Heart  as  a  Pump

Outline ‡ Overview of heart anatomy and function ‡ Cardiac cycle ‡ Volume-­‐Pressure  Diagram ‡ Cardiac  Output  and  Venous  Return ‡ Regulation  of  Cardiac  Output

Learning Objectives Describe the cardiac cycle by explaining Fig. 9-6 in Guyton and Hall Analyze ventricular pumping with a volume ‐ pressure diagram Understand  cardiac output and venous return - quantitatively know cardiac output Know how cardiac output is regulated  - Frank- Starling mechanism and autonomic regulation

Cardiovascular System Note, right side is the right side of the person or animal. Two pumps in the heart: Right side pumps blood through the lungs Left side through the peripheral organs Each side has an atrium and a ventricle Atrium is a primer pump for the ventricle Ventricle supplies the main pumping force

Heart  Anatomy Atrioventricular valves: tricuspid (right) and mitral (left) Semilunar valves: pulmonary (right) and aortic (left)

Cardiac Cycle The cardiac cycle includes the events that occur  from  the  beginning  of  one  heartbeat  to the  beginning  of  the  next The  cardiac  cycle  consists  of  two  periods: - Diastole  - period  of  relaxation  when  the  heart  fills with  blood - Systole  - period  of  contraction

Diastole: Passive ventricular filling. The AV valves open and Beginning just after a ventricular contraction Semilunar valves closed AV valves opened Diastole: Passive ventricular filling. The AV valves open and blood flows into the relaxed ventricles, accounting for most of the ventricular filling.

Diastole: Active ventricular filling. Semilunar valves closed AV valves opened Diastole: Active ventricular filling. Semilunar valves closed AV valves opened Diastole: Passive ventricular filling.

Semilunar valves closed AV valves opened Diastole: Active ventricular filling. The atria contract and complete ventricular filling.

Systole: Period of isovolumic contraction. Semilunar valves closed AV valves closed Systole: Period of isovolumic contraction. Semilunar valves closed AV valves opened Diastole: Active ventricular filling.

Semilunar valves closed AV valves closed Systole: Period of isovolumic contraction. Ventricular contraction causes the AV valves to close, which is the beginning of ventricular systole. The semilunar valves were closed in the previous diastole and remain closed during this period.

isovolumic contraction. ejection. Semilunar Semilunar valves opened valves closed AV valves closed AV valves closed Systole: Period of Systole: Period of isovolumic contraction. ejection.

Semilunar valves opened AV valves closed Systole: Period of ejection. Continued ventricular contraction pushes blood out of the ventricles, causing the semilunar valves to open.

Systole: Period of ejection. Semilunar valves opened AV valves closed Systole: Period of ejection. Semilunar valves closed AV valves closed Diastole: Period of isovolumic relaxation.

Semilunar valves closed AV valves closed Diastole: Period of isovolumic relaxation. Blood flowing back toward the relaxed ventricles causes the semilunar valves to close, which is the beginning of ventricular diastole. Note that the AV valves closed, also.

isovolumic relaxation. Semilunar valves closed AV valves closed Semilunar Diastole: Period of valves closed isovolumic relaxation. AV valves opened Diastole: Passive ventricular filling.

Cardiac  Cycle  in  Left  Side

Mechanical Events: The Cardiac Cycle

The Cardiac Cycle Cardiac cycle refers to all events associated with blood flow through the heart from the start of one heartbeat to the beginning of the next During a cardiac cycle Each heart chamber goes through systole and diastole Correct pressure relationships are dependent on careful timing of contractions

Phases of the Cardiac Cycle Atrial diastole and systole - Blood flows into and passively out of atria (80% of total) AV valves open Atrial systole pumps only about 20% of blood into ventricles Ventricular filling: mid-to-late diastole Heart blood pressure is low as blood enters atria and flows into ventricles 80% of blood enters ventricles passively AV valves are open, then atrial systole occurs Atrial systole pumps remaining 20% of blood into ventricles

Phases of the Cardiac Cycle Ventricular systole Atria relax Rising ventricular pressure results in closing of AV valves (1st heart sound – “lubb”) Isovolumetric contraction phase Ventricles are contracting but no blood is leaving Ventricular pressure not great enough to open semilunar valves Ventricular ejection phase opens semilunar valves Ventricular pressure now greater than pressure in arteries (aorta and pulmonary trunk)

Phases of the Cardiac Cycle Ventricular diastole Ventricles relax Backflow of blood in aorta and pulmonary trunk closes semilunar valves (2nd hear sound - “dubb”) Dicrotic notch – brief rise in aortic pressure caused by backflow of blood rebounding off semilunar valves Blood once again flowing into relaxed atria and passively into ventricles

Normal Volume of Blood in Ventricles After  atrial  contraction,  110-120  ml  in  each ventricle  (end-diastolic  volume) Contraction  ejects  ~70  ml  (stroke  volume output) Thus,  40-50  ml  remain  in  each  ventricle  (End‐ systolic  volume) The  fraction  ejected  is  then  ~60%  (ejection fraction)

Left Ventricle Volume-­‐Pressure Curve Be able to use these pressure and volume values Aortic valve closes Aortic valve opens Mitral valve opens Mitral valve closes End-systolic volume End-diastolic volume

Preload  and  Afterload Preload  - tension  on  muscle  when  it  begins  to contract  (end-diastolic  pressure) Afterload  - load  against  which  the  muscle exerts  its  contractile  force,  which  is  the pressure  in  the  artery  leading  from  the ventricle.    Phase  III  on  volume-pressure diagram

Cardiac Output and Venous Return Cardiac  output  is  the  quantity  of  blood pumped  into  the  aorta  each  minute. Cardiac  output  =  stroke  volume  x  heart  rate Venous  return  is  the  quantity  of  blood  flowing from  the  veins  to  the  right  atrium. Except  for  temporary  moments,  the  cardiac output  should  equal  the  venous  return

Normal Cardiac Output Normal resting cardiac output: - Stroke  volume  of  70 ml - Heart  rate  of  72 beats/minute - Cardiac  output  ~ 5 litres/minute During  exercise,  cardiac  output  may  increase to  >  20  liters/minutes You  should  be  able  to  get  stroke  volume  and heart  rate  from  volume-­‐pressure  curves  and ECG  recordings,  respectively

Cardiac Output Stroke Volume = the vol of blood pumped by either the right or left ventricle during 1 ventricular contraction. SV = EDV – ESV 70 = 125 – 55 CO = SV x HR 5,250 = 70 ml/beat x 75 beats/min CO = 5.25 L/min

Cardiac Output Regulation of Stroke volume Preload: Degree of stretch of heart muscle (Frank-Starling) – greatest factor influencing stretch is venous return (see Below) Contractility – Strength of contraction Increased Ca2+ is the result of sympathetic nervous system

A Simple Model of Stroke Volume

Cardiac Output Other chemicals can affect contractility: - Positive inotropic agents: glucagon, epinephrine, thyroxine, digitalis. - Negative inotropic agents: acidoses, rising K+, Ca2+ channel blockers. Afterload: Back pressure exerted by arterial blood. Regulation of Heart Rate Autonomic nervous system Chemical Regulation: Hormones (e.g., epinephrine, thyroxine) and ions.

Regulation of Cardiac Output Frank-Starling  Mechanism  -­‐ Cardiac  output changes  in  response  to  changes  in  venous return. Autonomic  control  -­‐ Control  of  heart  rate  and strength  of  heart  pumping  by  the  autonomic nervous  system.

Chemical Regulation of the Heart The hormones epinephrine and thyroxine increase heart rate Intra- and extracellular ion concentrations must be maintained for normal heart function

Regulation of Stroke Volume SV: volume of blood pumped by a ventricle per beat SV= end diastolic volume (EDV) minus end systolic volume (ESV); SV = EDV - ESV EDV = end diastolic volume amount of blood in a ventricle at end of diastole ESV = end systolic volume amount of blood remaining in a ventricle after contraction Ejection Fraction - % of EDV that is pumped by the ventricle; important clinical parameter Ejection fraction should be about 55-60% or higher

Factors Affecting Stroke Volume EDV - affected by Venous return - vol. of blood returning to heart Preload – amount ventricles are stretched by blood (=EDV) ESV - affected by Contractility – myocardial contractile force due to factors other than EDV Afterload – back pressure exerted by blood in the large arteries leaving the heart

Frank-Starling Law of the Heart Preload, or degree of stretch, of cardiac muscle cells before they contract is the critical factor controlling stroke volume; EDV leads to stretch of myocardium. preload  stretch of muscle  force of contraction  SV Unlike skeletal fibers, cardiac fibers contract MORE FORCEFULLY when stretched thus ejecting MORE BLOOD (SV) If SV is increased, then ESV is decreased!! Slow heartbeat and exercise increase venous return (VR) to the heart, increasing SV. VR changes in response to blood volume, skeletal muscle activity, alterations in cardiac output VR  EDV and in VR   in EDV Any  in EDV   in SV Blood loss and extremely rapid heartbeat decrease SV.

Frank-Starling Law of the Heart Relationship between EDV, contraction strength, and SV. Intrinsic mechanism: As EDV increases: Myocardium is increasingly stretched. Contracts more forcefully. As ventricles fill, the myocardium stretches: Increases the number of interactions between actin and myosin. Allows more force to develop. Explains how the heart can adjust to rise in TPR. Figure 14.3

Extrinsic Control of Contractility Strength of contraction at any given fiber length. Sympathoadrenal system: NE and Epi produce an increase in contractile strength. + inotropic effect: More Ca2+ available to sarcomeres. Parasympathetic stimulation: Does not directly influence contraction strength. Figure 14.2

Frank-Starling Mechanism The force of cardiac muscle contraction increases as the muscle stretches, within limits. Due to more optimal overlap of actin and myosin filaments during stretch - same in skeletal muscle So, with increase venous return and increased stretching, the force of contraction increases and the stroke volume increases. Moreover, stretching of the SA node increasing the firing rate of the pacemaker (increasing heart rate).

Frank-­‐Starling Summary: within physiological limits, the heart pumps  all  the  blood  that  returns  to  it  from  the veins. Venous  return  increases  when  there  is  an increase  in  the  blood  flow  through  peripheral organs.    So,  peripheral  blood  flow  is  a  major determinant  of  cardiac  output

Factors Affecting Stroke Volume

Extrinsic Factors Influencing Stroke Volume Contractility is the increase in contractile strength, independent of stretch and EDV Referred to as extrinsic since the influencing factor is from some external source Increase in contractility comes from: Increased sympathetic stimuli Certain hormones Ca2+ and some drugs Agents/factors that decrease contractility include: Acidosis Increased extracellular K+ Calcium channel blockers

Effects of Autonomic Activity on Contractility Sympathetic stimulation Release norepinephrine from symp. postganglionic fiber Also, EP and NE from adrenal medulla Have positive ionotropic effect Ventricles contract more forcefully, increasing SV, increasing ejection fraction and decreasing ESV Parasympathetic stimulation via Vagus Nerve -CNX Releases ACh Has a negative inotropic effect Hyperpolarization and inhibition Force of contractions is reduced, ejection fraction decreased

Contractility and Norepinephrine Sympathetic stimulation releases norepinephrine and initiates a cyclic AMP 2nd-messenger system Figure 18.22

Preload and Afterload Figure 18.21

Effects of Hormones on Contractility Epi, NE, and Thyroxine all have positive ionotropic effects and thus contractility Digitalis elevates intracellular Ca++ concentrations by interfering with its removal from sarcoplasm of cardiac cells Beta-blockers (propanolol, timolol) block beta-receptors and prevent sympathetic stimulation of heart (neg. chronotropic effect)

Autonomic Control of Cardiac Output Sympathetic increases cardiac output ‡Can increase heart rate 70 to 180-200 BPM ‡Can double force of contraction Sympathetic nerves release norepinephrine ‡Believed to increase permeability of Ca2+ and Na+. Parasympathetic (vagal) decreases cardiac output ‡Can decrease heart rate to 20-40 BPM ‡Can decrease force of contraction by 20-30% Parasympathetic nerves release acetylcholine ‡Increases permeability to K+

Cardiac Output and Peripheral Resistance Increasing the peripheral resistance decreases cardiac output. arterial pressure total peripheral resistance cardiac output =

Other Factors Affecting Cardiac Output Age Gender Exercise/body temperature