Malignant Hyperthermia (“MH”)—the rapid onset of extremely
high fever with muscle rigidity—is caused by a runaway heat production futile
cycle mediated via the sodium channels at the myoneural receptor sites. MH is
not triggered by non-depolarizing muscle relaxants; however, depolarizing
muscle relaxants may trigger it [1]. Here we present a de novo hypothesis of
how MH is triggered and develops. We believe that the acetylcholine
receptor/sodium channels in the muscles of MH susceptible pigs initiate MH by allowing
an increased flux of sodium ions when it is depolarized by acetylcholine or
other depolarizing agents, such as succinylcholine and Halothane. Our theory is
consistent with our observations of the effects of general anesthetics over
twenty years. Succinylcholine is a depolarizing agent that is a potent MH
trigger. Acetylcholine, the natural depolarizing muscle activator, may trigger
MH if the susceptible patient or animal is exposed to sufficient stress, i.e.,
during strenuous activity, such as transport, fighting, breeding, etc.
Halothane apparently destabilizes the myoneural sodium channels, which rapidly
induces MH. The increased sodium channel activity releases heat with cascades
that further releases of heat which results in the rapid onset of MH. MH
susceptible pigs have increased action potential amplitudes at their myoneural
junctions that are abnormally long in duration. This increased activity is
thought to induce hypertrophy of muscle mass, increase metabolic rate, and
cause other physical manifestations. When slaughtered, this increased metabolic
activity causes the rapid post mortem release of heat in the muscles of MH
susceptible pigs and, at the same time, the accumulation of low acidity, all of
which denatures the muscle proteins to result in a pale, soft, exudative, pork
meat considered to be of lesser quality for human consumption. The potency of
inhalation anesthetics as a MH triggers varies widely. The inhalation
anesthetic Halothane is a strong trigger of MH, causing MH within minutes of
exposure. In contrast, the anesthetic Sevoflurane is a very weak trigger of MH,
requiring several hours of inhalation exposure to trigger MH. Because of this,
changing from Halothane to Sevoflurane as the general anesthetic of choice for
surgeries in hospitals in the Greater Kansas City area during 1994 to 2006 led
to an 11-fold decrease in the incidence of MH, from 1:50,000 to 1:550,000 [2].
One non-depolarizing muscle relaxant, Organon 9426 (“Rocuronium”) temporarily
prevents MH in MH susceptible pigs when they are given sufficient dosages of it
before being challenged with either Halothane or succinylcholine. Binding
Rocuronium to the myoneural receptor sites apparently stabilizes them, thereby
preventing increased sodium channel activity, and resulting MH. However, other
nondepolarizing muscle relaxants do not have this protective effect— for
examples Vecuronium, Arduan, and Organon 9616 do not. Uncoupling of
mitochondria is not the source of accelerated heat production in MH susceptible
pigs, as heart, liver, and skeletal muscle mitochondria isolated from MH
susceptible pigs are all competent.
Author(s) Details
Charles H. Williams The Williams Research Laboratory, 100 Winterset Ct, Sunrise Beach, MO 65079, USA.
View Book :- http://bp.bookpi.org/index.php/bpi/catalog/book/206
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