1. The benzoylguanidine derivative
Hoe 694 ((3-methylsulphonyl-4- piperidino-benzoyl) guanidine methanesulphonate) was characterized as an inhibitor of Na+/H+ exchange in rabbit erythrocytes, rat platelets and bovine endothelial cells. The potency of the compound was slightly lower or comparable to ethylisopropyl
amiloride (
EIPA). 2. To investigate a possible cardioprotective role of the Na+/H+ exchange inhibitor
Hoe 694, rat isolated working hearts were subjected to ischaemia and reperfusion. In these experiments all untreated hearts suffered
ventricular fibrillation on reperfusion. Addition of 10(-7) M
Hoe 694 to the perfusate almost abolished reperfusion arrhythmias in the rat isolated working hearts. 3.
Hoe 694 reduced the release of
lactate dehydrogenase (LDH) and
creatine kinase (CK), which are indicators of cellular damage during ischaemia, into the venous effluent of the hearts by 60% and 54%, respectively. 4. The tissue content of
glycogen at the end of the experiments was increased by 60% and the high energy
phosphates ATP and
creatine phosphate were increased by 240% and 270% respectively in the treated hearts as compared to control hearts. 5. Antiischaemic effects of the Na+/H+ exchange inhibitor,
Hoe 694, were investigated in a second experiment in anaesthetized rats undergoing coronary artery
ligation. In these animals, pretreatment with
Hoe 694 caused a dose-dependent reduction of ventricular
premature beats and
ventricular tachycardia as well as a complete suppression of
ventricular fibrillation down to doses of 0.1 mg kg-1, i.v. Blood pressure and heart rate remained unchanged. 6. We conclude that the new Na+/H+ exchange inhibitor,
Hoe 694, shows cardioprotective and antiarrhythmic effects in ischaemia and reperfusion in rat isolated hearts and in anaesthetized rats. In view of the role which Na+/H+ exchange seems to play in the pathophysiology of cardiac ischaemia these effects could probably be attributed to Na+/H+ exchange inhibition.