Cardiac Continued

CO = SV x HR

Highly regulated by autonomic nervous system

• Normal resting: 70 bpm
• Max HR: 200 bpm
• Decreases w age (220 - age); active people tend to have less decrease w age

• Defined as volume of blood pumped per beat
• at rest, average SV = 70 ml; increased by exercise training

• Mostly controlled by regulation of strength of contraction, via 2 types of mechanisms:
• 1) length-dependent intrinsic mechanisms (Frank-Starling Law of the Heart)
• 2) length-independent mechs (intropy, typically via sympathetic nervous system)

• 4-6 L/min
• depends on size of person, metabolism, exercise, etc
• *remember to convert SV mL to L for CO L/min

• False. CO MUST be the same for left and right sides of heart.
• Closed loop system, therefore CO MUST equal venous return (VR = volume of blood flowing into right atrium per minute)

• CO increases by as much as 8 fold (up to 40 L/min in elite athletes; max normal people is 25 L/min)
• HR can increase 4 fold
• SV can increase 2 fold

• CO = arterial pressure / total peripheral resistance
• Q = P/R (think increased resistance, so decreased flow)

• First phase.
• Mitral valve is open.
• The end of diastole, so left atrium has passively filled w blood returning from pulmonary vein. Electrical signal from SA node triggers contraction of atrium.
• Left atrium contracts (atrial systole), so pressure increases for both atria and ventricle (filling passively with blood).

• As wave of electrical excitation arrives at left ventricle, it begins to contract.
• Aortic valve is closed as left ventricle begins to contract b/c aortic pressure is higher than ventricular pressure.
• As left ventricle contraction begins, mitral valve closes because ventricular pressure quickly exceeds atrial pressure.
• As ventricle begins to contract, the blood has no where to go (both valves are closed), so ventricular pressure rises rapidly.

As ventricle continues to contract, ventricular pressure increases until it's greater than the aortic pressure; at this point, aortic valve opens and blood flows from ventricle into aorta.

• After ejection phase.
• As wave of depolarization passes, ventricular myocytes relax, and ventricular pressure falls. Pressure decreases slowly at first.
• When ventricular pressure drops below aortic pressure, the aortic valve closes.
• Since the mitral valve is still closed, the ventricular pressure falls rapidly.

• As ventricle continues to relax, the pressure eventually falls below that of the atrium, allowing the mitral valve to open.
• Blood flows into the ventricle until next cardiac cycle is initiated by depolarization of the SA node.

• Diastolic Pressure Volume Relationship (DPVR)
• *passive tension curve: cardiac muscle is stiff & resists stretch passively; not much change normally in pressure w/ change in volume, except at very high volume where heart is just too full --> shallow slope of DPVR
• *represents PRELOAD of the heart (EDV): the load to which a muscle is subjected before shortening
• change in pressure as volume increases during diastole

• Systolic Pressure Volume Relationship (SPVR)
• much steeper than DPVR - pressure increases a lot, even at low volume/small volume changes
• includes the passive + active properties (ie: DPVR)
• change in pressure as volume increases during systole

• Afterload: the load against which a muscle contracts.
• For left ventricle, afterload = aortic pressure.
• range of afterload values lie along SPVR curve

• Active tension is difference between DPVR and SPVR = tension developed by the contraction (independent of passive properties/preload)
• *plot of active tension = "Starling Curve" or "Ventricular Function Curve": ascending and descending limbs (if you stretch it too far, the pressure decreases)

• 1) Heart always functions on the ascending limb of the venticular function curve.
• 2) Heart responds to an increase in EDV by increasing the force of contraction.
• 3) What goes in, must come out. Cardiac output must = VR.

Intrinsic

• 1) cardiac titin isoform is very stiff, resists stretch
• 2) Ca2+ sensitivity of myofilaments increases as sarcomeres are stretched. Same Ca2+ = greater force of contraction.
• 3) closer lattice spacing- stretched sarcomeres have altered spacing between actin & myosin, which results in more force generated per crossbridge

• Independent of autonomic nervous system regulation
• Analogous to, and dependent on, sarcomere length-tension relationship

• If you stretch the sinus node = increase HR
• via increased sympathetic tone (sensory afferents and brainstem); also intrinsic mechs in SA node
• another way in which increased venous return causes increased cardiac output

• Start at beginning of diastole, when mitral valve opens.
• Ventricular volume and pressure at their minimum values.
• Volume is ESV (note: not 0; heart doesn't pump out all blood)
• During diastole, the ventricular volume increases as blood flows into the left ventricle from the left atrium.
• Little pressure change, except slight hump that corresponds to atrial contraction.

• At point C, ventricle begins to contract
• Almost immediately, the pressure in the ventricle exceeds that in the atrium and the mitral valve is pushed close.
• Volume is EDV

• When left ventricular pressure exceeds the aortic pressure, the aortic valve is pushed open (point D) and the ejection phase begins.
• As blood leaves the ventricle, the volume decreases.
• At first the pressure continues to increase, as blood cannot leave the aorta fast enough.

• When ventricular pressure again falls below the aortic pressure, the aortic valve closes (point F).
• Again, both valves are closed, so no change in volume but pressure drops dramatically as ventricle continues to relax.

• Diastolic Pressure - Point D (where aortic valve opens)
• Systolic Pressure - Point E (highest pressure)
• Difference between systolic pressure and diastolic pressure = pulse pressure

SV = EDV- ESV

• EF = SV/ EDV
• normal ejection fraction is 50-70%
• <55% may indicate damage (previous heart attack)
• 35-40% may confirm diagnosis of systolic heart failure or cardiomyopathy
• <35% patient may be at risk for sudden heart attack, transplant indicated
• often measured by ECG

• Stoke work = amount of energy as work per beat
• area inside a PV loop diagram
• units = Joules
• NOT the same for right and left heart, as systemic circulation has higher pressure so left heart does more work

• Increased EDV (same thing as preload)
• Increase SV (in NEXT BEAT), via Starling's Law
• No change in ESV
• Slightly increased EF
• In next beat, SV back to normal b/c ESV is unchanged and contractility is unchanged

• filling pressure
• filling time
• ventricular compliance - important property in determining cardiac function

• Afterload is tension against which muscle must contract. For cardiac muscle, this is Aortic Pressure (~ mean systemic arterial pressure)
• Decrease SV (in NEXT BEAT) because ventricle has to work harder against increased aortic pressure, so less blood is ejected. Also, aortic P is higher, so aortic valve closes at higher P.
• EDV unchanged
• EF decreased
• ESV increases
• Subsequent beat: the increased ESV with constant venous return means increased preload, so increased SV

• Contractility controlled by amt of Ca2+ available to contractile proteins.
• Regulated by autonomic nervous system (sympathetic stimulation)

• Increase SV
• ESV decreases
• EF increases
• Subsequent beat: SV remains elevated as long as inotropy is high

• Uncontrollable: age, male gender, heredity & race
• Controllable: physical inactivity, overweight/obesity, high cholesterol, hypertension, diabetes, smoking (atherogenic = irritates vascular endothelial cells & increase platelet adhesion, increases BP, increases LDL and decreases HDL)

• Oxygen consumption of the heart exceeds supply.
• *Most common type of heart disease (6.8% of Americans)
• Most often caused by atherosclerosis in coronary arteries (atherosclerosis in cerebral arteries is leading cause of stroke)

• Def: an inflammatory response to damage of the vascular epithelium.
• hardening and thickening of arteries due to "plaques": deposits of fatty substances, cholesterol, and fibrin
• CVD risk factors cause endothelial damage. Once endothelium is damaged, plaques begin to form.

