Vertebrate Closed Circulatory Systems

• Closed circulatory systems• Cardiac anatomy & its O2 supply• The myogenic heart & the cardiac cycle• Blood pressure• Anatomical variations• Other ‘hearts’

Hearts

Cardiac cycle – pumping action of the heart

Two phases• Systole – contraction

• Blood is forced out into the circulation• Diastole – relaxation

• Blood enters the heart

Closed vertebrate circulatory system

• Multi-chambered heart• Capillaries connect arterial & venous systems• Respiratory pigments present in red blood cells

Tunica media = vascular smooth muscle + elastin fibres

Lower BP,thinner walled

Anatomy of the chambered heart

Fish: The simplest/earliest design•Four cardiac chambers• All contain muscle (cardiac & smooth)• Surrounded by a pericardial sac• Atrium & ventricle propel blood• Venous BP atrial contraction ventricular contraction

All vertebrates• Similar developmental pathway• Myogenic contractions• Similar intrinsic properties

Variations• Hagfishes: incomplete pericardial sac• Sharks & Rays: pericardial sac is stiff; conus arteriosus has cardiac muscle• Primitive Fishes: conus is reduced & bulbus also present• Teleosts: bulbus arteriosus (VSM & elastin fibres)

bulbus/conus arteriosus

Venousbloodpressure

Arterialbloodpressure

Advantages•Blood pressure can be regulated, even venous blood pressure • High blood pressure, high flow rate & faster circulation time• Exquisite control of blood flow distribution at arterioles (VSM)• High capillary density reduces blood velocity & the diffusion

distance to cells

Disadvantages•High resistance to flow b/c of small diameter arterioles (R = r4)•High resistance high blood pressure thicker-walled

hearts & higher cardiac O2 needs

Closed vertebrate circulatory system

Adult mammalian cardiomyocyte

Fish cardiac myocytes also have a reduced sarcoplasmic reticulum (SR), & lack an extensive t-tubular system

Consequence: Ca2+ handling during excitation-contraction varies

Myocardial cells

• Striated cells• Electrically connected (desmosomes)• ‘Unstable’ membrane potential

Adult fish cardiomyocyte

Myocardium

Two types• Compact – tightly packed cells arranged in a regular pattern• Spongy – meshwork of loosely connected cells

Relative proportions vary among species• Mammals: mostly compact• Fish and amphibians: mostly spongy

• Arranged into trabeculae that extend into the heart chambers

Cardiac muscle O2 supply

• A working muscle requires ATP• ATP requirement proportional to cardiac power output

Phylogeny & Ontogeny• Hagfishes & Lampreys: spongy• Sharks & Rays: spongy plus variable compact (athletic ability)• Teleosts: most spongy; some have variable compact (athletic/hypoxia)• Amphibians & reptiles: spongy; some have compact (athletic/hypoxia)• Neonatal birds & mammals: spongy• Adult birds & mammals: 99% compact

Compact•Coronary blood supply•Compact design•First organ supplied with O2

Spongy •Venous blood supply•Simplest, but intricate design•Last organ supplied with O2

Most fish = Trabeculae = venous

Mammals = compact = coronary Octopus coronaries

Variable compact/spongy

Cardiac muscle blood & O2 supply

Initiation of cardiac contraction

Neurogenic pacemakers: rhythm generated in neurons(some invertebrates)

Myogenic pacemakers: rhythm generated in myocytes(vertebrates and some invertebrates)

Artificial pacemakers:rhythm generated by device

Control of Contraction

• Vertebrate hearts are myogenic – cardiomyocytes produce spontaneous rhythmic depolarizations

• Cardiomyocytes are electrically coupled via gap junctions to insure coordinated contractions

• Pacemaker – cells with the fastest intrinsic rhythm• Fish: located in the sinus venosus• Other vertebrates: sinoatrial (SA) node in the right

atrium

Myogenic contractions

• All cardiomyocytes can contract without an external stimulus• Resting membrane potential is ‘unstable’ = Pacemaker potential• Specialised cells (pacemaker) set intrinsic heart rate• Relative timing & speeds of opening of specific ion channels

Increasing heart rate• Norepinephrine is released from

sympathetic neurons and epinephrine is released from the adrenal medulla

• More Na+ and Ca2+ channels open• Rate of depolarization and action

potentials increaseDecreasing heart rate

• Acetylcholine is released from parasympathetic neurons

• More K+ channels open• Pacemaker cells hyperpolarize• Time for depolarization takes longer

