Vertebrate Closed Circulatory Systems Closed circulatory systems Cardiac anatomy & its O 2 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 Venous blood pressure Arterial blood pressure

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 = r 4 ) High resistance  high blood pressure  thicker-walled hearts & higher cardiac O 2 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: Ca 2+ 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 O 2 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 O 2 Spongy Venous blood supply Simplest, but intricate design Last organ supplied with O 2

Most fish = Trabeculae = venous Mammals = compact = coronary Octopus coronaries Variable compact/spongy Cardiac muscle blood & O 2 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 Ca 2+ channels open Rate of depolarization and action potentials increase Decreasing 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 stimulus But 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 channels Fast Na + channel Slow L-type Ca 2+ 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 O 2 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

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 = bradycardia Fast 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 variability Effects 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 = O 2 need) Power output = Q x [blood pressure developed] Right vs left Atrium vs ventricle

Respiratory function: O 2 uptake = Q x (A-V O 2 difference) Species variability in routine & maximum Q values 37 o C ml/min/kg 10 o C10-30 ml/min/kg 10 o C15-50 ml/min/kg 28 o C ml/min/kg 0 o C100 ml/min/kg (Cao 2 -Cvo 2 ); tissue O 2 extraction [Hb] is a primary determinant of Cao 2 Q 10 effect ~ x8 ~ x8 ~ x2 ~ x16 Q 10 effect: O 2 uptake doubles for +10 o C The importance of cardiac output (Q)

Human exercising Contribution of Q during exercise O 2 uptake = Q x (A-V O 2 difference) 10-fold increase Q = 3-fold increase HR = 2.5-fold increase SVH= 20% increase A-VO 2 = 3-fold increase Volume = O 2 delivery to tissues Q = [heart rate] x [cardiac stroke volume]

Intrinsic pacemaker rate Temperature Body mass Extrinsic modulation of pacemaker CNS Hormones Ions Intrinsic contractile properties Cardiac stretch Temperature Extrinsic modulation of contractility CNS Hormones Ions Regulation of Q during exercise

Acute temperature effect on heart rate HR, bpm Temperature, o C Ectotherms & Endotherms Cooling by  10 o C  2x decrease Q 10 ~ 2 human trout

Temperature acclimation (resetting of pacemaker rate) HR, bpm Temperature, o C Ectotherms Acute Q 10 ~ 2 1. Compensation eg, trout, Q 10 = Downregulation eg, turtles, Q 10 > 3 trout

Control of intrinsic pacemaker rate Body mass & heart rate Rate, bpm Body Mass 1,000 hummingbird (1 g) whale 20 bpm human 60 bpm HR = k. BM Ectotherms 120 bpm is maximum for 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 chambers ventricular output must match atrial output – all vertebrates right & 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 volume Change in contractility - importance of calcium Heart rate Sympathetic & parasympathetic neural controls - mechanisms - species diversity Blood flow distribution Arteriolar 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 & atrium All vertebrate hearts Except hagfish & lampreys Sympathetic innervation of pacemaker, atrium & ventricle Some advanced, athletic teleost fishes, Amphibians, reptiles, birds & mammals Cardiac stores: primitive fish Innervated Chromaffin tissue: other fishes Adrenal medulla

Negative chronotropic effects (vagal inhibition) 0 mV -60 mV

Positive chronotropic effects (adrenergic stimulation) 0 mV -60 mV