index

1
Cardiac Pathophysiology
2

• Function of a cardiomyocyte
• 2. Systolic myocardial function
• 3. Diastolic myocardial function
• 4. Etiopathogenesis of systolic and
• diastolic dysfunction of the left
• ventricle and of cardiac failure

3
1. Function of a cardiomyocyte
Cardiomyocytes consist of three linked systems
- excitation system participates in spread of
the action potential into adjacent cells and
initiates further intracellular events -
excitation-contraction coupling system converts
the electrical signal to a chemical
signal - contractile system a molecular motor
driven by ATP
4
Excitation-contraction coupling system
System of intracellular membranes (sarcotubular
system, Fig. 1) provides for electrochemical
coupling between the sarcolemma and the
intracellular organelles
1
5
Coupling of excitation and contraction is
realized by a cascade of two circuits of
calcium ions, by the activity of which the
calcium spike is created in the cytosol,
inducing contraction of the myofibrilles (Fig.
2)
2
6
Depolarization and/or a ?-adrenergic influence ?
opening of dihydropyridin receptors (DHP) ? Ca2
from the T-tubules ? opening of the ryanodin
receptors ? outflow of Ca2 from the SR into
the myoplasm ? triggering of the
contraction Na/Ca antiport extrudes the
excessive Ca2 by the end of a diastole
important role in relaxation
7
Contractile system
Ca2 troponin C troponin I cross-bridge
binding to actin ?-stimulation ? ?cAMP ? ?PKA ?
phosphorylation and opening of Ca channels
(DHP) in the T-tubules? Ca/Ca cascade ?
?intracellular Ca2 ? enhancement of
contractility (inotropic effect) ?-stimulation
phospholamban SERCA ? speeding up of the
relaxation phase (s.c. lusitropic
effect) Concepts of preload and afterload
originated during experimentation with
neuro-muscular preparations, they passed later
into the clinical nomenclature (Fig. 3)
8
3
9
Velocity of shortening of a myofibrille (muscle)
is a funcion of preload, afterload and
contractility (Fig. 4)
4
10
is slowed down
afterload
forming of bridges
more binding sites on actin filaments
? developed tension
Velocity, and extent of shor tening is influ-
enced by
tension receptors ? ?Na ? ?Ca
Homeometric autoregulation
(Anreps efekt) preload activation dependent on
length ? F-S (heterometric strength
autoregulation)
Outdated theory optimum mean stretching Currently
higher sensitivity of contractile
proteins against Ca2 with the maximum
stretching (there is no declining branch of the
F-S curve in the myocardium)
contractility ?interaction of contract.
proteins with Ca2 number and frequency of
forming bridges
? ?Ca2?
?sensitivity
11
Contractility can be separated from the
preceding two terms only with difficulty, the
separation has only clinical application (Fig. 5)
5
12
2. Systolic myocardial function
Magnitude of the afterload determines the
developed active tension and influences the
velocity and extent of shortening (Fig. 6)
6
13
Laws studied on muscle strips can be applied to
a hollow muscle organ. In both cases, three
regimens of contractions could be imposed on
the muscle experimentally isotonic, isometric
and afterloaded contraction (Fig. 7)
14
7
15
Isometric isovolumic maxima curve represents a
limit (envelope) at the same time on which both
isotonic contraction curves and afterloaded
contraction curves end. The definitive length of
a muscle at the end of the contraction is
proportionally dependent on the afterload, but
it is independent on the length of a muscle
before the contraction, i.e, on a preload (Fig.
8)
8
16
The preload of a ventricle could be defined as an
end-diastolic tension in a wall and the
afterload as its maximum systolic tension (Fig.
9)
17
9
18
Laplaces law for a sphere Pr ? ???? 2h The
preload of a myocardium is defined as its
end-diastolic tension in its wall and
theafterload as its maximum systolic tension
Working diagramm of the myocardium is situated
between the myocardium compliance curve and the
end-systolic-pressure- volume-curve (ESPVL,
approaching considerably the isovolumic maxima
curve, Fig. 10)
19
10
20
Working diagram of myocardium changes typically
under the influence of preload, afterload and
changing contractility (Fig. 11 and again Fig.
8)
11
21
8
22
Sum of the external and internal work represents
the total mechanical work of contraction and
this is directly proportional to oxygen
consumption of the myocardium. Pressure work of
the heart consumes more oxygen than volume work,
so that the effectivity of the former is lower
than that of the latter (Fig. 12).
23
12
24
This theory enables us to guess in which way
preload, afterload and contractility influence
myocardial oxygen consumption ?-adrenergic
stimulation enhances the effectivity of cardiac
work. The characteristics of cardiac failure
represent a mirror picture of ?-adrenergic
effects (Fig. 13)
25
13
26
Myocardial contractility can be defined only with
a difficulty. Theoretically (and in an
out-dated manner) it is defined as a level of
contractional performance proper to myocardium
itself, independent on the loading conditions.
However, loading, heart rate and contractility
have much in common at the cellular level,
namely the interaction of contractile proteins
with calcium Contractility can be examined on a
muscle strip by means of Vmax, by means of
ejection fraction and of the slope of ESPVL
curve in a clinical setting. Enhancement of
contractility enables the myocardium either to
overcome enhanced blood pressure or to eject
larger pulse volume without enhancing the
end-diastolic volume (Fig. 11)
27

11
28
3. Diastolic myocardial function
active ability to exhaust Ca2 out of sarcoplasm
(against affinity of contractile proteins to Ca)
?
isovolemic drop of blood pressure
absolute thickness of a ventricle
Forces determining diastolic function
passive
relative rigidity of the myocardial tissue
itself myocardial turgor amount of connective
myocardial tissue
pericardium
from outside only
diastolic ventricle interaction
29
Course of myocardial tension in a diastole is
represented as a sum of active and passive
components of elongation (Fig. 14)