The Failing Heart and EC-coupling Flashcards
What is excitation-contraction coupling?
The process whereby action potential triggers myocyte to contract
Describe the B-adrenergic receptor signalling pathway
Noradrenaline/ adrenaline B1-adrenergic receptor Activates GTP-binding protein (Gs) Stimulates adenylyl cyclase (AC) cAMP PKA Phosphorylates several proteins related to EC-coupling (e.g. PLV, L-type Ca2+ channels, RyRs, Tropinin I and myosin binding protein C)
What is heart failure
Inability of the heart to supple adequate blood flow (and oxygen deliver) to tissues and organs).
Decreased perfusion of organs leads to
Reduced exercise capacity
Shortness of breath
Fatigue
Organ dysfunction (e.g. renal failure)
Symptoms of heart failure
Enlarges heart Weakened heart muscle Blood is pumped at reduced volume Less blood fills the chambers Weakness and fatigue Shortness of breath Swollen feet, ankles, abdomen, or veins in the neck.
What is myocardial infarction?
Heart attack
Progression to Heart failure begins with stage A causing diastolic dysfunction. What can cause this?
Hypertension, coronary artery disease, valvular disease, obesity, diabetes and kidney disease
What stages occur after stage A of heart dysfunction?
Diastolic dysfunction, Increase in atheroscelerosis, Cardiac ischemia, arrhythmias and ventricular dysfunction, ventricular enlargement, heart failure, pump failure, death.
Pathophysiology of cardiac heart failure
Decreased SV and CO
Increased ED pressure
Ventricular dilation or hypertrophy
Impaired filling (diastolic dysfunction)
Reduced ejection fraction (systolic dysfunction)
Pathophysiology of vascular heart failure
Increased systemic vascular resistance Decreased arterial pressure Impaired arterial pressure Impaired organ dysfunction Decreased venous compliance Increased venous pressure Increased blood volume
What compensatory mechanisms of heart failure (Cardiac)
Cardiac:
Frank-starling mechanisms- reduce output. Cardiac force therefore increase due to starling law; but at the expense of increase filling pressure (EDP).
Ventricular dilation
Tachycardia
What compensatory mechanisms of heart failure (Autonomic Nerves)
Autonomic Nerves:
Reduced BP initiates baroreceptor reflex - increases sympathetic adrenergic activity.
Reduced vagal activity to heart.
What compensatory mechanisms of heart failure (Hormones)
Hormones: Vasoconstriction of renal arteries increases hormone release.
Hormones Renin-angiotensin-aldosterone system
Vasopressin (antidiuretic hormone)
Circulating catecholamines
Natriuretic peptides
What are the cellular and molecular alterations in heart failure?
Changes occur in myocytes:
- alters contractile proteins
- alters calcium homeostasis
- alters signal transduction pathways (e.g. B adrenergic receptor signalling pathway
How are the contractile proteins altered in the failing heart?
Expression of myosin heavy chain isoforms are unchanged
ATPase activity are unchanged
Cross-bridge cycle rate is slower = causes a decrease in the maximal force developed
Phosphorylation state of troponin I is reduced due to decrease ac-cAMP-PKA pathway and affects the calcium sensitivity of the myofilament.