9.3 Flashcards
1
Q
stimulation of the sympathetic nerves to the heart elicits
A
a marked increase in coronary blood flow
2
Q
during stimulation of sympathetic nerves cause greater fraction of time is spent in
A
systole
3
Q
a greater fraction of time is spent in systole because
A
of the stronger myocardial contractions and the tachycardia
4
Q
this sympathetic situation tends to
A
restrict coronary flow
5
Q
whereas increase in myocardial metabolic activity
A
tends to dilate the coronary resistance vessels
as seen with rate and contractility changes
6
Q
increase in coronary blood flow observed with sympathetic nerve stimulation constitutes
A
the sum of these factors
7
Q
in perfused hearts what is eliminated
A
mechanical effects of extravascular compression
8
Q
in perfused hearts what are mechanical effects of extravascular compression eliminated by
A
cardiac arrest or by ventricular fibrillation
9
Q
what is often observed with cardiac sympathetic nerve stimulation
A
an initial coronary vasoconstriction before the vasodilation
10
Q
what is the vasodilation after vasoconstriction often observed in cardiac sympathetic nerve stimulation attributable to
A
the metabolic effect comes into play
11
Q
the B-adrenergic receptors are blocked to
A
eliminate the positive chronotropic and inotropic effects
12
Q
after the B-adrenergic receptors are blocked what happens
A
direct reflex activation of the sympathetic nerves to the heart increases coronary resistance
13
Q
observations indicate that the main action of the sympathetic nerve fibers on
A
coronary resistance vessels is vasoconstriction
14
Q
in perfused heart there is
A
constant perfusion pressure
15
Q
with ventricular fibrillation there is
A
initial reduction in coronary flow but eventual increase
16
Q
the a- and b-adrenergic drugs and their respective blocking agents reveal the
A
presence of a-adrenoreceptors (constrictors) and B-adrenoreceptors (dilators) on the coronary vessels
17
Q
coronary resistance is predominantly under
A
local nonneural control
18
Q
vagus nerve stimulation or intracoronary acetylcholine causes
A
slight dilation of coronary resistance vessels and at a constant perfusion pressure, increases coronary blood flow
19
Q
what is biggest control of flow
A
dilation (like vagal stimulation or acetylcholine)
20
Q
acetycholine infusion causes
A
quick increase in coronary flow
21
Q
vasodilation is initiated at
A
muscarinic receptors on endothelial cells that release nitric oxide (NO)
22
Q
what is NO synthase inhibited by
A
nitro-L-arginine methyl ester (L-name)
23
Q
when NO synthase is inhibited by L-name, what happens
A
vagal stimulation and acetylcholine are less able to increase coronary flow
24
Q
when NO blocked
A
less increase in coronary flow, less dilation
25
what is one of most striking characteristics of the coronary circulation
close parallelism between the level of myocardial metabolic activity and the magnitude of the coronary blood flow
26
where is the relationship between myocardial activity and magnitude of coronary blood flow also found
in the denervated heart and in the completely isolated heart, regardless of whether heart is beating or fibrillating
27
myocardial oxygen consumption represents
how hard heart is working
28
relationship in graph between myocardial oxygen consumption and
coronary blood flow during interventions that increased or decreased myocardial metabolic rate
29
if myocardial O2 consumption increases
coronary flow increases (highly coupled)
30
even if denervated what holds true
relationship between O2 consumption and blood flow
31
heart itself has
own control outside of nerve stimulation
32
a decrease in ratio of O2 supply to O2 demand releases
vasodilator substances from the myocardium into the interstitial fluid, where they can relax coronary resistance vessels
33
what can cause decrease in ration of O2 supply to O2 demand
reduction in O2 supply or by an increment in O2 demand
34
low O2 generates
metabolites that cause vasodilation
35
what decreases the O2 supply/demand ratio
decrease in arterial blood O2 content or in the coronary blood flow, or an increase in cardiac metabolic rate
36
O2 supply/demand
how much O2 heart getting/how much does heart need
37
decrease in O2 supply/demand ratio releases
vasodilator substances such as adenosine and NO
38
what do the vasodilator substances do
dilate the arterioles and thereby adjust O2 supply to demand
39
a decrease in O2 demand would
reduce the release of vasodilators and permit greater expression of basal tone
40
oxygen supply is determined by
arterial blood flow and O2 content (arterial PO2)
41
O2 demand is a function of
rate, preload, afterload, and contractility
42
substrate metabolism provides
ATP to support cardiac work, whereas reduced ATP formation leads to vasodilation
43
imbalance in the O2 supply/O2 demand ratio alters
coronary blood flow by the rate of release of vasodilator metabolites from the cardiomyocytes
