Lecture 5

Heart Rate and Stroke Volume Regulation

CO = SV X HR MAP = CO X TPR
 Cardiac Output (CO)

• The rate at which the heart pumps blood.

• ml (or L) / minute

CO = SV X HR MAP = CO X TPR

SV = stroke volume (ml of blood pumped per beat)

HR = heart rate (beats / minute)

• CO (left heart) = CO (right heart)

• Extrinsic and Intrinsic Regulation of CO
 Autonomic Regulation of Heart Rate

Vagus Nerve
(parasympathetic)

Pre-ganglionic
fibre

Post

Sympathetic
Nerve
Autonomic Regulation of Heart Rate
• SA Node: ↓ heart rate
• AV Node: ↓ Conduction speed
• SA Node: ↑ heart rate
• AV Node: ↑ Conduction speed

SA

complex effects on blood AV

pressure (lecture 8)
Ach: Acetylcholine
NE: Norepinephrine (noradrenaline)
EPI: Epinephrine (adrenaline)

http://www.cvpharmacology.com/autonomic_ganglia.htm
 Sympathetic Regulation of Heart Rate

Na+ moves through the funny channel.

β receptor: beta receptor

Gs: Stimulatory G protein
AC: Adenylyl cyclase
 Parasympathetic Regulation of Heart Rate

T-type Ca++ K+ channel

channel closes opens

Gs: Stimulatory G protein

Gi: Inhibitory G protein
 Parasympathetic and Sympathetic Tone to the Heart
Membrane potential (mV) Sympathetic Parasympathetic
stimulation (vagal) stimulation
Normal

Threshold

Pacemaker potential

Seconds

• Unregulated pacemaker AP frequency = 100-110/min

• Normal HR = 60-70/min The “brake”
The “accelerator”

• Parasympathetic
(vagal) tone (input)
>
Sympathetic tone 60-70 Neutral
(input)
Quantification of Parasympathetic and Sympathetic Tone to the Heart

The “brake” Muscarinic (M2) receptors

are blocked by atropine

The “accelerator” Beta (β) adrenergic

receptors are blocked
by atenolol

Nicotinic (N) receptors
are not blocked by atropine.
Norepinephrine normally
speeds up the heart.
Therefore, blocking it with
atenolol should decrease heart
rate.

Ach normally slows the heart.

Therefore, blocking it with
atropine should increase heart rate.
60-70
 Quantification of Sympathetic and Parasympathetic Effects
(Tone; Inputs) on Heart Rate

The “brake”
Sympathetic Parasympathetic
Normal stimulation stimulation

The “accelerator”

Resting Heart Rate

70 beats/min
Blocks M2
Blocks β adrenergic
muscarinic
Receptors Inject Atenolol Inject Atropine Receptors
(sympathetic;
(parasympathetic;
the “accelerator”)
the “brake”)
HR = 50 beats/min HR = 100 beats/min

Therefore, sympathetic input Therefore, parasympathetic input

increases HR by 20 beats/min decreases HR by 30 beats/min
Sympathetic tone = 20 beats/min parasympathetic tone = 30 beats/min
Cardiovascular-Related
Output from the
Brainstem

• Heart
• Arteries
• Veins
• Adrenal Medulla

Feedback from:

• Baroreceptors
• Skeletal Muscle
 Cardiac Output (CO)

• The rate at which the heart pumps blood.

• ml (or L) / minute

CO = SV X HR

SV = stroke volume (ml of blood pumped per beat)

HR = heart rate (beats / minute)

Blood Pressure (BP) = CO X Total Peripheral Resistance (TPR)

 Stroke Volume Regulation

1. Force of
Ventricular
Contraction

2. Afterload
(Blood Pressure)

3. End-Diastolic Volume
(EDV)

FAE
aorta
Regulation of Muscle Contraction
1. Acetylcholine release at the neuromuscular
junction → muscle action potential (AP: ).

sarcolemma

2. AP spreads along the

T-tubule sarcolemma (muscle cell
plasma membrane) and
down the T-tubules.
Sarcoplasmic reticulum

3. The AP triggers Ca2+ release

from the sarcoplasmic reticulum.

4. Ca2+ binds to troponin.

Stroke Volume Regulation:

Ventricular Contractility
 Regulation of Muscle Contraction

6. Ca++ is transported
back into the sarcoplasmic
reticulum.

7. Ca++ no longer bound

to troponin. Tropomyosin
once again blocks the
myosin-binding sites on
actin.

Stroke Volume Regulation:

EDV: Filling Time 5. Crossbridge formation
and muscle contraction.
Stroke Volume Regulation: Ventricular Contractility
sympathetic nerves or
adrenal glands.
 Stroke Volume Regulation: Afterload

Afterload: The pressure

that the ventricles must
work against during the
ventricular ejection phase
of the heart cycle.

