The document discusses various in vivo and in vitro models used to screen anti-arrhythmic drugs. It describes methods like chemically induced arrhythmia using aconitine in rats, electrically induced arrhythmias using current stimulation in dogs, exercise induced ventricular fibrillation in dogs, and mechanically induced arrhythmias through coronary artery ligation and reperfusion in dogs. The screening aims to evaluate drugs for their ability to prevent arrhythmias like ventricular tachycardia, fibrillation, and changes in hemodynamic parameters and mortality.

1. UNDER THE GUIDANCE OF:
Dr. T. VEDAVATHIM.PHARM, PhD
PHARMACOLOGICAL SCREENING OF
ANTI-ARRHYTHMIC DRUG
PRESENTED BY:-
RAKESH KUMAR
M.PHARMACY (PHARMACOLOGY)
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2. CARDIAC ARRHYTHMIAS
Deviation from normal
• Origin/Conduction
• Rhythm
• Rate
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3. CLASSIFICATION OF ARRHYTMIAS
• Normal heart rate – 60-100 beats/min
Based on the heart rate:
• Tachyarrhythmia - rapid heart beat - >100/min
• Bradyarrhythmia – slow heart beat - <60/min
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4. SCREENING OF ANTI-ARRHYTHMICS
DRUG SCREENING:
Pre clinical testing of drugs in experimental
animals or in vitro for their biological and toxic
effects and potential clinical applications
The screening of anti-arrhythmics is done by two
different methods.
• In-vitro models
• In-vivo models
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5. IN VIVO MODELS
• Chemically induced arrhythmia
• Electrically induced arrhythmia
• Exercise induced ventricular fibrillation
• Mechanically induced arrhythmia
• Genetically induced arrhythmia
•
•
•
•
•
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6. CHEMICALLY INDUCED ARRHYTHMIA
• A large number of agents are capable of
inducing arrhythmias
• Administration of anesthetics like chloroform,
ether, halothane followed by a precipitating
stimulus such as adrenaline, ouabain alkaloids
cause arrhythmia
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7. PURPOSE AND RATIONALE:
Aconitine – acts persistently on sodium
channels and activates them – ventricular
arrhythmias
REQUIREMENTS:
Animals - Male Ivanovas rats (300-400g)
Anesthetic – Urethane
Standard drug – Procainamide i.v (5mg/kg)
Lidocaine i.v (5mg/kg)
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8. PROCEDURE
Animals – selected

Anesthetized


Test / std/control – administered
↓
Aconitine (5μg/kg +0.1N HNO₃) (administered through
saphenous vein)
↓
ECG – Recorded
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9. •
•
•
•
•
•
EVALUATION
•Ventricular tachycardia
•Ventricular fibrillation
•Death
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10. • Electrical stimulations – flutters and
fibrillation
REQUIREMENTS :
• Animals – adult dogs (8-12kg)
• Anesthetic – sodium pentobarbital (35mg/kg)
ELECTRICALLY INDUCED ARHYTHMIAS
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11. PROCEDURE
Animal – selected
↓
Anesthetized
↓
Artificial respiration – Harvard respiratory pump
B.P – monitored
Body temperature – maintained by thermal blanket
↓
Chest cavity is opened
↓
Heart suspended in pericardial cradle
↓
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12. ↓
SA node – crushed
↓
For electric impulse – Ag-AgCl electrode embedded in a teflon
disc- sutured on left ventricle
↓
Test drug/ std/contol – femoral artery
↓
Constant current for 400ms is applied through electrode
↓
Recording elecrodes – surface of each ventricle
↓
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13. Recording elecrodes – surface of each ventricle
↓
ECG – monitored
↓
VFT is measured (minimal current intensity required to induce
sustained ventricular fibrillation)
When VF occurs – heart is defibrillated – recovered
EVALUATION
Ventricular Fibrillation Threshold
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14. EXERCISE INDUCED VENTRICULAR
FIBRILLATION
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REQUIREMENTS
Animals – Mongrel dogs (15 -19 kg)
Anesthetic – Sodium pentobarbitone (10mg/kg) i.v.

15. SURGICAL PREPARATION
Animals – selected
↓
Anesthetized
↓
Chest cavity – opened
↓
Heart suspended in pericardial cradle
↓
around left artery – Doppler flow inducer- to measure blood
pressure _
hydraulic occluder – place to occlude coronary
artery
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16. ↓
Pair of insulated silver coated wires – sutured on left and right
ventricles- measure HR
↓
Occlusion of LAD
↓
Myocardial infarction
↓
After 24 hrs- test drug/std/control - administered
During this experiment:
• Transdermal fentanyl patch (↓post operative discomfort)
• Bupivacaine HCl
• Antibiotic therapy(amoxicillin)
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17. 3-4 weeks after the production of MI
↓
Animals – run on a motor –driven treadmill
↓
Work load - ↑every 3 min for total of 18 mins
↓
During last minute-treadmill is stopped- left
artery- occluded for 2 mins
↓
After 10-20 sec of VF – defibrillation is achieved without
any delay by placing large metal plates across animal’s
chest
EVALUATION:
HR is measured
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18. MECHANICALLY INDUCED ARRHYTHMIA
Arrhythmias –induced directly by ischemia and
reperfusion
• Coronary artery ligation in anesthetized dog
results in:
↑ in HR
↑in heart contractility
↑ in BP
Ventricular arrhythmias
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19. REQUIREMENTS
Animals – Dogs (20-25Kg)
Anesthetic – Thiobutobarbital sodium (30mg/kg)
PROCEDURE:
Animals – selected
↓
Anesthetized
↓
Artificial respiration – positive pressure respirator
↓
Femoral artery – cannulated and connected to pressure transducer
↓
Chest cavity –opened
LAD is exposed
↓
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20. Silk suture is placed around LAD
↓
After 45 min(equilibration) – test/std/control-
administered through saphenous vein
↓
After 20 min- ligature of coronary artery is closed for 90
min
↓
Occlusion released – reperfusion period maintained for
30 min.
• All the parameters – recorded
• At the end – surviving animals are sacrificed by an
overdose of Pentobarbital sodium
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21. EVALUATION
• Mortality
• Hemodynamics
• Heart rate
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