1) cardiac action potential

2) Ca2+ enters during the plateau

3) Ca2+ induced Ca2+ release from SR

4) Ca2+ binds to troponin

5) Cross-bridge cycling leading to tension

6) Ca2+ reaccumulated in SR eventually leading to relaxation

Contractility is directly related with intracellular Ca2+ concentration

Contractility is also directly related to heart rate

positive inotropic effect - increased contractility

1) phosphorylation of the sarcolemmal Ca2+ channels leads to increased inward Ca2+ current during the plateau

2) phosphorylation of phospholamban, a protein that regulates Ca2+ ATPAse in the SR.

This results in greater uptake and storage of Ca2+ uptake by the SR it causes faster relaxation and increases the amount of stored Ca2+ for release on subsequent beats

negative inotropic effect - decreased contractility

it only affects the atria

1) ACh release decreases inward Ca2+ current during the plateau of the action potential

2) ACh increases Ik, thereby shortening the duration of action potential - decreasing the inward Ca2+ current overall the amount of Ca2+ entering the atria cells during the AP, decrease the trigger Ca2+, and decrease the amount of Ca2+ released from the SR

positive staircase effect - more action potentials per unit time causes more total Ca2+ entering the cell during the plateau phase, and more Ca2+ for accumulation by the SR. tension rises stepwise until a max. storage level of Ca2+ by the SR is reached

postextrasystolic potentiation - extrasystole (an "extra" beat) causes the tension on the next beat is greater than normal - causing increased stored Ca2+ by SR

positive inotropic effect - increased contractility

1) cardiac glycosides inhibit Na+-K+ ATPase at the extracellular K+-binding site

2) inhibition of the pump leads to decreased Na+ being pumped out and thus increased ICF Na+

3) increase in ICF Na+ decreases activity of the Ca2+-Na+ exchanger (Ca out, Na in - secondary active transporter) because the Na+ gradient is decreased

4) Less Ca2+ being transported out leads to increased ICF Ca2+

5) increased ICF Ca2+ leads to increased tension

Systole: period of contraction -> ejects blood to the lungs or the rest of the body

Diastole: period of relaxation -> heart fills with blood

Stroke volume: the volume of blood ejected from one ventricle in one beat (Normal = ~ 70 ml)

SV = end-diastolic volume - end-systolic volume = (110 to 120 ml) - (40-50 ml)

End-diastolic volume: volume of blood left in the ventricleafter normal filling during diastole (110-120 ml)

End-systolic volume: volume of blood remaining in the ventricle after systole (40-50 ml)

Ejection fraction: the fraction (%) of the end-diastolic blood volume ejected from one ventricle in one beat.

A good index of heart contractility (Normal range = 55-75%)

Ejection fraction = stroke volume / EDV

Preload: The ventricular wall tension at the end of diastole, i.e. the stretch on the muscle fibers just prior to contraction.

Preload is directly proportional to EDV

Indices or markers for preload:

Left ventricular end-diastolic volume (LVEDV)

Left ventricular end-diatolic pressure (LVEDP)

Left atrial pressure Pulmonary venous pressure Pulmonary wedge pressure (Swan-Ganz catheter) - catheter placed through vein all the way to lung through pulmonary artery, senses LA pressure

Afterload: The ventricular wall tension during contraction, i.e. the resistance that must be overcome to eject the stroke volume Index or marker of afterload:

Mean aortic pressure

*Hypertension = increase afterload (LV has to work harder)

*Hypotension = decrease afterload

Peak left ventricular pressure - e.g. aortic stenosis -> increase afterload

Contractility: property that accounts for changes in strength of contraction (independent of preload and afterload), often affected by neurotransmitter or hormonal influences and the contractility effect is mediated by changing intracellular calcium

Indices or markers of contractility

*Change in pressure vs. change in time (dp/dt) *Ejection fraction (stroke volume/diastolic volume) e.g. Exercise (increase sympathetic stimulation to the heart) -> increase contractility

P = 2*H*T / r

P = pressure of heart chamber

H = thickness of chamber wall

T = wall tension

r = radius of the chamber

Thus, geometry of the heart ventricle (chamber diameter and thickness) is important in relating force generated by cardio-myocytes and pressure in the chamber LV has thicker wall and smaller diameter compare to RV, thus LV generating higher pressure

Cardiac Output: the volume of blood ejected by the heart each minute. In average healthy man 70-Kg = ~ 5 L/min

Cardiac Output = Stroke volume X Heart rate

CO = SV X HR = 70 ml X 72 beat/min = 5000 ml/min= 5 L/min

1- Intrinsic: venous return- ventricular filling pressure - preload (Frank-Starling’s mechanism)

2- ANS (Symapthetic and parasympathetic nerves) regulate heart rate and strength of contraction

Increase blood return to the heart -> increase muscle length -> increase optimal overlap between actin and myosin -> increase heart contraction -> increase heart pumping

Thus, the more blood returning to the heart (venous return) the more blood pumped from the heart (cardiac output)

Stroke work is the amount of work done by the heart each beat Stroke work output is required to:

1) move blood from low-pressure areas (veins) to the high-pressure areas (arteries) [most of the work]

2) increase velocity of the blood to be ejected through aortic and pulmonary valves

* Work = force X distance = stroke volume (SV) X arterial pressure (P)

Conservation of mass Fick’s principle:

In steady state: Rate of O2 consumption in the body equal amount of O2 leaving the lung (pulmonary veins) minus amount of O2 returning to the lung (pulmonary artery)

Cardiac Output = O2 consumption / change in arteriovenous [O2]

Sympathetic stimulation: Heart rate -> increase from 70 beat/min to 180-200 beats/min

Force of contraction -> increase double normal

Parasympathetic stimulation (vagus nerves): Heart rate: can stop heart beats for a few seconds

Force of contraction: decrease only by 20-30%

Vagal nerves are distributed mainly to the atria and not much to the ventricle

Sympathetic stimulation -> increase cardiac output at any given right atrial pressure

Parasympathetic stimulation -> decrease cardiac output at any given right atrial pressure

Phase I = period of filling

Phase II = period of isovolumic contraction

Phase III = period of ejection

Phase IV = period of isovolumic relaxation

period of ejection

aortic valve opens because ventricular P is above aortic P

P increases to a peak during contraction

P decreases and the aortic valve closes

period of isovolumic relaxation

aortic valve and mitral valve closed

volume remains constant and LV relaxes and P decreases once pressure is low enough (LV lower than LA)

mitral valve opens and cycle starts over again with phase I

Increase preload (IV fluid) -> increase stroke volume, BUT end-systolic volume (ESV) remains the same.

Thus, normal LV can adjust its stroke volume according to its diastolic filling volume [Frank-Sterling mechanism]

Increase afterload (e.g. hypertension or aortic stenosis) -> increase ventricular systolic pressure -> higher LV end-systolic volume -> reduce stroke volume

The relationship between afterload and end-systolic volume is linear

Increase contractility (e.g. injection of epinephrine) -> increase stroke volume BUT smaller end-systolic volume

Thus, end-systolic volume depends on afterload and contractility of the ventricle BUT NOT on preload

Stroke volume increases by:

a) increasing preload

b) decreasing afterload

c) increasing contractility

Ventricular end-diastolic volume is affected by preload (e.g. ventricular compliance)

Ventricular end-systolic volume depends on afterload and contractility, BUT not preload