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1 OST 579 FS-15 Page 1 Part G Cardiac Cycle Dr. Robert Stephenson Cardiovascular Part G Preview As you know, each heart beat involves the contraction of all the cardiac muscle cells in the right and left atria, followed by a very brief pause (the AV delay), and then the synchronized contraction of all the ventricular muscle cells. The cardiac ventricles constitute two pumps that work together, side by side. In each cardiac cycle (heartbeat) the left ventricle takes in a volume of blood from the pulmonary veins and left atrium, then ejects that same volume of blood into the aorta. The right ventricle takes in a similar volume of blood from the systemic veins and right atrium, then ejects it into the pulmonary artery. Then follows relaxation (and refilling), as the cycle repeats. Each cardiac cycle (heart beat) consists of ventricular diastole (relaxation), followed by ventricular systole (contraction). Atrial systole (atrial contraction) occurs during ventricular diastole. Atrial contraction is initiated by atrial depolarization, which is indicated by the P wave in the ECG. Ventricular systole is initiated by ventricular depolarization, which is indicated by the QRS complex in the ECG. Ventricular diastole (relaxation) is initiated by ventricular repolarization, which is indicated by the T-wave. So, in reference to the ECG, ventricular diastole corresponds to the period between a T wave and the next QRS complex. During this time, the ventricular cells are at resting membrane potential... and therefore relaxed. Ventricular systole corresponds to the period between a QRS complex and the next T-wave. During this time, the ventricular cells are undergoing an action potential and are therefore contracting. To anchor your study of the cardiac cycle, we will ask you to come to grips with a graphical compilation of the blood pressures, blood flows, electrical events, heart sounds, and cardiac valve openings and closings associated with one heart beat. Glance ahead to page 3 for a preview of this "Diagram of the Cardiac Cycle", which is often called the "Wiggers Diagram". This diagram has been inflicted on generations of medical students, ever since it was first concocted by Dr. Carl Wiggers *. It is not inflicted upon you for punitive purposes, but rather because it unifies all the fundamentals of cardiac function. It is no exaggeration to say that, if you understand this diagram, you understand much of what you need to know about how the heart works. Our instructional objective is that, after working through this lesson, you will be able to take a blank sheet of paper and sketch a fairly accurate replication of this diagram... not because you memorized it, but because everything on the diagram is a direct reflection of two very basic facts of cardiac anatomy and physiology: (1) There are one-way valves between the atria and ventricles and one-way valves within the outflow tracts of the ventricles, and (2) The heart pumps blood by alternately contracting and then relaxing. In a very fundamental sense, that's all you need to know. * Professor and chair of the Department of Physiology at Case Western from 1918 to 1953.

2 Page 2 -- Part G In Part I, after you've become comfortable with the Wiggers Diagram, we'll throw you a curve ball by showing you a graph of left ventricular pressure vs. left ventricular volume during one cardiac cycle (i.e. a "Pressure/Volume loop"). Once you grasp that this is just another way of plotting the very same data that is in the Wiggers Diagram, you will be well prepared to think logically about both normal cardiac function and cardiac dysfunction. Topic Outline Events of one heart beat (one cardiac cycle) The Wiggers diagram Electrocardiogram (ECG) Ventricular systole and ventricular diastole End-diastolic volume, end-systolic volume, and stroke volume Role of atrial contraction in ventricular filling Ejection fraction Cardiac output Atrial, Ventricular, and Aortic pressures Opening and closing of cardiac valves in relation to phases of the cardiac cycle Heart sounds Venous pressure "waves" Online Presentation and Self-Study Begins on next page Diagram on following page modified from R. Stephenson. In: Cunningham's Textbook of Veterinary Physiology 5/ed, Fig 21-1, pg 201.

3 Page 3 -- Part G Events of one heart beat (one "cardiac cycle") The Wiggers diagram P-P interval = Start So, HR = with ECG: See Note (next page) re Ventricular systole and Ventricular diastole. Stroke volume (SV) = Volume of blood ejected in one beat. Ejection fraction (EF) = Fraction of end-diastolic ventricular volume ejected during systolic contraction. Normal EF is. See Note (next page) re role of Atrial systole in ventricular filling. Cardiac output (CO): Pressures (see Note ) Left ventricular systolic pressure: Left ventricular end-diastolic pressure: Heart sounds What causes them? (see Note )

4 Page 4 -- Part G Notes on Cardiac Cycle Each Heart Beat is divided into Ventricular systole and Ventricular diastole. Ventricular systole (contraction) Initiated by ventricular depolarization, which is "signaled" by QRS complex in ECG. Ejection happens during ventricular systole. During ejection, ventricular volume decreases to end-systolic volume (ESV). Ventricular diastole (relaxation) Initiated by ventricular repolarization, which is "signaled" by end of T-wave in ECG. Ventricular filling happens during ventricular diastole. During filling, ventricular volume increases to end-diastolic volume (EDV). Role of atrial systole (contraction) in ventricular filling: Minor role in normal persons, when heart rate is low (at rest) There is plenty of time between systoles for ventricular filling. Ventricles "almost full" by the time atria contract. Atrial contraction just "tops up" the almost-full ventricles. More important if heart rate is high (e.g. during exercise) Not enough time between systoles for normal ventricular filling. Atrial contraction adds significantly to EDV. Also important in persons with valve defects or myocardial failure. More about this later. Atrial pressure, Ventricular pressure, and Aortic pressure: First, draw in the correct locations of the cardiac valves, and label with them with correct anatomical names: Then proceed to the notes on next page.

5 Page 5 -- Part G Refer to the letter labels (A, B, C, D) on the cardiac cycle graphs (Note: The following commentary describes changes in the left heart, but corresponding events are occurring simultaneously in the right heart.) Left ventricle fills between Point D and Point A: Note that ventricular pressure very low (normally 0-5 mm Hg) during filling, because the ventricular muscle is relaxed, and relaxed ventricles are normally fairly compliant (stretchy). Point A: Start of ventricular systole (contraction). As ventricular pressure starts to rise, there is a momentary backflow of blood across the A-V valve (mitral valve in left heart), which swings the valve shut. The sudden cessation of backflow causes a momentary tubulence and vibration... heard as the First heart sound ("lub"), which marks the start of systole. Between A and B: Isovolumetric contraction. Both the mitral and aortic valves are closed, so although the ventricle is contracting and pressurizing the blood within, there is no ejection of blood and therefore no change in ventricular volume... hence iso (same) volumetric (volume) contraction. Point B: The rapidly rising ventricular pressure reaches (and slightly exceeds) the level of aortic pressure. Therefore, the aortic valve swings open and ejection of blood into the aorta begins. Between B and C: Ejection. The outflow of blood from the ventricle into the aorta is rapid at first (Rapid ejection) and then tapers off (Reduced ejection). Coincident with this, ventricular pressure peaks, then falls. Point C: Ventricular pressure falls below aortic pressure. There is a momentary backflow of blood across the aortic valve, which swings the valve shut. The sudden cessation of this backflow causes a momentary tubulence and vibration... heard as the Second heart sound ("dub"), which marks the end of systole. Between C and D: Isovolumetric relaxation. The ventricular muscle is relaxing, so pressure within the ventricle drops rapidly. However, both the mitral and aortic valves are closed, so there is neither ejection nor filling... hence iso (same) volumetric (volume) relaxation. Point D: The rapidly falling ventricular pressure reaches (and falls just below) the level of atrial pressure. Therefore, the mitral valve swings open and ventricular filling begins. Back to start. What makes the first and second heart sounds (S1 and S2)? It is NOT the valve leaflets "slamming shut"! (Normal valves are light and flexible to make a sound, even if forcefully closed.) Instead, it is the turbulence of blood flow and the vibration of the cardiac walls caused when the momentary backflow of blood comes to a sudden stop against the closing valves. Punch line: Heart sounds are caused by and by.

6 Page 6 -- Part G Additional things to notice about the Cardiac Cycle State the valve event that occurs at each of the labeled points: Point A -- Point B -- Point C -- Point D -- Heart sounds S1 and S2 can be ausculted in all normal patients. In some normal persons, two additional, fainter heart sounds (S3 and S4) can be ausculted. Look up the timing and cause of S3 and S4 (online or in textbook of internal medicine or cardiology), and make note of this below: Cause of S3 Cause of S4 -- Also, add S3 and S4 to the timeline of heart sounds on the Cardiac Cycle Diagram (on page 3). Aortic pressure is clearly pulsatile, as indicated on the cardiac cycle diagram. (Likewise, pulmonary artery pressure is also pulsatile.) On the graph of aortic pressure, find and label the exact points of maximum pressure (aortic systolic pressure) and minimum pressure (aortic diastolic pressure). Record the approximate values (including units) here: Aortic systolic pressure ~ Aortic diastolic pressure ~ Note that there are small pulsations in atrial pressure. Since there are no valves between the veins and the atria, these changes in atrial pressure occur also in the large veins (pulmonary on the left and vena cavae on the right). The resulting venous pulsations can be measured with a venous catheter, or (in a normal, recumbant person) can be observed visually in the jugular veins. These "venous pulsations" are designated as the a, c, and v waves. Look online, or look at Figure 13.3 in your Rhoades & Bell text, and find the a, c, and v waves on a diagram of the cardiac cycle. Label these waves on the cardiac cycle diagram (on page 3). Look online, or read on page 252 of Rhoades & Bell, to determine what causes these venous waves (pulsations) and summarize here: Cause of a wave: Cause of c wave: Cause of v wave:

7 Page 7 -- Part G Cardiac Cycle Quiz NOTE: Unless otherwise specified, "systole" means ventricular systole and "diastole" means ventricular diastole. This convention is followed generally by both physiologists and by clinicians. TRUE OR FALSE??? (for a normal heart in a resting person) 1. The aortic and mitral valves are never open at the same time. 2. The first heart sound is heard at the beginning of ventricular systole. 3. The first heart sound is caused by the rapid ejection of blood from the ventricles. 4. The end of systole is the beginning of diastole. 5. Left ventricular pressure is lower at the end of diastole than it is at the beginning of diastole. 6. Ventricular end-diastolic volume is greater than end-systolic volume. 7. Atrial systole occurs during ventricular diastole. 8. The ventricles eject blood during part (but not all) of systole 9. The aortic valve is closed throughout diastole. 10. The mitral valve is open throughout diastole. 11. Aortic pressure reaches its minimum level during ventricular systole. 12. Aortic pressure reaches its maximum level during ventricular systole. 13. Left ventricular pressure is always less than aortic pressure. 14. Left ventricular pressure exceeds left atrial pressure during systole. 15. Ventricular filling only occurs during ventricular diastole. 16. Ventricular filling occurs primarily during atrial systole. 17. The second heart sound is associated with the opening of the aortic valve. 18. The only moments of turbulent blood flow coincide with the S3 and S4 heart sounds. 19. Left atrial pressure steadily increased throughout ventricular diastole. Answers to Cardiac Cycle Quiz: 1-T 2-T 3-F 4-T 5-T 6-T 7-T 8-T 9-T 10-F 11-T 12-T 13-F 14-T 15-T 16-F 17-F 18-F 19 - F

8 Page 8 -- Part G Suggestions to Confirm Your Understanding of the Cardiac Cycle 1. Fill in any gaps in the notes on pages Correctly answer each question in the "Cardiac Cycle Quiz" on page 7, and be able to explain your answers. 3. Practice sketching the Wiggers Diagram, as stipulated in Learning Objective #2 on page 13. Remember to extend your diagram for two successive heart beats (cardiac cycles), as suggested during the online lecture. REMINDER: Every feature of the volume, flow, and pressure graphs on the Wiggers Diagram is a direct consequence of two facts: (1) There are one-way valves between the atria and ventricles, and one-way valves in the outflow tracts of the two ventricles. (2) The heart pumps blood by alternately relaxing and filling with blood, and then contracting and ejecting some of that blood. If you know only those two facts (and then think about it), you should be able to draw the Wiggers Diagram from scratch... not because you memorized it, but because it makes sense. If you can do that, then you understand how the heart works. If you can't do that, then you don't understand how the heart works... and you'll be "fuzzy" about cardiac function and dysfunction for the rest of this course and for the rest of your career. Doing this work now will pay big dividends. Suggestion: Don't try to master this in one sitting; "sleeping on it" is very likely to help. Then, try to explain the cardiac cycle to a colleague, or quiz a colleague as he/she explains the cardiac cycle to you. And remember, this really does make sense! Once you feel like you've "got it": Work through the following set of "Confirm Your Understanding Exercises", which provide a good recap of the Cardiac Cycle. Self-Assessment: Confirm your Understanding of the Cardiac Cycle. [Set of 20 Study Questions. Answers follow] Fill in the blank: 1. During isovolumetric contraction, the AV valves are. 2. During ventricular ejection, the AV valves are.. 3. During isovolumetric contraction, the aortic and pulmonary valves are. 4. During ventricular ejection, the aortic and pulmonary valves are.. 5. During isovolumetric relaxation, the AV valves are. 6. During ventricular filling, the AV valves are. 7. During atrial contraction the AV valves are. 8. During isovolumetric relaxation, the aortic and pulmonary valves are. 9. During ventricular filling, the aortic and pulmonary valves are.

9 Page 9 -- Part G 10. During atrial contraction the aortic and pulmonary valves are. 11. Are the AV valves ever open at a time when the aortic and pulmonary are also open? 12. The volume of blood ejected from a ventricle in a single beat is the. 13. The volume of blood in a ventricle at the end of diastole is the. 14. The volume of blood in a ventricle at the end of systole is the. 15. Stroke volume equals end- volume minus end- volume. 16. Ejection fraction equals stroke volume divided by. 17. Cardiac output equals. The next three multiple-course questions are based on the following graph, which shows aortic pressure, left ventricular pressure, and atrial pressure during two successive cardiac cycles. 18. In the above figure ventricular repolarization occurs within the time period between: A. L and M B. M and N C. N and P D. P and R 19. In the figure above, isovolumetric relaxation occurs between points: A. L and M B. M and N C. N and P D. P and R 20. In the figure above, rapid ventricular filling would occur within the time period between: A. L and M B. M and N C. N and P D. P and R E. R and S

10 Page Part G Answers to the twenty-question review of Cardiac Cycle: 1. closed 2. closed 3. closed 4. open 5. closed 6. open 7. open 8. closed 9. closed 10. closed 11. No 12. stroke volume 13. end-diastolic volume 14. end-systolic volume 15. diastolic... systolic 16. end-diastolic volume 17. stroke volume heart rate 18. B Check the position of the T wave in the Wiggers Diagram in your Course Pack (page 3 of Part G) or in Figure 13.3 of your Rhoades & Bell physiology text. 19. C 20. D

11 Page Part G Supplementary Material OPTIONAL Only if you need clarification If any of the foregoing material was unclear to you, it may help to consult pages in your Rhoades & Bell textbook. Similar discussions are presented in all other medical physiology textbooks as well. Or, for an approximate restatement of the online presentation, you may consult the following optional narrative regarding the Cardiac Cycle: Each cardiac cycle (heart beat) consists of ventricular diastole (relaxation), followed by ventricular systole (contraction) and. Atrial systole (atrial contraction) occurs during ventricular diastole. Atrial contraction is initiated by atrial depolarization, which is indicated by the P wave in the ECG. Ventricular systole is initiated by ventricular depolarization, which is indicated by the QRS complex. Ventricular diastole (relaxation) is initiated by ventricular repolarization, which is indicated by the T-wave. So, ventricular diastole corresponds to the period between a T wave and the subsequent QRS complex. During this time, the ventricular cells are at resting membrane potential. The volume of blood ejected from one ventricle in one beat is called stroke volume, expressed as follows: Stroke volume = end-diastolic volume end-systolic volume The ventricles do not empty completely during systole. The fraction of end-diastolic volume that is ejected during ventricular systole is called the ejection fraction, as follows: Stroke volume Ejection fraction = End - diastolic volume Values of ejection fraction between 50% and 65% are typical for resting subjects. As shown in the cardiac cycle diagram, left ventricular pressure is low at the beginning of ventricular systole, but the powerful contraction of the ventricular muscle causes the ventricular pressure to increase rapidly. The increase in left ventricular pressure causes a momentary backflow of blood from the left ventricle to the left atrium, which closes the left atrioventricular (AV) valve (the mitral valve). Blood is not immediately ejected from the left ventricle into the aorta at the beginning of systole, because the aortic valve remains closed until the left ventricular pressure exceeds the aortic pressure. Therefore, ventricular volume remains unchanged during this first phase of systole, which is aptly named isovolumetric contraction. When left ventricular pressure does rise above aortic pressure, the aortic valve is pushed open, and there is a rapid ejection of blood into the aorta. Rapid ejection is followed by a phase of reduced ejection of blood as both ventricular pressure and aortic pressure pass their peak (systolic) values and begin to decrease. (During the period of reduced ejection, the ventricular pressure actually falls below the aortic pressure, but ejection continues for a few moments, because the blood flowing out of the ventricle is carried along by the momentum imparted to it during rapid ejection.) As the ventricular pressure continues to decrease, ejection comes to an end. A momentary backflow of blood from the aorta into the left ventricle closes the aortic valve. The closure of the aortic valve demarcates the end of ventricular systole and the beginning of ventricular diastole.

12 Page Part G During the first phase of ventricular diastole, the ventricular muscle relaxes, and left ventricular pressure declines from a value near aortic pressure to a value near left atrial pressure. However, no filling of the ventricle can occur because the mitral valve remains closed until left ventricular pressure drops below left atrial pressure. This first phase of ventricular diastole is called isovolumetric relaxation because there is neither filling nor emptying of the ventricle. When left ventricular pressure does fall below left atrial pressure, the mitral valve is pushed open, as blood begins to flow from the atrium into the ventricle. First, there is a period of rapid ventricular filling, which is followed by a phase of reduced ventricular filling (diastasis). Diastasis persists until the sinoatrial node cells initiate an atrial action potential and atrial contraction (atrial systole). As depicted in the cardiac cycle diagram, ventricular volume is nearly at its end-diastolic level even before atrial systole. Typically, 80% to 90% of ventricular filling occurs before atrial systole. Atrial systole simply tops up the almost-full ventricles. An important clinical consequence of this fact is that the ventricles in a resting animal can pump a nearly normal stroke volume even in the absence of properly timed atrial contractions (e.g., during atrial fibrillation). During exercise, however, atrial contractions make a relatively greater contribution to ventricular filling because the rapid heart rate in exercise leaves a shorter time for diastolic filling. Therefore, animals with atrial fibrillation typically exhibit exercise intolerance. Ventricular filling also becomes more dependent on atrial systole in patients with certain valve defects, such as narrowing of the mitral valve (mitral stenosis). At the end of atrial systole, the atria begin to relax. The left atrial pressure drops slightly. Then, as the ventricles begin to contract, there is a momentary backflow of blood from the left ventricle to the left atrium. The backflow closes the mitral valve, which marks the end of ventricular diastole and the beginning of another left ventricular systole. By definition, the cardiac cycle is divided into ventricular systole and ventricular diastole. Closure of the mitral valve marks the beginning of ventricular systole. Closure of the aortic valve marks the beginning of ventricular diastole. Note that atrial systole takes place during ventricular diastole. The preceding six paragraphs discussed pressure changes in the left atrium, left ventricle, and aorta. However, all the events of the cardiac cycle also take place on the right side of the heart. Therefore, all the statements made about the left side of the heart also hold true for the right side of the heart; simply substitute pulmonary artery for aorta, pulmonic valve for aortic valve, and tricuspid valve for mitral valve. As indicated in the cardiac cycle diagram, the ventricular volumes are similar for the left and right sides, and so are the blood flow rates. The pressures, however, differ greatly on the two sides. Systolic (peak) pressure in the right ventricle and pulmonary artery is only about 20 mm Hg, whereas systolic pressure on the left side of the heart reaches 120 mm Hg. This explains why there are different scales on the pressure axes for the left and right hearts in the cardiac cycle diagram presented earlier in these notes. End of Optional Supplementary Material "Once more through the Cardiac Cycle"

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