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.

中文翻译：

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Hoe 694，一种新型的Na + / H +交换抑制剂及其在心肌缺血中的作用。

1.苯甲酰基胍衍生物Hoe 694（（3-甲基磺酰基-4-哌啶子基-苯甲酰基）胍基甲磺酸盐）的特征是在兔红细胞，大鼠血小板和牛内皮细胞中Na + / H +交换的抑制剂。该化合物的效力略低或与乙基异丙基阿米洛利（EIPA）相当。2.为了研究Na + / H +交换抑制剂Hoe 694的可能的心脏保护作用，对离体的工作心脏进行了局部缺血和再灌注。在这些实验中，所有未经治疗的心脏在再灌注时均发生心室纤颤。在大鼠离体工作心脏中，向灌注液中添加10（-7）M Hoe 694几乎消除了再灌注心律失常。3. Hoe 694减少了乳酸脱氢酶（LDH）和肌酸激酶（CK）的释放，这是缺血期间细胞损伤的指标，进入心脏静脉流出的比例分别为60％和54％。4.与对照心脏相比，在实验结束时，治疗后心脏的糖原组织含量增加了60％，高能磷酸盐ATP和磷酸肌酸分别增加了240％和270％。5.在第二次实验中，在接受冠状动脉结扎的麻醉大鼠中研究了Na + / H +交换抑制剂Hoe 694的抗缺血作用。在这些动物中，用Hoe 694预处理可引起剂量依赖性的室性早搏和室性心动过速的减少，以及直至0.1 mg kg-1剂量的室颤的完全抑制。iv血压和心率保持不变。6.我们得出结论，新的Na + / H +交换抑制剂Hoe 694，在大鼠离体心脏和麻醉大鼠的缺血和再灌注中显示出心脏保护性和抗心律失常作用。鉴于Na + / H +交换似乎在心肌缺血的病理生理中发挥作用，这些作用可能归因于Na + / H +交换抑制。