ACTIONS OF 4-AMINOPYRIDINE ON THE CARDIOVASCULAR SYSTEMS OF ANAESTHETIZED CATS AND DOGS

The effects of the anti-curare agent 4-aminopyridine on the cardiovascular systems of cats and greyhounds under barbiturate-chloralose anaesthesia have been studied. In both species, 4-amino-pyridine produced a transient atropine-sensitive decrease in arterial pressure followed by a prolonged adrenergically-mediated increase. In the cat, the cardiac responses to vagal stimulation and nictitating membrane responses to sympathetic stimulation were augmented after injection of 4-aminopyridine, and the evidence indicated that these effects were the results of increased release of neurotransmitters. In the greyhound, 4-aminopyridine produced increases in the left ventricular systolic pressure and dP/dt max, right atrial pressure, stroke volume, myocardial blood flow, myocardial oxygen consumption, external cardiac work, arterial oxygen content and blood haemoglobin. These effects were attributable to facilitation of sympathetic transmission to the blood vessels, heart and spleen. Heart rate was not much affected because facilitation of vagal transmission to the S-A node counteracted the increased sympathetic effect. In the greyhound, 4-aminopyridine also produced temporary cardiac arrhythmia which was only partly attributable to facilitated sympathetic transmission. In addition there was evidence of a central stimulant action of 4-aminopyridine and of a stimulant action on visceral activity. It is concluded that, while 4-aminopyridine may be useful in certain relatively rare conditions of neuromuscular transmission failure, its actions are too widespread for routine use as an antagonist to non-depolarizing neuromuscular blocking drugs.