BME 501 Advanced Topics in Biomedical Systems Spring 2014 Dr. KayBME 501 Lecture Notes – Apr 16 Gross Cardiac Structure • Layout of Components of Heart Cardiac Output • Cardiac Cycle • Cardiac Contractility • Stroke Work & Pressure-Volume Loop • Cardiac FillingGross Cardiac StructureGross Cardiac StructureGross Cardiac StructureCardiac Output Depends on Stroke VolumeCardiac CycleCardiac CycleCardiac CycleCardiac CycleCardiac CycleCardiac Cycle: Pressure-Volume LoopCardiac Cycle• Length-tension relationship • Greater initial stretch (preload) produces greater contractile force upon stimulation • Preload in heart: end-diastolic volume/pressure • Isovolumetric contraction similar to isometric contraction Cardiac Contractility: Starling’s Law of the Heart isometric contractionCardiac Contractility: Sarcomere Length & CrossbridgesCardiac Contractility: Sarcomere Length & Ca2+ • Stretching sarcomere increases Troponin C affinity for Ca2+ • Increases contractile force of sarcomere at same [Ca2+] • Additionally, amount of Ca2+ released by SR increases with increased sarcomere length• Greater preload produces greater force during isovolumetric contraction • Central venous pressure (CVP) determines right ventricular (RV) preload • Increasing CVP increases RV stroke volume (SV) • Increasing pulmonary vein pressure increases LV SV Cardiac Contractility: Starling’s Law & Stroke Volume ejection prevented for this experiment ejection allowed• Isotonic afterload-shortening relationship • Increasing afterload decreases rate and degree of shortening • Increasing starting length (preload) increases speed and degree of shortening Cardiac Contractility: Afterload• Afterload: “load” that heart must eject blood against • Factors increasing afterload – Elevated arterial blood pressure – Aortic stenosis (narrowing) and calcification – Aortic insufficiency (regurgitation) • Factors decreasing afterload – Mitral regurgitation – Vasodilation (drop arterial BP) Cardiac Contractility: Afterload• Stroke work depends on stroke volume and arterial pressure • Work = • Stroke work equals area inside pressure-volume loop Stroke Work & Pressure-Volume Loop DP × DV = DP × A× L• Pressure-volume loop confined inside active and passive boundary curves • Lower boundary: passive compliance curve of ventricle • Upper boundary: isovolumetric pressure relationship Stroke Work & Pressure-Volume Loop• Preload and afterload affect loop within its boundaries • Loop 1: LV ejects SV of 70 ml at low pressure • Loop 2: increase preload, shift P-V loop to right, increase SV • Loop 3: increase afterload, increase P required to open aortic valve, decrease SV • Line 4: prevent ejection, ventricle produces maximum systolic pressure Stroke Work & Pressure-Volume Loop• Top left corner of loop shows myocardium at instant of greatest shortening (end-systole) • Connecting line: end-systolic pressure-volume relationship • Slope of line: end-systolic elastance, measure of ventricular contractility Stroke Work & Pressure-Volume Loop• Positive inotropic agents increase contractility • Increased Ca2+ transient brought about by positive inotropes – Adrenaline – Noradrenaline – Digoxin – Phosphodiesterase inhibitors Stroke Work & Pressure-Volume Loop• Negative inotropic agents decrease contractility – Acute myocardial ischemia (via intracellular acidosis) – Chronic cardiac failure – Ca2+ channel blockers – Parasympathetic stimulation (faintly) Stroke Work & Pressure-Volume Loop• Any event that changes central venous pressure (CVP) changes stroke volume (SV) by Frank-Starling mechanism – Low blood volume reduces CVP – Standing reduces CVP via venous pooling in lower limbs – Sympathetic nerves regulate peripheral venous tone; increased tone increases CVP – Venous muscle pump boosts CVP during exercise • Coughing increases intrathoracic pressure, decreasing cardiac filling • Diseases of pericardium can increase cardiac extramural pressure, impair cardiac filling Cardiac FillingEqualization of Ventricular Outputs Guyton cross-plot: Cardiac output and venous return are equal at steady