Increasing Heart Rate

Decreasing Heart Rate

Modulation of heart rate

Depolarization travels through heart in two ways

1. Directly between cardiomyocytes

• Cardiomyocytes are electrically connected via gap junctions

• Electrical signals can pass directly from cell to cell

2. Specialized conducting pathways

• Modified cardiomyocytes that lack contractile proteins

• Specialized for electrical impulse conduction

• All cardiomyocytes of a chamber contract together• Electrically coupled cells (desmosomes)• Specialized conduction fibres• Cardiac chambers contract sequentially, after blood has moved• Delays in electrical conduction between chambers

Syncitial & sequential cardiac contractions

(EKG)

• Sums all the electrical activity of syncytial contractions & relaxations

• P wave: atrial depolarization• QRS complex: ventricular depolarization• T wave: ventricular repolarization

Impulse conduction – step 1

Impulse conduction – step 2a

Impulse conduction – step 2b

Impulse conduction – step 3

Impulse conduction – step 4

Conducting Pathways

EKG

Myogenic contractions

• All cardiomyocytes can contract without an external stimulusBut• Different myocardial cells activate different ion channels • Plateau phase – extended depolarization that corresponds to the

refractory period and last as long as the muscle contraction• Prevents tetanus

Absence of funny channelsFast Na+ channelSlow L-type Ca2+ channel

Excitation-contraction coupling

Cardiac action potentials

Cardiac pumping cycle

• ATP muscle contraction blood pressure blood flow• Isometric contraction blood pressure (wall tension) until valves open• Isotonic contraction blood flow (cardiac output) after valves open• Muscle thickness determines pressure

Vertebrate Hearts

Vertebrate hearts have 3 main layers•Pericardium•Myocardium•Endocardium

Myocardium

Vertebrate Hearts

Have complex walls with four main parts• Pericardium – sac of connective that surround the heart

• Two layers: parietal (outer) and visceral (inner) pericardium

• Filled with a lubricating fluid• Epicardium – outer layer of heart made of connective tissue

• Continuous with visceral pericardium

• Contain nerves that regulate the heart

• Contain coronary arteries• Myocardium – the middle layer of heart muscle• Endocardium – innermost layer of connective tissue covered by

epithelial cells (called endothelium)

Vertebrate hearts - Myocardium

• Muscle layer• Composed of cardiomyocytes• Specialized type of muscle cell

Oxygen supply to heart

• Myocardium extremely oxidative; has high O2 demand• Coronary arteries supply oxygen to compact myocardium• Spongy myocardium obtains oxygen from blood flowing through the heart

Mammalian cardiac anatomy

Two atria Two ventricles

Mammalian cardiac cycle

• Step 1: Late diastole, chambers relaxed, passive filling• Step 2: Atrial systole, EDV• Step 3: Isovolumic ventricular contraction• Step 4: Ventricular Ejection• Step 5: Early diastole, semilunar valves close

Electrical and Mechanical Events in the Cardiac Cycle

• Heart sounds: opening and closing of valves

Figure 9.26

Heart Pressures

• The two ventricles contract simultaneously, but the left ventricle contracts more forcefully and develops higher pressure

• Resistance in the pulmonary circuit is low due to high capillary density in parallel

• Less pressure is needed to pump blood through this circuit• The low pressure also protects the delicate blood vessels of the lungs

Heart Pressures

Heart Pressures

Cardiac Output

• Cardiac output (CO) – amount of blood the heart pumps per unit time

• Stroke volume (SV) – amount of blood the heart pumps with each beat

• Heart rate (HR): rate of contraction• CO = HR X SV• Bradycardia – decrease in HR• Tachycardia – increase in HR

Modulating cardiac output

• By changing heart rate• By changing stroke volume

Concept check: How would you modulate heart rate?