44
a decrease in the ratio of O2 supply/O2 demand elicits
an increase in vasodilator release
45
an increase in the ratio of O2 supply/O2 demand elicits
has opposite effect
decrease in vasodilator release
46
in face of low flow or low O2 availability there will be
vasodilators
47
if lots of O2 availability there will be
less vasodilators
48
if supply=demand of 02
no vasodilator release
49
metabolites have been suggested as
mediators of the vasodilation observed with increased cardiac work
50
among metabolites implicated are
CO2, O2 (reduced O2 tension), hydrogen ions (lactic acid), K+, adenosine, prostaglandins, NO, and opening of ATP-sensitive K channels (KATP)
51
key factors implicated appear to be
adenosine (most potent)
NO
Opening of KATP channels
52
buildup of metabolites is a warning sign for
problem with heart
increase metabolites, decreased O2 problem with supply/demand
53
what does a reduction of oxidative metabolism in vascular smooth muscle cause
reduction in ATP, which opens KATP channels and causes hyperpolarization (important for preventing Ca++ overload)
54
the potential change of reduction of oxidative metabolism in vascular smooth muscle cause
reduce Ca++ entry and relaxes coronary vascular smooth muscle to increase flow
55
in endothelial cells, hypoxia activates
KATP channels that signal an increased release of NO to relax vascular smooth muscle
56
what else does a reduction of ATP do
opens KATP channels in cardiac muscle and generates an outward current that reduces action potential duration and limits entry of Ca++ during phase 2 of AP (mitigates Ca++ overload)
57
what does the reduction of ATP action though to do
serve a protective role during periods of imbalance between O2 supply/demand
58
the release of vasodilators such as NO and adenosine
dilates the arterioles and thereby adjusts the O2 supply to the O2 demand
59
for example, a low concentrations adenosine appears to activate
endothelial KATP channels and to enhance NO release
60
a decreased O2 demand would sustain the
ATP level and also reduce amount of vasodilator substances released and permit greater expression of basal tone
61
if all three, adenosine, NO, and opening of KATP are inhibited
coronary blood flow is reduced, both at rest and during exercise
62
if all three agents are inhibited what 2 things become evident
contractile dysfunction and signs of myocardial ischemia
63
diminished coronary blood flow impairs
cardiac function
64
most of O2 in coronary arterial blood is extracted during
one passage through the myocardial capillaries (owing to high ratio of capillaries)
65
the O2 supply to the myocardial cells is
flow limited
66
myocardial ischemia occurs when the
coronary blood flow is insufficient
67
what does myocardial substrate metabolism during ischemia depend upon
the severity of the ischemia
68
complete elimination of flow quickly results in
depletion of high energy phosphates and accumulation of lactate
contractile akinesis
69
over time what does the akinesis evolve into
myocardial infarction and tissue necrosis
70
contractile akinesis
entire heart contracting except one area not moving
71
dyskinesis
part contracting at different times
72
a more modest reduction in flow (20-60%) causes
a decrease in myocardial O2 consumption (10-50%)
transient increased dependence on anaerobic glycolysis
oxidation of free fatty acids at a reduced rate
modest to severe contractile dysfunction
73
dependence on anaerobic glycolysis
glycogen depletion and lactate production
74
depending on metabolic demand these reductions in flow do not necessarily lead to
irreversible tissue damage
75
classic symptom of myocardial ischemia is
angina pectoris
76
what happens during myocardial ischemia
intracellular acidosis occurs and Na+ accumulates in myocytes
77
what protects against ischemic damage
inhibition of Na+-H+ exchange
78
high H+ concentration activates
Na+-H+ exchange and H+ is extruded from the cells in exchange for Na+
79
ischemia also inhibits
Na+, K+-ATPase which further reduced Na+ extrusion
80
the increased intracellular Na+ content enhances
Na+-Ca++ exchange, so as Na+ leaves the cells, Ca++ enters
81
what is result of Ca++ entering cell
Ca++ overload
82
what does Ca++ overload do
impairs myocardial contraction possibly leading to cell death
83
Inhibition of the Na+-H+ exchange or of Na+-Ca++ exchange hastens
recovery from ischemia during reperfusion (greater cardiac function)
84
inhinition of Na+Ca++ exchange
mitigates significant Ca++ overload
85
reductions in coronary blood flow (myocardial ischemia)
may critically impair the mechanical and electrical behaviour of the heart
86
what is one of most common causes of serious cardiac disease
diminished coronary blood flow as a result of coronary artery disease (usually coronary atherosclerosis)
87
ischemia may be
global (affecting an entire ventricle)
or regional (affecting some fraction of the ventricle)
88
