1. Cardiac Function in Disease Robert A. Augustyniak, PhD
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Robert A. Augustyniak, PhD
Describe how changes in plasma potassium impact the ECG and the nodal and ventricular action potentials.
Discuss how changes in afterload, venous compliance and blood volume impact Starling curves.
Explain how the following valvular diseases impact the pressure volume loop:
Aortic stenosis
Mitral stenosis
Aortic regurgitation
Mitral regurgitation

2. Does hyperkalemia increase or decrease heart rate?

3. Effect of Changes in plasma [K+] on the ECG
4.5
Normal K+
Hyperkalemia 3
Membrane potential is less negative
Phase 4 depolarization rate is less steep 4

4. Effect of Changes in plasma [K+] on the ECG
4.5 R
Normal K+
Hyperkalemia
“tent shaped”
T wave
Widening of the QRS complex T
Repolarization begins sooner and at a steeper rate
Depolarization rate is less steep
Hyperkalemia and the Heart: a measure of the electrical activity of the myocardial cells can be clinically useful for detecting rising plasma [K+].
As plasma [K+] begins to rise, there are a number of changes in the ECG that occur. See the panel to the right which displays an ECG (upper panel) and ventricular action potential (lower panel) during normokalemia (solid line) and hyperkalemia (dashed line). Hyperkalemia causes the following changes:
Resting membrane potential is less negative, thereby putting it closer to threshold.
The rate of ventricular depolarization is less steep. This occurs because there are fewer sodium channels available to open and contribute to depolarization.
The result of a reduced rate of depolarization is widening of the QRS complex.
Repolarization begins sooner and occurs at a steeper rate. This results from the fact the Ikr channels function better when potassium levels are elevated.
The T wave is “tent shaped”. This occurs again because the Ikr channel functions better when potassium levels are elevated.
The question that often confuses students is, “how does this show increased excitability with hyperkalemia?”
Because the resting membrane potential is less negative and therefore closer to threshold, the cells (heart) are more excitable. However, note that the rate if ventricular depolarization was less steep because fewer sodium channels are available. The same thing occurs in the conduction system of the heart. That is, because there are fewer sodium channels available to contribute to depolarization, cardiac conduction becomes slower. This is further evidenced that as potassium levels rise even higher (8 mM), the PR interval becomes prolonged. This too is the result of slower cardiac conduction. Further increases in potassium (9 mM) cause the QRS complex to become even wider and actually roll into the T wave. Finally, at 10 mM, cardiac conduction becomes so slow that the pacemaker cells (SA and AV nodes) no longer regulate the heart and ventricular fibrillation occurs. Thus, while true, it is definitely counter-intuitive that “increased excitability” leads to decreased cardiac conduction and the resultant changes in the ECG.
These changes on the ECG do not always occur in this precise order, and some patients with hyperkalemia may progress very rapidly to ventricular fibrillation. Any change in the ECG resulting from hyperkalemia requires immediate clinical attention.
Decreases in plasma [K+] also affect the ECG. Basically, repolarization becomes impaired as plasma potassium levels decrease. For example, moderate decreases in [K+] to ∼3 mM cause the QT interval to lengthen and the T wave to flatten. Lower values of [K+] lead to the appearance of a U wave (1.5 mM), which represents the delayed repolarization of the ventricles.
Membrane potential is less negative

5. PV Loop LV Pressure (mmHg) LV Volume (ml) SV 200 100 100 200 Systolic
blood
pressure
Aortic
valve
closing
Aortic
valve
opening
Ventricular
Ejection
LV Pressure (mmHg)
100 SV
Diastolic
blood
pressure
Isovolumic
relaxation
Isovolumic
contraction
Mitral
valve
closing
Ventricular
Filling
Mitral
valve
opening
EDV
ESV
100
200
LV Volume (ml)

6. Unknown 1 LV End-diastolic Vol LV End-Systolic Vol Stroke Vol
Cardiac Output
Systolic Aortic Press

7. Unknown 1- Mitral Stenosis
LV End-diastolic Vol ↓
LV End-Systolic Vol
Stroke Vol
Cardiac Output
Systolic Aortic Press
 LAP
 ESV
 EDV
Mitral stenosis  LA afterload   LA pressure
 LVEDV and LVEDP   SV and CO   aortic pressure
 afterload causes  ESV

