caa a22 4500 477072461 CHVBK 20180405111430.0 cr unu---uuuuu 170330e19960901xx s 000 0 eng 10.1007/BF00051107 doi (NATIONALLICENCE)springer-10.1007/BF00051107 Effects of felodipine on the ischemic heart: Insight into the mechanism of cytoprotection [Elektronische Daten] [R. Ferrari, A. Cargnoni, P. Bernocchi, G. Gaia, M. Benigno, E. Pasini, P. Pedersini, C. Ceconi] Summary: To assess whether the administration of felodipine protects the myocardium in a dose-dependent manner against ischemia and reperfusion, isolated rabbit hearts were infused with three different concentrations of felodipine: 10-10, 10-9, and 10-8 M. Diastolic and developed pressures were monitored; coronary effluent was collected and assayed for CPK activity and for noradrenaline concentration; mitochondria were harvested and assayed for respiratory activity; and ATP production and calcium content and tissue concentration of ATP, creatine phosphate (CP), and calcium were determined. The occurrence of oxidative stress during ischemia and reperfusion was also monitored in terms of tissue content and release of reduced (GSH) and oxidized (GSSG) glutathione. Treatment with felodipine at 10-10 and 10-9 M had no effect on the hearts when perfused under aerobic conditions, whilst the higher dose reduced developed pressure from 57.7 ± 2.6 to 30.0 ± 2.6 mmHg (p < 0.01). On reperfusion treated hearts recovered better than the untreated hearts with respect to left ventricular performance, replenishment of ATP and CP stores, and mitochondrial function. Recovery of developed pressure was 100% at 10-8 M, 55% at 10-9 M, and 46% at 10-10 M. The reperfusion-induced tissue and mitochondrial calcium overload, release of CPK and noradrenaline, and oxidative stress were also significantly reduced. The effects of felodipine were dose dependent. Felodipine inhibited the initial rate of ATP-driven calcium uptake but failed to affect the initial rate of mitochondrial calcium transport. It is concluded that felodipine infusion provides dose-dependent protection of the heart against ischemia and reperfusion. Because this protection also occurred at 10-9 M and 10-10 M in the absence of a negative inotropic effect during normoxia and of a coronary dilatory effect during ischaemia, it cannot be attributed to an energy-sparing effect or to improvement in oxygen delivery. From our data we can envisage two other major mechanisms—(1) membrane protection and (2) reduction in oxygen toxicity. The ATP-sparing effect occurring at 10-8 M is likely to be responsible for the further protection. Kluwer Academic Publishers, 1996 calcium antagonist nationallicence felodipine nationallicence myocardial ischemia nationallicence reperfusion nationallicence Ferrari R. Cattedra di Cardiologia, Universita' degli Studi di Brescia, c/o Spedali Civili, P.le Spedali Civili, 1, 25123, Brescia, Italy aut Cargnoni A. Fondazione Salvatore Maugeri, Centro di Fisiopatologia Cardiovascolare, Gussago, Brescia, Italy aut Bernocchi P. Fondazione Salvatore Maugeri, Centro di Fisiopatologia Cardiovascolare, Gussago, Brescia, Italy aut Gaia G. Fondazione Salvatore Maugeri, Centro di Fisiopatologia Cardiovascolare, Gussago, Brescia, Italy aut Benigno M. aut Pasini E. Fondazione Salvatore Maugeri, Centro di Fisiopatologia Cardiovascolare, Gussago, Brescia, Italy aut Pedersini P. Fondazione Salvatore Maugeri, Centro di Fisiopatologia Cardiovascolare, Gussago, Brescia, Italy aut Ceconi C. aut Cardiovascular Drugs and Therapy Kluwer Academic Publishers 10/4(1996-09-01), 425-437 0920-3206 10:4<425 1996 10 10557 https://doi.org/10.1007/BF00051107 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00051107 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ferrari R. Cattedra di Cardiologia, Universita' degli Studi di Brescia, c/o Spedali Civili, P.le Spedali Civili, 1, 25123, Brescia, Italy aut NATIONALLICENCE 700 1- Cargnoni A. Fondazione Salvatore Maugeri, Centro di Fisiopatologia Cardiovascolare, Gussago, Brescia, Italy aut NATIONALLICENCE 700 1- Bernocchi P. Fondazione Salvatore Maugeri, Centro di Fisiopatologia Cardiovascolare, Gussago, Brescia, Italy aut NATIONALLICENCE 700 1- Gaia G. Fondazione Salvatore Maugeri, Centro di Fisiopatologia Cardiovascolare, Gussago, Brescia, Italy aut NATIONALLICENCE 700 1- Benigno M. aut NATIONALLICENCE 700 1- Pasini E. Fondazione Salvatore Maugeri, Centro di Fisiopatologia Cardiovascolare, Gussago, Brescia, Italy aut NATIONALLICENCE 700 1- Pedersini P. Fondazione Salvatore Maugeri, Centro di Fisiopatologia Cardiovascolare, Gussago, Brescia, Italy aut NATIONALLICENCE 700 1- Ceconi C. aut NATIONALLICENCE 773 0- Cardiovascular Drugs and Therapy Kluwer Academic Publishers 10/4(1996-09-01), 425-437 0920-3206 10:4<425 1996 10 10557 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer