This monograph contains 20 selected papers presented at the Symposium on Subcellular Basis of Contractile Failure which was held in Ottawa during May 11-13, 1989 and is designed for the benefit ofthose who were unable to attend this event. It is now increasingly becoming clear that an excessive amount of calcium is intimately involved in the pathogenesis of a wide variety of heart diseases. Accordingly, the investigations concerning the role of calcium chan­ nels and their regulatory mechanisms in heart function as well as of the intra­ cellular calcium overload in cardiac dysfunction are presented here. Since sodium is also considered to influence the cardiac contractile force by chang­ 2 ing the intracellular concentration of calcium through the Na +-Ca+ exchange 2 mechanism in the cell membrane, the role of Na +-Ca+ exchange in heart func­ tion as well as pathology of contractile failure is discussed. In view of the new­ ly discovered implications of the oxygen free radicals in cellular injury, papers concerning the role of these radicals in heart disease are included in this book. For the purpose of clarity, different chapters have been organized under three main headings: (I) Role of cations in heart function, (II) Cardiac hypertrophy and cardiomyopathies, and (III) Ischemic heart disease and cardiac failure.

I. Role of Cations in Heart Function.- 1. Role for sodium channels and intracellular sodium in regulation of the cardiac force-frequency relation and contractility.- 2. Regulation of cardiac calcium current during suppression of second messenger intracellular enzymatic pathways.- 3. Hormonal and non-hormonal regulation of Ca2+ current and adenylate cyclase in cardiac cells.- 4. Calcium current in normal and hypertrophied isolated rat ventricular myocytes.- 5. Regulation of contractile activity in single adult cardiomyocytes isolated from four different species: The effect of reduced sodium gradient.- 6. Involvement of sodium-calcium exchange in cardiac pathology.- 7. Modifications in sarcolemmal regulation of Ca2+ with aging.- II. Cardiac Hypertrophy and Cardiomyopathies.- 8. Alterations of membrane proteins in cardiac hypertrophy.- 9. Signal transduction in myocardial hypertrophy and myosin expression.- 10. Molecular and subcellular mechanisms of thyroid hormone induced cardiac alterations.- 11. Membrane abnormalities and changes in cardiac cations due to alterations in thyroid status.- 12. Inhibitory effects of captopril on the onset of cardiomyopathy in cardiomyopathic hamsters.- 13. Altered myocardial contractility and energetics in renovascular hypertensive rats.- 14. Cardiac phosphatidylethanolamine N-methylation in normal and diabetic rats treated with L-propionylcarnitine.- III. Ischemic Heart Disease and Cardiac Failure.- 15. Dietary N-3 polyunsaturated fatty acids and ischemic heart disease.- 16. Role of free radicals in the development of ischemic heart disease.- 17. Cardiovascular membranes as models for the study of free radical injury.- 18. Oxidation of myofibrillar thiols: A mechanism of contractile dysfunction reversible by dithiothreitol.- 19. Cardiac contractile failure due to oxygen radicals in an ex vivo system.- 20. Subcellular basis of contractile failure in myocytes: Calcium overload or energy depletion?.