Cardiac Circulation, Myocytes, and Electrophysiology – Comprehensive Notes

Coronary Circulation: Source and Pathways

• The image discusses this as not an AV valve but the aortic valve; the two cusp-like openings are the ostia for the right coronary artery (RCA) and the left coronary artery (LCA).
• Blood leaves the left ventricle into the aorta and, through those ostia, feeds the heart via the coronary circulatory system.
• The aorta divides early into the right and left coronary arteries; these then branch into:
  • Right coronary artery: marginal arteries and posterior interventricular (posterior descending) artery.
  • Left coronary artery: anterior interventricular (LAD) artery and circumflex artery, among others.
• The heart has its own circulatory system (coronary circulation) that supplies the heart muscle (myocardium) with blood before the rest of the body, reflecting its critical role in pumping blood.
• In lectures, expect questions about coronary blood supply and pathways in lab (anatomy-focused), not direct location of blood flow post-aorta in lecture.
• Blood entering the coronary circulation ultimately supports heart muscle function, enabling the heart to pump blood to the body.
• There is a general circulatory route: major artery → smaller arteries → arterioles → capillary beds → venules → veins → heart. This route applies to systemic circulation and is contrasted with coronary circulation,
  which feeds the heart muscle itself.
• The blood supply to the heart originates from the aorta; oxygenated blood is delivered to the heart first to maintain pumping pressure for systemic circulation.
• The coronary arteries eventually drain deoxygenated blood via the coronary venous system into the coronary sinus, which opens into the right atrium, returning blood to the heart.
• Coronary sinus drainage: all venous drainage from the coronary circulation converges on the coronary sinus, which connects to the right atrium.
• Key terms introduced: anastomosis (union or joining of two blood vessels), collateral circulation (an alternate circulation route through anastomoses).
• Anastomoses can provide alternate routes if a vessel is blocked, preserving tissue viability by bypassing occlusions.
• If blood supply is insufficient, cells can die; in the heart, this manifests as chest pain (angina) or myocardial infarction (MI).
• Atherosclerotic plaque and thrombus can cause partial or complete blockage of a coronary artery, risking ischemia and tissue necrosis.
• Common risk factors cited: poor diet rich in fats and sugars, sedentary lifestyle, smoking, leading to plaque formation and arterial blockage.
• Management and intervention: lifestyle changes (exercise, diet), medications (cholesterol-lowering agents, blood thinners), and interventional procedures like stents to open blocked arteries.
• A stent is a metallic (or other material) scaffold placed inside a narrowed coronary artery to hold it open, improving blood flow; may require ongoing blood thinner therapy and carries potential risks.
• Concept emphasis: collateral circulation can prevent tissue death by providing alternative routes for blood flow when a primary vessel is obstructed.
• Ischemia is insufficient blood supply to a tissue; in the heart, increased metabolic demand (e.g., during exercise) can reveal ischemia as angina when supply cannot meet demand.
• Infarction is localized cell death (necrosis) from obstruction of blood supply; in the heart, infarction leads to loss of contractile function due to replacement by scar tissue.
• After infarction, edema and inflammation occur initially, followed by replacement with scar tissue, reducing pumping efficiency.
• The speaker emphasizes the goal of preserving cardiac tissue through collateral circulation and medical intervention to avoid infarction.

Cardiac Muscle Cells (Myocytes): Structure and Function

• Cardiac myocytes are not long, non-branching skeletal muscle fibers; they are shorter, branching, and still striated.
• Nuclei: most cardiac myocytes have one or two centrally located nuclei (as opposed to peripheral nuclei in some skeletal muscles).
• Intercalated discs: prominent, transverse dark lines that connect cardiac myocytes; unique to cardiac muscle (and present in some smooth muscles).
• Intercalated discs contain two key structural components:
  • Desmosomes: strong mechanical junctions that hold cells together during contraction.
  • Gap junctions: electrical connections that permit ion flow between cells, enabling rapid depolarization.
• Metabolic features: cardiac myocytes have large, abundant mitochondria; high density of capillaries; presence of myoglobin to store/attract oxygen within the cells.
• Myoglobin: a muscle-specific oxygen-binding protein with high affinity for oxygen, aiding oxygen delivery to mitochondria.
• Substrates for ATP production: cardiac myocytes can use glucose, fatty acids, and lactic acid; they rely on aerobic respiration due to their continuous activity.
• Contraction mechanics: sliding filament mechanism (like skeletal muscle) but with unique electrical properties; contraction is sustained and requires ATP and Ca2+ handling.
• Cardiac myocytes require a constant oxygen supply due to high mitochondrial content and continuous activity.
• Structural adaptations that maximize aerobic capacity:
  • Many large mitochondria
  • Myoglobin stores for rapid oxygen availability
  • High capillary density for efficient oxygen and substrate delivery
  • Flexibility to utilize multiple substrates (glucose, fatty acids, lactic acid)

Intercalated Discs and Functional Syncytium

• Intercalated discs enable electrical and mechanical coupling between adjacent cardiac myocytes.
• Functional syncytium means that cardiomyocytes contract as a coordinated unit, behaving like one large cell within each chamber (atria as a unit; ventricles as a unit).
• Two key distinctions:
  • Atrial myocytes are electrically connected to other atrial myocytes via gap junctions, allowing simultaneous atrial contraction.
  • There are no gap junctions between atrial and ventricular myocytes; the fibrous cardiac skeleton physically isolates atria from ventricles to maintain sequential contraction.
• Electrical conduction specifics:
  • Depolarization spreads rapidly across intercalated discs in atrial myocytes, enabling synchronized atrial contraction.
  • Ventricular myocytes also contract synchronously, but the atria and ventricles are electrically isolated from each other to prevent cross-talk of contractions.
• The fibrous skeleton’s separation ensures proper timing: atrial systole precedes ventricular systole, facilitating effective filling and ejection.

