms of insulin in human myocardium. Methods and Results - Experiments were performed in isolated trabeculae from end- stage failing hearts of 58 nondiabetic and 3 diabetic patients undergoing heart transplantation. The effect of insulin ( 0.3 and 3 IU/ L) on isometric twitch force ( 37 degrees C, 1 Hz) was tested in the presence of glucose or pyruvate as energetic substrate. Furthermore, intracellular Ca2+ transients ( aequorin method), sarcoplasmic reticulum ( SR) Ca2+ content ( rapid cooling contractures), and myofilament Ca2+ sensitivity ( semiskinned fibers) were assessed. In addition, potential signaling pathways were tested by blocking glycolysis, PI- 3- kinase, protein kinase C, diacylglycerol kinase, insulin- like growth factor- 1 receptors, or transsarcolemmal Ca2+ entry via the Na+/Ca2+ exchanger. Insulin exerted concentration- dependent and partially substrate- dependent positive inotropic effects. The phosphatidylinositol- 3- kinase inhibitor wortmannin and the Na2+/Ca2+ exchanger reverse- mode inhibitor KB- R7943 completely or partially prevented the functional effects of insulin. In contrast, insulin- like growth factor- 1 receptor blockade, protein kinase C inhibition, and diacylglycerol kinase blockade were without effect. The inotropic response was associated with increases in intracellular Ca2+ transients, SR Ca2+ content, and increased myofilament Ca2+ sensitivity. Conclusions - Insulin exerts Ca2+- dependent and - independent positive inotropic effects through a phosphatidylinositol3- kinase - dependent pathway in failing human myocardium. The increased [ Ca2+] (i) originates at least in part from enhanced reverse- mode Na+/Ca2+ exchange and consequently increased SR- Ca2+ load. These nongenomic functional effects of insulin may be of clinical relevance, eg, during insulin- glucose- potassium infusions
Letter regarding article by von Lewinski et al, "Insulin causes [Ca2+](i)-dependent and [Ca2+](i)-independent positive inotropic effects in failing human myocardium" - Reply
No full textAtrial myocardium is the predominant inotropic target of adrenomedullin in the human heart
No full textAtrial myocardium is the predominant inotropic target of adrenomedullin in the human heart. Am J Physiol Heart Circ Physiol 293: H3001-H3007, 2007. First published August 31, 2007; doi:10.1152/ajpheart.01276.2006. - Adrenomedullin ( ADM) is an endogenous peptide with favorable hemodynamic effects in vivo. In this study, we characterized the direct functional effects of ADM in isolated preparations from human atria and ventricles. In electrically stimulated human nonfailing right atrial trabeculae, ADM (0.0001- 1 mu mol/l) increased force of contraction in a concentration-dependent manner, with a maximal increase by 35 +/- 8% ( at 1 mu mol/l; P < 0.05). The positive inotropic effect was accompanied by a disproportionate increase in calcium transients assessed by aequorin light emission [ by 76 +/- 20%; force/ light ratio (Delta F/Delta L) 0.58 +/- 0.15]. In contrast, elevation of extracellular calcium ( from 2.5 to 3.2 mmol/l) proportionally increased force and aequorin light emission (Delta F/Delta L 1.0 +/- 0.1; P < 0.05 vs. ADM). Consistent with a cAMP-dependent mechanism, ADM ( 1 mu mol/l) increased atrial cAMP levels by 90 +/- 12%, and its inotropic effects could be blocked by the protein kinase A (PKA) inhibitor H-89. ADM also exerted positive inotropic effects in failing atrial myocardium and in nonfailing and failing ventricular myocardium. The inotropic response was significantly weaker in ventricular vs. atrial myocardium and in failing vs. nonfailing myocardium. In conclusion, ADM exerts Ca2+-dependent positive inotropic effects in human atrial and less-pronounced effects in ventricular myocardium. The inotropic effects are related to increased cAMP levels and stimulation of PKA. In heart failure, the responsiveness to ADM is reduced in atria and ventricles
Mechanistic insight into the functional and toxic effects of Strophanthidin in the failing human myocardium
No full textBackground: Cardiac glycosides are characterized by a narrow therapeutic range with Ca2+ -overload and arrhythmias occurring at higher concentrations. Data on cardiac glycosides in isolated failing human myocardium are scarce and the frequency-dependent actions and toxicity of Strophanthidin have not yet been characterized. Aims: To determine inotropic responses and toxicity of Strophanthidin in failing human myocardium. Methods and results: Experiments were performed in trabeculae from 64 end-stage failing hearts. Developed force, and intracellular [Ca2+] and [Na+](i) were recorded with Strophanthidin (0.01 to 1 mu mol/L; 37 degrees C, 1 Hz) and compared to interventions with distinct mechanisms of action (elevated [Ca2+](o), Isoproterenol, and EMD57033). The effects of Strophanthidin on force-frequency behaviour were also assessed. Strophanthidin exerted concentration-dependent positive inotropic effects. These were paralleled by increases in intracellular [Na+] as well as increasing [Ca2+](i)-transients and SR-Ca2+-load. At high concentrations (>0.5 mu mol/L), Strophanthidin caused afterglimmers and aftercontractions, with declining developed force despite further increasing [Ca2+](i)-transients. The force-frequency-relationship and diastolic function at higher pacing rates was worsened by Strophanthidin in a concentration-dependent manner. Conclusions: Strophanthidin toxicity was dependent on concentration, calcium load, beating rate and beta-adrenergic receptor activation. Our data support the view that low doses, heart rate control and additional P-adrenergic receptor blockade are essential in the use of cardiac glycosides in heart failure. (c) 2007 European Society of Cardiology. Published by Elsevier B.V. All rights reserved
Letter regarding article by von Lewinski et al, "Insulin causes [Ca2+](i)-dependent and [Ca2+](i)-independent positive inotropic effects in failing human myocardium" - Reply
No full textp38 MAP kinase and oxygen radicals mediate progressive right ventricular force decline after acute stretch
No full text
- …
