CVPR 03-24-14 11am-Noon Heart as a Pump - Proenza Flashcards
Cardiac output (CO) defn.
Volume of blood pumped per minute by left ventricle
Stroke volume defn.
Volume of blood pumped per beat
Cardiac output (amounts) & factors it depends on
CO = 4-6 L/min at rest; Depends on size of person, metabolism, exercise, etc.; Can increase by as much as 8 fold during strenuous exercise (max ~25 L/min in untrained ppl, up to 40 L/min in elite endurance athletes)
Equations to find CO
CO = arterial pressure / total peripheral resistance = flow equation / Ohm’s law CO = SV x HR
Cardiac index - defn. & normal range
CO normalized to body size, measured as surface area in meters squared; Normal range = 2.6 to 4.2 L/min/m squared
Two mechanisms for heart to control cardiac output
Heart rate & stroke volume; HR can increase by a larger % than stroke volume can, so HR can produce larger changes in cardiac output; High HR alone allows less time for filling so would tend to decrease in stroke volume in absence of other regulation
Heart rate - regulation
Set by pacemaker cells in sinoatrial node; Highly regulated by autonomic nervous system
Heart rate – resting & max rate
Resting HR = 70bpm (as low as 35bpm in elite endurance athletes); Max HR up to 200 bpm
Heart rate – variation with age
Maximum HR decreases with age; Estimated as 220 minus age, BUT that is highly variable & active people tend to have less decrease in max HR as they age.
Stroke volume – what determines it
Determined by strength of contraction of the heart, venous return (“preload”), and vascular resistance (“afterload”)
Two mechanisms that control strength of contraction of the heart
- Length-dependent intrinsic mechanism = Frank-Starling Law of the Heart.
- Length-independent mechanism = Inotropy (or “contractility”), regulated via sympathetic nervous system stimulation.
Cardiac output and Venous return
Cardiac output MUST equal venous return; CO must be equal on both sides of the heart; If these volumes are not closely matched, edema (peripheral or pulmonary) results.
Venous return
Volume of blood flowing into right atrium per minute
4 Phases of the Cardiac Cycle
Diastole –> Isovolumetric contraction phase –> Systole (Ejection) –> Isovolumetic relaxation phase
Pressure changes during diastole
At end of diastole, left atrium has filled w/oxygenated blood from pulmonary vein. Contraction is triggered by an electrical signal originating in SA node. As atrium contracts (atrial systole), atrial pressure increases, appearing as a wave (hump) in both atrial & ventricular pressure b/c the mitral valve at this stage is open, so blood can flow freely out into the ventricle.
Isovolumetric contraction phase
Wave of depolarization begins to reach the ventricle, which starts to contract. Ventricular pressure increases, pushing the mitral valve closed (b/c ventricular pressure quickly exceeds that in the now-relaxing atrium). However, aortic pressure is initially greater than ventricular pressure, so aortic valve is also closed during the initial stage of ventricular contraction. Thus, ventricular pressure increases dramatically (ventricle contracts but blood has no place to go).
Ejection Phase (Systole)
As ventricle continues to contract, ventricular pressure exceeds aortic pressure, pushing the aortic valve open. Blood flows out of the heart. As ventricle begins to relax, ventricular pressure falls. Pressure decreases slowly at first, and ejection continues. However, when ventricular pressure drops below aortic pressure, the aortic valve closes.
Isovolumetric relaxation phase
Ventricle continues to relax w/both valves closed, so the pressure falls rapidly. The pressure eventually falls below that in the atrium, allowing the mitral valve to open and blood to flow into the ventricle, beginning a new cycle.
Volume during the cardiac cycle
First, ventricle fills passively, with a slight hump toward the end of diastole when the atrium contracts. Then, during the isovolumetric contraction phase, there is no change in volume, b/c the aortic & mitral valves are closed. When aortic valve opens & blood can leave the ventricle, the volume decreases.
Curves bounding the Pressure & Volume changes in the Left ventricle
- Systolic pressure-volume relation
- End diastolic pressure-volume relation
* similar relationships exists for PV changes in all heart chambers
End diastolic pressure-volume relationship (EDPVR) – defn.
Pressure-volume relationship during filling of heart BEFORE contraction (depends on the passive elastic properties of the ventrile – it can expand as it is filled, so pressure does not increase dramatically before contraction)
End diastolic pressure-volume relationship (EDPVR) – elastic properties vs. compliance
EDPVR is determined by passive elastic properties of ventricle (similar to compliance, but note compliance is deltaV/deltaP, now we are plotting P as a function of V, so slope of EDPVR is inverse of compliance).
Slope of EDPVR – shallow vs. steep
Shallow in normal physiological range (there is not much change in pressure w/ change in volume as long as ventricle is compliant)…Steep in some pathologies which decrease compliance, impairing filling of the ventricle (can’t expand as much, so pressure goes up)…Steepens at very high volumes (can’t expand enough to compensate).