EDV

ESV

Afterload =
Aortic blood pressure
(left side)

 Afterload
 ↓ SV
 Stroke Volume Regulation: End Diastolic Volume
End-Diastolic Volume (EDV): Ventricular volume at the end of diastole.

EDV

a) Pre-Load (end diastolic pressure)

b) Ventricular Compliance
c) The Skeletal Muscle Pump
d) The Respiratory Pump
e) Filling Time
f) The Starling Effect
 Stroke Volume Regulation: End-Diastolic Volume

a) Effects of Pre-Load on End Diastolic Volume

• Pre-Load is the pressure in the ventricles at the end of diastole
• If end-diastolic pressure (EDP) in the ventricles (pre-load) increases,
then EDV increases. SV  CO
 Stroke Volume Regulation: End-Diastolic Volume

b) Effects of Ventricular Compliance on End Diastolic Volume

• Compliance is a measure of how easily the ventricle expands.
• The greater the compliance, the greater the EDV for any given change
in end-diastolic pressure.

Compliance = Δ Volume / Δ Pressure

Stiffness = Δ Pressure / Δ Volume

Compare Points 1, 2 and 3

3
Normal Curve 4 1 5
As EDP Increases; EDV Increases
2
Compare Points 1, 4 and 5
(i.e., EDV)
Normal and Abnormal Curves
As Compliance Decreases, EDV Decreases at any Given EDP
 Stroke Volume Regulation: End-Diastolic Volume
c) Effects of the Skeletal Muscle Pump on End Diastolic Volume

1) Muscle contracts
2) Blood forced toward
2.
the heart
3) Blood does not flow
backwards
Proximal valve open
↑ Pressure (vein)

1.

Vein
Distal valve closed
3.
 Stroke Volume Regulation: End-Diastolic Volume
c) Effects of the Skeletal Muscle Pump on End Diastolic Volume

1) Muscle relaxes
2) Blood moves into 3.
the vein
3) Blood does not flow
Proximal
backward from the
valve
heart closed
1.
Vein
↓ Pressure (vein)

Distal
valve
2. open
 Deep Vein Thrombosis and Pulmonary Embolism
Blood clot breaks free
Blood clot forms in a vein (embolus) and travels

Embolus travels toward the heart, enters the lungs (pulmonary embolism) and can block blood flow.

http://www.nhlbi.nih.gov/health/dci/Diseases/Dvt/DVT_WhatIs.html
 Stroke Volume Regulation: End-Diastolic Volume
d) Effects of the Respiratory Pump on End Diastolic Volume

• Inspiration  Diaphragm contracts

and moves downward

• P (abdomen) > P (thoracic cavity)

The pressure difference drives Thoracic

blood upward toward the Cavity
heart.

Abdomen
 Stroke Volume Regulation: End-Diastolic Volume
d) Effects of the Respiratory Pump on End Diastolic Volume

• Expiration  Diaphragm relaxes

and moves upward

• P (abdomen) < P (thoracic cavity)

• ↑ Thoracic pressure forces blood

from the central veins into the
heart

• Valves prevent backflow into the

abdomen

Inspiration/expiration and the baroreflex.

 Stroke Volume Regulation: End-Diastolic Volume

e) Effects of Filling Time on End Diastolic Volume

• Filling time – the amount of time available for blood to enter the ventricles

• If HR ↓
 ↑ Time spent in diastole

 ↑ Filling Time
passive filling

 ↑ End diastolic volume (EDV)

 ↑ Stroke Volume (SV)

passive filling
 180
160 Resting Heart Rate
140
120 EDV
100 SV x HR = CO
Left ventricular volume (ml)

80 (100 ml) x (60 beats/min) = (6.0 l/min)

60
40
20 ESV Cardiac
0
0.25 0.5 0.75 1.00 1.25 1.5 1.75 2.0
Output
180 Increases
160 Tachycardia with no Sympathetic Stimulation
140
120
100 SV x HR = CO
EDV
80
60 (60 ml) x (120 beats/min) = (7.2 l/min)
40
20 ESV
0
0.25 0.5 0.75 1.00 1.25 1.5 1.75 2.0
As heart rate increases, SV decreases
Time (sec) due to the reduced filling time. In this
case, CO still increases.
PA

Left

Right
 180
160 Resting Heart Rate
140
120 EDV
100 SV x HR = CO
80 (100 ml) x (60 beats/min) = (6.0 l/min)
60
40
20 ESV Cardiac
0
0.25 0.5 0.75 1.00 1.25 1.5 1.75 2.0
Output
Left ventricular volume (ml)