• "Crunchy on outside, greasy & thrombogenic on inside"
• Consist of fibrous cap (collagen + other ECM molecules secreted by ectopic smooth muscle cells) that overlays a lipid core (lipid core is intensely thrombogenic, with cellular debris and cholesterol)
• plaques form at branches and curves of arteries (areas with increased hemodynamic forces on walls, with turbulent instead of laminar flow)

Plaques themselves aren't usually the cause of acute problems. Stable plaques can be "stenotic" - that is, cause narrowing of arteries - but those occlusions tend to be relatively benign (at worst, cause angina)

Plaque rupture causes thrombosis, as the fibrous cap is destabilized over time and lipid core escapes. This can cause sudden and dramatic occlusion of artery = myocardial infarcation or ischemic stroke (80% of strokes)

• Damaged endothelium is leaky (leaky endothelium allows LDL cholesterol to enter intima)
• Leukocyte adhesion and migration (oxidized LDL promotes adhesion of leukocytes, which enter the intima and differentiate)
• Foam cells form (High cholesterol diet down-regulates normal LDL receptors. Differentiated leukocytes take up LOADS of cholesterol, forming "foam cells")
• Proliferative response in vessel wall (vascular smooth muscle cells (VSMCs) produce collagen = formation of fibrous cap which temporarily stabilizes the plaque)
• Plaque rupture and thrombosis (VSMCs de-differentiate and release cytokines that decrease collagen production and promote collagen degradation)

• Type of Ischemic Heart Disease.
• episodes of chest pain/tightness/heaviness (poorly localized, difficult to describe)
• transient decrease in blood flow (so cardiac demand transiently exceeds supply)

• Demand angina: provoked by exertion and stress; relieved within minutes at rest
• Supply angina: provoked by sudden decrease in supply (ex: occlusion from clot)
• Stable angina: usually demand angina; fairly good prognosis
• Unstable angina: usually worsening of stable angina, medical emergency with poor prognosis, caused by dynamic plaques

• Type of ischemic heart disease.
• death of cardiac myocytes caused by lack of blood supply
• most often in left ventricle
• myocardial cell death begins 15-40 minutes after occlusion of artery; very few cells left after 6 hours
• leaves scar tissue (collagen) - permanent damage, compromised cardiac function

• sudden onset (50% have warning signs)
• severe chest pain
• shortness of breath (dyspnea)
• autonomic symptoms: sweating, weakness, nausea, vomiting
• loss of heart function
• arrhythmias
• >30% silent/ no symptoms (esp in elderly and diabetic patients)

• damaged cells leak proteins into blood = markers for infarction (creatine kinase; troponin T)
• medical hx indicates ischemic chest pain >20 min
• ECG changes (ST segment shifts, abnormal Q waves)

• BP> 140/90 (normal is LESS THAN 120/80)
• Normal: < 120/80
• Prehypertension: 120/80 to 139/89
• Stage I: 140/90 to 159/99
• Stage II: >160/100

After 115/75, each increase of 20/10 DOUBLES risk of CVD incidents.

• - "Silent killer": assymptomatic until permanent damage has occurred
• - irreversible
• - increased afterload can lead to Left Ventricular Hypertrophy - eventual cause of heart failure
• - damages vascular endothelium - causes atherosclerosis
• - can cause aneurysms (bulges) in vessels - weak, chance of rupture; rupture in cerebral arteries = hemorrhagic stroke
• - usually results in arteriosclerosis - hypertrophy in vessels: reduced compliance - normal increase in BP w aging

• Hypertension
• 50% die from heart disease or heart failure
• 33% stroke
• 5% renal failure

• Disorders of cardiac rate and rhythm
• Can be benign or life-threatening
• a) Rate disorders (bradycardia = too slow, tachycardia = too fast). Caused by sinus node dysfunction and/or ectopic pacemakers
• b) Conduction abnormalities: Conduction block (AVN or block in His-Perkinje system or damaged myocardium)
• c) Disordered beating: premature beats caused by after depolarizations during EADs or soon after DADs normal repolarization, atrial fib (rapid irregular arrhythmia), ventricular fib (no pumping). Only hope is AED system.
• d) Cardiac arrest: heart stops; due to infarction or rhythm disorders

Progressive syndrome in which the heart cannot pump enough blood to meet demand and/or it cannot pump enough blood to prevent fluid backup in lungs and periphery (thus "congestive" heart failure)

No. Heart failure is not a disease. It is the end stage for other CV diseases, especially hypertension and coronary artery disease.

