Transcript Aging of Cardiac Muscle and Cardiac Failure

Today 3/20/06
1. Exercise
2. Aging of Skeletal Muscle
3. Aging of Heart
Exercise and Aging
• EXERCISE SLOWS AGING AND
COMPENSATES FOR EFFECTS OF AGING
• WHAT DOES EXERCISE DO?
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Cardiovascular Fitness
Metabolic Fitness—Obesity and diabetes protection
Muscular Strength
Anti-oxidant defenses
Freedom from Injury—bones and muscles,
osteoperosis
– Sense of Well Being
Measuring CV fitness
• Cardiovascular Fitness
– Exercising prevents CV disease and death from disease
– VO2 Max (Maximal oxygen consumption) declines
with aging and is increased by regular exercise
– VO2 Max is higher in trained elderly person.
– VO2 Max declines with age in both a trained and
untrained elderly person to become almost equal.
Metabolic Fitness
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Control age related increases in body fat
Decrease risk of diabetes
Maintain Ideal BMI
Exercise at 45-50% of VO2 Max to facilitate fat
loss and then start to metabolize carbohydrates
(cross-over concept)
Muscles
There are 660 skeletal muscles in adult humans
These constitute 45% to 50% of the normal body weight
Their primary purpose is to provide “MOTILITY”
In addition, they represent the major site for:
- energy transduction
- energy storage
- primary support system
Anatomy
• 2 membranes surround the muscles:
– outer membrane: the basement membrane (very permeable to
solutes and proteins or to other metabolites)
– inner membrane: SARCOLEMMA is located just beneath the
plasma membrane (a true cell boundary)
• An intact sarcolemma is critically important:
– it maintains a proper acid-base balance of the fibers
– propagates the action potential (starting at the neuromuscular
plaque leading to the muscle contraction)
Contraction
The actors:
• Ca++ passes through the sarcolemma; in its presence there is
hydrolysis of ATP (ADP+P) which releases energy
• ADP binds to ACTIN: meanwhile, a regulatory protein (enzyme)
TROPONIN (activated by this energy) binds to MYOSIN
forming TROPOMYOSIN--shifting the ACTIN helix and
leading to CONTRACTION
End result: the ACTOMYOSIN complex
• Contraction could involve lengthening or shortening
mechanisms, depending on the movement pattern
• MEMO the TETANIC contraction
SARCOPENIA:
Loss of muscle tissue
Most significant physiological change in muscle is with AGE
Looking at muscles, fat and bones, we see that:
At age 20, muscles are 45%, fat 20% and bones 12% of
the total weight
At age 75, muscles are 15%, fat 40% and bones 8%
After age 49, there is a loss of 1.2 kg (3lbs) of muscle per
decade
DURING SARCOPENIA:
The loss appears to be more significant for the FAST
FIBERS type 1 and 2 (or FO and FOG) while the SLOW
FIBERS (or SO) are more stable.
This fact clarifies at least in part why a 9-year-old
grandson can beat grandpa easily in a 100m run but
will tire much sooner in a 10km hike.
Reminder: The fast fibers (normally more pale) fatigue
more easily while the slow (more red) are more resistant
to FATIGUE.
THE ETIOLOGY of SARCOPENIA due to
a) inactivity
b) decreased protein synthesis
c) plus neural, hormonal and nutritional factors
SARCOPENIA is aggravated:
by the relative deficiency of the anabolic hormones (GH, Insulin-like
GH, DHEA)
BUT and AGAIN
of greater importance is the DECREASE of VIGOROUS MUSCULAR
WORK
Any acute illness forcing elderly persons to bed rest is provoking a
loss of muscle mass of about 1.5% per day
Hence for 1 day of bed rest, up to 2 weeks of intense reconditioning
is necessary.
Sarcopenia harder for the FAST PALE FIBERS,
but why?
WE DO NOT KNOW
but…
fiber characteristics can be modified by different
modalities like hormonal administration and/or by specific
exercises or activities
The change in the fiber characteristic is defined as
MYOPLASTICITY
MYOPLASTICITY
May occur with different clinical effects,
namely:
-muscles enlarge with resistance type of exercise
-increase their contractility (and the number of
mitochondria) with endurance type of exercises
-all these changes are due to stimulations and variations in
the characteristics of the MYOSINS (protein isoforms)
CLINICAL significance of Myoplasticity:
RESISTANCE training: increases amount of contractile
proteins permitting increasing efforts.
As a consequence, muscles do ENLARGE (a decrease in Ca++
concentration is needed to elicit 50% of maximal tension).
ENDURANCE training: increases the velocity of contraction,
increases the number of mitochondria, and increases the capacity to
oxidize substrate
•Increase the Vmax (velocity of contraction) of the SO (slow) fibers
•Decreases the Vmax of the FO (fast) fibers
•Vmax = velocity of shortening of a fiber
BENEFITS OF EXERCISE TRAINING
(see lecture by Prof. Brooks)
• Prevention of bone loss
• Improvement of postural stability
• Psychological benefits are to be added like preservation of
cognitive functions, reduced incidence of depression and enhanced
self-efficacy.
• Prevention of colonic cancer possibly due to increased GI transit time
and stimulation by GH and IGF-1.
CLEAR BENEFITS OBTAINED WITH EXERCISE:
• Metabolic: increased insulin sensitivity and glucose tolerance.
