Journal of cardiovascular pharmacology and therapeutics
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J. Cardiovasc. Pharmacol. Ther. · Sep 2016
Effects of Combined Milrinone and Levosimendan Treatment on Systolic and Diastolic Function During Postischemic Myocardial Dysfunction in a Porcine Model.
It is not known whether there are positive or negative interactions on ventricular function when a calcium-sensitizing inotrope is added to a phosphodiesterase inhibitor in the clinical setting of acute left ventricular (LV) dysfunction. We hypothesized that when levosimendan is added to milrinone treatment, there will be synergetic inotropic and lusitropic effects. This was tested in an anesthetized porcine postischemic global LV injury model, where ventricular pressures and volumes (conductance volumetry) were measured. ⋯ The latter effect could however not be attributed solely to levosimendan, since lusitropic state also improved spontaneously in time-matched controls at the same rate during the corresponding period. When levosimendan was added to milrinone infusion, there was no increase in systolic function (preload recruitable stroke work) compared to milrinone treatment alone. We conclude that in this model of postischemic LV dysfunction, there appears to be no clear improvement in systolic or diastolic function after addition of levosimendan to established milrinone treatment but also no negative effects of levosimendan in this context.
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J. Cardiovasc. Pharmacol. Ther. · Sep 2016
Berberine Pretreatment Confers Cardioprotection Against Ischemia-Reperfusion Injury in a Rat Model of Type 2 Diabetes.
Preclinical and clinical studies have demonstrated that berberine (BBR) improves diabetic complications and reduces mortality of patients with congestive heart failure. The therapeutic effects of BBR have been reported to be mediated by its regulation of adenosine monophosphate (AMP)-activated protein kinase (AMPK). We previously reported that BBR protects against ischemia-reperfusion injury via regulating AMPK activity in both ischemic and nonischemic areas of the rat heart. ⋯ In addition, pretreatment with BBR increased protein kinase B (AKT) phosphorylation and reduced glycogen synthase kinase 3β (GSK3β) activity in nonischemic areas compared to untreated diabetic controls. These findings indicate that BBR protects the diabetic heart from ischemia-reperfusion injury. In addition, BBR may mediate this cardioprotective effect through AMPK activation, AKT phosphorylation, and GSK3β inhibition in the nonischemic areas of the diabetic heart.