Cardiac Mechano-electric Coupling and Arrhythmias

Cardiac Mechano-Electric Coupling and Arrhythmias offers a thoroughly reviewed compendium written by leading experts in the field on the mechanism and consequences of cardiac mechano-electrical coupling. Its coverage ranges from stretch-activated ion channels to mechanically induced arrhythmias and mechanical interventions for heart rhythm correction. Information is grouped into logical sections, from molecular mechanisms, to cell, tissue and whole organ responses, right through to patient-based observations and insight emerging from clinical trials. The information provided carefully highlights both consensus insight and current shortcomings in our understanding of cardiac mechano-electric coupling. The book has been thoroughly revised and expanded since publication of the first edition in 2005, extensively updated to reflect recent developments in the field, and now offers a more balanced view of mechano-electrical interactions in the heart and develops a more clinical focus. Written with the practising cardiologist and junior doctor in mind, it offers interesting new insight for the established physician with an interest in cardiac arrhythmogenesis and heart rhythm management.BASIC SCIENCE, SECTION I: SUB-CELLULAR MECHANISMS OF CARDIAC MECHANO-ELECTRIC COUPLING; 1. Evolutionary origins of stretch-activated ion channels; 2. SACs in the heart; 3. The mechano-gated K2P channel TREK-1 in the cardiovascular system; 4. Cell VolumeDSSensitive Ion Channels and Transporters in Cardiac Myocytes; 5. Non-sarcolemmal stretch-activated channels; 6. Pacemaker, potassium, calcium, sodium: stretch modulation of the voltage-gated channels; 7. Role of caveolae in stretch-sensing: implications for mechanoelectric coupling; 8. The membrane/cytoskeleton interface and stretch-activated channels; 9. Cardiomyocyte stretch sensing; 10. The response of cardiac muscle to stretch: Calcium and force; 11. Stretch effects on second messengers; 12. Functional implications of Myocyte Architecture; BASIC SCIENCE, SECTION II: CELLULAR MANIFESTATIONS OF CARDIAC MECHANO-ELECTRIC COUPLING; 13. Mechanical modulation of pacemaker electrophysiology; 14. Mechano-electric coupling in working cardiomyocytes: diastolic and systolic effects; 15. Mechano-sensitivity of pulmonary vein cells: implications for atrial arrhythmogenesis; 16. Heterogeneity of sarcomere length and function as a cause of arrhythmogenic calcium waves; 17. Cellular mechanisms of arrhythmogenic cardiac alternans; 18. Remodeling of gap junctions in ventricular myocardium: Effects of cell-to-cell adhesion, mediators of hypertrophy and mechanical forces; 19. The origin of fibroblasts, ECM and potential contributions to cardiac mechano-electric coupling; 20. Advantages and pitfalls of cell cultures as model systems to study cardiac mechanoelectric coupling; BASIC SCIENCE, SECTION III: MULTI-CELLULAR MANIFESTATIONS OF MECHANO-ELECTRIC COUPLING; 21. Activation sequence of cardiac muscle in simplified experimental models: Relevance for cardiac mechano electric coupling; 23. Acute stretch effects on atrial electro-physiology; 24. Stretch effects on potassium accumulation and alternans in pathological myocardium; 25. The effects of wall stretch on ventricular conduction and refractoriness in the whole heart; 26. Mechanical triggers of long-term ventricular electrical remodeling; 27. Mechanisms of mechanical pre- and postconditioning; TRANSLATIONAL SCIENCE, SECTION IV: INTEGRATED MODEL SYSTEMS TO STUDY SPECIFIC CASES OF CARDIAC MEC AND ARRHYTHMIAS; 28. Mechano-electric coupling in chronic atrial fibrillation; 29. Mechanically induced pulmonary vein ectopy - insight from animal models; 30. Regional variation in mechano-electric coupling: The right ventricle; 31. Mechanical induction of arrhythmia in the ex-situ heart: insight into Commotio Cordis; 32. Arrhythmias in murine models of the mechanically impaired heart; 33. Studying cardiac mechano-sensitivity in man; 34. Mathematical models of cardiac structure and function: mechanistic insights from models of heart failure; 35. Mathematical models of human atrial mechano-electrical coupling and arrhythmias; 36. Mathematical models of ventricular mechano-electric coupling and arrhythmia; CLINICAL RELEVANCE, SECTION V: PATHOPHYSIOLOGY OF CARDIAC MECHANO-ELECTRIC COUPLING: GENERAL ASPECTS; 37. Load dependence of ventricular repolarisation; 38. Is the U wave in the electrocardiogram a mechanoelectrical phenomenon?; 39. Mechanical modulation of cardiac function: Role of the pericardium; 40. Mechanically-induced electrical remodelling in human atrium; 41. Drug effects and atrial fibrillation: potential and limitations; 42. Stretch as a mechanism linking short- and long-term electrical remodeling in the ventricles; 43. Volume and pressure overload and ventricular arrhythmogenesis; 44. Stretch effects on fibrillation dynamics; CLINICAL RELEVANCE, SECTION VI: PATHOPHYSIOLOGY OF CARDIAC MECHANO-ELECTRIC COUPLING: SPECIFIC CASES; 45. Commotio cordis: Sudden death from blows to the chest wall; 46. Repolarization changes in the synchronously and dys-synchronously contracting failing heart; 47. Ventricular arrhythmias in heart failure: Link to hemodynamic load; 48. Mechanical heterogeneity and aftercontractions as trigger of torsades des pointes; 49. Stretch-induced arrhythmias in ischaemia; CLINICAL RELEVANCE, SECTION VII: MECHANO-ELECTRIC COUPLING AS A MECHANISM INVOLVED IN THERAPEUTIC INTERVENTIONS; 50. Antiarrhythmic effects of acute mechanical stimulation; 51. Termination of arrhythmias by haemodynamic unloading; 52. Mechanical modulation of defibrillation and resuscitation efficacy; 53. Anti- and pro-arrhythmic effects of cardiac assist device implantation; 54. Anti- and pro-arrhythmic effects of cardiac resynchronization therapy; CLINICAL RELEVANCE, SECTION VIII: EVIDENCE FOR MECHANO-ELECTRIC COUPLING FROM CLINICAL TRIALS; 55. Evidence for mechano-electric coupling from clinical trials on AF; 56. Evidence for mechano-electric coupling from clinical trials in heart failure; 57. Mechano-electrical coupling and the pathogenesis of arrhythmogenic right ventricular cardiomyopathy; 58. Evidence for mechano-electric coupling from clinical trials on cardiac resynchronization therapy; 59. Mechano-electric coupling in patients treated with ventricular assist devices: insights from individual cases and clinical trials; OUTLOOK, SECTION IX: NOVEL DIRECTIONS IN CARDIAC MECHANO-ELECTIC COUPLING; 60. Measuring strain of structural proteins in vivo in real time; 61. Roles of SAC beyond M-E Transaction; 62. Distributions of myocyte stress, strain and work in normal and infarcted ventricles; 63. Evolving concepts in measuring ventricular strain in the canine and human hearts: non-invasive imaging; 64. Evolving concepts in measuring ventricular strain in the human heart: impedance measurements; 65. Mechanosensitive channel blockers: A new class of antiarrhythmic drugs?