Slow heart rate = bradycardiaFast heart rate = tachycardia

Stroke volume is regulated in two ways:

1) Extrinsically (by nervous system and hormones)2) Intrinsically (via local mechanisms)

Modulation of cardiac output

Control of cardiac output: Intrinsic control mechanisms

• The importance of cardiac output (Q)• Heart rate

Pacemaker rate: temperature; body size • Cardiac stroke volume

Species variabilityEffects of filling (venous) pressure

The importance of cardiac output (Q)

Flow (output) of blood per unit time from the heart (ml/min/kg)

Cardiac power output (= ATP need = O2 need)

Power output = Q x [blood pressure developed]

Right vs left

Atrium vs ventricle

Respiratory function:

O2 uptake = Q x (A-V O2 difference)

Species variability in routine & maximum Q valuesHumans @ 37oC 70-300 ml/min/kgHagfish @ 10oC 10-30 ml/min/kgTrout @ 10oC 15-50 ml/min/kgTuna @ 28oC 100-200 ml/min/kgIcefish @ 0oC 100 ml/min/kg

(Cao2-Cvo2); tissue O2 extraction

[Hb] is a primary determinant of Cao2

Q10 effect~ x8~ x8~ x2~ x16

Q10 effect: O2 uptake doubles for +10oC

The importance of cardiac output (Q)

Human exercising

Contribution of Q during exercise

O2 uptake = Q x (A-V O2 difference)

10-fold increase

Q = 3-fold increaseHR = 2.5-fold increaseSVH = 20% increaseA-VO2 = 3-fold increase

Volume = O2 delivery to tissues

Q = [heart rate] x [cardiac stroke volume]

Q = [heart rate] x [cardiac stroke volume]

Regulation of Q during exercise

Acute temperature effect on heart rate

HR,bpm

Temperature, oC0 4020

60

20

Ectotherms & Endotherms

Cooling by10oC 2x decrease

Q10 ~ 2

humantrout

Temperature acclimation (resetting of pacemaker rate)

HR,bpm

Temperature, oC0 4020

60

20

Ectotherms

Acute Q10 ~ 2

1. Compensationeg, trout, Q10 = 1-2

2. Downregulationeg, turtles, Q10 > 3

trout

Control of intrinsic pacemaker rate

Body mass & heart rate

Rate,bpm

Body Mass

1,000

hummingbird (1 g)

whale20 bpm

human60 bpm

HR = k . BM-0.25

Ectotherms120 bpm is maximumfor many ectotherms

Endotherms

Intrinsic control of stroke volume

How? The Frank-Starling mechanism:

2. Varying stroke volume Alter cardiac emptying (end-systolic volume) = D muscle contraction Alter cardiac filling (end diastolic volume) = D venous pressure

Roles

1. Automatic matching output of chambersventricular output must match atrial output – all vertebratesright & left ventricular matching – crocodiles, birds & mammals

Many fishes (2-3x increase)Small increases (<50%) other vertebrates

Control of Stroke Volume

Frank-Starling effect – an increase in end-diastolic volume results in a more forceful contraction of the ventricle and an increase in SV• Due to length-tension relationship

for muscle• Allows heart to automatically

compensate for increases in the amount of blood returning to the heart (autoregulation)

Level of sympathetic activity shifts the position of the cardiac muscle length-tension relationship

Venous pressure cardiac filling myocyte stretch stronger contraction

Frank-Starling mechanism:

passive stretch

z

actin

contractile unit z

myosin

Venous filling pressure

SV

An intrinsic property of all vertebrate cardiomyocytes

Control of Stroke Volume

The nervous and endocrine system can cause the heart to contract more forcefully and consequently pump more blood with each beat

Control of stroke volume

Control of cardiac output & flow distribution

• Cardiac stroke volumeChange in contractility

- importance of calcium

•Heart rateSympathetic & parasympathetic neural controls

- mechanisms- species diversity

• Blood flow distributionArteriolar controls

neural, humoral, paracrine, autocrine

Extrinsic control mechanisms

Changing heart rate (vagal inhibition)

Pacemaker rate rarely equals measured HR

Inhibition & excitation

Vagus innervation of pacemaker & atriumAll vertebrate heartsExcept hagfish & lampreys

Sympathetic innervation of pacemaker, atrium & ventricleSome advanced, athletic teleost fishes,Amphibians, reptiles, birds & mammals

Cardiac stores: primitive fishInnervated Chromaffin tissue: other fishesAdrenal medulla

Negative chronotropic effects (vagal inhibition)

0 mV

-60 mV

Positive chronotropic effects (adrenergic stimulation)

0 mV

-60 mV