Murat Ikizler

Cardioprotection with resveratrol pretreatment: improved beneficial effects over standard treatment in rat hearts after global ischemia

Objective—The major objective of the present study is to evaluate the potential role of resveratrol (RVT), a natural antioxidant found in grapes and red wine, in protecting the myocardium from the deleterious effects of ischemia‐reperfusion (I/R) injury using isolated rat hearts. Methods—Langendorff perfused isolated rat hearts were subjected to 60 min of global ischemia following 60 min of reperfusion. RVT was given according to chronic pretreatment and/or acute treatment protocols. Animals received RVT at the dose of 20 mg/kg via an intragastric tube for 14 days before the experiment and/or at the infusion concentration of 10 μM for 30 min before the onset of ischemia. The myocardial postischemic recovery was compared using hemodynamic data (peak systolic pressure, end diastolic pressure, and +dP/dt max ), coronary flow, biochemical parameters (LDH, CK‐MB, cTnI, myoglobin) from coronary effluent, and oxidative stress markers (MDA, GSH, carbonyl) from heart tissue homogenates in each group. Results—RVT pretreatment and treatment protocols have provided increased preservation in myocardial recovery following global ischemia compared to a non‐treated group. Furthermore, the ischemic damage of myocardium was significantly lower in chronic pretreated rats than in the acutely treated group. In contrast, no significant difference was observed in cardioprotective effects of RVT between the only pretreated group, and both the pretreated and treated group throughout reperfusion. Conclusion—The findings from this study indicate that RVT has potent cardioprotective properties against I/R injury in rat hearts. The study also highlighted that the administration of RVT, as pretreatment, has amplified the beneficial effects over the standard treatment.

An alternative agent for radial arterial graft spasm: application of topical iloprost.

Objective. This study is planned bringing about a new choice for the prophylaxis of RA spasm which is topical iloprost and compares its efficacy with papaverine and diltiazem. Design. Twenty eight CABG patients with RA grafts were categorized into four groups by taking into account the topical vasodilator (papaverine, diltiazem, iloprost and saline) that was utilized during harvesting. Arterial segments were separated into four rings and were than soaked with KCL, norepinephrine, phenylephrine and serotonin. Then, acetylcholine was given to induce relaxation and the preparations were put to rest for 10 minute. Results. The contraction response achieved by the vasoreactive agents was most effectively inhibited by papaverine. The effectiveness of the response obtained by iloprost was similar to that of papaverine and significantly stronger than that of diltiazem. Especially at high vasoreactive substance concentrations, diltiazem had a contraction close to that of the control while the protective effect was weaker than those of papaverine and iloprost. Conclusion. Iloprost can be recommended as a strong alternative to the topical agents used for preventing arterial graft spasm.

Positive inotropic, positive chronotropic and coronary vasodilatory effects of rat amylin: mechanisms of amylin-induced positive inotropy

Even though there are a few studies dealing with the cardiac effects of amylin, the mechanisms of amylin-induced positive inotropy are not known well. Therefore, we investigated the possible signaling pathways underlying the amylin-induced positive inotropy and compared the cardiac effects of rat amylin (rAmylin) and human amylin (hAmylin).Isolated rat hearts were perfused under constant flow condition and rAmylin or hAmylin was infused to the hearts. Coronary perfusion pressure, heart rate, left ventricular developed pressure and the maximum rate of increase of left ventricular pressure (+dP/dtmax) and the maximum rate of pressure decrease of left ventricle (-dP/dtmin) were measured.rAmylin at concentrations of 1, 10 or 100 nM markedly decreased coronary perfusion pressure, but increased heart rate, left ventricular developed pressure, +dP/dtmax and -dP/dtmin. The infusion of H-89 (50 μM), a protein kinase A (PKA) inhibitor did not change the rAmylin (100 nM)-induced positive inotropic effect. Both diltiazem (1 μM), an L-type Ca2+ channel blocker and ryanodine (10 nM), a sarcoplasmic reticulum (SR) Ca2+ release channel opener completely suppressed the rAmylin-induced positive inotropic effect, but staurosporine (100 nM), a potent protein kinase C (PKC) inhibitor suppressed it partially. hAmylin (1, 10 and 100 nM) had no significant effect on coronary perfusion pressure, heart rate and developed pressure, +dP/dtmax and -dP/dtmin.We concluded that rAmylin might have been produced vasodilatory, positive chronotropic and positive inotropic effects on rat hearts. Ca2+ entry via L-type Ca2+ channels, activation of PKC and Ca2+ release from SR through ryanodine-sensitive Ca2+ channels may be involved in this positive inotropic effect. hAmylin may not produce any significant effect on perfusion pressure, heart rate and contractility in isolated, perfused rat hearts.

The Effectiveness of Ischemic Preconditioning on Myocardial Protection and Comparison with K+ Cardioplegia

The purpose of this study is to investigate the effects of ischemic preconditioning on myocardial protection and to compare this method to K(+) crystalloid cardioplegia. Langendorff perfused isolated working rat hearts were used in the following groups. After 20 min of stabilisation, 30 hearts were divided into three groups. In group I (control, n=10), hearts were arrested with cold (+4 degrees C) Krebs-Henseleit (K-H) solution, in group II (cardioplegia, n=10) hearts were arrested with cold K(+) cardioplegia solution, and in group III (preconditioning, n=10) hearts were subjected to 5 min normothermic ischemia followed by 5 min reperfusion then arrested with cold K-H solution. All hearts were subjected to 30 min of global ischemia (24 degrees C) and 40 min of reperfusion. Hemodynamic measurements were performed with a left ventricular latex balloon using a data acquisition system. Creatine kinase (CK-MB) washout and Troponin I (cTnI) levels were determined from the coronary effluents. There was no significant difference among the three groups in any of the parameters (hemodynamic and biochemical) measured at the end of stabilisation period. During reperfusion, functional recovery and coronary flow were significantly improved in K(+) cardioplegia and preconditioned groups compared with control group. CK-MB washout and cTnI levels were significantly lower in groups II and III compared with group I at the reperfusion. However no significant difference was observed between K(+) cardioplegia and preconditioned groups among biochemical and hemodynamic parameters and coronary flow at the post-ischemic period. In conclusion, ischemic preconditioning is as effective as K(+) cardioplegia on myocardial protection and recovery of myocardial function during reperfusion.