what is the impairment of the mechanical contraction of the affected myocardium produced by
diminished delivery of O2 and metabolic substrates
also accumulation of potentially deleterious substances (K+, lactic acid) in cardiac tissues
89
if the reduction of coronary flow to any region of the heart is sufficiently severe and prolonged
necrosis of the affected cardiac cells results
90
with angina
could have no cell death and normal squeeze function
91
ischemia causes
cell death and dead tissue
92
what is reduced during myocardial ischemia
rate of oxidative phosphorylation and concentration of ATP falls
93
what happens to the ADP that is formed during myocardial ischemia
further hydrolyzed to adenosine monophosphate (AMP) and converted to adenosine
94
adenosis builds up in absence of
atp
95
what does heart use the adenosine for
to dilate vessel (is good thing)
96
where does adenosine go
readily leaves the cardiomyocyte and exerts effects in cardiomyocytes and vascular smooth muscle in the local vicinity
97
how much of increase of interstitial adenosine happens during myocardial ischemia
about a 100 fold increse
98
what is stimulated during myocardial ischemia
adenosine receptors
99
the effects are mediate by two types of adenosine receptors
A1 and A2a
100
where is adenosine A1 receptor located
on plasma membrane of cardiomyocytes
101
what happens when A1 receptor stimulated
results in an "antiadrenergic" effect on cardiomyocytes
102
what does stimulation adenosine A1 receptors in the SA node pacemaker do
results in decrease of heart rate viz the same path as ACh (acts similar to vagal activity)
103
what does adenosine A1 receptor stimulation do in ventricle cardiomyocytes
reduce the rate of O2 consumption
104
reduction of rate of O2 consumption from A1 receptors is particularly important during
myocardial ischemia when adenosine formation is greatly increased
105
intravenous injections of adenosine are used to treat
superventricular tachycardia
106
what does adenosine administration do for superventricular tachycardia
stimulates A1 receptors on the AV node and rapidly reduces the ventricular rate like acetylcholine does
107
adenosine A1 receptors are also on
cardiac sensory nerve endings
108
stimualtion of A1 receptors on cardiac sensory nerve endings results in
the sensation of angina pectoris
109
during ischemia what does rise in adenosine link to clinical symptom of angina pectoris
reduction of O2 delivery
oxidative phosphorylation
ATP content
110
A1 slows
HR to decrease myocardial consumption
111
the adenosine A2a receptor is located
on vascular smooth muscle cells of coronary arterioles
112
what do adenosine A2a receptors cause when activated
coronary vasodilation
113
adenosine is a most effective
endogenous (local) coronary vasodilator
114
in healthy humans, an intracoronary infusion of adenosine can
increase coronary blood flow five-fold
115
during myocardial ischemia adenosine formation is
dramatically increased in cardiomyocytes, resulting in an increase in interstitial adenosine
116
the increase in adenosine during ischemia stimulates
A2a receptors located on coronary arterioles, resulting in coronary vasodilation
117
overall adenosine reduces the severity of ischemia by
increasing coronary blood flow and decreased myocardial requirement for O2 consumption by decreasing the heart rate and contractility (masking effect)
118
in normal healthy heart what are interstitial levels of adenosine
very low and adenosine receptors are not stimulated
119
what may occur if the reduction of coronary flow is neither too prolonged nor too severe to cause myocardial necrosis
substantial but temporary mechanical dysfunction of the heart
120
what may be associated with pronounced mechanical dysfunction of the heart
a relatively brief period of severe ischemia, followed by reperfusion (called myocardial stunning)
121
when does myocardial stunning recover
eventually fully recover after a period of hours to days
122
myocardial stunning can be prevented by
preconditioning
123
what does the preconditioning procedure to prevent myocardial stunning consist of
one or more brief occlusions of a coronary artery
124
125
brief occlusions
prime LV to not be as stunned, like mini occlusions
promote better recovery after unblocked
126
preconditioning may involve
adenosine release from the myocardium in short (minutes) responses
127
protection from the ischemia-induced impairment of cardiac function can be achieved
by long term administration of dipyridamole
128
dipyridamole
a drug that blocks the cellular uptake of adenosine, which raises the blood levels of adenosine (vasodilation)
129
administration of an adenosine A1 receptor antagonist
abolishes the protective action of dipyridamole
130
myocardial stunning may be evident in patients who
have had an acute coronary artery occlusion
131
what happens to person who has had an acute coronary artery occlusion but is treated sufficiently early by coronary bypass surgery or balloon angioplasty and adequate blood flow is restored to ischemic region
