Transcript 4 - Regulation of the Heartbeat

Regulation of the
Heartbeat
Outline
 Control of the heart beat
 Intrinsic control of contractility
 Extrinsic control of contractility
Control of the heartbeat
 Parasympathetic pathway
 Parasympathetic fibers originate in the nucleus
ambiguus.
 They pass through the mediastinum to synapse with
postganglionic cells on the epicardial surface or within
the walls of the heart itself.
 The right vagus nerve effects the SA node
predominantly.
 The left vagus nerve mainly inhibits AV conduction.
Control of the heartbeat
 Acetylcholine is rapidly hydrolyzed via nodal
cholinesterase so the effect is brief.
 The muscarinic receptors are coupled directly to the
acetylcholine-regulated potassium channels by a G
protein; this direct coupling allows a prompt response
 Parasympathetic predominate over sympathetic
effects at the SA node.
 This is mediated by suppressing release of
norepinephrine from the sympathetic nerve endings
by acetylcholine
Control of the heartbeat
 Sympathetic pathway
 The cardiac sympathetic fibers originate in the
interomedial lateral columns of the T1-5 and C7-8
segments of the spinal cord.
 Preganglionic and postganglionic neurons synapse
mainly in the stellate and middle cervical ganglia.
 On reaching the base of the heart, these fibers are
distributed to the various chambers as an extensive
epicardial plexus.
Control of the heartbeat
 The effects of sympathetic stimulation decay
very gradually after stimulation.
 The response to sympathetic activity depends
mainly on the intracellular production of
second messengers, mainly cAMP
Control of the heartbeat
 Baroreceptor reflex
 Acute changes in blood pressure elicit inverse changes in
heart rate via the baroreceptors located in the aortic arch
and carotid sinuses
 Bainbridge reflex
 A fluid bolus accelerates the heart rate whether arterial
blood pressure rise or not
 Tachycardia occurs with CVP rises sufficient to distend the
right heart.
 Increases in blood volume not only evoke the Bainbridge
reflex, but they also activate the baroreceptor reflex that
tend to slow the heart rate.
 The actual change in heart rate evoked by an alteration of
the blood volume is the results of these antagonistic reflex
effects.
Control of the heartbeat
 How does the Bainbridge reflex work?
 Atria have receptors that influence heart rate located
in the venoatrial junction.
 Distention of these receptors send impulses centrally
in the vagus nerve.
 The efferent impulses are carried by fibers from both
autonomic divisions to the SA node.
 The increase in sympathetic activity is restricted to
the heart rate; there is no increase of sympathetic
activity to the peripheral arterioles nor increase in
contractility.
Control of the heartbeat
 Stimulation of atrial receptors also increases
urine volume.
 Atrial natriuretic peptide is released from atrial
tissue in response to stretch of the atrial wall.
 It has potent diuretic and natriuretic effects on
the kidneys and dilates blood vessels.
Control of the heartbeat
 Respiratory variation
 Heart rate accelerates during inspiration and
decelerates during expiration.
 Activity increases in the sympathetic nerve fibers
during inspiration, whereas activity in the vagal nerve
fibers increases during expiration.
 Acetylcholine released at the vagal endings is
hydrolyzed so rapidly that the rhythmic change in
activity are able to elicit rhythmic variations in heart
rate.
 Conversely, norepinephrine is released at the
sympathetic endings is removed more slowly, thus
dampening out the effects of rhythmic variations in
norepinephrine released on heart rate
Control of the heartbeat
 Hence, rhythmic changes in heart rate arise almost
entirely from oscillations in vagal activity.
 During inspiration, venous return to the right side of
the heart accelerated and elicits the Bainbridge reflex.
 After the time delay required for the increased venous
return to reach the left side of the heart, left
ventricular output increases and raises arterial blood
pressure.
 This reduces heart rate reflexively through the
baroreceptor stimulation.
Intrinsic control of contractility
 Frank-Starling mechanism
 When the load on the heart is
increased, it responds with a more
forceful contraction.
 In this experiment the right atrial
pressure [preload] was increased.
 The width of the tracing reflects
the stroke volume.
 For several beats after the rise in
preload, the ventricular volume
progressively increased.
Intrinsic control of contractility
 During a given systole, the volume of blood expelled
was not as great as the volume that had entered.
 This accumulation of blood dilated the ventricles and
lengthen the individual myocardial fibers in the wall of
the ventricle.
 Increased fiber length alters cardiac performance
mainly by changing the calcium sensitivity of the
myofilaments and, in part, by changing the number of
monofilament cross bridges that can interact.
