Ductus arteriosus

Blood from L pulmonary artery aorta

during intrauterine life
Closes in first 48 hours of life
Oxygenated blood
Decreased pulmonary resistance to flow
Decreased PGE2 levels
Ligamentum arteriosum

PDA : clinical
7% of congenital heart defects
(90% are isolated defects)
Hypoxia associated
Machinery murmer
Pressure problems Eisenmenger
Endocarditis
PGE inhibitors Rx

(BUT not if ?)

 Prostaglandin E preserves patency

Ischemic Heart Disease

Ischemic Heart Disease

Insufficient blood flow to myocardium
Leading cause of death in US
90% + Atherosclerosis Coronary
obstruction
Starts to build up in early life
Presents clinically in adult life

Ischemic Heart Disease :

The other 10%?
Increased demand by myocardium
Hypertension
Low blood volume
Shock / Hemorrhage
Decreased oxygenation
Pneumonia / congestive cardiac failure
Decreased O2 carrying capacity of blood
Anemia / CO

Classification
Angina pectoris
Acute myocardial infarction
Chronic myocardial ischemia
Sudden cardiac death

Epidemiology
1 million deaths in US in 1963
500K now
Lifestyle changes
Improved therapy
BUT may increase again
People live longer
Obesity epidemic

Pathogenesis
Narrowing by atherosclerosis
+/- Thrombosis
+/- Vasospasm
Up to 70% narrowing asymptomatic
70% + Stable angina
90% + Unstable angina
Coronary remodeling over years?
Collateral supply

Atherosclerotic plaque

Histology of atherosclerotic plaque

Factors in Atherosclerosis
and IHD
1 Inflammation
Induced by interaction between
endothelial cells and PMNs
2. Thrombosis
Secondary to plaque rupture
3. Vasoconstriction
Chemically induced

1. Inflammation
WBC interaction with endothelium
T cells and macrophages activated
Induce smooth muscle cell proliferation
matrix production
Later :
Macrophage metalloproteinase release
Destabilization of plaque

2. Thrombosis
Partial occlusion of lumen by plaque
Temporary occlusion ischemia
Unstable angina
Permanent occlusion (or delayed
fibrinolysis)
infarct
Thrombi may embolize to block distal vessel
Microinfarcts

3. Vasoconstriction
Turbulence plaque damage
Circulating adrenergic agonists
Platlet factors
NO entothelin imbalance
Due to Endothelial cell dysfunction
Inflammatory cell mediators
Within and around plaque

Angina

Stable
angina

What causes acute plaque

change?
Rupture of surface
Shear forces act on elevated
plaque
Hemorrhage into plaque
Sudden enlargement
Rupture

Structure of mature plaque

Fibrous cap interface with lumen
Central lipid core
Inflammatory interface with media

Fatty streaks

Which plaques are likely to

rupture?

Weak fibrous cap

Few smooth muscle cells
(produce collagen)
Many Macrophages
(produce metalloproteinases)

Which plaques are likely to

rupture?
66% of ruptured plaques are <50%
occlusive
85% are < 70%
6.00 am noon ?
Adrenergic contribution?
Also major catastrophies MI s ++

Angina pectoris
Stable
Narrowing of lumen
Exercise related, alleviated by rest, Nitroglycerine
Prinzmetal Spasm
Spasm related, attacks occur at rest,
Alleviated by nitroglycerine, Ca channel blockers
Unstable Thrombosis
Thrombosis related Pre MI
Increasing frequency,
Increasing severity

Unstable angina
Microinfarcts

Myocardial Infarction

Myocardial Infarction
1.5 million per annum in US
0.5 million deaths
0.25 million before hospitalization

Risks
: Those of Atherosclerosis
Male > Female, (to menopause)
B=W
Increasing incidence with increasing age
10% < 40 yrs 45% < 65 Yrs

Etiology Classification
90% thrombus on atherosclerotic plaque
10%
Coronary artery vasospasm
Emboli (A Fib or Valve lesion)
Increased demand + decreased perfusion
Extensive narrowing
Small vessel damage
Vasculitis, amyloid, Sickling

Typical MI
Thrombus formed on ruptured plaque
Platlets + coagulation proteins
In 90% of cases seen within 4 hours
BUT only in 60% at 12 hours
Fibrinolysis
Rationale for early treatment with tPA

MI sequence
ATP not produced,
Lactic acid accumulates
1 Minute
: Functional change
Loss in contractility
Up to 20 mins : Reversible Structural change
Glycogen depletion
Cell swelling, Mitochondrial swelling
After 20 mins :
Irreversible structural change
Necrosis of myocytes

Take away message

Treat early
May see Stunned myocardium
Inability to function properly for some
time
Arrythmias
Due to electrical instability of affected
region

MI progression
Early : Subendocardial involvement
mainly
Most fragile blood supply
High pressure from lumen
Later : Transmural
Extends to >50% of wall
May take 3 6 hours

Time

0 hrs

2 hrs

24 hrs

Distribution of infarcts

Distribution of infarcts
LAD 40 50%
Anterior LV
Anterior Vent septum
Apex of heart
LCX 20%
Lateral LV wall

Widowmaker
Blockage
of main
LCA

Collateral circulations may be established

Distribution of infarcts
RCA 30 40% : Right ventricle

Distribution of infarcts
RCA 30 40% : Right ventricle

Posterior descending artery

Posterior septum and LV wall
(90%) from RCA
(10% from LCX)

Left or Right Dominant?

