Cardiac Muscle

Cardiac Muscle

thin = acTIN

thick = myosin 

cross bridge = myosin globular head + actin - MEDIATED BY TROPONIN C-ACTIN

inside myocyte

• CICR - CONTRACTION  ryanodine receptor  (blocked by dantrolene in malignant hyperthermia)
• SERCA - RELAXATION
• Na - Ca exchanger - relaxation = Ca extrusion from cell
• Ca atpase = relaxation
• phase 3 - reduced Ca influx

ca channel blockers affect cardiac muscle but not skeletal - why?

ANS regulates heart rate

actual HR of 60 but intrinsic HR (all ANS receptors blocked) = 110  due mainly to PNS dominance

ANS regulates contractility

SNS increases via Gs 

cAMP PKA 

• ca influx
• phosphorylates ryanodine receptors
• phosphorylates phospholamden = increased serca = faster relaxation

PNS

• inhibits sns pathways via Gi
• inc. Kach channel = hyperpolarize

signal transduction pathways in heart

RV cardiac (Qp) output always equals LV cardiac output (Qs) unless there is an intracardiac shunt.  If right to left shunt is present Qs > Qp.  If left to right  shunt is present, Qp > Qs.  more on this to come.

Cardiac electrophysiology

Cardiac electrophysiology



2 billion heart cells
100,000 beats per day
<50 cells can produce arrythmias

gap junctions = connexins

• 2 um gaps
• modulated by Ca, pH, neurotransmitters, etc

anisotropy = longitudinal conduction/transverse conduction = nl = 3

av node slows conduction (giving time for ventricles to fill) - slows even more at higher hr (decremental conduction)  e.g., atrial flutter with atria rate of 300 bpm has ventricular rate of 150 bpm, not 300.

sa node 

• connected to left atrium by Bachmann's bundle
• sick sinus syndrome - too slow hr  (may need pacemaker)

bundle branchs

• left - more robust - essential
• right - less essential

pace making

• sa>av>HIS>ventricular escape
• overdrive suppression = faster pacemaker dominates

EKG

• bipolar - I,II,III
• unipolar
• aVR, aVF, aVL
• precordial
• V1, V2  RV
• V3 - V6 LV
• mean electrical axis (nl = -30 to +90 degees)
• determined by vector analysis
• right axis deviation 
• left axis deviation

Conduction Intervals

• PR - from P to Q (since Q may not br present in some leads)
• P
• QT - changes with heart rate  - longer with slow hr
• corrected for hr by Bazett formula  QTc = QT/sq.rt. RR
• quick method = if QT is > .5 RR, QT is abnormally long
• long QT interval
• polymorpic ventricular tachycardia (Torsade de Pointe)
• hr too high for filling - sudden death
• may be drug induced (e.g., tricyclic antidepressants)
• may be channelopathy (genetic)

heart rate

5 big boxes = 1 sec

1 big box = 1/5 sec

instead of memorizing, go from 1 box to next:

if R-R interval = 1 small box, hr is 5 beats/sec = 300 bpm 

if R-R interval = 2 small boxes, hr is 1/2 as fast = 150 bpm

if R-R interval = 3 small boxes, hr is 1/3 as fast = 100 bpm

if R-R interval = 4 small boxes, hr is 1/4 as fast = 75 bpm

if R-R interval = 5 small boxes, hr is 1/5 as fast = 60 bpm

if R-R interval = 6 small boxes, hr is 1/6 as fast = 50 bpm

if R-R interval = 7 small boxes, hr is 1/7 as fast = 43 bpm

if R-R interval = 8 small boxes, hr is 1/8 as fast = 37 bpm

mean electrical axis nl range = -30 to +90 degrees

if aVf and I have positive R wave axis is 0 to + 90 degrees (within nl range)

if aVf is negative and I is positive, could still be normal.  Use lead II to decide.

if I and II are positive, axis is between -30 to 90 degrees = normal.

Cardiac myocytes

Vagus input hyperpolarizes SA node - slow heart rate even with constant slope.
     
autonomic input affects both slope of phase 4 AND slope of phase 0 in SA node;  chronotropic and dromotropic effects (rate and conduction speed)

Parasympathetic (vagal) activation, which releases acetylcholine (ACh) onto the SA node, ALSO decreases pacemaker rate by increasing gK⁺ and decreasing slow inward gCa⁺⁺ and gNa⁺; the pacemaker current (I_f) is suppressed.  These ionic conductance changes decrease the slope of phase 4 of the action potential, thereby increasing the time required to reach threshold. Vagal activity also hyperpolarizes the pacemaker cell during Phase 4, which results in a longer time to reach threshold voltage.

total conduction time = 210 msec. = systole  at hr of 60 bpm there is one beat per sec.  so, diastole (filling) lasts 790 msec.  importance = higher heart rates reduce time of diastole (systole does not change).  danger of tachycardia in patients = reduced filling.

FIGURES TO SUPPLEMENT LECTURE