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• W2164880650 abstract "Background: Management of acute decompensation is a critical aspect of therapy in acute or chronic Coronary Heart Disease. PST2744 is a new non glycosidic Na+,K+-ATPase inhibitor, without sympathomimetic or PDE inhibitory activity. PST2744 has showed a positive inotropic and lusitropic effect with a remarkable safety ratio, in different experimental models (Micheletti et al., JPET, 2002, 303:592–600; Adamson et al., J Cardiovas. Pharmacol., 2003, in press). The aim of the study was to evaluate the hemodynamic responses and safety of PST2744 administration, in comparison with Dobutamine (Dob), in an acute, high after load, ischemia/reperfusion model. Methods: Anesthetized and instrumented dogs (Beagle, male, 12–16 months) were submitted to the following protocol: 1) basal, 2) drug administration, 3) partial aortic constriction (−45% flow, 10 min adaptation), 4) left anterior descending coronary artery (LAD) occlusion (Isc.,15 min), 5) reperfusion (Rep.,30 min). The animals were randomly assigned to the following groups of treatment: saline, Dob (1.25 or 2.5 μg/kg/min) or PST2744 (50 μg/kg bolus + 5 μg/kg/min infusion). All the hemodynamic parameters were continously acquired and recorded by a computerized data analysis system. Statistical analisys was done with two way ANOVA; p<0.05 was considered as statistically significant; n = 6–8 dog group. Results: PST2744 before ischemia, increases Left Ventricle performance at a level comparable to that observed for low dose of Dob. During acute myocardial ischemia all the contractility parameters were depressed and only marginally affected by compound administration. During reperfusion the ventricular contractility remained depressed especially in the ischemic area. Moreover, the rhythm disturb increased and 2 out of 6 dog developed Ventricular Fibrilation. In that condition PST2744 administration: 1) sustained the cardiac contractility (+dP/dt +68%) and relaxation (-dP/dt +17%) efficaciously, 2) reduced left ventricular end-diastolic pressure (−26%), 3) speeded up the recovery of contractility in the ischemic segment during reperfusion (antistanning effect; 32%), 4) increased Cardiac output (12%), 5) reduced slightly, but significantly Heart Rate (−3%), 6) did not increase Mean Blood Pressure (MBP) and Double Product, 7) reduced Isc./Rep. associated rhythm disturbances. These effects were shared only partially by Dob at both infusion rate tested. In fact, Dob was incapable to restore dP/dtmax, and FS% of the ischemic segment, to pre-ischemic levels. Moreover, it must be underlined that Dob increased HR, MBP and Double Product significantly. Conclusion: The administration of PST2744 in anesthetized dogs, undergoing to acute myocardial ischemia and reperfusion, not only exertes a significant positive inotropic action and improves relaxation, without affecting of oxygen request, but also protectes the animals from life-threatening arrhythmias. These data suggest a role for PST2744 in the treatment of acute decompensation also of ischemic origin." @default.
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• W2164880650 date "2003-10-01" @default.
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• W2164880650 title "PST2744 improves systo-diastolic contractility and reduces myocardial stunning in acute, high after-load ischemia/reperfusion canine model" @default.
• W2164880650 doi "https://doi.org/10.1016/s1071-9164(03)00547-5" @default.
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