CVS effects of AA

[Ref: SH4:p51]

Mean arterial pressure (MAP)

• HAL, ISO, DES, and SEVO all produce similar and dose-dependent decreases in MAP.
• N2O produces either no change or modest increase in MAP

Mechanism

• HAL reduce MAP by decreases in myocardial contractility (and cardiac output)
  * No effect on SVR
• ISO, DES, and SEVO reduce MAP by decrease in systemic vascular resistance

Heart rate (HR)

• ISO, DES, and SEVO increase HR
  * SEVO increase HR only at >1.5 MAC
  * ISO and DES increase HR at lower concentration
• HAL does not cause reflex HR (secondary to decreased BP)
  * Due to depressed carotid sinus reflex and depressed sinus node depolarisation

This increase in HR is prevented by a small dose of opioid

ISO vs DES

• At 0.5 MAC, ISO and DES produce similar decrease in MAP
• At 0.5 MAC, ISO increase HR, but DES does not

With ISO, the increase in HR is:
* Blunted in elderly
* More likely to occur in younger patients

Cardiac output and stroke volume

All AA (except N2O) decrease cardiac output by 15-30%

Increase in HR tend to compensate for the decrease in cardiac output

N2O causes mild increase in cardiac output
* Possibly due to mild sympathomimetic effect of N2O

Right atrial pressure (RAP)

--> Indicator of central venous pressure

HAL, ISO, and DES all increase RAP
* Due to myocardial depression
* Peripheral vasodilating effect may minimise the increase in RAP

N2O increases RAP
* Possibly due to increased pulmonary vascular resistance due to sympathomimetic effect

Systemic vascular resistance (SVR)

• ISO, DES, and SEVO decrease SVR
• HAL and N2O does not affect SVR

Blood flow distribution with ISO

• ISO increases blood flow in skeletal muscle and skin
  * beta agonist effect

Implications include:
* Excess perfusion relative to O2 requirement
* Loss of body heat
* Enhanced drug delivery to neuromuscular junctions

Cutaneous blood flow

• HAL does not increase overall SVR
  * But increase blood flow to brain and skin
• All AA (except for N2O) increase cutaneous blood flow
  ^ Most likely due to inhibition on temperature regulating mechanisms
• N2O may produce cutaneous vasoconstriction

Clinical relevance

Peripheral vasodilation:

• Undesirable in aortic stenosis
• Beneficial in mitral or aortic regurgitation

Pulmonary vascular resistance (PVR)

• All AA (except for N2O) exert little effect on PVR
• N2O causes pulmonary vasoconstriction
  * Exaggerate pulmonary hypertension
  * Increase magnitude of right-to-left intracardiac shunting of blood

Duration of administration

After 5 hours, cardiac output recovers from the cardiac depressant effects of AA

HR is increased and SVR is decreased
--> BP unchanged

This recovery is

• Most pronouced in HAL
• Least in ISO
  * ISO caused minimal drop in cardiac output anyway

Cardiac dysrhythmias

Alkane derivative (e.g. HAL)
--> Decreases the dose of epinephrine necessary to evoke ventricular cardiac arrhythmia

Ether derivatives (e.g. ENF, ISO, DES, SEVO)
--> Minimal effect

Both HAL and ISO
* Slow the rate of SA node discharge
* Prolong His bundle and ventricular conduction time

Accessory pathway and ablation procedures

ISO increases refractory of accessory pathways
--> Interfer with postablation studies

SEVO has almost no effect on AV or accessory pathways
--> Acceptable for ablation procedures

Spontaneous breathing

Spontaneous breathing during anaesthesia has 2 effects relevant to CVS

• Accumulation of CO2
  * Sympathetic stimulation
  * Direct relaxing effect on peripheral vascular smooth muscles
• Better venous return
  ^ Due to less pressure on pulmonary vessels

Thus,

During spontaneous breathing

• Cardiac output is higher
• HR is higher
• MAP is higher
• Total peripheral resistance is lower

Coronary blood flow

AA causes coronary vasodilation
* Preferentially dilates vessels with diameters from 20 microm to 50 microm

However,

Coronary steal syndrome is not clinically significant
* All AA (including ISO) are cardioprotective
* [SH4:56]

Neurocirculatory response

Abrupt increase in ISO and DES (from 0.55 to 1.66 MAC)
--> Sympathetic stimulation and increase renin-angiotensin activity
--> Increased HR and MAP
* Greater increase with DES
* Blunted by fentanyl, esmolol, and clonidine

Abrupt increase in SEVO
--> No neurocirculatory response

Effect of pre-existing disease

In patients with coronary artery disease,
* N2O produce myocardial depression which doesn't occur in patients without cardiac disease

Calcium channel blockers
--> Myocardial depression
--> More vulnerable to direct depressant effect of AA

Cardiac protection

Ischaemic preconditioning

Brief episodes on myocardial ischaemia
--> Offers protection against subsequent longer periods of ischaemia and infarct

Two phases

• First phase last for 1-2 hours
• Second phase occurs after 24 hours, lasting up to 3 days

Mechanism of ischaemic preconditioning

Release of adenosine
--> Binds to adenosine receptors
--> Increase protein kinase C activity
--> Phosphorylation of ATP-sensitive K+ channel (K_ATP)
--> Less sensitive to inhibition by ATP
--> More K+ current
--> Less Ca2+ accumulation and more hyperpolarization
--> More relaxation and mild negative inotropic effect

Anaeshetic preconditioning

Brief exposure to ISO, SEVO, DES
--> Activate K_ATP channel
--> Cardioprotection identical to ischaemic preconditioning

Cardiac surgical patients receiving SEVO has less troponin I release in the first 24 hours than patients receiving propofol