The Effects Of Carboxylic Ionophores On The Isolated Perfused Rabbit Heart

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Degree Name

Doctor of Philosophy (Ph.D.)


The pharmacological, physiological and physical-chemical properties of monensin, salinomycin and lasalocid were studied in model systems and the isolated perfused rabbit heart. These agents are carboxylic ionophores, electroneutral exchange diffusion carriers capable of transporting cations across biological membranes. Studies in 3 phase systems with ionic gradients similar to those within the myocyte suggested that the ionophores could influx Na('+) and efflux K('+) and H('+) from the myocyte. ('22)Na influx measurements and ion selective electrode determinations confirmed these results in the isolated heart. Concommitant with Na influx was an elevation of (alpha) Ca(,i)('2), as determined by the fluorescent Ca('2+) probe Quin 2. This increased ionic activity was accompanied by elevation of contractility, heartrate, lusitropy and cardiac efficiency and decreased coronary resistance. The increased heartrate and part of the increased contractility was due to the release of cardiac catecholamines, inhibitable by and adrenergic blockers. The putative cause for increased contractility and possibly other alterations in cardiac performance was a Na('+) - mediated increase in (alpha) Ca(,i)('2+), occuring through the displacement of sequestered Ca('2+) or stimulation of the Na('+) - Ca('2+) exchanger.


Health Sciences, Pharmacology

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