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Effects of Na+/H+ exchange inhibitors in cardiac ischemia. 1992

W Scholz, and U Albus, and W Linz, and P Martorana, and H J Lang, and B A Schölkens
Hoechst AG, Frankfurt/M., Germany.

To investigate a possible protective role of Na+/H+ exchange inhibition under ischemic conditions isolated rat hearts were subjected to regional ischemia and reperfusion. In these experiments all 6 untreated hearts suffered ventricular fibrillation on reperfusion. Addition of 1 x 10(-5) mol/l amiloride or 3 x 10(-7) mol/l 5-(N-ethyl-N-isopropyl)amiloride (EIPA) markedly decreased the incidence and duration of ventricular fibrillation or even suppressed fibrillation completely as in the case of 1 x 10(-6) mol/l EIPA. Both compounds diminished the activities of lactate dehydrogenase and creatine kinase in the venous effluent of the hearts during ischemia. At the end of the experiments tissue contents of glycogen, ATP and creatine phosphate were increased in the treated hearts as compared to control hearts. In an additional experiment the beneficial effects of Na+/H+ exchange inhibition during ischemia was confirmed in vivo with anaesthetized rats undergoing coronary artery ligation. In these animals amiloride or EIPA pretreatment caused a marked reduction of ventricular premature beats and ventricular tachycardia as well as a complete suppression of ventricular fibrillation. The concentration dependent inhibition of Na+ influx via Na+/H+ exchange by amiloride and EIPA was investigated in erythrocytes from hypercholesterolemic rabbits with Na+/H+ exchange activated by exposure to hyperosmotic medium. Furthermore the inhibition of Na+ influx by EIPA after intracellular acidification was studied in cardiac myocytes of neonatal rats. Both agents were effective in the same order of potency in the ischemic isolated working rat heart as in the erythrocyte model in which they inhibited Na+/H+ exchange.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D008297 Male Males
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D002352 Carrier Proteins Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes. Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D004912 Erythrocytes Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN. Blood Cells, Red,Blood Corpuscles, Red,Red Blood Cells,Red Blood Corpuscles,Blood Cell, Red,Blood Corpuscle, Red,Erythrocyte,Red Blood Cell,Red Blood Corpuscle
D006859 Hydrogen The first chemical element in the periodic table with atomic symbol H, and atomic number 1. Protium (atomic weight 1) is by far the most common hydrogen isotope. Hydrogen also exists as the stable isotope DEUTERIUM (atomic weight 2) and the radioactive isotope TRITIUM (atomic weight 3). Hydrogen forms into a diatomic molecule at room temperature and appears as a highly flammable colorless and odorless gas. Protium,Hydrogen-1
D000584 Amiloride A pyrazine compound inhibiting SODIUM reabsorption through SODIUM CHANNELS in renal EPITHELIAL CELLS. This inhibition creates a negative potential in the luminal membranes of principal cells, located in the distal convoluted tubule and collecting duct. Negative potential reduces secretion of potassium and hydrogen ions. Amiloride is used in conjunction with DIURETICS to spare POTASSIUM loss. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p705) Amidal,Amiduret Trom,Amiloberag,Amiloride Hydrochloride,Amiloride Hydrochloride, Anhydrous,Kaluril,Midamor,Midoride,Modamide,Anhydrous Amiloride Hydrochloride,Hydrochloride, Amiloride,Hydrochloride, Anhydrous Amiloride,Trom, Amiduret
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012964 Sodium A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. Sodium Ion Level,Sodium-23,Ion Level, Sodium,Level, Sodium Ion,Sodium 23
D017136 Ion Transport The movement of ions across energy-transducing cell membranes. Transport can be active, passive or facilitated. Ions may travel by themselves (uniport), or as a group of two or more ions in the same (symport) or opposite (antiport) directions. Antiport,Ion Cotransport,Ion Exchange, Intracellular,Symport,Uniport,Active Ion Transport,Facilitated Ion Transport,Passive Ion Transport,Cotransport, Ion,Exchange, Intracellular Ion,Intracellular Ion Exchange,Ion Transport, Active,Ion Transport, Facilitated,Ion Transport, Passive,Transport, Active Ion,Transport, Ion
D017202 Myocardial Ischemia A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (CORONARY ARTERY DISEASE), to obstruction by a thrombus (CORONARY THROMBOSIS), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (MYOCARDIAL INFARCTION). Heart Disease, Ischemic,Ischemia, Myocardial,Ischemic Heart Disease,Disease, Ischemic Heart,Diseases, Ischemic Heart,Heart Diseases, Ischemic,Ischemias, Myocardial,Ischemic Heart Diseases,Myocardial Ischemias

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