Lecture 3.0 - The Pathophysiology of Myocardial Ischaemia Notes PDF

The Pathophysiology of Myocardial Ischaemia Prof. Richard Brooksbank School of Physiology (6Q01) Myocardial ischaemia results in: decreased O2 supply to cardiomyocytes decreased washout of metabolites increased SNS activity Net effect: decreased ATP production accu...

The Pathophysiology of Myocardial Ischaemia Prof. Richard Brooksbank School of Physiology (6Q01) Myocardial ischaemia results in: decreased O2 supply to cardiomyocytes decreased washout of metabolites increased SNS activity Net effect: decreased ATP production accumulation of toxic metabolites (lactate, CO2) metabolic derangements Pathophysiological effects are on: intracellular ion and osmotic balances sarcolemmal function contraction and relaxation Metabolic effects of decreased ATP Osmotic imbalance Cell rupture Cell/membrane damage Na+K+ ATPase Ammonium Cytotoxic effects ECF[K+] – ECG changes Reactive oxygen species (S-T elevation) Adenosine deamination to ICF [Na+] - arrhythmias hypoxanthine and xanthine Pain (Angina) AMP ATP ADP + Pi cAMP Glycolysis Glyceraldehyde-3-phosphate dehydrogenase activity Lactate β-adrenergic receptor activation Oxygen Metabolite delivery washout Sympathetic activation Metabolic effects of increased lactate and SNS activation Damage to membranes, contractile proteins, mitochondria Cytoplasmic [Ca2+] FFA, acyl carnitine and acyl-CoA SR Ca2+ ATPase Na+K+ ATPase Na+Ca2+ exchanger cAMP cytoplasmic [Na+] ATP Na+H+ exchanger Lipolysis Glycolysis Glyceraldehyde-3-phosphate dehydrogenase activity Lactate β-adrenergic receptor activation Oxygen Metabolite delivery washout Sympathetic activation Effects on sarcolemma and Ca2+-induced Ca2+ release SNS + + Decreased SR [Ca2+] - ATP Increased Decreased Ca2+ release Ca2+ uptake Increased cytosolic [Ca2+] 1 = L-type Ca2+ channel 2 = Ryanodine receptor Net effects: 3 = SR Ca2+ ATPase Increased cytosolic [Ca2+] decreases relaxation SR = Sarcoplasmic reticulum Decreased SR [Ca2+] decreases contraction Direct effects on contraction  lactate + H+ - ADP + Pi - - - ATP ATP FFA SNS Net effect: Decreased contraction Overall effect of ischaemia on cardiac function Decreased contraction Decreased relaxation Treatment Treatment involves anything which: Increases oxygen supply and metabolite washout Reperfusion (nitrates, aspirin, thrombolysis) O2 face mask (increases PaO2) Decreases SNS activity -blockers Decreases intracellular Ca2+ L-type Ca2+ channel blockers