Cardiac Oxygen Supply and Demand Flashcards
Concept about the heart as a pump
The heart comprises 2 muscular pumps in series: Right ventricle and left ventricle
How much blood does the heart pump on average per beat
Pumps 70 ml/beat
Myocyte
-special cell that makes up the myocardium (heart muscle)
Composition of the myocardium
- nucleus
- cell membrane (sarcolemma)
- sarcoplasmic reticulum
- mitochondria
- various storage granules
- myofibrils made up of a linear series of sarcomeres *functional contractile unit
Z line
Delineates each sarcomere
Steps depolarization –> contraction
- Depolarization of the sarcolemma of the myocytes = opening Ca2+ channels
- Ca2+ entry into the sarcoplasm
- rise in Ca2+ stimulates release of Ca2+ from sarcoplasmic reticulum - leads to bigger rise in Ca2+ in the sarcoplasm
- Regulatory protein troponin C which is normally attached to active sites on actin - preventing myosin head attachment will bind to Ca2+ causing TpC to move and expose active site
- Myosin binds to actin
- Heads undergo flexion (in the presence of ATP) driving the actin filaments past the myosin filaments - actin filaments are attached to Z lines - so Z lines get closer together (mininum length of sarcomere)
- Heads detach and return to unflexed config and then cycle begins again
Cross bridge cycling in different crossbridges
Cross bridge cycling is in different phases in different cross bridges
Allows a process of smooth and progressive shortening during systole with many cycles of attachment
Cause of diastole
- Ca2+ leaves the attachment sites to reenter the sarcoplasmic reticulum
- all cross bridges release and the sarcomere relaxes
Origin of energy for contraction
- energy comes from high energy phosphate from ATP
- ATP synthesis requires continuous supply of fuels and oxygen
Cardiac fuel -preferred cardiac fuel in the fasting state
-free fatty acids 60-70% of cardiac needs
<30% glucose (and glycogen)
-10% lactate
Cardiac fuel - after a high carbohydrate meal
-glucose supplies about 70% of the needs
Cardiac fuel -after a fatty meal
-FFA supply up to 80%
Importance of O2
- O2 must be continuously available for cross bridge cycling
- when O2 supply is interrupted the generation of ATP by anaerobic glycolysis is minimal and within 3-4 s contractile perfomance falls dramatically
Determinants of myocardial oxygen supply
1) Coronary blood flow
2) Coronary O2 content and availability
Determinants coronary blood flow
1) Coronary perfusion gradient
2) Coronary resistance
Causes of coronary resistance
1) Myocardial compression
2) Tone of resistance vessles
- metabolic (principal mechanism)
- endothelial
- neurogenic
- myogenic
3) Stenoses and tone of conductance vessles
Origin of coronary arteries
-sinus of valsalva (coronary sinus) located just distal to aortic valve
Branches of coronary artery
- right and left coronary artery
- left branches very quicklly into left anterior descending and cricumflex
Left anterior descending coronary artery supply
- supplies the anterior wall of the left ventricle
- most of the interventricular septum (septal branches)
Circumflex coronary artery supply
- lateral wall of the left ventricle
- posterior surface of left ventricle
Right coronary artery supply
- the right ventricle
- posterior part of interventricular septum
- SA and AV nodes
Grouping of coronary arteries
1) Conductance vessels
2) Resistance vessels (arterioles and capillaries)
Conductance vessles
- vessels that run over the surface of the heart (epicardial vessels)
- and those that penetrate through muscle mass to bring blood to myocardium (myocardial penetrating vessels)
Resistance vessels
Small peripheral arterioles and include precapillary sphincters
What determines coronary resistance (3)
1) Myocardial compression
2) Tone of resistance vessels
3) Stenoses and tone of conductance vessels
Myocardial compression
Prevents any flow during systole
-vessels are squeezed shut by the pressure in the left ventricle
Epicardial and penetrating vesels in systole have same pressure as in LV so no flow
How tone of resistance vessels affects coronary resistance
Higher the tone of resistance vessels and precapillary sphincters the less the flow will be
4 determinants of tone of resistance vessels
1) Metabolic
2) Endothelial (factors arising from endothelium)
3) Neurogenic
4) Myogenic
Myogenic mechanism
-head of pressure from aorta may vary considerably - think about when doing exercise blood pressure really rises
-myogenic mechanism = a response of smooth muscles to variations in perfusion pressure
i) if pressure increases will consrict to not allow as much flow through
ii) if pressure drops will relax
= autoregulation (response of resistance vessels to amount of pressure that is perfusing them)
Major determinants of O2 demand
1) Heart rate
2) Wall stress
3) Contractility
Myocardial O2 demand with
a) increased LV radius
b) Decreased LV radius
a) increased demand
b) decreased demand
Myocardial O2 demand with
a) decreased LV thickness
b) increased LV thickness
a) increased demand
b) decreased demand
Myocardial O2 demand with
a) increased contractility
b) decreased contractility
a) increased demand
b) decreased demand
What determines how much blood flows per minute in coronary circulation- i.e. describe the coronary perfusion gradient
1) Aortic root pressure -head of pressure forcing blood through
2) What is resisting = LV chamber pressure -whatever is in left ventricle in diastole compresses the other side of the circuit
Coronary perfusion gradient = aortic root pressure- LV chamber pressure
Coronary perfusion gradient in systole vs. diastole