180 Increases
160 Tachycardia with no Sympathetic Stimulation
140
120
100 SV x HR = CO
EDV
80
60 (60 ml) x (120 beats/min) = (7.2 l/min)
40
20 ESV
0 Cardiac
0.25 0.5 0.75 1.00 1.25 1.5 1.75 2.0
180 Output
160
Greater Tachycardia with no Sympathetic Stimulation Decreases
140
120
100 SV x HR = CO
80
60 (35 ml) x (180 beats/min) = (6.3 l/min)
40
20 CO cannot increase indefinitely due to
0 changes in HR because SV decreases
0.25 0.5 0.75 1.00 1.25 1.5 1.75 2.0
due to a decrease in filling time.
Time (sec)
 Tachycardia with no Sympathetic Stimulation
180
160 Resting CO: 100 ml x 60 beats/min = 6.0 l/min
140
120
100 SV x HR = CO
80
60 (60 ml) x (120 beats/min) = (7.2 l/min)
40
Left ventricular volume (ml)

20
0 D S
0.25 0.5 0.75 1.00 1.25 1.5 1.75 2.0

Tachycardia with Sympathetic Stimulation

180
160
140
120
SV x HR = CO
100 (160 ml) x (120 beats/min) = (19.2 l/min)
80
60
40 With sympathetic stimulation, the heart
20 relaxes faster due to enhanced rates of
0 D S
0.25 0.5 0.75 1.00 1.25 1.5 1.75 2.0
calcium up-take by the SR. The heart
Time (sec)
spends more time in diastole with
sympathetic stimulation.
 Greater Tachycardia with no Sympathetic Stimulation
180
160 Resting CO: 100 ml x 60 beats/min = 6.0 l/min
140
120
100 SV x HR = CO
80
60 (35 ml) x (180 beats/min) = (6.3 l/min)
40
Left ventricular volume (ml)

20
0 D S
0.25 0.5 0.75 1.00 1.25 1.5 1.75 2.0

Greater Tachycardia with Sympathetic Stimulation

180
160
140
120
100 SV x HR = CO
80
60 (80 ml) x (180 beats/min) = (14.4 l/min)
40
20
0 D S
0.25 0.5 0.75 1.00 1.25 1.5 1.75 2.0
Time (sec)
 Stroke Volume Regulation: End-Diastolic Volume

e) Effects of Filling Time on End Diastolic Volume

• Filling time – the amount of time available for blood to enter the ventricles

• If HR ↓
 ↑ Time spent in diastole

 ↑ Filling Time
passive filling

 ↑ End diastolic volume (EDV)

 ↑ Stroke Volume (SV)

passive filling
 Coronary Circulation

Aortic valve and ostia

Coronary arteries originate at the base of the aorta from openings

called coronary ostia located behind the aortic valve leaflets.

Empty, via veins, into the heart

chambers.
Coronary Artery Blood Flow Occurs Mainly During Diastole

Most of the flow through

the coronary arteries is
during diastole.
 Stroke Volume Regulation: End-Diastolic Volume
f) The Starling Effect

• Greater amounts of blood entering the heart during diastole lead

to greater amounts of blood leaving the heart during systole.

↑ EDV
  Force of ventricular contraction

 ↑ Stroke Volume

 ↑ Cardiac Output

• Prevents an increase in heart volume with increased venous return.

Stretched muscle can generate a greater force of contraction
Stroke Volume Regulation: End-Diastolic Volume
f) The Starling Effect
 Stroke Volume Regulation: End-Diastolic Volume
f) The Starling Effect
• Cardiac muscle fibers are shorter than their optimal length.
• Stretching (due to ↑ EDV) increases the potential for cross-bridge formation
thick filament thin filament

Optimal
sarcomere length
Stroke volume (ml)

Normal resting length

A band
Sarcomere length

Ventricular end-diastolic volume (ml)

 Stroke Volume Regulation: End-Diastolic Volume
f) The Starling Effect
Starling Curves and Sympathetic Activity

Increased
• Stroke volume ventricular
can be regulated contractility
by altering EDV
and/or sympathetic
activity.

• Family of Starling Decreased

Curves ventricular
contractility
 Overview of Stroke Volume Regulation
1. Force of Ventricular Contraction
2. Afterload (Blood Pressure)
3. End-Diastolic Volume
a) Pre-load (end diastolic pressure)
b) Ventricular Compliance
c) The Skeletal Muscle Pump
d) The Respiratory pump
e) Filling Time
f) The Starling Effect

EDV

ESV
Inotropy = ventricular contractility