Measurement of inotropic effects by a newly developed guinea pig papillary muscle bioassay

In order to measure inotropic influences of physiologically occurring substances and drugs we used a newly developed guinea pig papillary muscle (GPPM) bioassay. GPPM were suspended in air and surface coated with buffer (Krebs-Henseleit solution). The muscles were stimulated (pulsating direct current, 1.5 V; 0.5 Hz, 20 ms duration) which led to contraction. This method enables measurements of inotropic effects up to 5 days, contrary to previous studies (1 day), in which immersions of GPPM in buffer were performed. In order to investigate the comparability of the new method we measured the effect of metabolites (citric acid cycle), lactic acid, lactate, and extracellular pH on muscle contractility. The H(+)-dependent decrease of the contractile force of the GPPM can be compensated by an increased Ca(2+)-concentration. Further, the influence of catecholamines (isoproterenol) on the contractility was investigated. As a result, isoproterenol caused arrhythmias and extrasystoles as it was observed in clinical studies. Several pharmaceutical substances were tested to show the reproducibility and repeatability of the bioassay.