Systole: Ao =120, LV = 120, gradient = 0
(nothing available to push blood through coronary vessels)
because aortic valve is open - so have LV in continuity with Ao
Diastole: Ao = 90, LV = 10 Gradient = 80
(head of pressure available for driving flow through vessels)
Effect of heart rate speeding up on coronary circulation
- coronary perfusion only during diastole (because here coronary perfusion gradient will be less than 0)
- when heart speeds up it is diastole that is going to be shortened (goes from being 2/3 of cycle to be about same length as systole)
- time to perfuse myocardium get smaller as rate goes up
Calculating coronary perfusion gradient
Diastolic aortic root pressure - Diastolic LV pressure
What determines coronary resistance
Derives from the small vessels (arterioles) and pre-capillary sphincters
Resists pressure available from coronary perfusion gradient
What is flow per minute through coronary arteries equal to (equation)
Flow = pressure/resistance
Where pressure = coronary perfusion gradient
and resistance = coronary resistance
Myocardial compression
Prevents any flow during systole
-vessels are squeezed shut by the pressure in the left ventricle
Epicardial and penetrating vesels in systole have same pressure as in LV so no flow
Metabolic control over tone of resistance vessels
Metabolites that are generated by myocardial contraction are determinants of tone in resistance vessels:
adenosine, H+, K+, lactate, low O2
Will tend to make resistance vessles relax and allow more flow
1) Increase myocardial contractile activity
2) Increase metabolism
3) Decrease myocardial PO2
4) Generation of metabolites (adenosine produced low O2, low PO2, high PCO2, low H+, low K+)
5) Decrease coronary vascular resistance (to increase perfusion)
-most important beat to beat determinant of flow
Endothelial secretion that determine tones
-working over longer phases of time
1) Endothelial derived relaxation factor (NO)
2) PGI2
both secreted by endothelium and have vasodilatory effects (on smooth muscle of resistance vessels)
3) Endothelin
-also secreted by endothelium
-has constrictive effect
Stenoses and tone of conductance vessels in determining resistance
- conductance vessels normally have 0 resistance
- in pathologies can get narrowing of vessles/change in tone that produces resistance
Contractility
-how hard the heart is contracting
Myocardial O2 demand with:
a) increased HR
b) decreased HR
a) increased demand
b) decreased demand
Myocardial O2 demand with
a) inceased LV systolic pressure
b) decreased LV systolic pressure
a) increased demand
b) decreased demand
Coronary blood flow in response to O2 demand
-as myocardial O2 demand and consumption increase coronary blood flow increases
Importance of close coupling of coronary blood flow to myocardial O2 demand
- myocardium depends on aerobic metabolism
- low coronary venous saturation (25-30%) - i.e heart efficient at extracting O2
- myocardium cannot incur significant O2 debt
Most common cause of ischemia
Coronary atherosclerosis
How stenosis changes coronary perfusion gradient
-past the stenosis the pressure is lower
-meaning that the perfusion gradient is also reuced
i.e. post stenois 45 instead of 90
45-10 (LV diastolic pressure) = 35 (perfusion grad)
instead of 90-10 = 80
-any of vessels distal to the stenosis the perfusion pressure is lowered and isn’t getting enough blood supply
How decrease coronary narrowing affects coronary flow reserve
a) at rest
b) maximum flow i.e. during exercise
- % diameter narrowing does not have much affect on coronary flow reserve at rest until very severely narrowed ie >80%
- however has big implication on coronary flow reserve under maximum flow
- no ischemia at rest but will get it at exertion (decreased ability to increase blood flow through the coronary arteries above normal resting volume)
Two causes of ischemia
1) Increased demand without sufficient increase in supply
2) Decreased supply without sufficient decrease in demand
Causes of acute fall in supply
-acute coronary syndrome where atherosclerosis vulnerable area ruptures and forms thrombus in coronary artery
-suddenly block artery off completely
-will cause necrosis of myocardial tissue if not treated
Other cause
-coronary artery spasm - sudden change in diameter due to sudden contraction of smooth muscle
Wall stress
-the pressure/force that is tending to tear the myocardium apart during systole
Increased by
1) Higher pressure
2) More distended the left ventricle at rest
3) Thinner wall
Autonomic nervous influences
- supplement or complement primary determinants of flow
- more important in states of exercise
- alpha receptors when stimulated will vasoconstrict
- beta -2 receptors when stimulated will result in vasodilation
- vagus influences = vasodilatory
Two determinants of myocardial O2 supply
1) Most important is coronary blood flow
2) Also influenced by coronary O2 content and availability (poorly functioning lung, high altitude, low Hb)
Conditions that increase systolic left ventricular pressure (2)
1) high peripheral vascular resistance
2) aortic valve stenosis (resistance to ejection at aortic valve -pressure must be higher in LV)
Formula for wall stress
Wall stress = pressure x radius/thickness
Starling curves of myocardial performance with changes in contractility
As ventricular EDV volume increases ((stretching of myocardium) The performance of the ventricle increases
-as contractile state declines then same relationship ventricular EDV and performance hold true but ventricular performance is relatively decreased
