Cardiovascular Physiology & Pharmacology MSOP1003 PDF

Cardiovascular Physiology & Pharmacology Dr Stella Koutsikou MSOP1003 Office: Anson 307 Email: [email protected]  What did we learn in Stage 1? ❖ Heart anatomy ❖ Blood flow  What did we learn in Stage 1? ❖ Circulation ❖ Coronary c...

Cardiovascular Physiology & Pharmacology Dr Stella Koutsikou MSOP1003 Office: Anson 307 Email: [email protected]  What did we learn in Stage 1? ❖ Heart anatomy ❖ Blood flow  What did we learn in Stage 1? ❖ Circulation ❖ Coronary circulation R L  Learning Objectives 1. Describe the heart’s intrinsic electrical conduction system 2. Understand the measuring of electrical activity of the heart 3. Electrocardiogram (ECG) 4. Excitability of the myocardium 5. Factors affecting heart excitability 6. Pharmacology relating to heart excitability  Isolated Hearts Question: Will the heart carry on beating if removed from the body? Isolated hearts: Heart transplants Lab experiments  Intrinsic Conduction System of the Heart Autorhythmic System: Internal regulating system responsible for the rhythmic contraction of the heart R L Specialised myocardial tissue makes up Sinoatrial (SA) node (Sinus rhythm) Internodal pathways (posterior, middle, anterior) Atrioventricular (AV) node AV bundle (a.k.a bundle of His) Bundle branches Purkinje fibres  Intrinsic Conduction System of the Heart Sinoatrial (SA) node = Pacemaker of the heart Sinoatrial (SA) node depolarises spontaneously & fires at regular intervals generating the Sinus Rhythm R L Heart beats with a rhythm of about 60-70 beats per minute (bpm) An electrical impulse from the SA node spreads along the atria, via the internodal tracts, and triggers an orderly sequence of further electrical events leading to atrial muscle contraction Electrical impulses converge on atrioventricular (AV) node Electrical signal pauses at AV node (0.1sec) – WHY? AV node is the only gateway for electrical signals between atria and ventricles – WHY?  Intrinsic Conduction System of the Heart Sinoatrial (SA) node = Pacemaker of the heart R L AV Bundle (Bundle of His) connects electrically the atria to the ventricles Bundle branches conduct the impulse through the septum down to the apex of the heart Purkinje fibres distribute impulses across both ventricles, causing ventricular contraction.  Intrinsic Conduction System of the Heart Pacemaker action potential Slow depolarisation (excitation) due to Na+ ions slowly Pacemaker (SA node) action potential entering the cell (slow Na+ currents) Slow depolarisation leads to ‘no true’ resting membrane with ionic permeabilities potential (~ -60mV) Rapid depolarisation (excitation) due to Ca 2+ ions entering the cell rapidly (fast Ca2+ currents) Repolarisation (returning to resting membrane levels ) due to K+ ions exiting the cell (K+ currents) The electrical cardiac cycle is spontaneously repeated (‘automaticity’)  Intrinsic Conduction System of the Heart Ion channels on pacemaker (autorhythmic cells) Cav = Voltage-gated calcium channel Kv = Voltage-gated potassium channel NCX = Sodium-Calcium exchanger Hcn = Hyperpolarisation-activated cyclic nucleotide-gated channel If = funny current (Hcn) SR = sarcoplasmic reticulum Electrical Conduction through the Heart Summary diagram of the electrical impulse conduction through the heart  Electrical Conduction through the Heart Spread of electrical activity along the myocardium Pacemaker action potential Cardiomyocyte action potential Gap junctions Allow instantaneous flow of ions between cells  Electrical Conduction through the Myocardium Myocardium is excitable and contractile ❖ The wall of the heart ❖ Myocardial cells (myocytes) Connection between two myocytes (see next slide) Myocytes are connected with intercalated discs Striated appearance of myocardium Myocytes branch  Electrical Conduction through the Myocardium Myocardium is excitable and contractile ❖ Connection between two