Electrical Excitability and Autonomy

• Some cardiac cells are autorhythmic (myogenic): they generate their own rhythm and action potentials, driving the heart’s rhythmic beating.
• The heart has dual autonomic innervation from the autonomic nervous system:
  • Sympathetic nerves (cardiac nerves): norepinephrine binds to adrenergic receptors to increase heart rate and force of contraction.
  • Parasympathetic nerves (vagus): acetylcholine binds to cholinergic receptors to decrease heart rate and contractility.
• Autorhythmic cells enable the heart to beat autonomously when isolated in a balanced nutrient solution; the brain can modulate this rhythm but cannot override the intrinsic rhythm completely.
• The majority of heart cells are contractile myocytes; a smaller subset are specialized conduction/autorhythmic cells that generate regular action potentials.

Autonomic Regulation: Heart Rate and Contractility

• Sympathetic activation increases heart rate (chronotropy) and contractile force (inotropy).
• Parasympathetic activation decreases heart rate and contractile force (via acetylcholine).
• The heart receives dual innervation, allowing fine-tuned control of heart rate and force to meet physiological demands.

Stretch Response and Preload (Length-Dependent Activation)

• Cardiac cells respond to stretch with a more vigorous contraction (akin to the length-tension relationship).
• Increased venous return (preload) stretches cardiac myocytes, leading to stronger subsequent contractions to maintain effective stroke volume.

Absolute Refractory Period and Contraction Timing

• Cardiac contractile cells have a long absolute refractory period, during which no stimulus can trigger another contraction.
• This long refractory period ensures proper timing for contraction and prevents tetanic summation, enabling complete relaxation and ventricular filling before next contraction.

Metabolic and Substrate Flexibility

• Cardiac metabolism relies on aerobic respiration with high oxygen demand and continuous perfusion.
• Substrates used by cardiac myocytes include:
  • Glucose
  • Fatty acids
  • Lactic acid
• These substrates are supplied via the coronary circulation, with myoglobin aiding oxygen availability within the cells.

Practical Implications and Clinical Connections

• Ischemia can cause angina pectoris (chest pain) during increased activity when oxygen supply cannot meet demand.
• If ischemia persists or is severe, infarction can occur, leading to myocardial necrosis and scar tissue formation, impairing pumping efficiency.
• Collateral circulation via anastomoses can help preserve tissue viability by providing alternative routes for blood flow around blocked vessels.
• Intervention strategies include lifestyle changes, medications to dissolve or reduce plaques, and stenting to mechanically reopen narrowed arteries.
• Angina and MI are contingent on the balance between oxygen supply and demand in the myocardium; prompt restoration of perfusion is critical to prevent irreversible damage.

Terminology Recap (Key Terms to Know)

• Ostia: openings in the aorta through which coronary arteries originate.
• Coronary arteries: RCA and LCA; RCA gives marginal and posterior interventricular arteries; LCA gives LAD (anterior interventricular) and circumflex arteries.
• Coronary sinus: large venous structure that drains coronary blood into the right atrium.
• Anastomosis: union or joining of two blood vessels.
• Collateral circulation: alternative blood flow route via anastomoses.
• Ischemia: insufficient blood supply to an organ or tissue.
• Infarction: localized tissue necrosis due to obstruction of blood supply.
• Angina pectoris: chest pain due to ischemia.
• Myocardial infarction (MI): death of heart muscle cells due to ischemia.
• Plaque and thrombus: causes of narrowing/occlusion of coronary arteries.
• Stent: a scaffold placed inside a vessel to keep it open.
• Myocyte: cardiac muscle cell.
• Intercalated discs: junctions between cardiomyocytes containing gap junctions and desmosomes.
• Gap junctions: electrical connections allowing rapid depolarization spread.
• Desmosomes: mechanical connections between cells.
• Functional syncytium: cardiomyocytes contract as a coordinated unit.
• Autorhythmic (myogenic) cells: cells that generate their own rhythm.
• Fibrous cardiac skeleton: structure that electrically isolates atria from ventricles.
• Absolute refractory period: time during which a cell cannot be stimulated to contract again.
• Myoglobin: oxygen-binding protein in muscle.
• Substrates for ATP: glucose, fatty acids, lactic acid.
• Dual innervation: sympathetic and parasympathetic inputs regulate heart function.
• Chronotropy and inotropy: heart rate and contractility effects of autonomic input.
• Preload/length-tension: stretch of cardiac muscle affecting contraction strength.
• Ischemia-induced changes: edema, inflammation, necrosis, scar formation.