End diastolic pressure-volume relationship (EDPVR) – what it represents
It represents the PRELOAD on the heart (“a small weight hanging down from a muscle before it begins to contract”…the length to which the heart is stretched by filling before contracting)
Preload defn.
Ventricular wall tension at the end of diastole (from Law of LaPlace); The length to which a muscle is stretched before shortening (how much the ventricle expands as it is filled, before it contracts); For the left ventricle, ~equal to end diastolic volume
Afterload defn.
The load against which a muscle contractions (wall stress during contraction; the load against which heart must contract to eject blood, coming from systemic circulation); For the left ventricle, ~equal to aortic pressure
Afterload analogy
Small weight (preload) PLUS large weight (afterload) lifted off a table; Muscle contracts with force equal to both
Systolic pressure-volume relationship (SPVR)
Pressure-volume relationship at the peak of isometric contraction (DURING contractions, not before, though it includes the passive elastic properties of the heart from EDPVR as well as its active contracting property); Maximum pressure that can be developed by the ventricle for a given set of circumstances
Steepness of Systolic pressure-volume relationship (SPVR)
Much steeper than EDPVR – pressure increases a lot even at low volume (since ventricle is contracting)
Afterload effects on ventricular pressure
For the ventricle, the pressure developed during a contraction (at the end systolic volume) depends on the afterload…Increased afterload increases the pressure with which the ventricle must contract to eject blood (force required to lift a bigger weight off the table).
“Active tension”
Difference in force between peak systolic pressure and end diastolic pressure curves, i.e., tension developed by the contraction itself, independent of the preload
Starling Curve (Ventricular function curve)
Plot of cardiac performance (such as active tension or CO or SV) as a function of preload (such as length or EDV); Ascending & descending limbs; Analogous to sarcomere length-tension curves; There is not a single Starling curve…Families of Starling curves describe different inotropic states of heart.
Frank Starling Law of the Heart – what is it & what its violation means
INTRINSIC mechanism by which heart adapts to changes in preload (in normal physiological range)…Violation of Starling’s law corresponds to Heart Failure.
Three ways to state Starling’s Law:
- Heart responds to an increase in EDV by increasing the force of contraction (i.e., ventricular output/active tension increases as the end diastolic volume increases).
- Healthy heart always functions on the ascending limb of the ventricular function curve
- What goes in, must come out (Cardiac output MUST equal venous return & cardiac output from left and right ventricles MUST match (on average))
Purpose of Frank-Starling mechanism
Helps balance output between left and right ventricle. EX: Lt. ventricular stroke volume = 60.0 ml/beat, Rt. ventricular SV = 60.1 ml/beat. How much would pulmonary blood volume change over 1 hour if the heart rate is 60 beats/min? 0.1 ml/beat x 60 beat/min x 60 min/hr = 360 ml/hour increase…Starlings mechanism would usually compensate for this by increasing left ventricular stroke volume in response to increased venous return from the pulmonary circulation.
Molecular basis for Starling’s law
- Cardiac titin isoform is very stiff, resists stretch (acts as spring).
- Ca2+ sensitivity of myofilaments increases as sarcomeres are stretched; so the same intracellular Ca2+ produces a greater force of contraction.
- Closer lattice spacing (stretched sarcomeres have altered spacing between actin & myosin which results in more force generated per crossbridge.
Bainbridge Reflex
Another way in which increased venous return causes increased cardiac output; Stretching the sinus node leads to increase in heart rate; Mainly via increased sympathetic tone (via sensory afferents & brainstem), but intrinsic mechanisms in the sinoatrial node also exist.
PV loop diagrams defn. & use
Graphical representation of relationship between ventricular pressure & volume during the cardiac cycle; Useful b/c they illustrate some measures of cardiac performance & b/c they demonstrate how changes in preload, afterload, and contractility affect cardiac performance.
Phases of cardiac cycle on PV loop diagram
Filling phase, Isovolumetric contraction phase, Ejection phase, Isovolumetric relaxation phase
Filling phase of cardiac cycle on PV loop diagram
At beginning of diastole, when mitral valve opens, volume is the END SYSTOLIC VOLUME (ESV), which is NOT ZERO b/c the heart does not pump out all the blood (always some left). As ventricle relaxes & fills, ventricular pressure falls to its minimum value. During diastole, ventricular volume increases as blood flows into left ventricle from the left atrium, with little change in pressure, except the “a wave” (slight hump near point C, aka “atrial kick”) that corresponds to atrial contraction.
Isovolumetric contraction phase on PV loop diagram
Ventricle begins to contract with an almost immediate rise in ventricular pressure to exceed that in the atrium –> mitral valve is pushed closed. Since both valves are closed, blood can neither enter nor leave the ventricle, and the volume is constant (thus isovolumetric/isovolumic). The constant volume during this phase is the END DIASTOLIC VOLUME (EDV), which is the maximum reached at the end of filling.