myocytes ❖ Gap junctions between myocytes Membrane of Membrane of myocyte 2 myocyte 1 ion flow Facilitate instantaneous spread of electrical impulses between myocytes This ensures that myocytes contract as a single unit Electrical Conduction through the Myocardium ❖ Ventricu Myocardial action potential Rapid depolarisation due to Na+ influx (Phase 0) Early brief repolarisation due to closure of Na+ channels and opening of transient K+ channels (Phase 1) Slow depolarisation called the plateau phase due to opening of Ca2+ channels and calcium influx (Phase 2) Rapid repolarisation due to opening of K + channels and efflux of potassium ions (Phase 3) Resting membrane potential (Phase 4) Electrical Conduction through the Heart Summary diagram of the electrical impulse conduction through the heart  ElectroCardioGram (ECG) The recording of cardiac electrical activity It measures the depolarisation of atrial and ventricular myocytes ❖ 12-Lead ECG ❖ Normal ECG (Sinus Rhythm)  ElectroCardioGram (ECG) The recording of cardiac electrical activity It measures the depolarisation of atrial and ventricular myocytes P wave: QRS Complex: Depolarisation Depolarisation of of the atria in ventricles response to SA signaling T wave: Ventricular PR Segment: repolarisation Delay at the AV node ST Segment: Beginning of ventricular repolarisation  ElectroCardioGram (ECG) – P wave The recording of cardiac electrical activity It measures the depolarisation of atrial and ventricular myocytes  ElectroCardioGram (ECG) – PR segment The recording of cardiac electrical activity It measures the depolarisation of atrial and ventricular myocytes  ElectroCardioGram (ECG) – QRS complex The recording of cardiac electrical activity It measures the depolarisation of atrial and ventricular myocytes  ElectroCardioGram (ECG) – ST segment The recording of cardiac electrical activity It measures the depolarisation of atrial and ventricular myocytes  ElectroCardioGram (ECG) – T wave The recording of cardiac electrical activity It measures the depolarisation of atrial and ventricular myocytes  ElectroCardioGram (ECG) – TP interval The time during which the ventricles are relaxed and start filling up with blood coming through the pulmonary veins and vena cava  Quiz – spot the ECG abnormality 1 ❖ Normal ECG 2 Summary of cardiac excitation  Factors affecting Cardiac Rate and Rhythm An isolated heart beats at ~ 100bpm but the average heart rate of an adult is ~60-70bpm – WHY? Factors affecting Cardiac Rate and Rhythm ANS effects on pacemaker potentials Factors affecting Cardiac Rate and Rhythm Parasympathetic System Cardiac slowing Reduces automaticity Inhibition of AV conduction Releases acetylcholine Activation of muscarinic M2 receptors (abundant in atrial and nodal tissue) Activation of M2 receptors reduces cAMP formation which prevents the opening of Ca2+ channels M2 receptors also open a type of K + channel which leads to reduced excitation Factors affecting Cardiac Rate and Rhythm Sympathetic System Increases heart rate (positive chronotropic effect) Increases automaticity Repolarisation and restoration of function after depolarisation Influences SA node, AV node and ventricular myocardium Release of catecholamines (e.g. noradrenaline) Activation of beta1 adrenoreceptors leads to increasing cAMP formation which leads to opening of Ca2+ channels and increased influx of Ca2+. Effects of beta blockers (e.g. Bisoprolol)  Effects of Ca2+ channel blockers Cell membrane X Blue dotted line indicates the effects of the drug on the action potential  Effects of Na+ channel blockers Cell membrane Blue dotted line indicates the effects of the drug on the action potential  Effects of K+ channel blockers Cell membrane Blue dotted line indicates the effects of the drug on the action potential  Additional reading Rang & Dale’s Pharmacology Any human physiology textbook of your choice Human Biology by Mader & Windelspecht