Preload, Afterload, and Contractility Alter Systolic Arterial Pressure and Stroke Volume (Homsher)

Question 1

Isometric force

Answer 1

Pressure the heart develops during systole when ejection is prevented (when both valves are closed, so there is no change in volume)

Question 2

When muscle diastolic length (sarcomere length, or preload) increases, what happens to systolic force?

Answer 2

Increases too!

Length proportional to Force produced

Question 3

Two mechanisms that describe why increased length of sarcomere means increased force

Answer 3

1) Longer sarcomere has more cross bridge attachment sites available on thin filament (less over lap) (MINOR mechanism–20-40%)
2) Longer sarcomere’s troponin has higher affinity for Ca2+ (MAJOR mechanism–60%). Probably because when troponin spread out, it has conformational change that makes it want to bind Ca2+ better. Could be because titin pulls thick and thin filaments closer to each other when sarcomere streched.

Question 4

Two physiological functions of Starling Length-Tension curve

Answer 4

1) Assure that output of left and right hearts are matched
2) Starling mechanism is needed to overcome LaPlace’s demand for wall stress OR pressure to increase when preload (radius) is increased. Starling ensures that systolic force (wall stress) actually increases A LOT (more than required by LaPlace) when radius increases. We generate a lot more stress during systole than LaPlace wants, because of Starling.

Question 5

Since we can’t measure end-diastolic sarcomere length, what do we measure instead?

Answer 5

1) Right ventricle end diastolic pressure (normal: 2-8 mmHg)
2) Left ventricle end diastolic pressure (normal: 4-12 mmHg)

These correspond to sarcomere lengths of 1.9-2.2 um

Question 6

What factors control preload (aka end-diastolic wall STRESS)

Answer 6

1) End diastolic radius (r)–Compliance of ventricle
2) End diastolic filling pressure (P)–Blood vol, atrial contraction, venous compliance, peripheral resistance, venous return
3) Myocardial wall thickness (H)–Normal growth, compensatory hypertrophy

Question 7

Since we can’t measure systolic wall stress, how do we measure afterload?

Answer 7

Arterial blood pressure

Systemic vascular resistance (if catheterization used)

Question 8

What factors control afterload (aka systolic wall stress)?

Answer 8

1) Ventricular systolic radius (r)–End diastolic radius (bigger radius means bigger afterload)
2) Ventricular systolic pressure (P)–Systemic arterial pressure (increased SVR, blood vol, decreased arterial compliance all increase afterload), output resistance (valvular resistance or obstructive cardiomyopathy)
3) Myocardial wall thickness (H)–Normal growth, compensatory hypertrophy

Question 9

How does length of sarcomere influence rate of shortening?

Answer 9

Shorter sarcomeres get shorter at a SLOWER rate

Also generates force for shorter time

This shorter sarcomere causes a smaller stroke volume!

Obvi: smaller pre-load means lower stroke volume!

Question 10

How does stress relate to number of cross bridges formed?

Answer 10

More stress means more cross bridges formed

Question 11

Sympathetic stimulation causing a positive inotropic effect causes 5 important changes

Answer 11

1) Increased isometric force
2) Increase rate of rise of force during isovolumic contraction
3) Increased rate of shortening at beginning of ejection
4) Increased extent of shortening (so SV increased and EDV decreased!)
5) Reduced duration of contraction-relaxation cycle

Question 12

Sympathetic stimulation causing positive inotropic effect causes 5 changes in cardiovascular performance

Answer 12

1) Increased EF
2) Increased rate of rise of pressure during isovolumic contraction
3) Increased rate of rapid ejection
4) Increased SV and CO
5) Increased arterial pulse pressure

Question 13

What does ischemia do to the heart OVERALL?

Answer 13

Reduce amount of Ca2+ released by SR

Slow Ca2+ removal by SR

Reduce amount of Ca2+ bound to troponin following release

Inhibit cross bridge power stroke

Slow cross bridge detachment from thin filaments

Question 14

What does ischemia do to the heart ACUTELY?

Answer 14

Reduced ability to re-synthesize high energy phosphate needed for contraction/relaxation

Switch to glycolytic metabolism

Reduced intracellular ATP and pH (increased H+ competes with Ca2+ for troponin and now Ca2+ doesn’t bind to troponin as much)

Increased Pi

Inhibition of Na/K pump

Inhibition of SR Ca2+ pump

Question 15

Ischemia causing a negative inotropic effect causes 5 important changes

Answer 15

1) Decreased maximal isometric force
2) Decreased rate of rise of the force during isovolumic contraction
3) Decreased rate of shortening
4) Decreased extent of shortening
5) Increased duration of contraction-relaxation cycle

Question 16

Ischemia causing negative inotropic effect causes 5 changes in cardiovascular performance

Answer 16

1) Decreased EF
2) Decreased rate of rise of pressure durin isovolumic contraction
3) Decreased rate of rapid ejection
4) Decreased CO
5) Decreased arterial pulse pressure

Question 17

What can affect ejection fraction, rate of rapid ejection and CO?

Answer 17

1) Inotropic effects (sympathetic stimulation vs. ischemia)
2) Preload
3) Change in systemic vascular resistance

Question 18

What can affect rate of rise of pressure during isovolumic contraction, arterial pressure?

Answer 18

1) Inotropic effects
2) Preload

Question 19

When you increase afterload, what happens to muscle/ventricle?

Answer 19

Shortens/contracts more slowly

Ejects less blood

Question 20

As sliding speed increases, what happens to cross bridges?

Answer 20

As sliding speed increases, the number and and amount of force exerted by attached cross bridges decreases

So, cardiac wall stress decreases as sliding speed increases

The smaller the load, the faster the muscle shortens