Cardiovascular Effects

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Cardiovascular Effects of Alcohol S. Zakhari
National Institute on Alcohol Abuse and
Alcoholism Editor E. Rubin Thomas Jefferson
University
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Goal Outline

• To describe physiological, biochemical properties
  of the CVS
• To illustrate alcohols effects on these
  processes
• To discuss effects of moderate drinking on CVS
• To address alcohols interactions with CV
  medications

• Heart
• Contractility/Metabolism
• Rhythmicity/Conductivity
• Blood Vessels
• Coronary Arteries
• Cerebral Vessels
• Blood
• Moderate Drinking
• Interactions with Medications

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Performance of the Human Heart
Stroke Volume 80 ml at rest Heart Rate 70
beats/min. at rest, 180 during exercise Cardiac
Output SV HR 5600 ml/min. Blood pumped in
70 years 206 million liters or 50
million gallons
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Myocardial Contraction
Myocardial fiber
Myofibril
myosin
Myofilaments

actin
relaxed
contracted
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Processes Involving Energy Production and
Utilization by the Myocardium
Ca
Ca
O2
Ca
C O N T R A C T I O N
TCA cycle (Aerobic)
ATPase
ATP
Ca
Fatty Acids Lactate Pyruvate

ATP
ADP
PC
CAT T
Glycolysis (Anaerobic)
C
ATP
CPK
ATPm A MA ADP
Myokinase
Glucose
Glucose-1-PO4 Glycogen
Energy Sources
Energy Pool
Energy Use
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Analysis of Ventricular Function The Ejection
Fraction (EF)

• End Diastolic Volume - End Systolic
  Volume
• EF
• End Diastolic Volume
• (150 - 60) 100
• 150

EF
60
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Acute/Chronic Effects of Ethanol (E) on
Myocardial Contractility

• E depresses myocardial contractility (at as low
  as 0.05)
• E releases catecholamines that may obscure
  myocardial depression
• E (acute) generally increases CO reflecting
  changes in HR and PVR
• E decreases EF
• E (chronic) decreases ventricular contractility\

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Alcoholic Cardiomyopathy
Control
Alcoholic
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(No Transcript)
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Mechanisms of Alcohol-Induced Depression in
Myocardial Contractility
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Ca
Na
F
2
5 FAEE
3
4
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Hearts Electrical System
Bundle of His
LA
Sinus (SA) node
Mitral Valve
AV node
RA
Purkinje fibers
Tricuspid Valve
LV
RV
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Electrocardiogram (EKG)
SA node
AV node
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Alcohol and Coronary Arteries
Aorta
pulmonary Artery
Left Coronary Artery
Circumflex branch
Right Coronary Artery
Interventricular branch
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monocytes
Atherosclerosis
Oxidized LDL
B
Foam cell
A
C
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Alcohol and Stroke

• Hemorrhagic Stroke

A
B
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Alcohol and Stroke

• Ischemic Stroke

A
B
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Chronic Heavy Alcohol Consumption Causes
Hypertension
systolic
diastolic
160 -
120 -
80 -
Blood Pressure (mm Hg)
40 -
0 -
ND SD LD MD HD
Alcohol Consumed
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Some Factors that Affect Blood Pressure
Some Factors that Affect Blood Pressure
Alcohol
Stroke Volume
Venous Return
Reflexes From Carotid Sinus and Aortic Arch
Cardiac Output
Heart Rate
Myocardial Contractility
Sympathetic Discharge
Systemic Arterial Pressure
Peripheral Vascular Resistance
Adrenal Medulla
Mg/Ca
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Alcohol and Platelets
aggregation
TxA2
Thrombin
ADP
R1
R2
R3




Plasma Membrane
PLA2
PLC
PIP2
PL
PKC

AA
DAG

IP3
TxA2
Ca2
Release of platelet granules and ADP
Alcohol
Actin
Actomyosin
change of shape
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Regulation of EC Fibrinolysis and Normal
Hemostasis
Fibrin(ogen) degradation products
Fibrin(ogen)
PAI-1
Fibrinolysis
t-PA
Pmg
Plasmin
u-PA
t-PAR
PmgR
u-PAR
Endothelial Cell
Coagulation
Normal Hemostasis
Fibrinolysis
Alcohol
Fibrinolysis
Coagulation
Fibrinolysis
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Moderate Drinking
One Drink 12 ounces of beer 5 ounces of wine,
or 1.5 ounces of 80-proof distilled spirits
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Alcohol and Coronary Artery Disease

• Honolulu Heart Study
• Belfast, Northern Ireland
• London Civil Servants
• Kaiser-Permanente
• Yugoslavia Heart Study
• Busselton, Australia
• Puerto Rico Heart Study
• North Karelia Project
• Zutphen Study
• Albany Study
• Thailand Heart Study
• Nurses Health Study
• British Regional Heart Study

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Alcohol CAD Possible Mechanisms of Action

• HDL/LDL?
• Ischemia/reperfusion
• PKC
• Platelets
• Fibrinolysis

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Moderate Alcohol Decreases I/R Injury
Alcohol
?
Adenosine
PIP2
PLC
RACK
Active PKC
Adenosine A1 Receptor
DAG
?
IP3
Alcohol
I/R Injury Protection
Inactive PKC
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Interactions of Alcohol with Cardiovascular
Medications

• Adrenergic blockers (Propranolol)
• Antihypertensive agents (Guanethidine, Reserpine,
  Clonidine)
• Vasodilators (Nitroglycerin)
• ACE Inhibitors (Captopril, Lisinopril)

• Ca channel blockers (Verapamil, Nifidepine)
• Antiarrhythmic agents (Procainamide, Quinidine,
  Disopyramide)
• Inotropic agents (Digitalis)
• Anticoagulants (Warfarin, Aspirin)