Ventricular Pressure-Volume Loops Steve Wood, PhD scwood@salud.unm.edu

+ + - + - + + + II. The Ventricle as a Pump: Cardiac Output = HR x SV Heart Rate Stroke Volume + + - + - Preload Afterload Inotropy + + + Sympathetic/ Parasympathetic Heart   Chronotropy (rate) + + +/ − − −   Inotropy (contractility) + + + /− 1   Lusitropy (relaxation) + + +/ − 1   Dromotropy (conduction velocity) + +/ − − − Vessels   Arterial constriction + + + /0 2   Venous constriction + + +/ 0 PNS SNS

III. The Ventricle as a Pump: Frank-Starling Curves Single Starling Curve Normal values are LVEDP  8 mmHg and SV of  70 ml/beat. Cytosolic Ca++ constant. Inotropy (contractility) is constant. The increased force of contraction at greater preload is due to: (1) favorable overlap of thin and thick filaments; and (2) increased affinity of Ca++ for Troponin C. Pulmonary edema occurs when LVEDP = 25 mm Hg. Preload

Frank-Starling Curves Changes in afterload and contractility (inotropy ) shift the Frank-Starling curve up or down (at any given preload) PV loops explain this – slide 18 Inotropy afterload inotropy afterload Preload

A drug which caused vasoconstriction of systemic veins (alpha agonist) would shift point 1 to point ___. A B C D

(or end-diastolic volume) (or cardiac output) Stroke Volume Left Ventricular end-diastolic pressure (or end-diastolic volume) Normal Heart failure Increased contractility a b c Starling Curves in Heart Failure Hypotension Pulmonary congestion From Lilly, p. 229. reduced EF causes increased ESV with nl venous return = increased EDV. Increase in SV is minimal due to flatness or curve

IV. Pressure-Volume Relationships in the Ventricles This isovolumic curve is also called Po (pressure at zero ejection), or the end-systolic pressure volume relationship (ESPVR). This "resting" curve represents pressures during diastolic filling of the ventricle, and reflects passive properties of the ventricular wall that resist stretch; i.e., the compliance of the ventricle and factors that impair Ca++ reuptake into SR (e.g., hypoxia) (Lusitropy)

c d b a V. PRESSURE-VOLUME LOOPS ESPVR Afterload SV EDPVR Preload LV Volume, ml 200 50 120 LV Pressure, mm Hg 100 3 c LV Pressure, mm Hg Afterload 2 3 4 2 d SV 1 b EDPVR EDV LV Volume, ml 1 4 ESV a Preload

http://cvphysiology.com/Cardiac%20Function/CF024.htm

http://cvphysiology.com/Cardiac%20Function/CF024.htm

Cardiac Work = Stroke work x HR Work of the Heart Cardiac Work = Stroke work x HR Work = force x distance = force x cm P = force/unit area = force/cm2 Volume = cm3 P x V = force/cm2 x cm3 = force x cm

Oxygen Demand of the Heart HR x SBP  VO2 http://www.cvphysiology.com/CAD/CAD004.htm Myocyte contraction is the primary factor determining myocardial oxygen consumption (MVO2) above basal levels. Therefore, factors that enhance tension development by the cardiac muscle cells, the rate of tension development, or the number of tension generating cycles per unit time will increase MVO2. For example, doubling heart rate approximately doubles MVO2 because ventricular myocytes are generating twice the number of tension cycles per minute. Increasing inotropy also increases MVO2 because the rate of tension development is increased as well as the magnitude of tension, both of which result in increased ATP hydrolysis and oxygen consumption. Increasing afterload, because it increases tension development, also increases MVO2. Increasing preload (e.g., ventricular end-diastolic volume) also increases MVO2; however, the increase is much less than what might be expected because of the LaPlace relationship. The LaPlace relationship says that wall tension (T) is proportional to the product of intraventricular pressure (P) and ventricular radius (r). (Law of  LaPlace) Wall tension can be thought of as the tension generated by myocytes that results in a given intraventricular pressure at a particular ventricular radius. Therefore, when the ventricle needs to generate greater pressure, for example with increased afterload or inotropic stimulation, the wall tension is increased (i.e., increased myocyte tension development). This relationship also shows us that a dilated ventricle (as occurs in dilated cardiomyopathy) has to generate increased wall tension to produce the same intraventricular pressure. We observe empirically that wall tension and MVO2 are closely related. For this reason, changes in intraventricular pressure and ventricular radius affect MVO2. As stated above, changes in ventricular preload volume do not affect MVO2 to the same extent quantitatively as changes in afterload. This is because preload is usually expressed as the ventricular end-diastolic volume, not radius. If the ventricle is assumed to be a sphere, then the ventricular volume (V) is related to radius (r) by: Wall tension determines O2 uptake. And radius is proportional to the cube root of volume. This is why volume has a smaller effect on VO2 than the other factors.

Inotropy Stroke Work Curve inotropy When stroke work is plotted against preload ONLY changes in inotropy will shift curve. Stroke Work (P x V)

A. Effect of Preload on Stroke Volume VI. Effects of Preload, Afterload, Inotropy and Lusitropy on Ventricular Pressure-Volume Loops A. Effect of Preload on Stroke Volume Effect of Increased Preload At constant afterload and inotropy SV increases and ESV remains constant EF increases Dashed lines are systolic and diastolic pressures

Effect of Decreased Preload At constant afterload and inotropy SV decreases and ESV remains constant EF decreases slightly Effects of changing preload = Starling’s Law

B. Effect of Afterload on Stroke Volume Effect of Increased Afterload At constant preload and inotropy SV decreases and ESV increases EF decreases No change in contractility (aortic closure occurs on the same line) This is an acute effect of sudden increase in afterload; in subsequent beat increased EDV will increase SV

Effect of Decreased Afterload At constant preload and inotropy SV increases and ESV decreases EF increases No change in contractility (aortic closure occurs on the same line)

Effect of Increased Contractility (+ Inotropy) C. Effect of Contractility on Stroke Volume Effect of Increased Contractility (+ Inotropy)  At constant preload and afterload SV increases and ESV decreases EF increases

Effect of Decreased Contractility (- Inotropy) At constant preload and afterload SV decreases and ESV increases EF decreases Over time, EDV increases causing increased LV and LA pressure – next slide

D. Systolic and Diastolic Heart Failure Systolic Failure EDV increases with loss of inotropy because increased ESV is added to normal venous return. Increased EDV causes increased LV and LA pressure. EF decreased Shown at constant heart rate. The reason for preload rising as inotropy declines is that the increased end-systolic volume is added to the normal venous return filling the ventricle. For example, if end-systolic volume is normally 50 ml of blood and it is increased to 80 ml in failure, this extra residual volume is added to the incoming venous return leading to an increase in end-diastolic volume and pressure

Compliance = V/P Diastolic Failure Reduction in ventricular compliance Mechanisms: Hypertrophy; Reduced Lusitropy LV  Increased LA and pulmonary venous pressure  pulmonary congestion RV  Increased RA pressure and systemic venous pressure  peripheral edema EF may not change

Combined Systolic & Diastolic Failure Decreased SV and EF Increased end diastolic pressure Compensatory volume expansion further increases end diastolic pressure

VII. Practice Questions http://www.unmphysiology.org/boardreview/cardioquestions.html

Summary

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