15.1 Lecture Cardiac Muscle Contraction

Muscle Contraction

• Cardiac muscle fibers' interconnection facilitates rapid action potential spread to adjacent cells.
• Action potential propagation and muscle contraction occur as an all-or-none response.
• Myocardial cells have sarcomeres (Z line to Z line composed of actin and myosin filaments), and the troponin complex inhibits actin and myosin interaction.
• For muscle contraction, calcium bonds to the troponin-tropomyosin complex, causing a conformational change that exposes active binding sites on actin.
• Myosin cross-bridges bind and move along active actin filaments by attaching and detaching, shortening Z lines, a process requiring ATP.
• ATP is required for excitation-contraction coupling and calcium uptake into the sarcoplasmic reticulum to conclude contraction.
• Moving calcium into the sarcoplasmic reticulum decreases cellular calcium concentration, causing the troponin-tropomyosin complex to inhibit actin-myosin interaction.
• High metabolic demands are related to oxygen and metabolic substrate supplies; decreased supplies (e.g., coronary artery disease) can cause myocardial ischemia and infarction.

Length-Force Relationship

• Sarcomere length for efficient muscle cell function is between 2 and 2.4 nanometers.
• Compromised actin and myosin interaction occurs at greater sarcomere lengths.
• Sarcomere cannot generate an efficient contraction at shorter lengths.
• Ideal filling pressure for the left ventricle achieves optimal cardiac output.
• Filling pressures reflect ventricular volumes and myocardial stretch at rest.
• Excessively high filling pressures (e.g., congestive heart failure) and low filling pressures (e.g., hypokalemia) compromise stretch and decrease cardiac output.
• Basis for the Frank-Starling curve, relating preload to contractility

Differences Between Skeletal and Myocardial Cells

• Myocardial cells have branching, interconnected fibers at junctions to facilitate action potential conduction.
• Sarcomeres have increased mitochondria due to high metabolic rate.
• Rich capillary blood supply allows for rapid diffusion and perfusion.
• Extensive tubular system and sarcoplasmic reticulum enable rapid calcium release and reabsorption.

Myocardial Sarcomere Properties

• The myocardial sarcomere has properties common to neural tissue.
• Degeneration of a resting membrane potential.
• Ability to generate and conduct an action potential.
• Resting membrane is permeable to potassium but impermeable to sodium and calcium.
• Resting membrane potential relies on ion concentration differences between intracellular and extracellular environments (sodium, potassium, calcium).
• The sodium-potassium pump (requiring ATP) sets the electrical and chemical gradient: three sodium molecules are pumped out for every two potassium molecules pumped in.
• Equilibrium potentials of ions are calculated with the Nernst equation (single ion); the Goldman-Hodgkin-Katz equation accounts for multiple ions.
• Electrostatic gates open and close depending on cell membrane electrical potential (gates exist for sodium, potassium, calcium, and chloride).

Action Potential Phases

• Divided into five phases:
  • Phase 0: Depolarization; fast sodium channels open causing rapid sodium influx; local anesthetics inhibit the voltage-gated sodium channel, thus diffusion of phase zero.
  • Phase 1: Sodium gates close, sodium influx stops, calcium influx begins, potassium gates open, potassium moves from intracellular to extracellular.
  • Phase 2 (Plateau Phase): Unique to cardiac ventricular muscle; slow calcium channels open for slow calcium influx, delaying repolarization and prolonging the absolute refractory period.
  • Phase 3: Calcium channels close, potassium efflux accelerates, returning transmembrane potential to resting value.
  • Phase 4: Sodium-potassium pump re-establishes proper intracellular-extracellular ionic concentrations; lasts from completion of repolarization to the next action potential.

Drug Interference

• Many drugs interfere with the opening and closing of the action potential channels:
  • Sodium channel blockers interfere with phase 0.
  • Calcium channel blockers affect phase 2, decreasing contractility, heart rate, and cardiac conduction velocity.
  • Potassium channel blockers interfere with phase 3.
  • Beta-blockers affect the slope of phase 4 by reducing sodium and calcium flow.