Ejection phase on PV loop diagram
When left ventricular pressure exceeds aortic diastolic pressure, aortic valve is pushed open and ejection phase begins. As blood leaves ventricle, volume decreases. At first pressure continues to increase as blood cannot leave aorta as fast as it enters. As myocytes in ventricle stop contracting, ventricular pressure begins to fall.
Isovolumetric relaxation phase on PV loop diagram
When ventricular pressure again falls below aortic pressure, aortic valve closes. Again, both valves are closed, so ventricular volume is constant (at the end systolic volume, the minimum reached at the end of ejection). When ventricular pressure falls below atrial pressure, mitral valve opens & filling begins again.
Blood pressure & the PV loop
End diastolic pressure = max at end of filling & before aortic valve opens = ~80 mmHg…… Peak systolic pressure = max pressure attained as blood is both entering and leaving the ventricle (enters faster than exits at first) = ~130 mmHg……. Difference between the two = pulse pressure = ~50 mmHg.
Stroke volume (SV) - equation
SV = EDV – ESV
Ejection fraction (EF) defn. & equation
The fraction of the EDV ejected during systole. EF= SV/EDV = (EDV – ESV) / EDV…….Normal EF = ~50-70% (reduced in systolic heart failure)
Stroke work
Energy per beat (in Joules); Corresponds to area inside the PV loop diagram. NOT the same for left & right sides of the heart (as systemic circulation has higher pressure & thus left heart does more work)
Factors affecting preload
- Blood volume (IV fluid, hemorrhage), 2. Filling pressure (venous BP), 3. Filling time (reduced at high HRs), 4. Resistance to filling (e.g., right atrial pressure, AV valve stenosis), 5. Resistance to emptying, or Afterload (e.g., HTN, pulomonic or aortic stenosis), 6. Reduced inotropy, 7. VENTRICULAR COMPLIANCE (most important)
Ventricular compliance – defn.
Defined as change in V over change in P
Ventricular compliance - on PV plots
Reciprocal of the slope of EDPVR; steeper EDPVR = less compliant (stiffer)
Effects of Decreased Compliance
–> lower EDV at any given pressure
Causes of decrease ventricular compliance
Thicker walls in some types of hypertrophy, Impaired ventricular relaxation associated with diastolic heart failure
Causes of increased ventricular compliance
Dilated cardiomyopathy
Effect of increased preload (increased EDV) with constant afterload & inotropy
Immediate effect: Increased stroke volume via Starling’s law (i.e., heart contracts with more force b/c sarcomere length is increased); Ventricle matches stroke volume to compensate for an increase in venous pressure on a beat-to-beat basis…thus, the same ESV is achieved and ejection fraction is increased; Note stroke work is also increased (area inside curve)……..On subsequent beats, SV returns to normal since ESV and contractility are unchanged.
Afterload (Aortic pressure) – equation
T = (deltaP x r) / mu = Law of LaPlace, showing that wall stress (T) increases as radius (r) increases and wall thickness (mu) decreases, for example in dilated cardiomyopathy.
Afterload (aortic pressure) – determining factors
- 1.* Normally, aortic pressure is the major determinant of afterload for left ventricle
- 1.* Pulmonary artery pressure is the main source of afterload for the right ventricle.
2. Wall thickness & ventricular radius also affect afterload.
Effect of increased afterload, with constant preload & inotropy
Causes decrease in stroke volume on the next beat: 1. Ventricle must generate more pressure before the aortic valve opens, allowing less time for ejection. 2 From the force-velocity relationship: shortening velocity is reduced when afterload is increased. Thus, in the relatively fixed time period of systole, the ventricle will develop less pressure, and the ejection velocity will be reduced. Overall, this means less blood is ejected (decreased stroke volume)………Summary of immediate effects: EDV unchanged, EF decreased, ESV increased, SV decreased; Stroke volume recovers on subsequent beats because the increased ESV with constant venous return means increased EDV (preload), which increases stroke volume (see above).
Inotropy defn.
Contractility; reflects the strength of contraction at any given preload and afterload (i.e., independent of fiber length, and therefore independent of Frank-Starling response); Changes in inotropy describe new Starling curves (systolic ventricular function curves).
Inotropy – regulation
Regulated by nervous & humoral agents, esp. sympathetic stimulation
Inotropy – what can change it
Some pathology (systolic heart failure) can reduce inotropy via changes in gene expression & loss of myocytes…. Changes in inotropy describe new ventricular function (Starling) curve
Inotropy & exercise
Changes in inotropy are esp. important in exervise…help to maintain high stroke volume even at high heart rate.
Effect of increased inotropy with constant preload & afterload
Results in new Starling curve which corresponds to greater systolic pressure development at any given volume…… Increased inotropy is associated with increases in stroke volume and ejection fraction and a decrease in end systolic volume (these effects persist as long as inotropy remains high, i.e. they do not recover on the next beat).
