2015A07 Briefly outline the effects of sevoflurane on skeletal, smooth and cardiac muscle tissues.
Include how these effects are mediated and their clinical significance.



·      Sevoflurane: relevant cellular effects

·      Cardiac muscle

·      Smooth muscle

·      Skeletal muscle


Sevoflurane: relevant cellular effects

·         ↑activity at GABA-A and glycine receptors -> Cl- influx -> prevent action potential

·         ↓L-Ca2+ activity (↓L-Ca2+

·         ↑nitric oxide release (↑NO)

·         ↓medullary sympathetic outflow (↓SNS)

·         ↓nicotinic ACh receptor activity (↓nAChR)

·         Most effects are dose-dependent


Cardiac muscle:


Heart rate

·     Direct effect: ↓

o ↑GABA/glycine -> ↓SNS output from medulla

o ↓L-Ca2+ channel activity

o ↑NO release

·     Indirect effect: ↑

o Baroreceptor reflex relatively preserved

o Reflex tachycardia common

Anaesthetic preconditioning

·     Activates ATP-sensitive K+ channels in mitochondria and sarcolemma

·     Mimics ischaemic preconditioning -> ↓risk myocardial ischaemia

·     Active at MAC >0.25

·     Onset in minutes, offset 3-4 days

↑QT interval

·     ? Mechanism

·     ↑Risk torsades de pointes (rarely significant)

·     Sevoflurane, enflurane, isoflurane

Coronary steal syndrome

·     ↓ L-Ca2+ channel, ↑NO

·     Awake:

o Stenotic vessel maximally dilated

o Other vessels mid-dilated

o Preserved flow through stenosis

·     Under GA:

o Stenotic vessel no change

o Other vessels ↑dilatation

o ↓CO, ↓SVR -> ↓aortic root diastolic pressure -> ↓total coronary flow

o ↓flow through stenosis

·     Rarely significant

·     Isoflurane > others due to greater reduction in SVR


Smooth muscle:


·     ↓L-Ca2+, ↑NO, ↓SNS

Systemic vasodilatation

·     Arteries: ↓SVR, ↓mAP; ↑heat loss

·     Veins: ↓preload -> cardiac output; easier to cannulate

Pulmonary vasodilatation

·     ↓PVR, ↓HPV, ↑V/Q mismatch, ↓PaO2

Cerebral vasodilatation

·     Overrides ↓CMRO2 at >1MAC

·     Risk of ↑ICP concomitant intracranial pathology


·     ↓Airway resistance

·     Used in status asthmaticus

Uterine relaxation

·     ↑Bleeding during GA Caesarean (hence supplement with N2O, propofol)




·     CNS and α-motor neurons: ↑GABA-A, ↑glycine

·     Pre-synaptic: ↓L-Ca2+ -> ↓ACh release

·     Post-synaptic: ↓nAChR


·     Potentiates paralytics

·     Facilitates surgery


·     Relaxation of intercostals > diaphragm

·     Depression of chemoreceptors and respiratory centre

·     ↓↓Response to ↓PaO2

·     ↓Response to ↑PaCO2

Airway obstruction

·     ↓Pharyngeal dilator tone

·     Need for airway device

Malignant hyperthermia

·     Rare, life-threatening hypermetabolic reaction to volatile anaesthetics or suxamethonium

·     Mutation in RYR1 gene encoding skeletal muscle ryanodine receptor

·     Continuous Ca2+ release from SR causing continuous contraction

·     Idiosyncratic, not dose-dependent like all the above




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