Refractory Period

• The extended duration of the action potential protects the myocardial cell against premature excitation.
• Divided into absolute and relative refractory periods, resulting from sodium channel properties during the action potential.
  • Absolute Refractory Period: An action potential cannot be evoked, even with a stimulus. Lasts from phase 0 to the middle of phase 3.
  • Relative Refractory Period: An action potential can be stimulated but will have decreased amplitude, upstroke velocity, and conduction velocity. Extends from the middle of phase 3 to the beginning of phase 4.

SA Node

• The SA node is the primary pacemaker due to its sodium permeability
• More permeable to sodium than other myocardial cells.
• Sodium leak gradually raises the membrane potential to threshold (-55 to -60 mV), initiating an action potential.
• Intrinsic rate is 60-100 beats per minute.
• Lacks phases 1 and 2; only has phases 0, 3, and 4.
• Phase 0 involves opening sodium channels.
• Phase 3 is caused by potassium efflux.
• Phase 4 involves the sodium-potassium pump and sodium leakage, causing a gradual upslope until the action potential threshold is reached.

Cardiac Cycle

• Atrial systole ends, and the mitral valve closes, beginning isovolumetric contraction.
• When pressure reaches a threshold, the aortic valve opens, initiating blood ejection.
• Then the aortic valve closes, followed by isovolumetric relaxation. The mitral valve opens, and ventricular filling begins.
• ECG impulse precedes mechanical action.
• The P wave represents atrial systole, the QRS complex signifies ventricular systole, and the T wave represents ventricular repolarization.
• During ventricular systole, atria fill with blood from the venous system (right) and pulmonary circulation (left).
• Fluid flows based on pressure gradients.
• The first phase of diastole is isovolumetric relaxation.
• Ventricular muscle relaxes and pressure drops below atrial pressure. So the mitral valve opens and rapid passive filling begins.
• Atrial filling is in three phases: rapid inflow, reduced inflow, and atrial systole.
• Atrial systole increases ventricular volume by ~20% ("atrial kick") and is critical for maintaining stroke volume during exercise or with pathology.
• Diastole lasts from aortic valve closure until mitral valve closure. Isovolumetric relaxation is followed by rapid ventricular filling, then reduced ventricular filling, then atrial systole.
• After mitral valve closure, isovolumetric contraction begins, myocardial fibers shorten, and pressure increases. Systolic ejection begins with the aortic valve opening when left ventricular pressure exceeds aortic pressure.
• There is rapid ejection (first one-third of systole) and reduced ejection (remaining two-thirds).
• Left ventricular systolic pressure peaks, and the largest volume is ejected during rapid ejection.
• The dicrotic notch on the aortic pressure waveform occurs during isovolumetric relaxation: represents retrograde blood flow before aortic valve closure.

Coronary Artery Blood Flow

• Blood flow rate is the change in pressure within a vessel divided by resistance.
• Alterations in vessel radius change flow to the fourth power (Poiseuille’s Law).
• At rest, ~225 ml/min flow through coronary circulation, with a greater amount to the left ventricle during diastole.
• Blood flow is decreased to the sub-endocardium during systole due to vessel compression; flow through epicardial vessels is not affected as much.
• Regulated by intrinsic (coronary artery arrangement, perfusion pressure) and extrinsic (myocardial compression, metabolic, neural, hormonal factors) factors.
• Myocardial oxygen supply is determined by arterial blood content, diastolic blood pressure, diastolic time (determined by heart rate), oxygen extraction, and coronary blood flow.
• Demand is influenced by heart rate, preload, afterload, and contractility.
  • Increased heart rate increases demand and decreases supply time (diastolic filling is 80-90% of coronary filling).
  • Increased heart rate is the most important factor negatively affecting oxygen consumption.
• Beta-blockers increase supply and decrease demand by slowing the heart rate and decreasing contractility.

Myocardial Oxygen Consumption

• Determinants consist of myocardial contractility, myocardial wall tension/preload, heart rate, and mean arterial pressure/afterload.
• The myocardium extracts 65-70% of available oxygen; blood flow increase is the only way to increase oxygen delivery.
• Coronary blood flow is maintained at a constant rate when MAP is between 60 and 140 mmHg.
• When above or below these limits, coronary blood flow becomes pressure-dependent.
• During hypertension and when coronary arteries are maximally dilated, coronary blood flow is determined by MAP minus right atrial pressure.
• Ischemia occurs if blood flow is less than required.
• Coronary reserve is the difference between maximum and auto-regulated flow; a lower reserve indicates closeness of these values.