• 10% death rate annually (50% dead in 5 years)
• 5 million people in US currently diagnosed (1-2% of population; 25% of people over 85)

• Progressive deterioration of myocardium
• Molecular changes in cardiac myocytes
• Premature myocyte cell death
• Pathological hypertrophy – heart grows but in a maladaptive way.
• Affects right or left ventricle (or both... eventually)

• Systolic Heart Failure: decreased ability to pump (decreased ejection fraction)
• - most common cause = myocardial damage from infarction --> therefore underlying cause is atherosclerosis
• Diastolic Heart Failure: impaired ability to fill due to decreased compliance (cardiac hypertrophy from increased afterload reduces compliance)
• - most common cause = hypertension (often w diabetes and/or obesity); EF can be preserved

• Dypsnea (shortness of breath) - cardinal symptom
• ○orthopnea: SOB when lying down
• ·Fatigue (weakness, fainting from lack of O2)
• ·Peripheral edema (swelling feet and ankles)
• ·Pulmonary edema (fluid backup into pulm. vein -> increased hydrostatic pressure = net filtration, fluid into air spaces of lungs)

Huge increase in CO

• blood flow regulation in exercising muscle - local metabolites decrease vascular resistance by increasing vasodilation in arterioles in exercising muscle
• capillary recruitment in exercising muscle
• vasoconstriction in inactive tissues - via sympathetic stimulation

• Maximum rate of O2 consumption during strenuous exercise
• range: 30 ml/kg/min = couch potato to >80 ml/kg/min = elite athletes

• ○cardiac output (dominant factor) --> determined by HR & SV
• ○O2 carrying capacity of blood -> determined by hematocrit & O2 uptake in pulmonary capillaries
• ○blood flow through vessels in exercising muscle-> determined by resistance in arterioles
• ○muscle O2 uptake -> determined by mitochondrial oxygen consumption

• VO2 = CO (CaO2-CvO2)
• VO2 = oxygen consumption (L/min)
• CO = cardiac output (L/min)
• CaO2 = oxygen content of arterial blood
• CvO2 = oxygen content of venous blood

• (CaO2-CvO2) describes the contributions of O2
• carrying capacity, blood flow, and O2 uptake
• *NOTE: CO is main determinant of VO2max

• Decreased heart rate
• oat rest and at all submaximal levels
• opartly due to increased stroke volume (lower
• HR for any given CO)
• opartly due to decreased sympathetic and
• increased parasympathetic tone
• olow HR increases filling time (= increased
• EDV = increase SV via Starling’s law)

• · Physiological hypertrophy
• ○ increased chamber volume & mass
• ○ different from pathological hypertrophy in heart failure
• · Increased blood volume
• ○ 10-15% increase
• ○ increases EDV, so SV increased via Starling’s law
• · Decreased blood pressure
• ○ decreases afterload; can increase cardiac performance
• Increased contractility
• ○ increased RATE of Left Ventricular pressure development
• ○ increased ejection fraction

• Up to 50%
• ○ Directly reduces CVD risk, independent
• of other risk factors (~40% of benefit).
• ○ Reduces other CVD risk factors (~60% of
• benefit). Decreases blood
• pressure, cholesterol, weight, diabetes, stress
• - Mostly via decreases in "inflammatory factors" (eg: cytokines & vascular adhesion molecules, which are atherogenic)

• ○Minimum of 30 min 5 days a week of moderate-intensity aerobic exercise (eg: walking)
• OR
• 20 min 3 days a week of vigorous-intensity (eg: running)
• AND
• ○Minimum 2 days a week of muscle-strengthening activity (eg: weight-lifting, calisthenics/yoga, etc)

• Risk of CVD events decreases linearly with increased levels of activity.
• ○<200 kcal/week exercise = used as baseline
• ○200-600 kcal/week exercise = 27% decreased risk of CVD events in 10 years
• ○600-1500 kcal/week = 32% decrease
• ○>1500 kcal/week = 41% decrease