RESUMO
1. The antiischemic properties of the flavonoids acetylvitexin-rhamnoside (AVR) and luteolin-7-glucoside-(LUT), combining phosphodiesterase (PDE)-inhibitory and antioxidant properties, were studied in comparison to amrinone (AMR) or superoxide dismutase (SOD). The effects of the new dihydropyridine-type calcium-agonist Bay T 5006 were studied in comparison to Bay K 8644. 2. In isolated Langendorff-rabbit hearts perfused at constant pressure, acute regional ischemia (MI) was induced by coronary artery occlusion (CAO) and quantitated from epicardial NADH-fluorescence photography. Drugs were applied either before or after CAO (pre-treatment or treatment) to permit distinguishing the influence of functional and direct cytoprotective actions in the poorly collateralized rabbit hearts. 3. SOD did not affect left ventricular pressure (LVP) or coronary flow (CF) and reduced MI only if applied before CAO. LVP and CF were enhanced by LUT or AMR but not by AVR. MI was reduced to a similar extent in hearts treated with either drug. Cardioprotection by LUT was not improved by starting drug application before CAO. 4. Bay K 8644 reduced LVP and particularly CF, whereas Bay T 5006 did not affect functional parameters. MI was enlarged by Bay K 8644 and remained unaffected by treatment or pretreatment with Bay T 5006. 5. AMR, LUT and AVR possess antiischemic properties related to an improvement of myocardial perfusion. Although oxygen free radicals contribute to ischemic tissue injury, as shown by the cardioprotective effectiveness of SOD, antioxidant properties of the flavonoids LUT and AVR do not seem to be relevant for the antiischemic effects. Our findings also give no evidence for antioxidant properties of dihydropyridines relevant for cardioprotection.
Assuntos
Antioxidantes/farmacologia , Cardiotônicos/farmacologia , Isquemia Miocárdica/fisiopatologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Agonistas dos Canais de Cálcio/farmacologia , Circulação Coronária/efeitos dos fármacos , Circulação Coronária/fisiologia , Vasos Coronários/fisiologia , Técnicas In Vitro , Masculino , Miocárdio/citologia , Miocárdio/metabolismo , NAD/metabolismo , Inibidores de Fosfodiesterase/farmacologia , Coelhos , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
Calcium (Ca) agonists like Bay k 8644 ((-)-S-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl) pyridine-5-carboxylate (CAS 93468-89-4), may represent a new principle in the treatment of heart failure. Because of marked vasoconstrictive properties, these agents may have a deleterious effect on myocardial ischemia (MI). It was however demonstrated that contractility enhancement and coronary flow (CF) reduction do not automatically enlarge MI. Therefore, we investigated the influence of Bay k 8644 (10(-8) mol/l) in comparison to ouabain (1.5 x 10(-7) mol/l) in non-arrhythmogenic concentrations on MI in electrically paced isolated rabbit hearts (Langendorff, constant pressure: 70 cm H2O, Tyrode solution, Ca2+ 1.8 mmol/l, 180 beats/min). MI was induced by coronary artery ligation and quantified by epicardial NADH-fluorescence. Left ventricular pressure (LVP) was significantly increased by ouabain (+10-20%) but slightly diminished by Bay k 8644 (-10%) (p < 0.05). CF reduction after Bay k 8644 (-30%) was more pronounced than after ouabain (-10%) (p < 0.05), but both substances did reduce relative CF (CF/LVP x heart rate) to the same extent (-20-30%) (p > 0.05). Nevertheless, ouabain did not significantly influence epicardial NADH-fluorescence area or intensity (p > 0.05), whereas MI was significantly enlarged by Bay k 8644 (+30%) (p < 0.05). It is concluded that in isolated rabbit hearts ouabain and Bay k 8644 might influence CF-distribution differently with a more pronounced diminuation of the nutritive CF induced by Bay k 8644.
Assuntos
Agonistas dos Canais de Cálcio/farmacologia , Di-Hidropiridinas/farmacologia , Hemodinâmica/efeitos dos fármacos , Isquemia Miocárdica/fisiopatologia , Éster Metílico do Ácido 3-Piridinacarboxílico, 1,4-Di-Hidro-2,6-Dimetil-5-Nitro-4-(2-(Trifluormetil)fenil)/farmacologia , Animais , Circulação Coronária/efeitos dos fármacos , Fluorescência , Frequência Cardíaca/efeitos dos fármacos , Técnicas In Vitro , Masculino , Contração Miocárdica/efeitos dos fármacos , NAD/metabolismo , Ouabaína/farmacologia , Coelhos , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
1. We investigated the effects of the new calcium-agonists (+/-)-Bay W 5035 and (+/-)-Bay T 5006 in comparison to (-)-S-Bay K 8644 on hemodynamics and epimyocardial perfusion in Langendorff rat hearts. 2. At equieffective inotropic concentration, vasoconstriction of coronary resistance vessels was significantly less after (+/-)-Bay W 5035 or (+/-)-Bay T 5006 than after (-)-S-Bay K 8644 application. 3. FITC-Dextran 3 elution kinetics indicated that the epimyocardial vascular volume was significantly reduced only by (-)-S-Bay K 8644. 4. Moreover, (-)-S-Bay K 8644 enhanced transcoronary exchange more markedly than (+/-)-Bay W 5035 or (+/-)-Bay T 5006, reflecting the differences in coronary constrictor activity. 5. We conclude that in comparison to (-)-S-Bay K 8644 the relation between inotropy and vasoconstriction is more favorable for (+/-)-Bay W 5035 or (+/-)-Bay T 5006.