Coronary Steal

• Stenosis exists in one area so the area is already maximally dilated to meet demands.
• If a vasodilator is applied, it causes dilation only in areas with intact auto-regulation, increasing flow to those areas, but decreasing flow to areas with stenosis.
• Flow means oxygen, so by losing the flow of blood, oxygen supply is decreased, and a steal occurs.
• Coronary steal is unlikely if adequate CPP is maintained.

Cardiac Output

• Cardiac output is the amount of blood ejected by the left ventricle per minute.
• Cardiac index is cardiac output indexed for size.
• Primary determinants of cardiac output are heart rate and stroke volume.
• Key factors affecting stroke volume: preload, afterload, and myocardial contractility.
• Preload: Tension on the ventricular wall at the end of diastole.
• Increased preload increases contractility (Frank-Starling law), allowing compensation and avoidance of over-distension.
• Afterload: Wall tension the myocardium generates to eject stroke volume against systemic vascular resistance, the pressure within the left ventricle during peak systole.
• Contractility: the state of isotropy that is preload or afterload independent.

Ventricular Pressure-Volume Loops

• Simultaneous measure chamber pressures and volumes.
• Movement from left to right on the horizontal axis increases volume and movement up the vertical axis increases pressure.
• Four phases:
• Area one (B to C): Filling of the ventricle.
• Area two (C to D): Contraction against a closed valve, resulting in pressure increase without volume change.
• Area three (D to A): Ejection.
• Area four (A to B): Relaxation.
• Interior of the curve represents stroke volume.
• Stroke volume is calculated by subtracting end-systolic volume from end-diastolic volume (D-A).
• Ejection fraction (EF) is the percentage of end-diastolic volume ejected during systole. A normal EF is 60-65%; <40% indicates impairment.
• Factors that alter pressure-volume loops include preload, afterload, and contractility.

Hemodynamic Reflexes

• There's a direct correlation between cardiac output and venous return.
• Cardiac output is determined by blood return to the heart if contractility or heart rate isn't compromised
• Regulation of cardiac output depends on regulating heart rate and contractility, as well as vascular constriction/distention.
• Valsalva maneuver: Forced expiration against a closed glottis.
  • Inhibits the sympathetic nervous system and stimulates the parasympathetic, which decreases heart rate, contractility, and impulse conduction, and induces vasodilation.
  • Results in decreased blood pressure.
  • Increases intrathoracic pressure, decreasing venous return/preload and, thus, cardiac output.
• Cardiac nerves travel along the vagus nerve, while cardiac carotid sinus afferent nerves travel via Hering’s nerve (branch of the glossopharyngeal nerve).
• Baroreceptors respond to arterial blood pressure fluctuations. Decreases cause increased sympathetic tone, increased myocardial performance, and vasoconstriction. Hypertension causes the opposite effect.
• Inhibited by inhalational anesthetics in a dose-dependent manner, decreasing reflex responsiveness.
• Oculocardiac reflex: Traction on extraocular muscles/conjunctiva/orbital structures can cause hypertension, reflex bradycardia. Mediated by the trigeminal and vagus nerves.
• Celiac reflex: Traction on the mesentery/gallbladder or vagal stimulation causes bradycardia, apnea, and hypotension. Can be caused by insufflation or pneumothorax, and is resolved by stopping the stimulus.
• Bainbridge reflex: increased blood volume in the heart causes sympathetic stimulation through stretch receptors in the right atrium.
• Cushing reflex: Increased intracranial pressure exceeding MAP decreases cerebral perfusion pressure and may cause ischemia.
  • Intense sympathetic response causes vasoconstriction.
  • Cerebral infarction results if ischemia isn't relieved.
  • Cushing’s triad (hypertension, bradycardia, respiratory irregularity) is a late sign of high, sustained intracranial pressure.
• Central chemoreceptors are stimulated by acidic spinal fluid pH and increased arterial CO2.
• Peripheral receptors in the carotid arteries and aortic arch are stimulated by decreased arterial oxygen and, to a lesser extent, increased arterial CO2.
• Activation results in sympathetic stimulation, increasing ventilation, blood pressure, and heart rate, also inhibited by inhalational agents.

