Cardiac Muscle:

• Cardiac Muscle Tissue:

○ Cardiac Myocyte
○ Endothelia cells
 Referred to as endocardium
○ Cardiac fibroblasts
• Cardiac Myocyte:
○ Features similar to Skeletal Muscle:
 Each cardiac myocytes is surrounded by a basal lamina
 Striated
 Similar mechanism of contraction
○ Features different from skeletal muscle:
 Involuntary
 Smaller (Micrometers, not millimeters)
 Nucleus is centrally located
• 1-2 nuclei per cell (not 100’s)
 Cardiac cells bifurcate
 Highly vascularized
 MB-creatine kinase (compared to MM-creatine kinase)
• High levels are indicative of a heart attach
 Cross-striations faint
 Myofibrils are barely discernable
○ Differences at the electron microscopic level
 Highly enriched in glycogen, myoglobin and mitochondria
 Triads are replaced with dyads:
• Located at the Z-line (not A-I jxn)
 Intercalated discs (know ultrastructure)
• Intercellular attachments cause cardiac myocytes to work
together
• Behaves like a synctium but isn’t
• Transverse part:
○ Transmits force of contraction
○ Half a z band, consists of:
 A fascia adherens (does not encircle cell)
 Desmosome (macula adherens)
○ Actin filaments butt into half Z bands (reminiscent
of zonaula adherens)
 N-cadherins are present
• Lateral Part:
○ Of the intercalated disk fxns in cell-cell signaling:
 Via nexuses (gap jxns)
• Maintain rhythmicity of heatbeat
 • Made up of connexins
○ Has desmosomes
• Regional differences among cardiac myocytes:
○ Atrium:
 Fewer t-tubules, smaller than ventricular myocytes
 Atrial Natriuretic Factor
• Membrane-bound granules near nuclei
• Causes kidney to excrete water and sodium
 Right Atrium
• SA and AV nodes
○ Nodal myocytes are very small and embedded in
dense CT
○ Few myofibrils and are adapted for impulse
propagation
 AV bundle of his
• Large purkinje myocytes
• Few myofibrils
• Copious glycogen
• Inconspicuous intercalated discs
• Development of purkinje fibers
○ Endothelia cells in coronary arteries secrete endothelin
 Induces cardiac myocytes to differentiate into purkinje cell fibers
• Endocardium
○ Lining of cardiac endothelial cells
○ Simple squamous epithelium
○ Lines all chambers of the heart
○ Continuous with endothelium lining the vascular system
• Cardiac fibroblasts
○ Most abundant cell type in the heart
• Cardiac Mycocyte Energy Requirements:
○ Triglycerides are major fuel
 Stored in membrane bound lipid droplets near nucleus
 Cardiac myofibers occupied by mitochondria
• 20X higher than skeletal muscle
 Heart continuously operates as an aerobic organ
• High myoglobin, mitochondria and rich vascular supply
enable this.
• Clinically relevant differences between cardiac and skeletal myocytes:
○ MB-CK, high serum levels of this enzyme is diagnostic of a myocardial
infarction
 Located in M line
 ○ Skeletal muscles have mm-ck (diagnostic of skeletal dystrophy
 Located in M line
○ Troponin-I has diagnostic value for cardiac muscle
• Cardiac Myocyte Innervation
○ Vagus and autonomic nerves modulate heart rate
○ Heart will beat without nervous stimulation
• Chronology of heart attack:
○ Myocyte death begins immediately, apoptosis/necrosis begin
○ Inflammation occurs 12-16 hours lateractivates cytokine release
○ Wound healing begins after 48-72 hours
 Collagen III then collagen I is secreted and deposited
○ Angiogenesis begins within 48096 hours
○ Scar formation ensues
 Mediated by lysyl oxidase
• Inhibiting this would prevent scarring
• Management of cardiac-insufficient patient:
○ Re-muscularized via transplantation of patient matched pluripotent
cells and multipotent resident adult stem cells
○ Re-musculariztion via proliferation of healthy resident cardio myocytes:
g0prolifertionre-muscularzation.
○ Cardiac myocyte regernation
 Hypertrophy
• Bad type: stress induced by chemical insult or high blood
pressure
○ Pathological hypertrophy—re-expression of
embryonic cardiac genes.
• Good: seen in athletes
 Ischemic Injury
• Interruption of blood supply that results in myocyte death
• Possible sources of myocyte replacement:
○ Cardiac fibroblasts—heal the wound of infarction
 Creates non-contractile scar
 Researchers speculate that fibroblasts serve as a reservoir of
myocyte stem cells
 Not a likely source of myocyte replacement
○ Stem Cells
 Embryonic
• Requires transplantation
 Adult
• May or may not require transplantation
• May originate from bone marrow or heart
 • Whether or not they can differentiate into functional
cardiomyocytes is controversial
• Transplanted hearts accumulate cardiac myocytes while in
hosts.
○ Myocytes come from hosts bone marrow
○ Evidence that stem cells can differentiate into
cardiac myocyte
○ Animal studies refute these findings
 Embryonic Stem Cells (ESC):
• Pluripotent
• Derived from inner cell mass of blastocyst
• Pluuripotent cells can differentiate into functional
cardiomyocytes
○ Not debated
○ But it is not known whether or not this can be with
high efficiency.
• In embryo:
○ Precardic endoderm induces adjacent cells in the
precardiac mesodermbecome cardiac myocytes
○ If precardiac endoderm is cultivated with ESC,
ESC’s become myocytes
• Can surviving adult cardiomyocytes be induced to proliferate and regenerate
after myocardial infarction?
○ Prevailing dogma: we have received all our cardiomyocytes by the end
of the neonatal stage of development.
 b/c cardiomyocytes cannot divide and because there are no
stem cells in the myocardium, we can’t make more
cardiomyocytes.
 Dogma is being disproven with emerging stem cell evidence.
 Evidence is emerging that G0 cardiomyocytes can be induced to
proliferate.
• See notes