Transcript lab # 6

313 PHL
Lab # 6
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
Effect
Receptors
Transmitter
Sympathetic nervous
system
- Stimulation of
myocardium .
- Positive inotropic
(increase force of
contraction) .
- positive chronotropic
(increase heart rate) .
Para sympathetic
nervous system
- Inhibition of
myocardium .
-negative inotropic
(decrease force of
contraction) .
-negative chronotropic
(decrease heart rate) .
β1
M2
Adrenaline
Ach
Autonomic nervous system supply of the heart:
Autonomic nervous
system
Synthetic agonist
Sympathetic nervous
system
Para sympathetic
nervous system
Isoprenaline
Methacholine
MOA
+ Gs protein→ + adenyl
+ Gi protein→ - adenyl
cyclase→↑ cAMP→↑ calcium cyclase→↓cAMP→↑K &
→contraction
↓calcium
→hyperpolarization
Blocker
- Propranolol “non-selective”
- Atenolol , metaprolol
“selective”
- Labetalol → α , β blocker
- phentolamine → α blocker
Atropine
Autonomic nervous system supply of the heart:
• Isoprenaline is 10 times more potent than adrenaline on the
isolated heart .
• Its effect are often more prolonged because it is not naturally
occurring inside the body so it can not be reuptake .
• Atropine can cause bradycardia followed by tachycardia .
• If large enough dose of Ach are given to the heart this will cause
cardiac arrest .
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 .
- They produce mild stimulation of heart muscle but this effect
is species dependant, Guinea-pig and rats heart show this
action but is rarely seen in isolated rabbit heart .
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
N
Kcl
N
Cacl2
Ach
Atropine
N
Ach
Isoprenaline
Propranolol
Isoprenaline
Experiment
N