Bezold-Jarisch Reflex

• Intense parasympathetic stimulation can cause cardiovascular collapse.
• Rapid decreased venous return activates mechanical receptors in the left ventricle, causing vasodilation, bradycardia, and potentially asystole.
• Can be caused by neuraxial anesthesia, histamine release, or vasodilators.
• May be mediated by serotonin receptors; antagonists (ondansetron) may mitigate the effect, reducing spinal anesthesia-induced hypotension.

Vascular System

• The Vascular system is divided into pulmonary and systemic circulations:
  • Arteries transport blood under high pressure from the heart to the peripheral tissues; have a large diameter to maintain flow.
  • Arterioles are the last small branches of the arterial system, acting as control valves for blood release into the capillary beds.
  • Constriction causes the greatest increase in systemic vascular resistance.
  • Capillaries facilitate the exchanges of fluids, nutrients, electrolytes, and hormones between blood and interstitial fluids; walls are one cell thick.
  • Venules collect blood from capillaries, merging into progressively larger veins.
  • Veins transport blood back to the heart and act as a large blood reservoir due to their distensibility.
• Arteries are divided into conducting (major arteries like the aorta) and distributing (medium-sized arteries to specific organs).

Aorta Subdivisions

• The thoracic aorta is divided into the ascending, transverse (arch), and descending aorta.
• After traveling through the diaphragm, it is the abdominal aorta.
• The first branches of the ascending aorta are the right and left coronary arteries.
• The transverse goes into the brachiocephalic artery, left common carotid, and left subclavian:
  • The brachiocephalic artery divides into the right common carotid and right subclavian artery.
  • The left and right common carotid arteries branch into internal and external carotid arteries.
  • The internal carotid artery supplies ~80% of the blood to the brain (via the circle of Willis).
• Subclavian arteries have multiple branches which enter the upper arm.
• Axillary artery supplies the axillary region and branches into the brachial artery; the brachial artery divides at the radius into the radial and ulnar arteries.
• Passing through the diaphragm, the thoracic aorta becomes the abdominal aorta, branching to supply abdominal organs before dividing into iliac arteries in the pelvis.
• Internal iliac arteries supply the pelvis, whereas external iliac arteries supply the legs.
• Femoral arteries are branches of the external iliac arteries.

Microcirculation

• Composed of arterioles, capillaries, and venules.
• Nutrient delivery to capillary beds.
• Removal of waste.
• Maintaining ionic concentrations as well as transporting hormones.
• Arterioles connect to metarterioles, which connect to true capillaries (sphincters are present in the capillary).
• Intercellular clefts in the capillary membrane allow diffusion of water-soluble ions and small solutes.
• Diffusion is determined by lipid solubility, molecule size, and concentration gradients.
• Starling’s forces determine the movement of fluid volume between plasma and interstitial fluid.
• The lymphatic system transports excess fluid from the interstitial space to prevent edema.
• Blood flow to capillary beds is regulated by local tissue metabolic needs:
  • Oxygen Delivery.
  • Waste Removal.
  • Maintenance of ionic concentrations.
• Blood vessels dilate due to hypoxemia or vasoactive substances release:
  • For example, the kidneys in which case blood flow is dependent on filtration needs as opposed to blood flow to the skin that is dependent on temperature regulation.

Autoregulation

• Certain organs keep blood flow through capillary beds constant despite changes in perfusion pressure (brain, kidneys, coronary circulation).
• Between a certain range, above or below, blood flow is pressure-dependent.

