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

Contractility

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

Mechanism

·     ↓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

Bronchodilatation

·     ↓Airway resistance

·     Used in status asthmaticus

Uterine relaxation

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

Mechanism

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

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

·     Post-synaptic: ↓nAChR

Immobility

·     Potentiates paralytics

·     Facilitates surgery

Hypoventilation

·     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