Lecture 4 relationships between cardiac output and venous return

DRUGS USED IN DISORDERS OF THE CARDIOVASCULAR SYSTEM Lecture 4:

RELATIONSHIPS BETWEEN CARDIAC OUTPUT AND VENOUS RETURN Marc Imhotep Cray, M.D.

Photo: Photograph of chordae tendineae attached to papillary muscles of a ventricle. Seeley’s anatomy & physiology. 10th ed. New York, NY: McGraw-Hill 2010

Topics Discussed o o o o o o o

CVS Pharmacology Lecture 4

Cardiac Function Curve (CO) Vascular Function Curve(VR) Right Atrial Pressure (RAP) Mean Systemic Pressure (MSP) Slope of the Vascular Function Curve Combining Cardiac and Vascular Function Curves Cardiovascular parameters that can alter CO, VR and RAP • Inotropy • Total Peripheral Resistance (TPR) • Blood Volume (BV)

Marc Imhotep Cray, M.D.

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Cardiac and vascular function curves

CVS Pharmacology Lecture 4

1- Operating point of heart (cardiac output and venous return are equal) 2-↑TPR, e.g., exercise, AV shunt 3-↓ TPR, e.g., hemorrhage before compensation can occur 4- As in heart failure, narcotic overdose 5- X-intercept of venous return curve = mean systemic filling pressure Source: Tao Le T and Bhushan V, Cardiovascular, IN First Aid for the USMLE Step 1 2013; McGraw·Hill 2013:255

Marc Imhotep Cray, M.D.

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CVS Pharmacology Lecture 4

Cardiac cycle The mechanical and electrical events that occur during one cycle are shown.  Atrial systole (A); 

isovolumetric ventricular contraction (B);

 rapid ventricular ejection (C); 

reduced ventricular ejection (D);

 isovolumetric ventricular relaxation (E);  rapid ventricular filling (F);  reduced ventricular filling (diastasis) (G) Marc Imhotep Cray, M.D.

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Cardiac function curve (or Cardiac output curve)

CVS Pharmacology Lecture 4

Is based on Frank-Starling relationship for the left ventricle Increase Inotropy

SV/CO/VR

Normal | Reference Point Decrease Inotropy

LVEDV / RAP/Preload

Marc Imhotep Cray, M.D.

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Cardiac and vascular function curves

CVS Pharmacology Lecture 4

o The cardiac function curve is cardiac output as a function of right atrial pressure. o The vascular function curve is venous return as a function of right atrial pressure. o The curves intersect at the steady state operating point (filled circle) where cardiac output and venous return are equal o In steady state, volume of blood left ventricle ejects as cardiac output equals or matches volume it receives in venous return

Marc Imhotep Cray, M.D.

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Vascular Function Curves (or Venous return curve) o Plots show effect of central venous pressure on cardiac output • Central venous pressure equivalent to pressure at right atria • Flow greatest at right atrial pressure of 0 mm Hg, so greatest cardiac output • If right atrial pressure increases, return is compromised and see less cardiac output o Mean systemic pressure is right atrial pressure or central venous pressure at which cardiac output is zero

Marc Imhotep Cray, M.D.

CVS Pharmacology Lecture 4

Changes in Vascular Function Curves o Total Peripheral Resistance • ↑ TPR causes counter-clockwise shift in curve • ↓TPR causes clockwise shift in curve o Blood Volume or shift in flow to organs and tissues • ↑ blood volume or ↑ restriction of flow to organs or tissues shifts curve upward • ↓ blood volume or ↑ flow to organs or tissues previously restricted shifts curve downward

Marc Imhotep Cray, M.D.

CVS Pharmacology Lecture 4

Combined Cardiac and Vascular Function Curves o Cardiac output or venous return on y-axis o Right atrial pressure or end-diastolic pressure on x-axis o Intersection of two curves is equilibrium or steady-state point: • point at which system operates o Changes in either cardiac output curve and/or vascular function curve will cause a shift in the equilibrium point Marc Imhotep Cray, M.D.

CVS Pharmacology Lecture 4

Inotropic Agents oPositive inotropic agent specific for the heart (e.g. digitalis) will shift cardiac output curve counterclockwise oNegative inotropic agent (e.g. metoprolol) specific for heart will shift cardiac output curve clockwise. • similar shift for heart failure

Marc Imhotep Cray, M.D.

CVS Pharmacology Lecture 4

Effects of inotropic agents on the cardiac and vascular function curves

CVS Pharmacology Lecture 4

o Effects of positive inotropic agents (A) o Effect of negative inotropic agents (B) • The solid lines show the normal relationships, and the dashed lines show changes • The circle intersecting the dashed line shows the new steady state operating point Marc Imhotep Cray, M.D.

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Total Peripheral Resistance o Increase in TPR shifts cardiac output curve clockwise and vascular function curve counter-clockwise o Decrease in TPR shifts cardiac output curve counterclockwise and vascular function curve clockwise

Effects of increased total peripheral resistance (TPR) on the cardiac and vascular function curves

CVS Pharmacology Lecture 4

o Effects of increased (TPR) (A) o Effects of decreased TPR (B) on the cardiac and vascular function curves • The solid lines show the normal relationships, and the dashed lines show the changes • The circle intersecting the dashed lines shows the new steady state operating point Marc Imhotep Cray, M.D.

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Effect of changes in stressed volume on mean systemic pressure (MSP)

CVS Pharmacology Lecture 4

o Total blood volume is the sum of unstressed volume (in the veins) and stressed volume (in the arteries)

o Increases in stressed volume produce increases in mean systemic pressure So, two factors influence the value for MSP: (1) blood volume and (2) The distribution of blood between the unstressed volume and the stressed volume.

Marc Imhotep Cray, M.D.

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Effects of blood volume on the cardiac and vascular function curves

CVS Pharmacology Lecture 4

o Effects of increased blood volume (A) o Effects decreased blood volume (B) on the cardiac and vascular function curves • The solid lines show the normal relationships, and the dashed lines show changes • The circle intersecting the dashed line shows the new steady state operating point Marc Imhotep Cray, M.D.

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THE END

Marc Imhotep Cray, M.D.

CVS Pharmacology Lecture 4

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Further study (SDL):

CVS Pharmacology Lecture 4

Online resource center: Medical Pharmacology Cloud Folder

Lectures/discussions to follow: 2. Hypercholesterolemia and Atherosclerosis 3. Angina 4. Heart Failure 5. Arrhythmias 6. Hypertension 7. Peripheral Vascular Disease Suggested reading: Costanzo LS, Cardiovascular Physiology. In Physiology: with STUDENT CONSULT Online Access, 5e; Saunders 2013:189-95 Klabunde RE, Ch. 4-Cardiac Function and Ch. 5-Vascular Function. In Cardiovascular Physiology Concepts.2e; LLW 2011:60-120 Tao Le T and Bhushan V, Cardiovascular, In First Aid for the USMLE Step 1 2015; McGraw-Hill 2013:254-57 Marc Imhotep Cray, M.D.

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