caa a22 4500 477072755 CHVBK 20180405111431.0 cr unu---uuuuu 170330e19961001xx s 000 0 eng 10.1007/BF00823595 doi (NATIONALLICENCE)springer-10.1007/BF00823595 Beneficial effects of felodipine on myocardial and coronary function during low-flow ischemia and reperfusion [Elektronische Daten] [Eugene Bernstein, Franz Eberli, Adam Silverman, Gary Horowitz, Carl Apstein] Summary: An acute coronary occlusion causes severe lowflow ischemia in the occluded region. Calcium antagonists have the potential to reduce the rate of ischemic injury by decreasing myocardial oxygen demand, as well as by other mechanisms, especially when given prior to the onset of ischemia. However, their clinical use may be limited by their negative inotropic effects. The purpose of this study was to assess the effects of felodipine as a potentially protective agent against myocardial ischemia and reperfusion injury, independent of any negative inotropic actions, when given after the onset of low-flow ischemia. Isolated isovolumic (balloon-in-LV), blood-perfused rabbit hearts, paced at a constant heart rate, were subjected to 90 minutes of low-flow ischemia at a coronary perfusion pressure of 10 mmHg, which reduced coronary blood flow to 22-24% of baseline. After 15 minutes of low-flow ischemia, hearts received 2 × 10-6 M felodipine (n=7) or no drug (controls, n=8). Felodipine was given until 15 minutes of reperfusion. During lowflow ischemia both groups of hearts had identical coronary blood flow, heart rate, left ventricular (LV) developed pressure, lactate production, and O2 consumption. However, felo-dipine markedly protected against ischemic diastolic dysfunction. At the end of low-flow ischemia, LV end-diastolic pressure (LVEDP) had increased from 10±1 to 28±5 mmHg in the felodipine group, while in the controls LVEDP increased to 48±8 mmHg (p<0.05). During 30 minutes of reperfusion, felodipine had a beneficial effect upon coronary blood flow (initial postischemic hyperemia 245±38% of baseline in the felodipine group vs. 124±18% in the controls; p<0.01) Felodipine markedly improved the recovery of contractile function [LV developed pressure recovered from a baseline of 104±4 to 75±6 mmHg (72%) in the felodipine group vs. 34±10 mmHg (32%) in the control group; p<0.01], as well as diastolic function (LVEDP=25±4 mmHg in the felodipine group vs. 61±10 mmHg in the controls; p<0.05), and ATP levels (8.5±1.4 μmoles/g d.w. in the felodipine group vs. 3.9±1.4 μmoles/g d.w. in the control group, p<0.05). Felodipine, given after the onset of low-flow ischemia, protects the myocardium during both ischemia and reperfusion by mechanisms other than reducing myocardial oxygen demand. Kluwer Academic Publishers, 1996 felodipine nationallicence diastolic dysfunction nationallicence calcium channel blocker nationallicence myocardial ischemia nationallicence reperfusion nationallicence Bernstein Eugene Cardiac Muscle Research Laboratory, Whitaker Cardiovascular Institute, Center for Advanced Biomedical Research, Boston University School of Medicine, Boston, MA aut Eberli Franz Cardiac Muscle Research Laboratory, Whitaker Cardiovascular Institute, Center for Advanced Biomedical Research, Boston University School of Medicine, Boston, MA aut Silverman Adam Cardiac Muscle Research Laboratory, Whitaker Cardiovascular Institute, Center for Advanced Biomedical Research, Boston University School of Medicine, Boston, MA aut Horowitz Gary Cardiac Muscle Research Laboratory, Whitaker Cardiovascular Institute, Center for Advanced Biomedical Research, Boston University School of Medicine, Boston, MA aut Apstein Carl Cardiac Muscle Research Laboratory, Whitaker Cardiovascular Institute, Center for Advanced Biomedical Research, Boston University School of Medicine, Boston, MA aut Cardiovascular Drugs and Therapy Kluwer Academic Publishers 10/2(1996-10-01), 167-178 0920-3206 10:2<167 1996 10 10557 https://doi.org/10.1007/BF00823595 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00823595 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Bernstein Eugene Cardiac Muscle Research Laboratory, Whitaker Cardiovascular Institute, Center for Advanced Biomedical Research, Boston University School of Medicine, Boston, MA aut NATIONALLICENCE 700 1- Eberli Franz Cardiac Muscle Research Laboratory, Whitaker Cardiovascular Institute, Center for Advanced Biomedical Research, Boston University School of Medicine, Boston, MA aut NATIONALLICENCE 700 1- Silverman Adam Cardiac Muscle Research Laboratory, Whitaker Cardiovascular Institute, Center for Advanced Biomedical Research, Boston University School of Medicine, Boston, MA aut NATIONALLICENCE 700 1- Horowitz Gary Cardiac Muscle Research Laboratory, Whitaker Cardiovascular Institute, Center for Advanced Biomedical Research, Boston University School of Medicine, Boston, MA aut NATIONALLICENCE 700 1- Apstein Carl Cardiac Muscle Research Laboratory, Whitaker Cardiovascular Institute, Center for Advanced Biomedical Research, Boston University School of Medicine, Boston, MA aut NATIONALLICENCE 773 0- Cardiovascular Drugs and Therapy Kluwer Academic Publishers 10/2(1996-10-01), 167-178 0920-3206 10:2<167 1996 10 10557 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer