Regulation of Cardiac Output IX by sanmelody


									Regulation of Cardiac

     Dr. W.G. Wier
   Dept. of Physiology

                  Regulation of CO
• CO may have to increase to maintain MAP

    MAP = CO x TPR

   Exercise: TPR may fall to 1/3 of the basal state level. If CO did
     not increase 3-fold, MAP would fall to 1/3 (not compatible
     with life

• CO may have to increase to provide adequate supply of oxygen

   VO2 = D(A-V)O2 x CO

   Exercise: VO2 may increase 12-fold, in order to supply adequate
     O2 to exercising muscle, heart and brain. The arterio-venous
     oxygen difference can only increase 3-fold. Therefore, CO
     must be able to increase at least 3-fold.
           2 Preload               3 Contractility
    Filling pressure determines               E-C coupling mechanisms
    strength of contraction via
    length dependence of cardiac

       CO = HR x SV
Ventricular Compliance                          4 Afterload
                                      Mechanical load on the heart
                                      Affects shortening velocity, peak force
      Effects of changes in Heart Rate on Cardiac
•   Increasing HR increases CO by increasing the number of pump strokes
    per minute (CO = HR x SV).
•   Increasing HR also increases contractility, thereby affecting stroke
    volume (giving increased ability to shorten and/or develop force)
•   “Bowditch” effect or „treppe‟. Cellular basis involves frequency
    dependent increase in L-type Ca2+ current, and increased SR Ca2+

 The left ventricular P-V loop will
help us understand how changes
       in preload, afterload,
   contractility, and ventricular
  compliance are translated into
  changes in stroke volume and
           cardiac output

• Skeletal muscle or cardiac muscle strip - preload was a force (weight)
  that stretched the muscle to some initial length, prior to contraction.
• Left ventricle (as in P-V loop) - left ventricular end-diastolic pressure
  (I.e. the pressure in the left ventricle, just prior to contraction). This
  ‘filling pressure’ stretches cardiac cells, just prior to contraction, and
  determines their length.
• Right ventricle - right ventricular end-diastolic pressure. Note that
  r.v.e.d.p. is approximately equal to the mean right atrial pressure (mrap),
  which is approximately equal to central venous pressure (CVP).
• Intact CVS - preload is considered to be CVP. Preload of the right
  ventricle determines it‟s output, and that output becomes the preload for
  the left ventricle, thus CVP functions as the preload for the intact CVS.

• The quantitative relationship between preload and SV (or CO) is
  quantified with the cardiac function curve (CFC)
 SimulDOG will be used to
display cardiac cycle and PV
      loop dynamically

Actual, experimentally recorded P-V loop (canine left

                           LV Pressure
                                         LV Volume

The P-V loop occurs within limits established by the passive
   and active length-tension relations of cardiac muscle

                                           Active, increased contractility
                                                      (NE, Epi, digitalis)
  Force (g) or Tension

                                              Active, Basal state

                                                   Strip of cardiac muscle: Length-tension relation
                                                       Left Ventricle: Volume-pressure relation
                                                    During Cardiac cycle: Pressure-volume loop

                                              Passive (unaffected)

                         Length (set by preload)                                           9
                                   The left ventricular P-V loop
                                                                       End-systolic P-V
                        160                                            (Contractility index)

                        120                                   ejection
L.V. Pressure (mm Hg)


                                  Isovolumic relaxation
                                                                                   Isovolumic contraction
                                                            Diastolic filling
                              0                    50 ESV           100
                                                                                EDV 150
                                                  L.V. Volume (ml)
                         The Cardiac Function Curve shows the entire relationship
                         between preload and stroke volume (or cardiac output)
L.V. Pressure (mm Hg)


                                                       Stroke Volume


                              0     50     100 150
                                  L.V. Volume (ml)                     Preload (mm Hg)

Ventricular Function Curve in Humans

     Parker & Case, 1979. Circulation, 60;4-12   12
• Skeletal muscle or cardiac muscle strip - afterload was a force
  that the muscle had to develop in order to lift a wieght and end
  the isometric contraction phase, thus beginning shortening
  (isotonic phase of contraction).
•   Left ventricle - pressure to open aortic valve, (i.e the point at
    which L.V. generates enough force to open aortic valve, and
    end isovolumic (isometric) contraction phase and begin
    shortening. Thus, the diastolic blood pressure could be said to
    be the “initial afterload”.
• A more advanced definition of afterload involves:
     – Arterial compliance; changes as the stroke volume is ejected
       into the arterial system.
     – Total peripheral resistance
     – Pulse wave reflections (particularly important in the aged).
                        Effect of changing afterload on the P-V loop and the
                                     the Cardiac Function Curve
L.V. Pressure (mm Hg)


                                                     Stroke Volume


                              0     50     100 150
                                  L.V. Volume (ml)                   Preload (mm Hg)

                        Effect of changing contractility on the P-V loop and
                                   the the Cardiac Function Curve
L.V. Pressure (mm Hg)


                                                     Stroke Volume


                              0     50     100 150
                                  L.V. Volume (ml)                   Preload (mm Hg)

                        Effect of decreasing ventricular compliance on the P-V loop
                                    and the the Cardiac Function Curve
L.V. Pressure (mm Hg)


                                                        Stroke Volume


                              0     50     100 150
                                  L.V. Volume (ml)                      Preload (mm Hg)

Summary of factors that change the CFC and thus
          can affect Cardiac Output

                                    1.   Increased HR
                                    2.   increased contractility
                                    3.   decreased afterload
  Stroke Volume

                                    1.   Decreased HR
                                    2.   decreased contractility (myocardial
                                    3.   increased afterload

                  Preload (mm Hg)

Analysis of the regulation of CO is not as simple as
              implied in the last slide.

Although preload does determine CO, it is also true
      that CO has an influence on preload.

 This influence occurs because the CO must flow
  through the systemic vasculature before blood
   returns to the right side of the heart, where it
                 influences preload

The effect of CO out preload is quantified using the
          Vascular Function Curve (VFC)
Use of SimulDOG model to demonstrate how increasing CO
        tends to cause cardiac filling pressure to fall

                                    Vascular Function Curve
                                                                               •   In SimulDOG (or in an
                                                             PA (MAP)
                                                                                   experimental animal),
                                                                                   the VFC is obtained
                                                                                   by varying the CO.
                                                  DP=PA-PV                     •   As CO is increased, it
P(mm Hg)

                                                                                   can be seen that
                                                             P=7.0mmHg (dead
                                                                                   arterial pressure rises
           7.0                                                                     and venous pressure
                                                             PV (CVP)              (CVP) falls
                                                             (CVP)             •   Then, the CO is
                                                                                   plotted as a function
                                                                                   of the CVP
                 CO=0 CO=1   CO=2    CO=3 (L/m)
                                                                               •   This shows that
                                                                                   increases in CO tend
                             Time                                                  to decrease CVP (i.e.
                                                                                   the „filling pressure of
                                                                                   the heart in the intact

    Vascular Function Curve: effects of changes in
      blood volume (BV), venous tone, and TPR

Use SimulDOG to show that            Use SimulDOG to show that
increasing BV causes CVP to          increasing TPR causes CVP to drop,
increase, and also increases „dead   but has no change on „dead
pressure‟                            pressure‟

The operating point: the stable point to which CO and CVP return after
                      perturbations of the system

                                            1. Suppose CO increased to
                                            here, for some reason
                                            2. From VFC, we know that
                                            this would tend to lower CVP
                                            3. With lower CVP, CO would
                                            be lower on next beat
                                            4. Operating point would be
                                            approached gradually

Cardiac cycle

 Pressure-volume loop

     Cardiac Function Curve
   Shows effect of preload on          Conditions in heart
     CO, and is affected by
                                          and systemic
    afterload, contractility
   HR, ventricular compliance
                                       together determine
                                             the CO
    Vascular Function Curve
           Shows effect of CO on
         preload, and is affected by
            TPR, blood volume
                venous tone
The Pressor Response

                 Pressor response is called into play
                 when an increase in MAP is needed.

                 A fall in MAP is sensed by arterial

                 Pressor response increases MAP
                 by increasing both CO and TPR. Heart
                 and blood vessels are affected.

        See Guyton Fig. 20-15, Eighth Edition      24
                  Analysis of Pressor Response
       (e.g. in response to fall in MAP after hemorrhage)
                                                 •   Hemorrhage causes a
                                                     severe decrease in blood
                                                 •   In terms of cardiovascular
                                                     system analysis, this is
                                                     characterized as a decrease
                                                     in „dead pressure‟ (change
                                                     in intercept of VFC)
                                                 •   New operating point is at
                                                     much lower CO, therefore
                                                     MAP falls
                                                 •   Pressor response: Massive
CO (L/m)                                             activation of sympathetic
                                                     nervous system
                                                       – Increases HR and heart
                                                           contractility (NE on b1
                                                           adrenoceptors on heart)
                                                       – Increases venous tone
                                                           (NE on a1-
                                                           adrenoceptors on veins)
                                                 •   Result: CO increases, TPR
                                                     increases, MAP increases
                                                     toward normal

               Central Venous Pressure (mm Hg)                               25
      Preliminary Analysis of Acute Myocardial Damage

                                                 • heart becomes
                                                   damaged, as in acute
                                                   myocardial ischemia

                                                 • There is an immediate
                                                   decrease in cardiac
                                                   contractility, reflected
                                                   in the depressed CFC

CO (L/m)                                         • CO falls, CVP rises,
                                                   MAP falls

                                                 • Pressor response
                                                   tends to restore CO
                                                   and MAP, but CVP
                                                   remains high

               Central Venous Pressure (mm Hg)                         26

• The essential problem for the cardiovascular system in severe
  exercise is that TPR can fall to 33% of the basal state level.
• This fall in TPR is due to the fact that blood vessels within the
  exercising skeletal muscle have dilated greatly.
• If TPR falls to 33% of basal, CO must increase 3-fold to maintain

• The increase in CO is accomplished by changes that occur in
  both heart and systemic vasculature

Analysis of cardiovascular system function during heavy exercise;
  new operating point at ‘B’ with greatly increased CO, slightly
                         increased CVP

                                          ++ contractility

                                                Greatly decreased TPR

                                                        ++ venous tone
                                                       ‘muscle pump’

                       Or central venous pressure

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