Cardiac Physiology And The Manifestations Of Cardiac Disease

23.11.05

Myocardial function, dysfunction and heart failure.

Cardiac output affected by:
• Filling - atrial pressure.
• Contractility - strength of contraction.
• Resistance - largely contributed by arterioles.

Definitions:
• CO = cardiac output (5l/min).
• SVR = systemic vascular resistance.
• PVR = pulmonary vascular resistance.
• LAP = left atrial pressure.
• RAP = right atrial pressure.
• BP = blood pressure.
• PAP = pulmonary artery pressure.
• HR = heart rate.
• SV = stroke volume.
• CO = SV x HR.
• MAP (mena-arterial pressure) = CO x SVR.

Autonomic nervous system
Sympathetic response:
• Increases heart rate.
• Increases contractility.
• Increases venous return.
• Redistribution of peripheral flow.
• Adrenergic receptors.
• Adrenaline/noradrenaline (similar, but different effects).

Parasympathetic response:
• Generally opposite effects to sympathetic response.
• Acts via muscarinic receptors.
• Acetylcholine.

Cardiac response to decreased cardiac output:
• Acute sympathetic activation.
• Chronic effects of adrenergic stimulation.
-Salt/water retention via renal absorption system.
-Cardiac hypertrophy.

Neurohumoral consequence of reduced cardiac output:
• Reduced tissue perfusion.
• Reduced renal perfusion.
• Renin release.
• Angiotensin generation.
1. Salt and water retention; congestive symptoms.
2. Oxidative stress; inflammation and myocardial impairment.
3. (Possibly) cardiac remodelling; cardiac enlargement; increased wall stress.
4. Vasoconstriction; increased afterload.
• Sympathetic activation.
1. Tachycardia; increased oxygen demand.
2. Peripheral vasocontriction; increased afterload.
3. Increased salt/water retention; oedema.

Inappropriate activation: sympathetic - renin-angiotensin, adrenal.
Body tried to deal with decreased cardiac output as if it is caused by trauma and blood loss - this causes a problem when it is not.
Inappropriate activation of rennin-angiotensin, sympathetic nervous system.

Vascular injury, healing and atherothrombosis
Properties of normal endothelium:
• Anti-thrombotic.
• Anti-proliferative.
• Anti-inflammatory.
• Maintenance of tight junctions between cells.
• Nitric oxide.
• Prostacyclin - CRUCIAL TO HOW MUSCLE LAYER CONTRACTS.

Atherosclerosis/thrombosis:
• When blood vessels are damaged, vessels proliferate so they are blocked.
• Eccentric skew of lumen leads to decreased blood flow.
• More prone to ischaemia.

Normal artery:
• Endothelium releases nitric oxide, prostanoids, prostacyclin etc. - keeping it relaxed.
• Factors like smoke, physical pressure (increased blood pressure) cause endothelium to stop working properly.
• No longer anti-inflammatory.

Atherogenesis:
• Endothelium starts to express new molecule allowing attachment of inflammatory cells.
• Cells migrate into subendothelium.
• Basement membrane broken down.
• Smooth muscle cells migrate to subepithelium - causes more inflammation and more activation of smooth muscle - spirals.
• Chronic inflammatory disease.
• Develops atherosclerotic plaque.
• Less blood gets through.
• Less blood to tissues.
• Accumulation of lipid/cholesterol within plaque.
• Symptoms increase gradually.

CHD - sudden death, sudden severity.

Atherosclerotic plaque
Stable:
• Intact endothelium.
• Thick muscle/connective layer.

Unstable:
• Eroded endothelium.
• Thin muscular cap.
• Far more inflammatory cells.
• Macrophages activated - chemicals dissolve connective tissue.
• Increases fragility of cap
• Plaque ruptures - releases nasty stuff.
• Develops blood clot, which rapidly progresses to acclude artery.
• Therefore, very sudden symptoms.