Transcript Case 4 cont.

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Myocardial Remodeling
Class two Ding Ma, Nan Li, Jin Zhou, Huan Luo,
Lan Mi, Han Yan
Case 4
A 71-year old male
Complains: 15-years
history of paroxysmal
chest pain, increasing for
5 hours, associated with
dyspnea and unable to lie
flat
Case 4 cont.
15 years
ago
As a result of
fatigue and
humoursome,
he suddenly
had a server
pain at the
front of his
heart.
10 years
later
2-year
history
He has pain at
the front of his
heart after
fatigue,
exercise or
when he is
humoursome
Discontinuous
paroxysmal
chokey and
suffocation
Case 4 cont.
1
2
3
At 11pm of the day
before he was sent to
the hospital, without
obvious inducement, he
suddenly had a server
pain at the front of his
heart while lying on the
bed at rest.
The pain radiated to
the left shoulder and
limb associated with
chokey, suffocation,
sudation except nausea,
vomiting, fever and
cough.
He took Suxiao Jiuxin
Wan 2 times, 16
granules in all, but the
symptom didn’t become
unrelieved. The man
was sent to the
emergency at 2am and
taken examinations
Case 4 cont.
ECG
Timeworn
inferior
myocardial
infarction
V3-6,
ST↓0.05-0.2mv
CK-MB（+）
CTn(-)
Myo(-)
DRUG
The symptom
could be slightly
unrelieved after
taking KeSai
and GTN.
Change
1 hour ago, the
patient sat up
changing his
clothes and
complained
breathless. Later
on, he could not lie
flat and then had
sudation and
dyspnea.
Case 4 cont.
BP
Blood
Lipid
History
Hypertension for 7-8 years;
BPmax=220/110mmHg. Taking Xin tong
ding to maintain BP at 160-170/90100mmHg.
Serum cholesterol is a litter higher.
Deny of previous history of diabetes,
hepatitis and tuberculosis. No history
of being sensitive to any drugs.
Case 4 cont.
Test
TestCont.T
cont.
Med. Test
Temperature: 36.2℃
Respirations: 16/min
Pulse: 120/min
BP: 190/100mmHg
In his right senses,
sit up state,
rapid respiration,
low-grade of cyanose of
the lip.
No neck vein distention,
no cardiomegaly,
Rales. HR=120/min,
normal rhythm, no
cardiacs at all valve
areas.
Abdomen is soft,
couldn’t touch liver
and spleen, there is
no swelling in either
lower legs.
Assistant Test
Chest radiograph: fargrained. Radiographic
cardiomegaly
Serum cholesterol:
TG:181mg/dl
(normal<150mg/dl)
T-CHO:211mg/dl
(normal<220mg/dl)
LDL-C: 154mg/dl
(normal<140mg/dl)
HDL-C:42mg/dl
(normal>36mg/dl)
Case 4 cont.
Hyperlipidemia
Hypertension
Timeworn inferior
myocardial
infarction
Coronary heart disease
Diagnose
Acute anterior
myocardial infarction
Acute left-side heart failure
Question
What happened to the
heart after infarction
during these 10 years
that kept him in a stable
state?
Compensatory
Mechanism
Agenda
1
Early remodeling in 72h
2
Late remodeling after 72h
Early remodeling
Adaptive responses
Infarct expansion
-Starling
-Perturbations in
circulatory
hemodynamics
matrix
metalloproteinases
(MMPs) released
→degeneration of
collagen
MMP
Cardiomyocyte
Collagen
Infarct
Late remodeling
Late remodeling
Leading to…
Neurohormonal
activation
Activation
of RAS
Myocardial
stretch
Cytokines
Neurohormonal activation
Myocardial infraction → activation of sympathetic nerve system →
release α1 receptor of myocyte Signal pathway of Gq hypotrophy
of NE→
β1receptor of juxtaglomerular apparatus →release of renin →AngⅡ↑
promotes the presynaptic release of NE
→
blocks its reuptake,
increases catecholamine synthesis,
potentiates the postsynaptic action of NE
NE and AngⅡ →ET-1 →
hypothophy
ANP →inhibition of hypotrophy
→hypotrophy
Hypotrophy
Myocardial stretch
PKC → AngⅡ↑
AngⅡ↑
Calcium-dependent activation of
tyrosine kinase
↓
Mechanical stretch
AT1 receptor
→ fetal gene program
Early genes
→ time-dependent increase in protein synthesis
Activation of RAS
Serine
proteases
local RAS in
the
noninfarcted
myocardium
Ang gene
expression
&increase
d local
ACE
activity
local
AngⅡ↑
hypotrophy
in
noninfarcted
myocardium
Cytokines
Necrotic myocytes
macrophages
→
NO↑
INF-γ
→
→ Vascular permeability ↑
macrophages
ACE↑
myofibroblasts
TGF-β１
macrophages
fibroblasts
fibroblast proliferatin
fibroblasts →myofibroblasts
→ local AngⅡ↑
→ synthesis of collagen types 1 and 3
In short
AngⅡ
G protein
pathway
Upregulation
gene
expression
Cardiac
remodeling
Cardiomyocyte
hypotrophy
Summary
Reference
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Hiroyuki Tsutsui. Mitochondrial Oxidative Stress and Heart Failure.
The Japanese Society of Internal Medicine.
2006.DOI:10.2169/internalmedicine.45.1765
William C. Stanley, Fabio A. Recchia, etc. Myocardial Substrate
Metabolism in the Normal and Failing Heart. 2005. Physiol Rev
85:1093-1129
A. D. Struthers. Pathophysiology of Heart Failure Following
Myocardial Infarction. 2005;91;14-16
Hiroyuki Morita, Jonathan Seidman, etc. Genetic Causes of Human
Heart Failure. The Journal of Clinical Investigation. 2005.
Volume115 Number3
Jun REN, Cindy X FANG. Small Guanine Nucleotide-binding
Protein Rho and Myocardial Function.2005. Acta Pharmacologica
Sinica. Volume 26 Page 279
Da-yue DUAN2, Luis LH LIU,etc. Functional role of anion channels
in cardiac diseases. Acta Pharmacologica Sinica. 2005. Volume
26 Page 265
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