6533b857fe1ef96bd12b3898

RESEARCH PRODUCT

�ber die Dissoziation von Funktion und Stoffwechsel des isolierten Meerschweinchenherzens unter dem Einflu� von Phosphodiesterase-Hemmstoffen

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The influence of several phosphodiesterase-blocking agents on some mechanical and metabolic parameters of isolated perfused guinea pig hearts was studied in order to reinvestigate the repeatedly demonstrated close correlation between these functions. 1. In concentrations which caused 50% inhibition of the phosphodiesterase, theophyllin (1.8×10−4M), ethacrynic acid (4×10−4M) and papaverine (1×10−5M) produced positive inotropic effects by increasing the rate of contraction of the heart muscle (dp/dt). The other substances tested, furosemide (5×10−4M) and hydrochlorothiazide (1.5×10−3M), did not significantly influence the mechanical function of the hearts (Fig.1, upper chart). 2. The coronary flow was increased by all these drugs, especially by furosemide and hydrochlorothiazide (Fig. 1, lower chart). 3. Rather uniform metabolic effects were always observed: The oxygen consumption was increased (most prominently by substances with positive inotropic actions) (Fig.2), the glycogen content was reduced (Fig.3, upper chart), and the lactate efflux from the hearts was raised (Fig.3, lower chart). The lactate content (Fig.3, middle chart) and the lactate-pyruvate-ratio were increased only under the influence of hydrochlorothiazide and ethacrynic acid. 4. Moreover, the myocardial content of phosphorylase-a was significantly increased by all these pharmacological agents (Fig. 4). The control activity was 15.3±0.25% of the total phosphorylase activity and this value was augmented to 23–26% (theophylline, papaverine, furosemide, hydrochlorothiazide) or even to 38% (ethacrynic acid).