Protection of the hypoxic myocardium by the bispyridine derivatives AWD 122-14 and milrinone: studies on isolated, working right rabbit hearts.
Isolated rabbit hearts were perfused via the aortic root with Muralt solution at a constant perfusion pressure of 52 mm Hg ("preload"). After passing the coronary system, the right ventricle pumps the perfusion medium against an "afterload" of 5.15 +/- 1.3 mm Hg through the arteria pulmonalis with a spontaneous heart rate of 131 +/- 11 beats/min. In this model, the right ventricle works under "physiological" conditions. The model was characterized by applying the parameters of Döring et al. The following parameters of this model were measured: RVPsyst. + diast., Qpulm., MVO2, HR, dp/dtmax, dp/dtmin. By applying the method of Neely et al. the external pressure work (w), the efficiency (e) and the coronary resistance (R) were calculated. After a short period of hypoxia of 5 min (the pO2 in the perfusion medium was decreased from 530 mm Hg to 160 mm Hg), the ventricle functions are reversibly depressed, and restored partially under reperfusion (15 min) of the myocardium in dependence of the hypoxia and reperfusion lesions. The application of 3 x 10(-6) mol/l of the two bispyridine derivatives AWD 122-14 and milrinone into the perfusion medium during the total experimental time protected the myocardium partially against the hypoxia and reperfusion lesions. This protecting activity can be shown in a better preserve and recovery of the ventricle functions (pulmonalis flow, external pressure work, efficiency). The application of 5 x 10(-8) mol/l nifedipine, a known protective substance, showed a lower activity in this model compared with the activity of the bispyridines.(ABSTRACT TRUNCATED AT 250 WORDS)
Löwe
H
H
Institute of Drug Research, Berlin.
Jacobsohn
E
E
D000818:Animals; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D020105:Milrinone; D009025:Morpholines / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000502:physiology; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology*; D011728:Pyridones / Q000494:pharmacology*; D011817:Rabbits; D014665:Vasodilator Agents / Q000494:pharmacology*
D009025:Morpholines; D011725:Pyridines; D011728:Pyridones; D014665:Vasodilator Agents; C077469:3-cyano-2-morpholino-5-(pyrid-4-yl)pyridine; D020105:Milrinone