Hemodynamics and Physics Principles

• Ohm’s Law describes the relationship between current, voltage, and resistance; in medicine applies to blood flow through a tube (Flow = Pressure difference / Resistance).
• Reynolds Number predicts laminar/turbulent flow by the ratio (Velocity x Density) / Viscosity), with values <2000 being laminar and >3000 turbulent. Turbulent flow is harder to move and increases resistance.
• Poiseuille's Law describes fluid flow through a tube: Flow = (πr4 x Pressure difference) / (8 x Viscosity x Length). Radius affect on flow is highest.
• Radius is the most important factor in determining flow with IV catheters, endotracheal tubes, and blood vessels.
• Resistance is the impediment to blood flow in a vessel:
  • Cannot be measured directly; it can be calculated.
  • Calculated utilizing cardiac output and pressure.
• Resistance in series (vasculature) are additive, while in parallel (capillary beds) are reciprocal. Circuits in parallel have lower resistance.

Blood Pressure Regulation

• Short-term BP regulation aims to return MAP to normal within 30 minutes, relying on the autonomic nervous system (baroreceptors, chemoreceptors, atrial stretch reflex, CNS ischemic reflex).
• Parasympathetic/sympathetic activation is controlled in the medulla and pons.
• Baroreceptors increase impulses when stretched but cease when MAP is <60 mmHg.
• Chemoreceptors excite the vasomotor center with changes in blood chemistry, specifically decreased arterial oxygen.
• Hormones (epinephrine, norepinephrine, vasopressin, angiotensin) are released from the CNS and contribute to short-term BP regulation. Vasopressin has short and long-term effects (vasoconstriction and decreased urinary output).
• Capillary fluid shift and stress-relaxation mechanisms compensate for hypovolemia.
• Long-term regulation is supplied by the kidneys, eventually returns MAP within normal range, and involves the renin-angiotensin system, the nervous system.
• The venous system accommodates large volume changes, buffering hyper/hypokalemia, is extensively innervated, and responds to intravascular volume changes during surgery/resuscitation.
• Chronic hypertension affects the heart, brain, and kidneys, accelerating atherosclerosis, increasing congestive heart failure/cardiomyopathy risk due to increased afterload and can also increase the risk of stroke or MI.
• Guidelines for treatment: Systolic BP >150 or diastolic BP >90.
• Dysfunction of the sympathetic nervous system is responsible for central hypertension, leading to vasoconstriction and secretion.
• The goal of antihypertensive therapy is to maintain consistent normal tension.

Perioperative Management of Hypertension

• Thorough history of cardiovascular system, especially ischemic disease.
• Symptoms related to coronary artery disease should be investigated.
• Untreated hypertension can have adverse consequences on the brain, kidney, and ocular function. Higher chances of stroke with long term hypertension.
• Pharmacologic control of blood pressure decreases the occurrence of nonfatal MI and mortality in stable coronary artery disease patients.
• Blood pressure should be maintained within 20%.
• Beta-blockers should be instituted before surgery and titrated to a heart rate between 50 and 60 beats per minute.
  • If Started within one day of surgery, beta-blockers prevent nonfatal demise but increase the risk of hypertension, bradycardia, stroke, and death. Therapy initiated rather than two days is preferable.

Cardiac Valves

• Leaflets that separate the heart chambers.
• When open, they allow blood flow between the chambers and vessels, and when closed, they prevent backward flow.
• A valve orifice, a normal size, presents only a small degree of significant flow obstruction.
• Abnormalities are cyanotic (Tetralogy of Fallot), insufficient (regurgitant), or mixed valvular.
• Valvular stenosis is narrowing of the valve valvular orifice, which increases resistance and turbulence.
• Insufficiency results in regurgitation secondary to incomplete or partial valve closure, which allows blood to flow back into the previous chamber or vessel to maintain cardiac function despite progressive ocular dysfunction.
• Evaluation should include recognition of sympathetic compensatory mechanisms and strategies to maintain hemodynamic stability.
• Valvular dysfunction that has evolved over time can have severe consequences.
• The cardiac rhythm and its effect on the diastolic filling time, as well as heart rate should be noted.
• Bradycardia with regards to lesions can significantly decreased stroke volume, whereas tachycardia with synodic lesions can severely decrease stroke volume.

