Impact of ammonia on in vitro diaphragmatic contractility

Following strenuous exercise, in vivo diaphragmatic contractility has been shown to decrease in some individuals. The reduction in diaphragmatic contractility has been suggested to be the result of an increase in metabolic by-products of intense exercise. Ammonia (NHβ), a product of the purine nucleotide cycle in skeletal muscle, is produced during strenuous exercise. The effect of NHa on diaphragmatic contractility was assessed by exposing strips from the lateral costal portion of the rat diaphragm to 1 of 8 experimental conditions: KrebsRinger control solution (CON (n=14)>, or CON solution and either 0.1 mM NH3 (E1(n=14)), 2.5mM NHa (E2 (n=6)), 5mM NH3 (E3 (n=6)>, 10mM NHa (E4 (n=8)), 14mM NHs (E5 (n=6)), 14mM NHs (E6 (n=6)) or 18 or 36mM NH3 (E7 (n=7)). Initial contractility in all strips was assessed by stimulating the strips at twitch through 200 Hz in CON solution. This was termed force-frequency curve 1 (F/É1). The solution was then changed after F/F1. Strips were exposed to 1 of the 8 solutions for 15 min and contractility was then reassessed after a total of 15 min of rest with a second force-frequency curve (F-2). Two-way ANOVA with a post-hoc test revealed no significant differences between groups at F/F1 while significant differences (rx.0001) between groups at F/F2 were found. Reduced diaphragmatic contractility was observed at [NH3J of 5mM or greater (E3-E7). This study suggests that NHa "as a varied effect on diaphragmatic contractMyfo vitro. However, these data are not consistent with the diaphragmatic fatigue associated with exercise induced arterial concentrations of NHa seen in humans.