19) **** Cardiovascular Remodeling **** Flashcards
What is Cardiac Remodeling? (EICR?)
What is it caused by?
Cardiac remodeling → a group of molecular, cellular and interstitial changes that manifest clinically as alterations in the size, mass, geometry and function of the heart after a stressful stimulus (ie changes in left ventricular geometry)
Exercise-induced cardiac remodeling (EICR)
- Due to ↑ pressure & volume (load)
- Results in ↑ muscle mass
- ↑ in cardiac myocyte size (hypertrophy)
Heart adapts to sustained ↑BP or Volume by increasing mm mass
- Cross-sectional data and longitudinal studies have demonstrated that endurance- and strength-based exercise leads to divergent forms of EICR (months/years of training)
Athletes Heart?
Athlete’s heart → a constellation of structural and functional changes that occur in the heart of people who train for prolonged durations (ie.>-1 hour most days) and/or frequently at high
intensities
- No tx necessary (must r/o serious cardiac disorders)
Changes are usually asymptomatic, signs include:
- bradycardia (↓HR)
- systolic murmer
- extra heart sounds
- ECG abnormalities
Physiological not pathalogical changes
Physiological vs Pathological Cardiac Hypertrophy
Physiological cardiac hypertrophy → associated with normal or enhanced cardiac function
- Reversible
Pathological cardiac hypertrophy → occurs in cardiovascular disease (e.g., hypertension), can ultimately decompensate to heart failure
- Irreversible
- Cell death and fibrosis (collagen in heart prevents gas/nutrient exchange and blocks AP leading to electrical abnormalities)
-Hypertrophic cardiomyopathy (HCM)
* Heritable disease caused by mutations in sarcomeric proteins that can progress to heart failure
Cardiovascular Responses to Exercise
Main Haemodynamic features:
Physical exercise is associated with ? changes and alters the ? conditions of the heart
Physical exercise is associated with haemodynamic changes and alters the loading conditions of the heart
Exercise stress on body → ↑Load
↑CO in athletes → ↑ Blood returning to heart
Dynamic exercise: movement with no or minimal development of force (ie. endurance running)
-Main haemodynamic features:
* Increases in heart rate and stroke volume
* Systemic vascular resistance decreases but the net result is a slight to moderate** rise in blood pressure**
- Load on the heart is predominantly that of volume
Static exercise: force is developed with no or minimal movement (ie weight lifting)
-Main haemodynamic features:
* Slight elevation of cardiac output, caused by the increase of heart rate
* More pronounced rise of blood pressure
* Load on the heart is predominantly that of pressure
Haemodynamic changes in Dynamic exercise vs Static Exercise
Dynamic exercise: movement with no or minimal development of force (ie. endurance running)
-Main haemodynamic features:
* Increases in heart rate and stroke volume
* Systemic vascular resistance decreases but the net result is a slight to moderate** rise in blood pressure**
- Load on the heart is predominantly that of volume
Static exercise: force is developed with no or minimal movement (ie weight lifting)
-Main haemodynamic features:
* Slight elevation of cardiac output, caused by the increase of heart rate
* More pronounced rise of blood pressure
* Load on the heart is predominantly that of pressure
What are the limits of Athlete’s heart?
- LV wall thickness >13mm uncommon and is associated w/ an enlarged left ventricular cavity (chamber enlarged)
- Upper limit to which the thickness of LV wall may be increased is 16mm
Normal LVWT: 7-11mm
Mild LVWT: 11-13mm
Moderate LVWT: 14-15
Sever LVWTL >15mm
CV responses to exercise
CV responses to Strength-based exercise?
Strength-based exercise (eg. weightlifting, wrestling):
* Large ↑ in systemic arterial pressure
* Systolic/diastolic pressure: very high during concentric contraction, decline during eccentric contraction
Can reach BP as high as 480/350
Changes in heart rate, oxygen uptake, and left ventricular mass were observed only with 3 or more hours of exercise per week
* Regular exercise for long duration/high intensity may result in CV changes
* Athletic conditioning is rarely purely dynamic or static
(Strength) Exercise-Induced Cardiac Remodeling (EICR)
How does the structure of the heart change in response to Chronic Strength (static) training?