Mitral Stenosis

• Mitral valve orifice narrows.
• Reduced flow from the left atrium to the left ventricle during diastole.
• As the cross-sectional area of the orifice decreases, the flow is restricted.
• Left ventricular volume is decreased.
• Severe stenosis results in pulmonary congestion, decreased cardiac output, and potentially right ventricular overload.
• When the valvular area becomes less than one (1) centimeter squared, the prolonged diastolic filling time is incapable of maintaining normal left ventricle in diastolic volume and normal stroke volume.
• As heart rate increases greater than 90, diastolic time is shortened and stroke volume is decreased.

Mitral Regurgitation

• During ventricular systole.
• When the mitral valve is closed, it prevents blood flow from the left ventricle back into the left atrium. However, if not completely closed, backward flow can occur.
• Aortic stenosis seen as a high-impedance outlet, where as MR is seen as a low-impedance outlet.
• Amount of regurgitation depends on the time for regurgitation (systolic time inversely proportional to heart rate), aortic impedance/systemic vascular resistance (increased afterload increases regurgitation and decreases stroke volume),
• Associated pathology with mitral regurg is volume overload of the left atrium and right ventricle.
• Chronic regurgitation produces gradual increasing left atrial pressure and dilation in acute Mitral Regurg the pulmonary vascular is exposed to the immediate and marked pressure and congestion occurs.
• Reducing afterload reduces impedance to outflow and can increase forward flow, whereas a 20% increase in MAP can cause decreased forward flow and increased regurgitation.

Aortic Stenosis

• Elevated left ventricular systolic pressure occurs to overcome the left ventricular outflow track obstruction caused by the narrowed aortic valve orifice to ensure normal flow rates and cardiac output.
• Left ventricular considerable hypertrophy is the change associated with aortic stenosis. -Decrease in left ventricular compliance. -Hypertrophic remodeling. -Decrease in the intrinsic contractility of the myocardium.
• Concentric hypertrophy increases myocardial oxygen consumption, while at the same time coronary profusion is decreased due to decreased left ventricular end diastolic pressure.
• To maintain cardiac output with a noncompliant ventricle the left atrial pressures increase and pulmonary congestion occurs.

Aortic Regurgitation

• Blood volume ejected from the left ventricle into the aorta regurgitates back into the ventricle because of incomplete closure of the aortic valve.
• Causes volume overload where the ventricle enlarges.
• Causing eccentric ventricular hypertrophy and chamber dilation.
• The degree of regurgitation depends on these factors.
• Elevated heart rate of 90 to 100 decreased the diastolic time.
• Reduced SVR decreases the gradient between the aorta and left ventricle, allowing for decreased resistance of blood moving for patients with chronic aortic insufficiency can remain asymptomatic for long periods, and except for during times of stress, symptoms are not incapacitating.

Mitral Valve Prolapse

• Generally has the effect of weakness, dizziness, syncope, atypical chest pain, and palpitations.
• Atrial matriculated arrhythmias are common.
• Beta blockers are traditionally used for treatment with increase in diastolic volume and decrease the degree of prolapse.
• Most patients do not require medical or former electrical management.
• Arrythmias can occur.

Cardiomyopathy

• Heart muscle disease that is chronic and progressive; all forms can result in congestive heart failure and death.
• Hypertrophic Cardiomyopathy
• Can be categorized as with or without left ventricular outflow obstruction ventricular hypertrophy and decreased left ventricular compliance leads to systolic and diastolic dysfunction and can cause a left ventricular outflow track obstruction.
  • Increase preload, decreasing myocardial contractility, controlling heart rate, and maintaining or increasing afterload.
• Dilated Cardiomyopathy -The Most common form of cardiomyopathy. -Eccentric hypertrophy that affects both left and right ventricles where tensions on the ventricular walls are aresult in decreased stroke volume.
• Intervention includes diuretics, Ace inhibitors, and to Jackson.
• Restrictive Cardiomyopathy
• Characterized by infiltration and deposition of fibrous tissue into the myocardium.

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)

• An autosomal dominant genetically inherited disorder that most often manifest during adolescence.
• Fibrous fatty infiltrates invade the right ventricular myocardium and cause myocytes dysfunction and death, resulting in decreased right ventricular cardiac output.
• Management should focus on identification and treatment of fatal arrhythmias.
• Ventricular arrhythmias are common, and sympathetic stimulation can increase them.