MIT-WPU | School of Pharmacy

WORLD’S FIRST UNIVERSITY

FOR LIFE TRANSFORMATION

2. EFFECT OF DRUGS ON ISOLATED FROG’S HEART

Dr. Chinmay Deshmukh

Assistant Professor
Email: chinmay.deshmukh@mitwpu.edu.in
 Reference books

1. A Practical book of Pharmacology II by Dr. Pankaj M. Choudhari, Dr. Dheeraj T. Baviskar and Dr. Prakash Patil,

PV books, S Vikas and company (medical publishers) Jalandhar, 2019.

2. Ghosh M.N., Fundamentals Of Experimental Pharmacology, 3 rd Edition.

3. Kulkarni S.K., Practical Pharmacology And Clinical Pharmacy, Vallabh Publication,.

4. A Practical book of Pharmacology-II by Hemant Suryawanshi, Mukesh Patel and Sunil Pawar, Nirali

Prakashan, Second edition, January 2020.

 Requirements
• Apparatus

• Starlings heart leaver, Marriott’s constant pressure bottles, symes venous cannula, Sherrington’s
recording drum, syringes and needles

1. Acetylcholine 1 mg=1000 µg, Dissolve 1 mg of accurately weighed acetylcholine in 100 ml of distilled water. i.e.
1 mg in 100 ml water i.e. 1000 µg in 100 ml distilled water (10 µg in 1 ml)
2. Adrenaline hydrochloride 10 and 100 µg/ml
3. Potassium chloride 10 mg/ml
4. Calcium chloride 10 mg/ml
5. Propranolol 10 µg/ml
6. Atropine sulphate 100 µg/ml
7. PSS: Frog ringer
Langendorff Assembly set up for heart
 Principle
• Many drugs act on heart. Adrenergic and cholinergic drug produce opposite effect on it by acting
on different receptors.

• These drugs may influence the rate (chronotropy) and force (inotropy) of contraction of heart. An
increase in the heart rate is called positive chronotropic response whereas decrease in heart rate is
negative chronotropic response.

• Similarly an increase in force of contraction is called a positive inotroic effect and decrease in the
force of contraction is called a negative inotropic effect.

• Sympathomimetic amines such as adrenaline and noradrenaline produce positive inotropic and
positive chronotropic response whereas parasympathomimetics such as acetylcholine produce
negative chronotropic and negative inotropc response on heart.
 Effect of drugs on heart
Acetylcholine:

• Parasympathomimetics such as acetylcholine (in low dose) produce negative chronotropic and negative
inotropc response on heart.

• Ach liberated at post ganglionic parasympathetic nerve fibers exerts inhibitory effects on muscle cells due to its
ability of increasing the permeability of the cell membrane for potassium ions.

• The potassium ions under influence of Ach cause quick repolarization of cell membrane causing rapid
repolarization to shorten action potential. Thus heart is inhibited. This is called as muscarinic action

Calcium chloride (CaCl2): Calcium chloride in lower dose (less than 1%) increases heart rate and force of
contraction but in high doses inhibits the heart in systole.

Potassium chloride (Kcl) produces same effect as that of Ach and makes the heart to relax completely.

Atropine as such does not produce any effect except slight increase in heart rate and force of contraction
• Adrenaline:

• Sympathomimetic amines such as adrenaline and noradrenaline produce positive inotropic and positive
chronotropic response.

• The recording is characterized by increase in amplitude and beats. Adrenaline binds to beta receptor on cell surface
inducing conformational change which permits interaction of G protein with stimulatory G protein.

• This activation causes binding of GTP to alpha subunit causing dissociation of adenylate cyclase enzyme.

• This causes conversion of ATP to c AMP and activation of protein kinase A. This PKa causes increase in intracellular
calcium ion concentration by increasing release from store by releasing entry from extracellular fluid.

• This also causes increase interaction of Troponin and with calcium and subsequent contractility of myocardial cell.

• PKa also causes activation of phosphorylase enzyme which breaks down glycogen and increase glucose
concentration as energy source for myocardial contraction so overall activity of heart increases (both rate and force)

• Propranolol on low doses sometimes increases heart rate and contraction and in high doses it inhibits same
 Effect of drugs on heart
Sr. Drug Effect
No.
1 Acetylcholine Decrease in heart rate and force of contraction
2 Adrenaline: Increase in heart rate and force of contraction
3 Calcium Calcium chloride in lower dose (less than 1%)
chloride increases heart rate and force of contraction but
(CaCl2): in high doses inhibits the heart in systole.
4 Potassium Produces same effect as that of Ach and makes
chloride (Kcl) the heart to relax completely.
5 Atropine as such does not produce any effect except
slight increase in heart rate and force of
contraction
6 Propranolol on low doses sometimes increases heart rate
and contraction and in high doses it inhibits
same
 Short Questions

Explain the effects of following drugs on frog’s heart with mechanism

1. Acetylcholine
2. Calcium chloride
3. Potassium chloride
4. Adrenaline and
5. Propranolol
THANK YOU
S. No.124, Paud Road, Kothrud, Pune,
411038

10