Comparison of Enoximone, Amrinone, or Levosimendan Enriched St. Thomas’ Hospital Cardioplegic Solutions Used for Myocardial Preservation in Isolated Guinea Pig Hearts

Myocardial contractile function after cardioplegic arrest is often depressed and an ideal cardioplegic solution has not been developed yet. The aim of this study was to assess the efficacy of phosphodiesterase III inhibitors, amrinone and enoximone, and levosimendan, a novel Ca2+ sensitizing agent, on recovery of hearts after normothermic cardioplegic arrest when added to the St. Thomas’ hospital cardioplegic solution. In the control group, isolated guinea pig hearts were perfused in Langendorff apparatus and arrested with standard St. Thomas’ solution. In other groups, amrinone (10-5 mol.L-1), levosimendan (10-5 mol.L-1), or enoximone (10-4 mol.L-1) were added to the cardioplegic solution. In all hearts, intraventricular pressure, +dp/dtmax, -dp/dtmax, area under pressure-time curve, heart rate, coronary flow, lactate dehydrogenase and creatine kinase enzyme leakage, and oxygen consumption were measured. In the enoximone group, contractility force and +dp/dtmax, were found to be significantly high in the reperfusion and inotropic periods in comparison with other groups (pmax and area under contractility-time curve values were significantly high in inotropic period in enoximone group (p<0.05). No statistically significant difference was noted in other groups. Cardioplegic solution enrichment with enoximone augmented mechanic functions in reperfusion period. No positive effect of amrinone or levosimendan was observed in this study

Cardioprotective effects of zofenopril, enalapril and valsartan against ischaemia/reperfusion injury as well as doxorubicin cardiotoxicity

İstanbul Bilim Üniversitesi, Tıp Fakültesi.Objective The aim of this study is to compare possible protective effects of zofenopril, enalapril and valsartan against both ischaemia/reperfusion injury as well as acute doxorubicin cardiotoxicity. All three agents have never been compared in this setting before. Methods and results Sixty-four male rats were divided into eight groups by computer-generated random numbers and each group included 8 rats. Groups 1, 2, 3 and 4, respectively, received 0.5 ml distilled water, 15 mg/kg/day zofenopril, 2 mg/kg/day enalapril, and 30 mg/kg/day valsartan intragastrically for 7 days. Groups 5, 6, 7, and 8 underwent the same procedures as groups 1, 2, 3 and 4. On the 7th day, groups 1-4 and groups 5-8, respectively, were injected with serum saline or 20 mg/kg doxorubicin intraperitoneally. On the 9th day, isolated rat hearts were perfused in the Langendorff perfusion system. At the end of each Langendorff experiment, the rat hearts were kept for histological analysis. Left ventricular systolic pressures were negatively affected by doxorubicin with ischaemia (group 5 initially: 61.4 +/- 13.6 mmHg post-ischaemic (PI): 20.7 +/- 17.5 mmHg (P=0.0002), group 6 initially: 63 +/- 18.2 mmHg - PI: 24.2 +/- 24.3 mmHg (P = 0.0135), group 7: 82 +/- 26 mmHg - PI: 14.3 +/- 12.1 mmHg (P < 0.0001), group 8:73.1 +/- 27.8 mmHg - PI: 20.4 +/- 27.3 mmHg (P<0.0001). The lowest troponin 1 levels (group 2: 0.3 +/- 0.2 ng/ml, group 6: 0.2 +/- 0.1 ng/ml (P = 0.003) versus the groups' baseline value) were recorded in the groups of zofenopril in the coronary perfusate during post-ischaemic period. Light microscopic evaluation revealed marked cardiac damage with doxorubicin, since zofenopril treatment prevented a doxorubicin induced increase in the histopathological scores. Conclusions In respect of our results zofenopril could be considered more effective than enalapril and valsartan in protecting against both ischaemia/reperfusion injury as well as doxorubicin induced-cardiotoxicity

Effects of erucic acid supplemented feeding on chronic doxorubucin toxicity in rats

One of the undesired complications of the chemotherapy with doxorubicin is cardiotoxicity. Cardiac effect of erucic acid, which is a member of omega-9 fatty acid, is investigated on doxorubicin treatment in this study. Forty-eight rats were divided into eight groups and each group contained six rats. First group rats were fed with milk. In the third and fifth groups we fed rats with milk supplemented 0.5% and 5% erucic acid respectively. The groups 2, 4, 6 were fed as the groups 1, 3, 5 respectively; we injected 2 mg/kg twice weekly intraperitoneal doxorubicin to these groups whereas we injected isovolumous normal saline to the groups 1, 3, 5. Two other groups (groups 7 and 8) were fed with standard pellet. Group 8 received 2 mg/kg doxorubicin twice weekly; group 7 received normal saline. After 4 weeks hearts were isolated and mounted on a Langendorff apparatus perfused by modified Tyrode solution. Surviving rats were significantly less in erucic acid + doxorubicin groups at the end of the treatment period (p<0.05). No significant difference was found between groups for malondialdehyde, catalase, cytochrome c oxidase and isolated heart measurements. Concomitant application of erucic acid and doxorubicin showed profound toxicity