Hyperpolarized / Polarized

arrest as an alternative to Depo

larized arrest

Guo Wei

Zhejiang University School of Medicine

Elective cardiac arrest can be achieved by indu

cing depolarization, polarization, hyperpolriz

ation or influencing calcium mechanisms

Depolarized arrest

Depolarized arrest: induced by elevating the extr

acellular potassium concentration, is currently

the most commonly used technique.

Hyperkalemia: usually within 15 to 40 mmol/L.

Depolarized arrest

Hyperkalemia leads t

o a depolarization of

the membrane potent

ial (Em) from about -

80 mv to around - 50

mv in cardiac tissue

At this depolarized potential, the fast Na+ chann

els are inactivated (since the threshold is - 70 to

- 65 mv, resulting in diastolic arrest

However ,The reversal potential of the Na+– Ca 2+ exchanger also occurs at - 50 mv

Depolarized arrest

Moreover, higher potassium concentrations, wh

ich depolarize the membrane further (to aroun

d -40 mv), would tend to activate the slow calci

um channel and cause calcium influx into the m

yocyte

Other ionic mechanisms also exist (such as Na–

H exchange)

hyperkalemia disadvantages

Other ionic currents remain active

Energy-dependent transmembrane pumps re

main active in an attempt to correct these abn

ormal ionic gradients, depleting critical energ

y supplies

High potassium-induced endothelial injury

A potentially beneficial alternative to hyperkale

mic cardioplegia is to arrest the heart in a hype

rpolarized or polarized state, which maintain

s the membrane potential of the arrested myoca

rdium at or near to the resting membrane pote

ntial

Polarized /hyperpolarized arrest

hyperpolarized/ Polarized arrest: induced by so

dium-channel blockers or by agents that activat

e potassium channels

Polarized /hyperpolarized arrest

advantages : ionic movement (particularly Na+

and Ca2+) reduced, because the threshold

potential for activation of the ion channels will

not be reached and window currents will not be

activated. This reduction in ionic imbalance

should, in turn, reduce myocardial energy

utilization

Polarized /hyperpolarized arrest

Polarized arrest can be achieved in a number of

ways

Sodium-channel blockade [ Procaine and TTX ]

Na/H exchange inhibitor [HOE 694]

Na/K/2Cl cotransport inhibitor [furosemide])

influencing Ca2+ desensitization [BDM]

Polarized /hyperpolarized arrest

Adenosine or potassium channel openers (KCO

s) , which are thought to induce hyperpolarized

arrest have demonstrated improved protection

when compared to hyperkalemic (depolarized)

arrest

Adenosine

Adenosine can induce arrest through a hyperpo

larization effect, particularly on myocardial co

nductive tissue, and was shown to provide good

myocardial protection when used alone (at a co

ncentration of 10 mmol/L) as a cardioplegic age

nt or as an additive (1 mmol/L) to K+ cardiople

gia

Adenosine

Some studys showed that the adenosine plus hy

perkalemic solution induced an initial transient

hyperpolarization before depolarization; this in

itial hyperpolarization was thought to arrest S

A node conduction before myocyte contractility

arrest

ATP-sensitive potassium channel

ATP-sensitive potassium-channel activation myo

cardial resting Em (around -80 mv) is close to th

e equilibrium

potential of K+

(about -94 mv)

.

ATP-sensitive potassium channel

Hyperpolarization with KCOs has been demon

strated in isolated guinea pig and human ventri

cular myocytes

KCOs have also been used as additives to hyper

kalemic cardioplegic solutions and have been s

hown to enhance postischemic recovery of funct

ion

ATP-sensitive potassium channel

The improved protection compared to the K+

cardioplegic solution may be related to its abi

lity to maintain minimal metabolic

activity, thereby maintaining transmembrane i

onic gradients

Calcium antagonists

Hypocalcemia The absence of extracellular Ca2

+ induces cardiac arrest in diastole

High concentrations of calcium antagonists pre

vent Ca2+-induced Ca2

+ release and induce arres

t by inhibiting excitation-contraction coupling,

thus exerting a protective effect on cardiac arre

st

Calcium antagonists

But the membrane binding property of these

drugs may result in slow recovery.

The absence of Ca2+ increased the risk of a

"calcium paradox"

In conclusion, myocardial protection during ca

rdiac surgery or cardiac transplantation has rel

ied on hyperkalemic solutions for many years.

However, hyperkalemic solutions have a numbe

r of problems

Hyperpolarization or polarization should avoid

or reduce some of the damaging effects associat

ed with depolarization

Considerable additional studies are required