Left or Right Dominant?

Left and Right dominant hearts
Depending on source of
Posterior Descending artery

Transmural or
Subendocardial?

Transmural or
Subendocardial?
Transmural
Subendocardial
Elevated ST segment
STEMIs
Negative Q waves
Loss or R wave amplitude

NO
NO

Subendocardial infarcts

Transient local obstruction

Global hypotension

Small vessel disease

Pathology of infarction

Pathology : Gross
No change
Pallor
Increasing pallor

(< 12hrs)
(- 24 hrs)
(1 - 3 days)

Hyperemic border

(4 7 days)

Softening,

(5 - 10 days)

Collagen deposition

(2 weeks - months)

Microscopic
No change
Necrosis

(< 4 hours)
( 4 hours - )

PMNs

(24 hours +)

Macrophages

(3 days +)

Fibroblasts

(7 days +)

Triphenyl tetrazolium chloride

Redox indicator
Turns red when applied to living cells
Respiratory enzyme intact
Remains white when applied to dead tissue
Respiratory enzymes denatured

Lack of triphenyl tetrazolium chloride staining

One-day-old
infarct
showing
coagulative
necrosis
along with
wavy fibers

Dense
PMN
infiltrat
e
2- to 3day

Macropha
ge
phagocyto
sis (7-10
days).

Granulation
tissue
loose
collagen ++
+ capillaries

Dense
collagenou
s scar

Reperfusion Injury

Reperfusion injury
Oygen free radicals (from PMNs)
Microvascular injury reduced flow
Hemorrhage due to capillary
damage
Contraction band necrosis.

Contraction band necrosis

Contraction band necrosis

Hypercontracted sarcomeres
Calcium cell
Drive actin-myosin interactions
ATP not present to allow relaxation

Clinical aspects : Pain

Severe, crushing substernal chest pain
Radiate to left arm, elsewhere
20 minutes to several hours
Not relieved by nitroglycerin or rest
Silent infarcts (10% to 15%)
Diabetes mellitus (peripheral
neuropathies)
Elderly

Clinical aspects
Rapid weak pulse
Patients diaphoretic +/- nauseated
Dyspnea
Impaired myocardial contractility
Pulmonary congestion and edema
Cardiogenic shock
>40% of the LV

EKG
Q waves (indicating transmural
infarcts)
ST-segment abnormalities
T-wave inversion
(Abnormal in myocardial
repolarization)

Arrhythmias SCD

Lab tests
TnI and TnT
2 -4 hrs 48 hr peak 7 to 10
days
CK-MB
2 to 4 24 to 48 72 hours

Complications of MI

Complications of MI
1960s in-hospital death rate 30%
Now 10% - 13% today
7% with aggressive reperfusion therapy

50% deaths occur before arrive at hospital

Usually <1 hour of onset (Arrythmias)
Poor prognosis in older diabetic females
who had previous MI

Complications of MI (in
75%)
Left ventricular failure
Hypotension
Pulmonary congestion / Edema
Cardiogenic shock in 10% to 15%
(>40% of the left ventricle)
70% mortality
70% of hospital deaths
Arrhythmias.

Complications of MI (contd)
Rupture. 1- 5%
(3 7 days)
7% to 25% of deaths from MI
Ventricular free wall
(hemopericardium)
Ventricular septum
Papillary muscle rupture

Complications of MI (contd)
Pericarditis
Stretching of infarct region
Mural thrombus (stasis endothelial
damage)
Thromboembolism
Ventricular aneurysm
Papillary muscle dysfunction
Progressive late heart failure

Chronic IHD
Ischemic cardiomyopathy

Chronic IHD
Ischemic cardiomyopathy
Postinfarction cardiac
decompensation
Gradual loss of ability of
healthy myocardium to perfuse
body
Without prior infarction
(extensive atherosclerosis)

Sudden cardiac death

300 to 400K United States
Death from cardiac causes
Without symptoms
Within 1 to 24 hours of onset

Sudden cardiac death

Ventricular fibrillation
Electrical irritability of myocardium
distant from the conduction system
Cardioverter defibrillators
Sense and electrically terminate
episodes of V Fib

SCD : pathology
90% have 75% coronary
stenosis
10 20 % plaque disruption
40% have healed MI
10 20% non-atherosclerotic origin

Non-atherosclerotic causes
of SCD

See in younger patients

Hereditary channelopathies
Congenital abns of coronary arteries
Mitral valve prolapse
Myocarditis / sarcoidosis
DCM or HCM
Pulmonary HT
Myocardial hypertrophy