hyperpolarized / polarized arrest as an alternative to depolarized arrest guo wei zhejiang...
TRANSCRIPT
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