| Summary: | A dissertation submitted to the Faculty of Medicine
University of the Witwatersrand, Johannesburg
for the degree of Doctor of Philosophy In Medicine
Johannesburg, 1988 === The p u rp o s e of this th e s is was to in v e stig a te the value In clin ic a l s itu a tio n s of
th e well k n o w n ir. vi tro a n tl-a d re n e rg lr effects of m agnesium . R esearch Interest
In m a g n e s iu m has been g ro w in g ra p id ly over the last tw e n ty years H ow ever,
m ost c f this interest has focu sed on the c lin ic a l c o n s e q u e n c e s of m agnesium
d e f i c i e n c y s ta te s and l i t t l e a t t e n t io n has been g iv e n to m a g n e s iu m as a
th e r a p e u tic agent. D espite the w id e use of Infusions of m agn e s iu m su lp h a te in
o b s te tric p ra c tic e , the re Is a d e a rth of k n o w le d g e re g a rd in g the a c tio n s o*
m a g n e s iu m on a c a rd io v a s c u la r system . In la b o ra to ry studie s, m agn e s iu m was
s how n to In h ib it the release of c a te c h o la m in e s from a d re n e rg ic nerve term inals,
an a c tio n w h ic h m ight have great c lin ic a l Im p lic a tio n s.
The effects of In creasing d o sage s of m agnesium on the c a rd io v a s c u la r system
of the in ta c t b a b o o n w ere investigate d. It w%s fo u n d that m a g n e siu m p ro d u c e d
a c o n s is te n t v a s o d ila to r effect w h ic h c o rre la te d w ell w ith th e serum m agnesium
levels but th e h y p o te n s iv e effects at serum levels b e lo w 5 m m o i/l w ere m inim al
d ue to a c o n c o m ita n t Increase c a rd ia c o u tp u t w h ich was p rim a rily m ediated
t h r o u g h an In c re a s e s l r o i . * v o lu m e T h e re w as no e v id e n c e o f n e g a tiv e
I n o t r o p i c e f f e c t s . T h e a c t i o n s o f m a g n e s i u m on a d r e n a l i n e - i n d u c e d
c a rd io v a s c u la r d is tu rb a n c e s were inv e s tig a te d . M agnesium s u lp h a te infu sio n s
exe rte d v a s o d ila to r and anti a rrh y th m ic effects of n m a g n itu d e lik e ly to be of
c lin ic a l b enefit w ith o u t p ro d u c in g nega tive in o tr o p ic effects. To d e m o n s tra te
the safety of m agn esium Infusions in the presence of alpha and beta b lo ck a d e ,
th e In te ra c tio n s of m agnesium in the prese nce of a d re n a lin e w l'h p h e n to lo m in e
and p r o p ra n o lo l w ere investigated. No d e le te rio u s In te ra c tio n s were n oted and
it a p p e a re d that m a g n e s iu m /p ro p ra n o lo l c o m b in a tio n s did not p o te n tia te the
n e g a tive in o tro p ic effects of beia b lo c k a d e
In t h e c l i n i c a l s t u d i e s , t h e a b i l i t y o f m a g n e s iu m I n f u s i o n s t o i n h i b i t
c a te c h o la m in e release in response to the stress of e n d o tra c h e a l In tu b a tio n was
d e m o n s t r a t e d . C o n d i t i o n s In w h ic h c a t e c h o la m in e e x c e s s c o n s i s t e n t l y
p ro d u c e s m ajor d iffic u ltie s include te ta n u s and p h a e o c h ro m o c y to m a . These
tw o c o n d itio n s are re la tive ly un c o m m o n and th is fact p re c lu d e d c o n tro lle d
trials. N evertheless, when suitable p a tie n ts p resen ted s tu d ie s on the use of
m a g n e s iu m In th e s e c o n d i t io n s w e re c o n d u c t e d . In t e t a n u s m a g n e s iu m
I n f u s i o n s Im p r o v e d c a r d i o v a s c u l a r c o n t r o l a n d r e d u c e d c p t e c h o l a m l n e
p io d u c t lo n . In p h a e o c h r o m o c y to m a s m a g n e s iu m e n h a n c e d In tra -o p e ra tiv e
c o n t r o l of c a r d io v a s c u la r d is tu r b a n c e s and a p a rt fro m p e r io d s of tu m o u r
h a n d lin g re d u c e d c a te c h o la m in e p ro d u c tio n . It Is c o n c lu d e d that m agnesium
Infu sio n s may be a v a luable a djun ct to the a n a e s th e tic m a n a g e m e n t of patie n ts
w ith high c a te c h o la m in e o u tp u t states.
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