Twitch potentiating effects of theophylline on rat diaphragm are enhanced by foreshortening

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