Failing heart muscle
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What is excitation-contraction coupling?
The process whereby action potentials trigger myocyte contraction
What mediates calcium in the cytoplasm?
Ryanodine receptors L-type channels SERCA Na/Ca exchangers
What is heart failure?
Inability of the heart to supply adequate blood flow (and oxygen delivery) to organs and tissues
What is the consequence of decreased perfusion of organs?
Reduced exercise capacity Fatigue Shortness of breath
What is the incidence of heart failure?
15 million new cases worldwide each year
What are the symptoms of heart failure?
Enlarged heart Weakened heart muscle Blood pumped at reduced volume Shortness of breath Weakness and fatigue Swollen feet, ankles, abdomen or veins in the neck
What are risk factors in heart failure?
Hypertension Coronary artery disease Valvular disease Obesity Diabetes Kidney disease
What is the cardiac pathophysiology of heart failure?
Decreased stroke volume and cardiac output Increased end-diastolic pressure Ventricular dilation or hypertrophy Impaired filling Reduced ejection
What is the vascular pathophysiology of heart failure?
Increased systemic vascular resistance Decreased arterial pressure Impaired arterial pressure Impaired organ perfusion Decreased venous compliance Increased venous pressure Increased blood volume
What are the cardiac compensatory mechanisms?
Frank-Starling mechanism Ventricular dilation or hypertrophy Tachycardia
What are the autonomic nerves compensatory mechanisms?
Reduced blood pressure initiates baroreceptor reflex Increases sympathetic adrenergic activity Reduced vagal activity
What are the hormonal compensatory mechanisms?
Renin-angiotensin-aldosterone system Vasopressin Circulating catecholamines Natriuretic peptides
What changes occur in myocytes in cardiac failure?
Altered contractile proteins Altered calcium homeostasis Altered signal transduction pathways
How are contractile proteins altered in the failing heart?
Expression of myosin heavy chains isoforms is unchanged ATPase activity unchanged Cross-bridge cycling rate is slower Phosphorylation of troponin I is reduced
How is calcium homeostasis altered in the failing heart?
Decline in intracellular calcium homeostasis Prolonged duration of the action potential Systolic Ca concentrations stay the same Threshold for Ca released from SR increases Increase in diastolic Ca concentrations Decreased uptake of Ca into SR
What happens to signal transduction in the failing heart?
Decrease in Badrenoreceptor number Alteration in cAMP signalling pathway
What is the cause of decreased contractile force?
SR calcium stores are significantly reduced
What happens to the Na/Ca exchanger?
Upregulated Promotes removal of vital calcium from the cell Development of delayed depolarisation and triggers arrhythmias
What happens to RyRs in failing cardiac muscle?
Hyperphosphorylation to overcome Ca deficiency
How is heart failure treated isotropically?
Positive ionotropic drugs • phosphodiesterase inhibitors • catecholamine-mediated inotropy
How do inotropic agents treat cardiac failure?
Increase force of the B adrenoreceptor system
What is the effect of nitric oxide?
Vasodilation
What is the role of phophodiesterase inhibitors?
Increase heart contractility Vasodilates vessels Alleviates increased pressure