Compendium of Physiology1 CARDIOVASCULAR PHYSIOLOGY E-C coupling. Heart as a pump. Compendium of Physiology2 Events connecting electrical activity of the heart (depolarization of sarcolemma), EXCITATION and its mechanical response, CONTRACTION Link between these events is Ca2+ FUNCTION • Triggering of contraction • Regulation of contraction force EXCITATION – CONTRACTION COUPLING Compendium of Physiology3 KEY STRUCTURES / ORGANELLES / RECEPTORS • Transverse tubules of sarcolemma (T-tubules) • Sarcoplasmic reticulum (SR) • Calcium channels: DHPR (dihydropyridine receptor) in T-tubules/sarcolemma RYR (ryanodine receptor) in SR SARCOTUBULAR SYSTEM Compendium of Physiology4 FUNCTIONAL ORGANISATION of SARCOTUBULAR SYSTEM RHABDOMYOCYTE CARDIOMYOCYTE TRIAD DIAD DHPR T-tubuleterminal SR cistern terminal SR cistern T-tubule terminal SR cistern RYR Ca2+ Ca2+Ca2+ Compendium of Physiology5 RHABDOMYOCYTE DHPR RYR1 (voltage-gated) „Mechanical“ relation between DHPR and RYR sarcolemma AP terminal SR cistern terminal SR cistern Ca2+ Calsequestrin = Ca2+ buffer SERCA SERCA- Sarcoplasmic Endoplasmic Reticular Ca2+-ATPase Ca2+ 10-4M 10-7M [Ca2+]c „Closed system“ of Ca2+ movement Compendium of Physiology6 CARDIOMYOCYTE DHPR (in sarcolemma and in T-tubules) RYR2 (calcium-gated) AP 10-5M 10-7M [Ca2+]c Calsequestrin = Ca2+ buffer SERCA Ca2+ Ca2+ ICa CICR (calcium-induced-calcium-release) „Open system“ of Ca2+ movement Strong dependence on [Ca2+]e ! ICa ICa Ca2+ ATPase Na+/Ca2+ exchanger Compendium of Physiology7 HEART AS A PUMP Compendium of Physiology8 CARDIAC OUTPUT (CO) CO HR SV CO = HR x SV CORONARY FLOW EDV Venous return Compliance Aortal pressure LV = RV SV = EDV - ESV Ejection fraction EF = EDV – ESV / EDV 5l/min 70ml >60% REGULATION ANS AUTOREGULATION of cardiac contraction Heterometric: Starling law Homeometric: Frequency effect CONTRACTILITY Ability to contract Depends on tissue perfusion (substrates and oxygen supply for ATP production; Ca2+ availability) Compendium of Physiology9 Henry Pickering Bowditch (1840 – 1911) HOMEOMETRIC AUTOREGULATION (FREQUENCY EFFECT) During increasing HR (stimulation frequency) the force of developed contraction rises Ratio between intra- and extracellular calcium concentrations increases Compendium of Physiology10 CARDIAC RESERVE = maximal CO / resting CO CORONARY RESERVE = maximal CF / resting CF CHRONOTROPIC RESERVE = maximal HR / resting HR VOLUME RESERVE = maximal SV / resting SV 4 - 7 3,5 3 - 5 1,5 CO = cardiac output CF = coronary flow HR = heart rate SV = stroke volume Compendium of Physiology11 CARDIAC RESERVE CO (l/min) WORKLOAD (W/kg) ATHLETHS HEART PHYSIOLOGICAL RESPONSE HEART FAILURE 1 2 3 4 10 30 20 Compendium of Physiology12 AFTERLOADED CONTRACTION PRELOAD, AFTERLOAD 1 2 3 4 AP PRELOAD (~ enddiastolic filling) AFTERLOAD (~ pressure which must be developed) Compendium of Physiology13 P (mmHg) V (ml)50 120 10 100 80 125 A B C D ESV EDV (RV) Work of the heart = P . V LAPLACE law: T = P . R / h P = T . H / r AB – isovolumic contraction BC – ejection CD – isovolumic relaxation DA – filling CARDIAC CYCLE – P-V LOOP Compendium of Physiology14 HEART SOUNDS Caused by vibration of various anatomical structures and event. blood: • Closure and stretching of valves • Isovolumic contraction of heart muscle (papillary muscles, tendons) • Turbulent blood flow Vibration of ventricular wall I. – mitral (+ tricuspidal) valve closure II. - aortal (+ pulmonary) valve closure III. - fast filling of ventricles - pathological IV. - contraction of atria – mostly pathological Z mitral valve aortal valve I. II. III. IV. C C O O O – open, C - closed Compendium of Physiology15 Z mitral valve aortal valve I. II. Z Z O O O – open, C - closed systole diastole PHYSIOLOGICAL SOUNDS AORTAL STENOSIS MITRAL REGURGITATION MITRAL STENOSIS AORTAL REGURGITATION MURMURS – pathological phenomena based on turbulent blood flow 1. SYSTOLIC • Stenosis – aortal, pulmonary (1) • Regurgitation – mitral, tricuspidal (2) 2. DIASTOLIC • Stenosis – mitral, tricuspidal (3) • Regurgitation – aortal, pulmonary (4) 3. SUSTAINED: • Defects of septum