Cardiac Function in Disease Robert A. Augustyniak, PhD Readings: None 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

Does hyperkalemia increase or decrease heart rate?

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

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

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)

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

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

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

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

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

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

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

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

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

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

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

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