ELECTROPHYSIOLOGICAL CHANGES DURING MYOCARDIAL ISCHAEMIA

Transcription

1 ELECTROPHYSIOLOGICAL CHANGES DURING MYOCARDIAL ISCHAEMIA 1. Definition of myocardial ischaemia "The blood supply to the myocardium is inadequate" (Opie) "The absence of arterial blood flow" (Jennings) "Supplydemand imbalance" (Schelbert) The fundmental concept: "Ischo" = "to hold back" "haima" = "blood" Imbalance between blood supply and blood demand of the myocardium (the oxygen supply is not able to keep up with the oxygen demand of the myocardium) "Reversible" phase when it is sufficiently severe to cause characteristic metabolic, mechanical, electrocardiographic changes that are diminished when the ischaemia ceases "Irreversible" phase as ischaemia progresses infarction (= stuffed in) cell death (= necrosis; "necro" = death) Reperfusion (eg. thrombolysis) as early as possible benefit for cells that are reversibly damaged

2 mild ischaemia stenosis severe ischaemia occlusion

3 Coronary stenosis/spasm/occlusion Physical/emotional stress supply / demand Reduced perfusion Metabolic changes Impaired contractility (little blood, little work) Electrophysiological changes

4 Mild ischaemia Metabolic changes ATP, CP breakdown, Pi phosphofructokinase (ratelimiting enzyme) phosphorylase Glycolysis, glucose uptake Glycogen breakdown PYRUVATE LACTATE

5 Severe ischaemia Metabolic changes 1 Accumulation of the products of anaerob glycolysis (lactate, Pi, H +, NADH 2 ) glycolysis ischaemic damage acylcoa ATP/ADP transport membrane damage Impaired mitochondrial function

6 Severe ischaemia Metabolic changes 2 Acute pain catecholamines Plasma free fatty acid (FFA) acylcoa membrane damage Krebs ciklus Intracellular FFA Triglyceride (TG) demand ATP

7 Membrane damage enzyme loss Ca 2+ overload arrhythmias ROS, CA, FFA Impaired diastolic relaxation Ca 2+ Ca 2+ Ca 2+ 1 hypercontraction + Lack ofatp uptake of Ca 2+ into the SER Ca 2+ pump activity phospolypases 3 Ca 2+ DAD ADP Ca 2+ ATP utilised ATP ADP 2 Ca 2+ MITO ATP production ATP utilisation Ca 2+ ROS formation SER

8 Endothelium Activated xanthine oxydase hypoxanthine neutrophils H 2 OH H 2 OH ischaemia inosine AMP ADP ATP Reduced state arachidonic acid H 2 O membrane Cytosol O 2 O 2 O 2 CATECHOLMINES ADRENOCHROME

9 ischaemia reversible poor delivery poor washout Depressed mitochondrial metabolism ATP FFA metabolites Lactate, H +, C glycolysis, protons glycolitic ATP NE camp Ion pumps inhibited ROS formation severe cellular acidosis Phospholipase activation Ca 2+ cell swelling membrane damage lysosomal activation contracture ATP increasing ischaemia enzyme loss proteolysis infarction irreversible

10 Electrophysiological changes K + loss normal EKG EKG alterations: STsegment deviations (elevation, depression) peaked T vawe Ca 2+ overload Arrhythmias extrasystole (ES) tachycardia (VT) fibrillation (VF)

11 Rhythm disturbances (Arrhythmias) early (EAD) and delayed (DAD) afterdepolarisations Place of origin atrial junctional szupraventrikuláris ventricular Effects on heart rate tachycardia bradycardia Mechanism disturbance in impulse generation disturbance in impulse conduction késıi korai kétirányú blokk egyirányú blokk reentry

12 arterial blood pressure left ventricular pressure LV contractility (+/dp/dt) inhomogeneity of electrical activation epicardiál EKG 1 epicardiál EKG 2 coronary blood flow limb lead EKG alap okklúzió

13 arterial blood pressure left ventricular pressure LV contractility (+/dp/dt) inhomogeneity of electrical activation epicardiál EKG 1 epicardiál EKG 2 coronary blood flow limb lead EKG reperfúzió

14 OCCLUSIONINDUCED VENTRICULAR ARRHYTHMIAS IN ANAESTHETISED DOGS

15 REPERFUSIONINDUCED VENTRICULAR ARRHYTHMIAS IN ANAESTHETISED DOGS

16 Consequences of acute myocardial infarction ventricular arrhythmias atrial fibrillation heart failure early arrhythmias (within 24 h) ES, VT, VF sudden cardiac death often occurs after MI, especially in severe coronary artery diesease, bad prognosis Impaired LV pump function due to the muscle loss present future Treatment of arrhythmias (antirrhythmic manouvers) 1. Pharmacological treatment Antiarrhythmic drugs 2. Special pacemakers 3. Cardioverter defibrillators (ICD) 1. Ischaemic precondicioning 2. Gene therapy

17 Ischaemic precondicioning Short periods of ischaemia (coronary occlusions) protect the heart against the severe consequences of a subsequent, more prolonged ischaemia/reperfusion insult Precondicioning stimulus Coronary occlusion/stenosis Volumen overload Increased heart rate electrical stimulation physical exercise Protective effect Preserved metabolism (ATP utilisation, lactate production ) Ischaemic injury (infarct size) Enhanced recovery of myocardial function during reperfusion Protection against ischaemia and reperfusioninduced ventricular arrhythmias Protection against endothelial dysfunction

18 PRECONDITIONING PROTOCOL CONTROL Occlusion Reperfusion PRECONDITIONED 5 min Occlusion Occlusion Reperfusion Reperfusion 5 min 5 min 25 min 20 min 20 min Preconditioning

19 DISTRIBUTION OF VPBs DURING A 25 min OCCLUSION OF THE LAD phase Ia phase Ib 25 n = VF S1

20 VENTRICULAR ARRHYTHMIAS IN DOGS SUBJECTED TO CORONARY ARTERY OCCLUSION AND REPERFUSION Duration of occlusion (min) VPBs VT VF REPERFUSION

21 ANTIARRHYTHMIC PROTECTION BY BRIEF CORONARY ARTERY OCCLUSIONS phase Ia phase Ib Classic PC Control CONTROL (n = 110) PRECONDITIONED (n = 77)

22 TIMECOURSE AND INTENSITY OF PROTECTION INDUCED BY PRECONDITIONING EARLY PROTECTION DELAYED PROTECTION FIRST WINDOW CLASSIC PRECONDITIONING SECOND WINDOW SWOP ONSET: IMMEDIATE DURATION: From minutes to 1 or 2 hours INTENSITY: STRONG PROTECTION HOURS From 12 to 72 hours MILDER PROTECTION