TWITCH POTENTIATING EFFECTS OF THEOPHYLLINE ON RAT DIAPHRAGM ARE ENHANCED BY FORESHORTENING

In patients with chronic obstructive pulmonary disease (COPD) and acut e respiratory failure, acute hyperinflation is likely to induce foresh ortening of inspiratory muscles. Since no data are available on the ef fects of inotropic agents at lengths below the optimal length (L(o)), we compared the effects of theophylline on forty rat diaphragm bundles placed at L(o) and at 70% L(o). Twitches and tetanic stimulations wer e recorded before and after addition of theophylline, in concentration s of 20, 100, 200 or 400 mg.l(-1). Compared with values obtained befor e theophylline, twitch tension (P-t) and maximal tetanic tension (P-o of the bundles placed at L(o) sightly decreased at 20 and 100 mg.l(-1) whereas a clear increase in P-t was obtained at 400 mg.l(-1) (15+/-21 % (mean+/-SD)). In contrast, P-t of the bundles placed at 70% L(o) inc reased with all theophylline concentrations, and vastly more than at L (o) (e.g. at 400 mg.l(-1): 74+/-34%, p<0.05); whereas P-o slightly dec reased, except at 400 mg.l(-1). Moreover, the difference between the e ffects at L(o) and at 70% L(o) increased with increasing theophylline concentrations. We conclude that even at low, in vivo attainable serum levels, theophylline exerted greater positive inotropic effects on tw itch tension (P-t) of rat diaphragm when foreshortened than when at op timal length.