Kazuyoshi Nakahashi

Effects Of Milrinone On Left Ventricular End-Systolic Pressure–Volume Relationship Of Rat Hearts In Situ

1. We have already shown that the left ventricular (LV) end‐systolic pressure–volume relationship (ESPVR) of rat hearts in situ is an upward convex curve and that LV end‐ systolic pressure (ESPmLVV) and the systolic pressure–volume area (PVAmLVV) at a mid‐range LV volume (mLVV) sensitively reflect acute changes in LV contractility and work capability. Milrinone is a non‐glycosidic, non‐sympathomimetic drug that increases myocardial cAMP concentrations by selective inhibition of cardiac phosphodiesterase III. Therefore, milrinone could act on the entire cardiovascular system and cause an increase in inotropy, arterial vasodilatation and venodilatation. The aim of the present study was to investigate whether the approach we have recently instituted is able to detect the effects of milrinone on the entire cardiovascular system.

Positive inotropic effect of nicorandil in adult rats in situ

PurposeAlthough the cardiac protective and negative inotropic effects of nicorandil via opening the sarcolemmal or mitochondrial KATP channel and NO-like action are well known, positive inotropic effects of nicorandil in normal hearts have not been reported. The aim of the current study was to investigate how nicorandil affects left ventricular (LV) function of in situ adult rat hearts through the entire cardiovascular system.MethodsWe performed simultaneous and continuous measurements of LV pressure (P) by a catheter-tip micromanometer and LV volume (V) using a conductance catheter. We obtained steady-state LV P-V loops and intermittent curvilinear LV end-systolic pressure–volume relations (ESPVRs), LV end-systolic pressure (ESPmLVV), and systolic pressure–volume area (PVAmLVV) at midrange LVV (mLVV). We evaluated the effects of nicorandil on LV function by these mechanical indexes sensitively reflecting changes in LV contractility and work capability, preload (end-diastolic volume, EDV), and afterload (effective arterial elastance, Ea).ResultsNicorandil (10 and 20 µg·kg−1·min−1) (blood concentration: 0.53 ± 0.14 and 1.48 ± 0.21 µg/ml) largely shifted ESPVR upward and thus significantly increased ESP0.06, PVA0.06, stroke volume due to increase in EDV, and ejection fraction without significant changes in Ea and heart rate. In contrast, an NO donor, nitroglycerin (1 µg·kg−1 · min−1), significantly decreased Ea but did not change ESP0.06, PVA0.06, and EDV. Furthermore, either a nonselective KATP channel blocker, glybenclamide, or a mitochondrial KATP channel blocker, 5-hydroxydecanoate, abolished these nicorandil-induced positive inotropic actions.ConclusionThese results suggest that nicorandil exhibited positive inotropic actions on LV function of in situ hearts in adult rats with resultant increased preload (EDV).