The influences of HCO
3-induced and CO
2-induced pH changes on the action of nondepolarizing muscle relaxants (MRs) were investigated using a rat phrenic nervehemidiaphragm preparation. Changes in pH were induced by varying HCO
3 concentration of the modified Krebs' solution (mK') or by varying the CO
2 concentration in the gas aerating the mK'. Changes in [Ca
++] and [Mg
++], associated with changes in HCO
3 concentration, were measured and corrected. A change in HCO
3 from 50mM to 13.5mM or a change in CO
2 from 2.5% to 9%, augmented the partial neromuscular blockade produced by d-Tc or vecuronium (p<0.01), while inhibiting that produced by metocurine or pancuronium (p<0.01). A change in HCO
3 from 13.5mM to 50mM or a change in CO
2 from 9% to 2.5%, inhibited the partial neuromuscular blockade produced by d-Tc or vecuronium (p<0.01), while augmenting that produced by metocurine or pancuronium (p<0.01). These findings suggest that the HCO
3-induced and CO
2-induced pH changes have a similar influence on the action of MRs. A difference exists between mono- and bisquaternary MRs with regard to their response to pH changes.
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