Pathophysiology of Heart and Circulation (AP_1015)
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Lecture 2 Cardiac energetics
Chapter 1
Cardiac arrangement
Pulmonary and systemic circulation. Across species there are different adaptations, not always a
septum. Crocodile has shunt in heart, when it goes into the water, no longer a pulmonary circulation
because lungs cannot take up any oxygen.
Oxygen is needed to fuel the sarcomeres = smallest contractile unit requires ATP. Stimulus from
outside causes depolarization of muscle cells. Release of calcium from the sarcoplasmic reticulum,
through RYR and binds to troponin moving tropomyosin away and letting actin and myosin bind.
Calcium needs to be reuptake by SR, actively done through SERCA pumping, which requires lots of
ATP. Myosin detachment from actin also requires ATP for relaxation.
Myocardial energetics
During the ventricular systole a lot of work needs to be done to push the heart
into the arteries. Internal work = work per heartbeat. Formula for this is:
Internal work = stroke volume x mean pressure
Metabolic work = oxygen uptake by cardiac muscle, coronary blood flow.
Myocardial efficiency = internal work / metabolic work
This is usually a low value around 25% because majority of energy is converted
into heat. In severe heart failure, the myocardial efficiency can drop to <10%, due
to mitochondrial dysfunction. This causes less ATP present for sarcomeres and
SERCA and therefore decrease in cardiac output. Compensatory mechanisms do
not work in long run and oxygen not fully reduced, causing ROS for more damage
into vicious cycle.
Research techniques
In vivo techniques to study metabolic function:
Metabolic treadmill running performance by respiratory exchange ration CO 2 / VO2
o RER = 0.7 main fuel fatty acids
o RER > 1.0 main fuel glucose
PET / MRI measure MVO2 and cardiac work, can also be used in skeletal muscles
In vitro techniques to study function:
Ouroboros respirometry measure respiration by mitochondria in piece of muscle put in
ATPase activity measure how much ATP myosin needs to detach
Histologic enzymatic assay on muscle cryosections to determine NADH and SDH activity
by staining
, Lecture 3 Arrythmias
Cardiomyocytes contract upon stimulation by action potential. Occurs by excitation-contraction
coupling. Sodium an calcium are the depolarizing factors, potassium is for repolarization of the cells.
Calcium entering the cell start a process of the secondary calcium release from the sarcoplasmic
reticulum = calcium induced calcium release (CIRC). The calcium then binds to myofilaments giving
power stroke. After this there is reuptake of calcium in SR because it is released
from the myofilaments.
ECG
The signal of the heart beat starts in sinoatrial node atrioventricular node
AV bundle bundle branches purkinje fibers. The ECG has different parts:
P-wave = depolarization through atria
PR-interval = conduction through AV node
QRS = depolarization ventricles and repolarization atria
T-wave = repolarization ventricles
The ECG has 12 different leads, Einthoven’s triangle has the first three. Lead 1 = right arm – left arm,
lead 2 = right arm – left leg, lead 3 = left arm left leg. These are for the determination of the frontal
plane, for this also the aVR (right arm), aVF (left foot) and aVL (left arm) are used. The precordial
leads and allow a 3D construction going from right to left. V1 – right atrium, V2 – right ventricle, V3 –
right ventricle, V4 – septum, V5 – left ventricle and V6 – left ventricle
Arrhythmia 1. A-
fib, 2. V-fib
The sinus rhythm = normal rhythm, started in the SA-node. In the assessment of an ECG looks at:
rhythm, frequency, conduction times, heart axis, P-wave, QRS complex and ST morphology. Some
abnormal rhythms are: bradycardia < 60, tachycardia > 110. An irregular rhythm can be atrium
fibrillation = chaotic depolarizing atrium and conduction through AV node not regular (PR-interval)
no p wave, increases risk on stroke. Treatment with blood thinners (prevent stroke) and
defibrillation.
Ventricular fibrillation = heart does not pump efficiently, causing immediate collapse. Can be caused
by commotio cordis blunt object strikes chest just above the heart during the initial repolarization
phase this can trigger V-Fib. Treatment is with defibrillation also an ICD = implantable cardioverter
defibrillator can be placed at high risk for repeated V-fib.
Myocardial infarction can be detected by an ST-elevation in lead 2, caused by no electrical
difference, all cells in same state. Ischemic part does not undergo action potential. Treatment of this
can be with PCI and stent used to reopen the blocked coronary artery.
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