8. Unknown 2 LV End-diastolic Vol LV End-Systolic Vol Stroke Vol
Cardiac Output
Systolic Aortic Press

9. Unknown 2- Aortic Stenosis LV pressure exceeds aortic pressure
LV End-diastolic Vol ↑
LV End-Systolic Vol
Stroke Vol ↓
Cardiac Output
Systolic Aortic Press
LV pressure exceeds aortic pressure
ESV
EDP
Aortic stenosis causes there to be very high afterload
afterload impairs ventricular emptying   SV  LVESV
 SV and CO may lead to  aortic pressure
LV hypertrophy leads to increased  LVEDP

10. Unknown 3 LV End-diastolic Vol LV End-Systolic Vol Stroke Vol
Cardiac Output
Systolic Aortic Press

11. Unknown 3- Mitral Regurgitation
LV End-diastolic Vol ↑
LV End-Systolic Vol ↓
Stroke Vol
Cardiac Output
Systolic Aortic Press
Systolic
arterial
blood
pressure
Early
Emptying
of LV
 EDV
As long as LV pressure < LA pressure, blood flows from the LA into the LV
Lack of isovolumic relaxation or contraction phases
During diastole,  LA pressure is transmitted to the LV, so that LVEDP and LVEDV 
In mitral regurgitation there is afterload
Taken together, SV,  LVESV,  CO and  systolic arterial pressure

12. Unknown 4 LV End-diastolic Vol LV End-Systolic Vol Stroke Vol
Cardiac Output
Systolic Aortic Press

13. Unknown 4- Aortic Regurgitation
LV End-diastolic Vol ↑
LV End-Systolic Vol
Stroke Vol
Cardiac Output ↓
Systolic Aortic Press
 Systolic
arterial
blood
pressure
 PP
Aortic
valve
closes
Aortic
valve
closes
 PP
Aortic
valve
opening
Aortic
valve
opening
Mitral
valve
opens
 EDV
As long as LV pressure < aortic pressure, blood flows from the aorta into the LV
Lack of isovolumic relaxation or contraction phases
EDV leads to SV which leads to  systolic arterial pressure
Diastolic arterial pressure results from rapid runoff of blood both into arteries and back into the LV

14. Stroke Volume LVEDP or CVP
Use the following Starling Curves to answer the following questions C
8. An increase in afterload or venous compliance can cause stroke volume to change from the point marked X (Control) to which point?
Note: Assume there are no neural reflexes involved. B
Stroke Volume A X D
A. Point A
B. Point B
C. Point C E
D. Point D
E. Point E
F. Unable to determine from Figure
LVEDP or CVP

15. Stroke Volume LVEDP or CVP
Use the following Starling Curves to answer the following questions
Increased Contractility or Decreased Afterload C
8. An increase in afterload or venous compliance can cause stroke volume to change from the point marked X (Control) to which point?
Note: Assume there are no neural reflexes involved. B
Stroke Volume A X D
A. Point A
B. Point B
C. Point C E
Decreased Contractility or Increased Afterload
D. Point D
E. Point E
F. Unable to determine from Figure
LVEDP or CVP
An increase in afterload would result in increase in ESV. If EDV left alone, then SV decreases.
An increase in venous compliance reduces CVP so preload decreased also. A decreased preload would decrease contractility shifting curve lower.
E. Point E is most correct since it represents an decreased contractility with decreased SV

16. Stroke Volume LVEDP or CVP
Use the following Starling Curves to answer the following questions C
9. A mild hemorrhage will cause stroke volume to change from the point marked X (Control) to which point? Note: Assume neural reflexes ARE involved. B
Stroke Volume A
A. Point A X D
B. Point B
C. Point C
D. Point D E
E. Point E
F. Unable to determine from Figure
LVEDP or CVP

17. Stroke Volume LVEDP or CVP
Use the following Starling Curves to answer the following questions
Increased Contractility or Decreased Afterload C
A mild hemorrhage will cause stroke volume to change from the point marked X (Control) to which point? Note: Assume neural reflexes ARE involved. B
Stroke Volume A
A. Point A X D
B. Point B
C. Point C
D. Point D E
Decreased Contractility or Increased Afterload
E. Point E
F. Unable to determine from Figure
LVEDP or CVP
A hemorrhage reduces BV so MAP decreased and afterload. This will unload baroreceptors so contractility and HR increased. Curve shift upward is increased contractility or decreased afterload
The decreased BV results in lower CVP. In addition, the increased HR will decrease filling times so SV decreased.
A. Point A is most correct since it represents an increased contractility with decreased SV