the myocardial cells in this region may eventually fully recover
132
treatment of person who has had an acute coronary artery occlusion
coronary bypass surgery or balloon angioplasty and adequate blood flow is restored to ischemic region
133
after the surgeries for acute coronary artery occlusion, what may still occur
the contractility of the myocardium in the affected region may be grossly subnormal for many days or even weeks
134
when is it best to start exercising after myocardial infarction
sooner the better for heart
for every week delaying exercise, 4 weeks more you need
135
what develops in response to impairment of coronary blood flow
coronary collateral vessels
136
in normal human heart there are virtually no
functional intercoronary channels
137
in dog heart there are
a few small vessels that link branches of the major coronary arteries
138
abrupt occlusion of a coronary artery, or of one of its branches in a human or dog leads to
ischemic necrosis and eventually to fibrosis of the areas of the myocardium that are supplied by the occluded vessel
139
however, if narrowing of a coronary vessel occurs slowly and progressively over a period of days or weeks or longer
collateral vessels develop
140
what can the development of collateral vessels do
may furnish sufficient blood to the ischemic myocardium to prevent or reduce the extent of necrosis
141
142
the clinical picture of coronary atherosclerosis as it occurs in humans can be
stimulated by gradual narrowing of a normal dog's coronary arteries
143
where do collateral vessels develop
between the branches of occluded and nonoccluded arteries
144
where do collateral vessels originate
from preexisting arterioles that undergo proliferative changes of the endothelium and smooth muscle by process of arteriogenesis
145
the stimulus of arteriogenesis is
the shear stress caused by the enhance blood flow velocity that occurs in the arterioles proximal to the site of occlusion
146
with the occlusion of a coronary artery, what happens to pressure gradient
the pressure gradient along the proximal arterioles increases because of a greater perfusion pressure upstream from the occlusion
147
the stress activated endothelium
upregulates expression of monocyte chemoattractant protein-1 (MCP-1)
148
What does MCP-1 do
attracts monocytes that then invade the arterioles
149
what participates with MCP-1
other adhesion molecules and growth factors
150
what do adhesion molecules and growth factors do with MCP-1
Participate in inflammatory reactions and cell death in the potential collateral vessels
151
the stage of inflammatory reactions and cell death is followed by
remodeling and development of new and enlarged collateral vessels that are indistinguishable from normal arteries after several months
152
on xray how do you know its collateral vessels
because get sprouting of vessels in not normal places
153
capillary proliferation is stimulated by
vascular endothelial growth factor (VEGF)
154
what is upregulated by hypoxia
expression of vascular endothelial growth factor (VEGF)
155
The enhanced production of VEGF is mediated
in part by adenosine release caused by the hypoxia
156
what else can enhance capillary density by greater expression of VEGF protein
drug induced chronic bradycardia
157
what has been made to enhance the development of coronary collateral vessels
many surgical attempts
158
however what has occurred with many surgical attempts to enhance development of coronary collateral vessels
the techniques used do not increase the collateral circulation over and above that produced by coronary artery narrowing alone
159
what seems to be the only treatment for cv disease
beta blockade
slows HR, lowers O2 requirement thus slowing remodeling of heart
160
what directly constricts the coronary resistance vessels
activation of the cardiac sympathetic nerves
161
what causes the enhanced myocardial metabolism
associated increase in heart rate and contractile force
162
what does the enhanced myocardial contraction, increased HR and contractile force produce
vasodilation
163
what does the vasodilation do
overrides the direct constrictor effect of sympathetic nerve stimulation
164
what releases vasodilators that decrease coronary resistance
a decrease in O2 supply or an increase in O2 demand
165
what are the key factors that mediate vasodilation
adenosine, nitric oxide, and activation of the ATP-sensitive K+ channels
166
transient periods of severe ischemia followed by reperfusion may
induce myocardial stunning, which is temporary stage of impaired mechanical performance by the heart
167
in response to gradual occlusion of a coronary artery
collateral vessels from adjacent unoccluded arteries develop and supply blood to the compromised myocardium distal to the point of occlusion
168
collateral vessels mask
established CV disease