Strength based (static):
-Concentric LV Hypertrophy
- Due to increases in pressure load (heart adapts by ↑wall thickness)
- LV wall thickening and minimal LV dilation (chamber size relatively unchanged)
- Mild LA Hypertrophy
- Increased LV wall thickness due to parallel add’n of sarcomeres
- Reversible
Endurance-based exercise (distance running/swimming)
- Eccentric LV Hypertrophy
- Due to ↑ Volume Load
- LV dilation and proportional LV wall thickening
// - dilation due to increase in longitudinal dimension of cardiac myocytes (sarcomeres added in series)
- Mild RV dilation
- Bi-atrial enlargement
- Reversible
- Changes in structure enhance CO to meet demands of training
(Endurange) Exercise-Induced Cardiac Remodeling (EICR)
How does the structure of the heart change in response to Endurance (Dynamic) training?
Endurance-based exercise (distance running/swimming)
- Eccentric LV Hypertrophy
- Due to ↑ Volume Load
- LV dilation and proportional LV wall thickening
// - dilation due to increase in longitudinal dimension of cardiac myocytes (sarcomeres added in series)
- Mild RV dilation
- Bi-atrial enlargement
- Reversible
- Changes in structure enhance CO to meet demands of training
Strength based (static):
-Concentric LV Hypertrophy
- Due to increases in pressure load (heart adapts by ↑wall thickness)
- LV wall thickening and minimal LV dilation (chamber size relatively unchanged)
- Mild LA Hypertrophy
- Increased LV wall thickness due to parallel add’n of sarcomeres
- Reversible
ECG and the Athlete’s Heart
Conduction/rhythm abnormalities associated with Athlete’s heart (ECG)
Athlete’sheart:
* High intensity dynamic endurance sports are usually associated with electrocardiographic rhythm and conduction abnormalities
* Structural cardiac adaptations and parasympathetic predominance induce morphological changes of the QRS complex, repolarisation abnormalities
Several ECGs may mimic cardiac disease
- Factors which play a role in these changes:
- A lower intrinsic heart rate,
- increased parasympathetic/vagal tone,
- decreased sympathetic tone,
- structural cardiac adaptations, and
- non-homogeneous repolarisation
of the ventricles
Is Athlete’s Heart Physiological?
Does long term high-intensity exercise cause pathological changes in the heart, or is athlete’s heart strictly physiological?
Long-term, high-intensity exercise training does not cause pathological LV remodeling, cardiac dysfunction or adverse clinical events; effects are reversible with detraining
* A threshold may exist above which exercise training may increase the risk of arrhythmias
or sudden cardiac death (SCD)
The Diseased Heart Vs the Athletes Heart
Changes in the heart associated with:
- Endurance training
- Strength Training
- Combination training
Endurance Training:
- Increased LVWT
- significant dilation of LV
Strength Training:
- Increased LVWT
- Mild-Moderate LV dilation
Combination:
- Greatest degree of LVWT and
- LV dilation
How does IGF1 mediate exercise induced cardiac hypertrophy?
IGF1 -> Hypertrophy
* Activation of IGF1R leads to downstream signaling events including activation of PI3K and Akt1 (mediators of cell growth and survival)
What is the proposed IGF-1 pathway for athlete’s heart?
Athlete’s heart:
* IGF-1increased in athlete’s heart
* IGF-1 binding to receptor activates PI3K (p110α)
* PI3K (p110 α) → lipid kinase; phosphorylates lipids in the plasma membrane to form phosphatidyl-inositol 3,4,5-trisphosphate (PIP3)
* PIP3 (2nd messenger) activates Akt1
* Akt1 is a kinase that increases protein synthesis
- Akt1 knockout mice: blunted hypertrophic response to a physiological stimulus (swim training) and an accelerated heart failure phenotype in response to a pathological stimulus (pressure overload)
Stimuli for Pathological Hypertrophy and HF
Pathological Hypertrophy mediated by upregulation of which hormones?
Pathological hypertrophy:
* AngII and ET-1 secreted from cardiac myocytes due to
mechanical stress (stretch due to pressure overload)
* Pro-hypertrophic hormones that are upregulated in heart failure but not in the athlete’s heart
* Ang II and ET-1 signal by binding to GPCR
* Inhibition of GPCR signaling in transgenic mice blocked pressure overload-induced hypertrophy
* Calcineurin activity was elevated in hearts of patients with LV hypertrophy and heart failure
HCM due to mutations in sarcomere leads to problems with contractile proteins -> Heart failure