• Cardiovascular: reduces blood pressure, helps vasodilation,
reduces incidence of arrythmias
•Cerebral: enhanced brain blood supply and reduced episodes of
thrombosis
• Improved equilibrium hence fewer falls
• Lower mortality rate
• Higher HDL/LDL ratio
Aging of Cardiac Muscle
and
Cardiac Failure
In absence of specific disease the heart adjusts
very well to advancing age.
Physiological Changes with Age: exercise and diet
are important!
Parameter
20 years
60 years
VO2 Max (mL x kg x min)
39
29
Maximum Heart Rate
194
162
Resting Heart Rate
Max. Cardiac Output (L x min)
EJECTION FRACTION
63
22
70-80%
62
16
50-55%
Resting BP
Total Lung Capacity (L)
120/80
6.7
130/80
6.5
Vital Capacity (L)
5.1
4.4
Residual Lung Volume (L)
1.5
2.0
Body Fat %
20.1
22.3
Blood Pressure Physiolgic Changes with Age
Hypertension: most common treatable cardiovascular change in the elderly
Definition: values above 140/190
In young, if standing BP
but in elderly it may to 20 mmHg
Orthostatic hypotension: drop of 20 mmHg in the systolic and 10 or
more in the diastolic BP on standing upright
Pathology of the Aging Heart
Changes due to:
• Normal Aging Processes
• Superimposed Processes
(i.e. endocarditis)
• Residuals of other conditions
(i.e. hypertension, bicuspid, aortic valve
Pathological Changes of the Aging
Heart
• Size: can atrophy, remain unchanged or develop
moderate hypertrophy.
• Cardiac myocytes: in size, not numbers (some
replaced with fibrous tissue). Cardiac myocytes
effective in reentering the cell cycle & proliferating,
partly offsetting cell loss due to necrosis or apoptosis.
• Amyloid deposition: half of those +70 years have some
amyloid deposits in the heart but mostly in small
amount & confined to the atria.
• Vasculature (atherosclerosis) Walls of large arteries
thicken, vessels become dilated and elongated. Increase
intimal thickness (due to cellular and matrix deposition)
Pathological Changes Continued
• Aortic Stenosis: Narrowing of the aortic
orifice of the heart or of the aorta itself. Due
to fatty alteration of collagen, calcification,
rigidity and various degrees of aortic
stenosis, amyloid infiltration of the valves
• Valves of heart become thickened and
calcified. Complications include heart
block, infections and embolic events
Heart Failure:
Cardiac Output (CO) insufficient to meet physiologic demands
In the elderly, heart failure due to:
• Mostly systemic arterial hypertension
• Coronary artery & valvular diseases (due
to impaired cardiac filling & chronic
volume overload)
• Combined right & left cardiac failure
most common, but isolated occurrence of
left or right also probable
Contributory Causes to Heart Failure in the Elderly
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Hypertension (poor elasticity of arterial system)
Alcohol, but only if in excess
Viral infections
Autoimmunity
Heredity (specially for the cardiomyopathies)
Senile amyloid
Diabetes (due to the microvascular disease)
Arrhythmias and especially the TACHYCARDIAS
Heart Failure in the Elderly
• Symptoms: dyspnea, orthopnea, fatigue on
exertion and dependent edema
• Severity: classified according to the NY Heart
Association Scale
Cardiomyopathy: Any heart muscle disorder not
caused by coronary artery disease, hypertension or
congenital valvular or pericardial diseases.
Prevalence of heart failure:
25-54 yrs: 1%
55-65 yrs: 3%
65-74 yrs: 4.5%
+75 yrs: 10%
• > 75% of patients with heart failure +60 years of age
•Primary reason is Coronary Heart Disease (CHD)
•Secondary reason is Hypertension
•Third reason is cardiomyopathy
Dilated
Cardiomyopathy
Normal Heart
Hypertrophic
Cardiomyopathy
Normal Heart
Restrictive
Cardiomyopathy:
The classic example
is the senile cardiac
amyloidosis of the
elderly, especially
over 95 years old.
Normal Heart
Sudden Death from a
cardiomyopathy
• In young athletes (also in middle aged men),
SUDDEN DEATH can occur in patients with
congenital hypertrophic cardiomyopathy
– Usually due to severe arrythmia (ventricular fibrillation)
– If diagnosis is made a cardiac defibrillator should be
implanted.
• The SUDDEN DEATH of runners are usually limited
to 1 case per 15,000 runners per year-- hence, very
rare.
• MEMO: There is still the possibility of
ANAPHYLACTIC SHOCK in runners or walkers, if
stung by a bee.
Syncope in Elderly
Definition: temporary suspension of consciousness due to
cerebral ischemia
Causes
• Orthostatic Hypotension
• Vaso-Vagal Reflex (?)
• Arrhythmias (brady- & tachyarrhythmias)
• Drugs
– Antihypertensives (vasodilators/diuretics)
– Cardiac drugs: beta-blockers, digitalis, anti- arrhythmias, Ca+2
channel blockers, nitrates.
– Recreational: alcohol, marijuana and cocaine.
– Psychiatric: Antidepressants and phenothiazines
Conduction System in Aged Heart
• Sinoatrial Node: Increased fibrous tissue; seldom origin for
arrythmias
• Atrio-Ventricular Node: Slight increase in collagen fibers
• Bundle of His: Increased fibrous tissue with higher
frequency of First or Second degree heart block (the
mobitz)
• Also the possibility of: L or R BBB (Bundle Branch Block)
-this is seldom a complete heart block.
• In the conduction system fibrosis occurs: 40%
– Coronary Artery Disease : 20%
– Calcification : 10%
Normal ECG
Ventricular
Fibrillation
Atrial
Fibrillation