Relative importance of the enzymic hydrolysis of suxamethonium in plasma and tissues: studies in cats.

1. The effects of intravenous infusions of suxamethonium on the twitch tension of the indirectly stimulated tibialis and gastrocnemius muscles of anaesthetized cats were recorded. From these data the infusion rate giving a 50% reduction in twitch tension after 15 min (IR50), was calculated.2. Marked inhibition of cholinesterase activity in plasma with less inhibition of cholinesterase activity in tissues, obtained by repeatedly withdrawing blood samples, incubating them with DFP and reinjecting them, had only a small effect on the IR50 of suxamethonium.3. Injection of iso-OMPA produced marked inhibition of cholinesterase activity in plasma and tissues, and lowered the IR50 to 10% of that in controls. The IR50 in cats treated with iso-OMPA could be restored to normal only by raising the suxamethonium hydrolysing capacity of plasma 10-50 times above normal by the intravenous injection of purified cholinesterase of human plasma.4. Exchange blood transfusion between normal cats and cats treated with iso-OMPA failed to affect the IR50 of suxamethonium in either of the two.5. It is concluded that in cats, unlike in man, the effectiveness of suxamethonium is not determined by the cholinesterase activity in plasma but by the cholinesterase activity in tissue. The role in this of cholinesterase at the neuromuscular junction and other sites is discussed.