Tutorial 6 - Cardiac & case studies

Question 1

State some confirmed risk factors for the development of coronary artery disease (CAD)?

Answer 1

1. Hypercholesterolemia (especially LDL)

2. Hypertension (especially systolic BP)

Question 2

State some significant, but indirect risk factors for CAD?

Answer 2

1. Lack of exercise
2. alcohol
3. stress
4. diet - high sat fats, low antioxidants
5. obesity
6. age - men over 60, women over 65

Question 3

Explain how the pathophysiology of coronary circulation can be described as a ‘vicious cycle’

Answer 3

Basically - Ischemia induced contractile dysfunction precipitates hypotension, and therefor, further myocardial ischemia.

Extended way to say it - The heart’s function is to supply blood to systemic circulation, however it’s ability to do so depends upon its own perfusion with blood (and O2) - which is determined by the blood pumped into systemic circulation. It is a paradoxical problem whereby the cause (impeded delivery of blood to the heart) becomes the effect (impeded systemic circulation and thus impeded delivery of blood to the heart). This is a POSITIVE FEEDBACK CYCLE!

Question 4

Define the term ‘nadir’

Answer 4

the lowest or most unsuccessful point in a situation

(not that related just a cool new word haha)

Question 5

Control of coronary blood flow - explain what occurs during systole, and why.

(hint: think subendocardial and subepicardial layers)

Answer 5

1. subendocardial, intramural vessels become compressed and so blood flow in these areas halts completely
2. coronary venous outflow from the subendocardial layers peaks, as small intramural vessels collapse and empty their contents
3. subepicardial blood flow hindered but much less so then subendocardial

Question 6

Control of coronary blood flow - explain what occurs during diastole, and why.

(hint: think subendocardial and subepicardial layers)

Answer 6

1. coronary arterial inflow (of subendocardial vessels) increases as transmural gradient favors perfusion, vessels open up
2. blood flow through subepicardial layers increases also, however not as much as subendocardial
3. coronary venous outflow falls

Question 7

How is increased oxygen delivery to the heart achieved and why?

Answer 7

Must be met by increased blood flow as heart takes extracts 60-80% of O2 from Hb at rest

Question 8

What’re the major determinants of myocardial oxygen consumption?

Answer 8

1. HR
2. SV
3. Left ventricular contractility
4. systolic pressure (or ‘myocardial wall stress’)

Question 9

The major determinants of myocardial oxygen consumption are SV, HR, L.V. contractility and systolic pressure. A two fold increase in any of these determinants requires a __% increase in coronary blood flow.

Answer 9

50%

Question 10

State the basal myocardial oxygen requirements needed to maintain critical membrane function.

Answer 10

15% of resting O2 consumption (low)

Question 11

t/f: cost of electrical activation is trivial when
mechanical contraction ceases during diastolic arrest and diminishes during
ischemia.

Answer 11

true

Question 12

define coronary autoregulation

Answer 12

the capacity of the heart to maintain steady myocardial perfusion across a range of perfusion pressures

Question 13

Coronary autoregulation - what occurs when pressure falls to the lower limit? What is the lower/ upper limit for coronary autoregulation?

Answer 13

Coronary resistance arteries maximally dilate and flow becomes pressure dependent - end result is onset of sub-endocardial ischemia

MAP of 70-150 mmHg are tolerance limits

Question 14

Resting coronary blood flow under normal
hemodynamic conditions averages __ to
__ mL/min

Answer 14

0.7-1.0 ml/ min

Question 15

By how much may coronary blood flow increase due to vasodilation

Answer 15

4-5 fold

Question 16

The ability to increase flow above resting values in

response to pharmacologic vasodilation is termed what?

Answer 16

Coronary flow reserve

(It’s not really ‘in response to vasodilation’, vasodilation is how it’s achieved, mauro just worded like that bc he is super clever)

Question 17

When are maximal perfusion of heart and coronary flow reserve reduced?

