ISCHEMIA-DEPENDENT EFFICACY OF PHOSPHODIESTERASE INHIBITION

To evaluate the inotropic efficacy of phosphodiesterase inhibition in hearts with and without ischemic injury, 27 sheep were evaluated sonom icrometrically during incremental volume loading on right heart bypass . Contractility was assessed with the preload recruitable stroke work relationship. Active relaxation rate was estimated using the time cons tant of isovolumic pressure decay (tau). For nonischemic assessment, g roups 1 and 2 (n = 6 each) underwent 45 minutes of vented perfusion af ter which milrinone was administered to group 1; group 2 served as non ischemic controls. There was no detectable increase in preload recruit able stroke work or decrement in tau after milrinone administration. G roups 3 and 4 underwent 15 minutes of 37 degrees C ischemia (aortic cr ossclamping) followed by 30 minutes of vented reperfusion. Milrinone w as then administered to group 3 (n = 7); group 4 (n = 8) served as isc hemically injured controls. Inotropic and lusitropic effects were pres ent (group 3 preload recruitable stroke work: 35.4 +/- 5.8 mJ.beat(-1) .100 g(-1).mL(-1) before milrinone to 49.5 +/- 4.4 mJ.beat(-1).100 g(- 1).mL(-1) after milrinone [p < 0.05]; group 3 tau: 51.8 +/- 5.5 ms bef ore milrinone to 32.2 +/- 2.5 ms after milrinone [p < 0.02]). Although milrinone restored contractility and increased the rate of active rel axation in the postischemic hearts, there was no detectable inotropic effect in nonischemic hearts. In this model, milrinone augments contra ctility and relaxation in postischemic myocardium but offers little in otropic benefit in nonischemically injured hearts.