313 PHL

Lab # 7

Effect & site of action of different drugs on isolated rabbit's heart (Langendorff preparation)

- The heart is innervated by both sympathetic and parasympathetic nerve.

- This innervations alter the basic rhythm of the heart which is initiated by the pacemaker tissue of the sinoatrial node (SA node) atria AV node Bundle of His Purkinjee fibers ventricles .

- When the heart is removed from the intact animal and maintained in an isolated organ system the heart will beat spontaneously by virtue of the myogenic rhythm controlled by SA node .

Heart muscle Properties:

•The Heart consist of special muscle called syncitium, The properties of this muscle are :

Contractility .

Rhythmicity (at certain heart rate) .

Conductivity (conduction from one area to other area) .

Automaticity (response to intrinsic stimuli) .

Excitability (response to external stimuli) .

Receptors present in the isolated rabbit heart:

• Neural nicotinic receptors (Nn receptors): present in parasympathetic ganglia (embedded in the heart).

• Muscarinic receptors (M2 receptors ) : present at postganglionic parasympathetic nerve terminal.

• Adrenergic receptors (β1 receptors ) : present at postganglionic sympathetic nerve terminal.

• Histaminergic receptors (H2 receptors ).

Autonomic nervous system supply of the heart:

Autonomic nervous system

Sympathetic nervous system

Para sympathetic nervous system

Effect - Stimulation of myocardium .- Positive inotropic (increase force of contraction) .- positive chronotropic(increase heart rate) .

- Inhibition of myocardium .-negative inotropic (decrease force of contraction) .-negative chronotropic(decrease heart rate) .

Receptors β1 M2

Transmitter Adrenaline Ach

Autonomic nervous system supply of the heart:

Autonomic nervous system

Sympathetic nervous system

Para sympathetic nervous system

Synthetic agonist Isoprenaline Methacholine

MOA + Gs protein→ + adenyl cyclase→↑ cAMP→↑ calcium →contraction

+ Gi protein→ - adenyl cyclase→↓cAMP→↑K & ↓calcium →hyperpolarization

Blocker - Propranolol “non-selective”

- Atenolol , metaprolol “selective”

- Labetalol → α , β blocker

- phentolamine → α blocker

Atropine

Other agents that influence the heart function:

• Histamine:

Receptor: H2

MOA:+ Gs protein → ↑ cAMP →↑calcium → contraction

Antagonist : Ranitidine .

Other agents that influence the heart function:

• xanthines :Examples: theophylline, caffeine & theobromine .

MOA: Phosphodiesterase enz. Inhibitors (PDEI) → ↑ cAMP → ↑Ca+2 → Contraction .

Effect:

- Positive inotropic & chronotropic .

Direct acting drug:

Direct acting stimulant:

e.g. calcium chloride (Cacl2) .

Direct acting depressant:

e.g. potassium chloride (Kcl) .

Arrhythmia and anti-arrhythmic drugs:

e.g. alkaloid aconitine .

Action:

ectopic focus and generation of cardiac dysrhythmia → ventricular tachycardia and fibrillation → it can be reversed by antidysrhythmic drug such as lignocaine .

Determination of heart rate

Example:

Speed= 1square/sec, Number of beat/sq=6 beats/square

Calculate the HR (beat per minute)?

6 beats 1 sec.

x 60 sec

x = 60*6 = 360 BPM