Summary
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.
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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).
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2.
The coronary flow was increased by all these drugs, especially by furosemide and hydrochlorothiazide (Fig. 1, lower chart).
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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.
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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).
The results do not support the concept of a common regulation of the mechanical and metabolic function of the heart muscle based solely on the cyclic-AMP-phosphorylase system. The difficulties in correlating the metabolic changes described with the simultaneous changes in contractile force and coronary flow of the heart muscle are discussed.
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Über einige Ergebnisse wurde anläßlich der 10. Frühjahrstagung der Deutschen Pharmakologischen Gesellschaft in Mainz berichtet (Seitz et al., 1969).
Stipendiat der Deutschen Forschungsgemeinschaft.
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Klaus, W., Krebs, R. & Seitz, N. Über die Dissoziation von Funktion und Stoffwechsel des isolierten Meerschweinchenherzens unter dem Einfluß von Phosphodiesterase-Hemmstoffen. Naunyn-Schmiedebergs Arch. Pharmak. 267, 99–113 (1970). https://doi.org/10.1007/BF00999393
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DOI: https://doi.org/10.1007/BF00999393