Intrinsic control of contractility
 Increased afterload
 Changes in diastolic fiber length compensate for an
increase in afterload.
 When the afterload is first increased, the stroke
volume ejected by the ventricles during systole is less
than the filling volume.
 The consequent excess of volume in the ventricles
stretches the myocardial fibers in the ventricular
walls.
 This increase in myocardial fiber length enables the
ventricles to eject a given stroke volume against an
increased afterload.
Intrinsic control of contractility
 Heart rate effects
 When the heart rate is suddenly increased, the force
increases over the next several beats.
 This progressive increase in developed force induced
by changing contraction frequency is known as the
staircase phenomena.
 The initial rise in developed force when the interval
between beats is suddenly decreased is achieved by
a gradual increase in the intracellular calcium content.
Intrinsic control of contractility
 Two mechanisms for the rising calcium:
 An increase in the number of depolarization per minute
 An increase in the inward calcium current per depolarization
 As the interval between beats is suddenly diminished,
the inward calcium current progressively increases
with each successive beat until a new steady-state
level is attained at the new basic cycle length.
Intrinsic control of contractility
 PVCs also affect the strength of contraction.
 When a PVC occurs, the premature
contraction itself is feeble, whereas the beat
after the subsequent pause is very strong.
 This response depends partly on the Frank
Starling mechanism.
Intrinsic control of contractility
 The beat is weak because not enough time has
elapsed to allow much of the calcium taken up by the
sarcoplasmic reticulum during the preceding
relaxation to become available for release.
 Conversely, the postextrasystolic beat is considerably
stronger than normal.
 The reason is that after the pause between beats, the
sarcoplasmic reticulum had available for release the
calcium had been taken up during two heartbeats: the
extrasystole and the preceding normal beat.
 This effect is in addition to the increased preload from
the PVC.
Extrinsic control of contractility
 Sympathetic
 Changes contractility can be evoked by stimulation of
the left stellate ganglia.
 Neurally released norepinephrine or circulating
catecholamines interact with beta adrenergic
receptors on the cardiac cell membrane.
 The peak pressure and the maximal rate of pressure
rise [dP/dt] during systole are markedly increased.
 The duration of systole is reduced and the rate of
ventricular relaxation is increased during the early
phases of diastole.
 The briefer systole allows more time for diastole and
hence for ventricular filling.
Extrinsic control of contractility
 Parasympathetic
 Vagal stimulation decreases the peak left ventricular pressure,
maximal rate of pressure development [dP/dt], and maximal rate
of pressure decline during diastole.
 The acetylcholine interact with muscarinic receptors which
inhibits adenyl cyclase.
 The consequent fall in cAMP diminishes the calcium conduction
of the cardiac cell membrane, reduces phosphorylation of the
calcium channels, and hence decreases myocardial contractility.
 The acetylcholine released from vagal endings can also inhibit
norepinephrine release from neighboring sympathetic nerve
endings.
Extrinsic control of contractility
 Other hormones
 Cortisol
 Hydrocortisone potentates the cardiotonic effects of
catecholamines. This may be mediated in part by inhibition
of the extraneuronal uptake of catecholamines.
 Thyroid hormones
 The rate of calcium uptake and of ATP hydrolysis by the
sarcoplasmic reticulum are increased in response to excess
thyroid hormones.
 Thyroid hormones increase protein synthesis in the heart
which can lead to cardiac hypertrophy.
 These hormones also affect the composition of myosin
isoenzymes in cardiac muscle. They increase principally
those isoenzymes with the greatest ATPase activity, and
thereby enhance myocardial contractility
Extrinsic control of contractility
 Insulin
 Insulin has a predominant, direct, positive inotropic
effect on the heart.
 Glucagon
 Effect of glucagon on the heart closely resemble
those of the catecholamines. Both glucagon and
catecholamines activate adenyl cyclase to
increase the myocardial tissue levels of cyclic
AMP.
Extrinsic control of contractility
 pH, PaO2, PaCO2
 Moderate degrees of hypoxia increase heart rate, cardiac
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output, and myocardial contractility via the sympathetic
nervous system
Severe degrees of hypoxia depress myocardial contractility.
Neither the PaCO2 nor blood pH is a primarily determinant of
myocardial function, intracellular pH matters.
The reduced intracellular pH decreases the amount of
calcium release from the sarcoplasmic reticulum in response
to excitation.
The diminished pH also decreases the sensitivity of the
myofilaments to calcium.
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