Answer 17

1. Tachycardia - when the diastolic time available for subendocardial perfusion is decreased
2. Preload increase - compressive determinants of diastolic perfusion increased

Question 18

Define coronary flow reserve (real definition, not Mauro’s shitty one)

Answer 18

maximum increase in blood flow through coronaries above resting volume; achieved by vasodilation

Question 19

Other then tachycardia and preload increase, what else may reduce coronary flow reserve?

Answer 19

Anything increasing resting flow…

1. increases in hemodynamic determinants of O2 consumption - systolic pressure, HR, contractility
2. reductions in arterial O2 supply - anemia, hypoxia

Question 20

Subendocardial flow occurs primarily in ____ and begins to decrease below a mean coronary pressure of __ mm Hg.

Answer 20

diastole; 40mmHg

Question 21

Sub-epicardial flow occurs ________ and is maintained until coronary pressure falls below __ mm Hg.

Answer 21

throughout the cardiac cycle; 25mmHg

Question 22

t/f: Epicardial conduit arteries contribute significantly to coronary vascular resistance.

Answer 22

false

Question 23

The net effect of many agonists on coronary arteries is critically dependent upon what?

Answer 23

whether or not a functional endothelium is present

Question 24

What is the most common endothelium-dependent relaxing factor for the dilation of coronaries?

Answer 24

nitric oxide

so drug, ie. ACh –> effects NO in wall –> dilation

Question 25

ACh: a. ) Vasodilation or constriction? b. ) Mode of action on coronaries?

Answer 25

a. ) dilation b. ) 1. ACh release induces... 2. release of NO 3. NO binds to guanylyl cyclase 4. increased cyclic guanosine monophosphate (cGMP) 5. reduction in intracellular Ca+2 thus SM relax

Question 26

resistance arteries are?

Answer 26

arterioles; small diameter BV's

Question 27

resistance arteries are?

Answer 27

arterioles; small diameter BV's

Question 28

When the endothelium of a coronary artery is removed (due to damage), how does ACh effect this vessel?

Answer 28

Instead of dilating it causes vasoconstriction (due to muscarinic receptor)

Question 29

t/f: shear stress and paracrine mediators effect on resistance vessels vary with the size of resistance vessel

Answer 29

true

Question 30

t/f: NO is an endothelium derived constricting factor

Answer 30

false - dilating

Question 31

NO: a. ) What cells produce it? b. ) How is it produced - what enzyme? c. ) Where does it move once it's produced? d. ) Why does it cause SM to relax?

Answer 31

a. ) endothelial cells produce it b. ) type III NO synthase (NOS) c. ) diffuses abluminally (other side BV wall, away from lumen) into vascular smooth muscle d. ) increased cGMP thus decreased Ca+2 relaxes SM

Question 32

How is NO mediated vasodilation affected by cyclic or pulsatile changes in coronary shear stress?

Answer 32

Changes in coronary shear stress enhance NO mediated vasodilation - chronic upregulation of NOS occurs in response to increased coronary flow, such as during exercise

Question 33

How is NO mediated vasodilation affected by CAD?

Answer 33

CAD and risk factors associated impair NO mediated vasodilation of coronary vessels

Question 34

CAD and risk factors associated impair NO mediated vasodilation of coronary vessels - how?

Answer 34

1. CAD/ other things cause oxidative stress 2. oxidative stress produces superoxide anion 3. superoxide anion inactivates NO

Question 35

Other then NO mediated vasodilation, state another endothelium-dependent mechanism for dilation of BV's?

Answer 35

Endothelium dependent hyperpolarisation factor

Question 36

What may stimulate EDHF?

Answer 36

1. selected agonists (ie. bradykinin) | 2. shear stress-induced

Question 37

EDHF: a. ) What's it stand for? b. ) What does it do? c. ) Where is it produced? d. ) How does it bring about it's action - mechanism?

Answer 37

a. ) Endothelium-dependent hyperpolarising factor b. ) Hyperpolarizes vascular SM causing dilation c. ) Endothelium d. ) Opens Ca+2 dependent K+ channels (KCa)

Question 38

State the "hallmark of impaired NO-mediated vasodilation in atherosclerosis, hypertension and diabetes".

Answer 38

superoxide anion (produced due to oxidative stress) inactivates NO, thus impairing ability of BV's to dilate

Question 39

Exact biochemical species for EDHF - what chemical causes it?

Answer 39

Unclear, maybe.. 1. endothelium derived hydrogen peroxide 2. epoxyeicosatrienoic acid

Question 40

Prostacyclin effect on coronaries?

Answer 40

vasodilator

Question 41

Prostaglandins effect on coronaries?

Answer 41

vasodilator

Question 42

By how much must a coronary vessel undergo stenosis until symptoms are felt?

Answer 42

``` 50-60% = may be 80-90% = definitely ```

Question 43

Describe coronary perfusion following total coronary artery occlusion.

Answer 43

Residual perfusion still occurs due to native coronary collateral channels - these open due to development of an inter-coronary pressure gradient (between source and recipient vessel)

Question 44

in most animal species, native collateral flow through coronaries: a. ) Is what % of resting flow? b. ) Is able to maintain tissue for what max time?

Answer 44

a. ) 10% | b. ) 20 mins max, probs less

Question 45

t/f: Little variation is seen in the function of coronary collaterals amongst patients with chronic stenosis

Answer 45

false - it is trememdous how much coronary collateral function varies! In some, coronary pressure falls below 10mmHg. In others (with hella good coronary collaterals), normal resting perfusion is maintained and stress-induced ischemia is prevented

Question 46

Irreversible myocardial injury begins after ___ minutes of coronary occlusion in the absence of significant collaterals

Answer 46

15-20

Question 47

Coronary occlusion causes irreversible injury to myocardium, after 15-20 minutes. a. ) Where does this begin? Where does it progress toward? b. ) Why does it occur this way? c. ) How long does it take for this transmural progression? d. ) What may accelerate this?

Answer 47

a. ) begins sub-endocardial progress to sub-epicardial b. ) this is reflection of... 1. higher O2 consumption in sub-endocardium 2. redistribution of blood to sub-epicardial layers (due to compressive determinants - it's harder to get blood into sub-endocardium) c. ) 4-6 hours d. ) Increased myocardial O2 consumption (tachycardia), decreased O2 delivery (anemia, hypotension)

Question 48

Coronary occlusion causes irreversible injury to myocardium - what may occur before this stage, to reduce this irreversible injury? (hint: counter-intuitive one here)

Answer 48

Repetitive, reversible ischemia resulting in angina before the full occlusion can actually reduce the permanent damage - as it causes preconditioning of the heart! (get used to not having O2 bitch!!)

Question 49

What is Echocardiography?

Answer 49

a test that uses sound waves to produce live images of your heart - kind of like an ultrasound for your heart!

Question 50

What is left-ventricular remodelling?

Answer 50

Surgery to restore natural shape of the heart in those who've had a heart attack

Question 51

Studies suggest that failing human cardiac myocytes undergo a number of changes that might lead toa progressive loss of contractile function, including what? (6, get at least 4)

Answer 51

1. decreased alpha-myosin heavy chain gene expression 2. increase in beta-myosin heavy chain expression, 3. progressive loss of myofilaments in cardiomyocytes 4. alterations in cytoskeletal proteins 5. alterations in excitation-contraction coupling 6. desensitization of beta-adrenergic signaling

Question 52

a. ) What occurs to the left ventricle (LV) during cardiac remodeling? b. ) Why does this occur? c. ) What does this contribute to?

Answer 52

a/b/c.) LV dilates due to changed biology of cardiomyocytes, contributing to heart failure

Question 53

With regard to LV heart remodeling - how does it change the morphology of the heart? is this a good or bad thing?

Answer 53

LV becomes larger and more spherical, bad thing as contributes to heart failure

Question 54

State some mechanical disadvantages due to LV remodelling?

Answer 54

1. increased 'meridional' wall stress (afterload) 2. increased O2 use - energetic burden 3. worsening of hemodynamic overloading etc. (basically fucks up the matching of heart structure to function, contributing to heart failure)

Question 55

The LV becomes more large and spherical due to LV remodeling. a. ) What was it's original shape? b. ) What is the consequence of this change?

Answer 55

a. ) prolate ellipse | b. ) energetic burden for failing heart - exasperates underlying problems it was there to fix