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Magnesium in supraventricular and ventricular
arrhythmias
Zehender M.
Germany
Zeitschrift fur Kardiologie (Germany), 1996, 85/Suppl. 6
(135-145)
The use of magnesium as an antiarrhythmic agent in
ventricular and supraventricular arrhythmias is a matter of an
increasing but still controversial discussion during recent
years. With regard to the well established importance of
magnesium in experimental studies for preserving electrical
stability and function of myocardial cells and tissue, the use
of magnesium for treating one or the other arrhythmia seems to
be a valid concept. In addition, magnesium application
represents a physiologic approach, and by this, is simple,
cost-effective and safe for the patient. However, when one
reviews the available data from controlled studies on the
antiarrhythmic effects of magnesium, there are only a few
types of diac arrhythmias, such as torsade de pointes,
digitalis-induced ventricular arrhythmias and ventricular
arrhythmias occurring in the presence of heart failure or
during the perioperative state, in which the antiarrhythmic
benefit of magnesium has been shown and/or established.
Particularly in patients with one of these types of cardiac
arrhythmias, however, it should be realized that preventing
the patient from a magnesium deficit is the first, and the
application of magnesium the second best strategy to keep the
patient free from cardiac arrhythmias.
Effect of intravenous magnesium sulfate on cardiac
arrhythmias in critically III patients with low serum ionized
magnesium
Kasaoka S.; Tsuruta R.; Nakashima K.; Soejiina Y.; Miura T.;
Sadamitsu D. ; Tateishi A.; Maekawa T.
Critical Care Medical Center, Yamaguchi University Hospital,
1144 Kogushi, Ube, Yamaguchi 755 Japan
Japanese Circulation Journal (Japan), 1996, 60/11
(871-875)
Magnesium affects cardiac function, although until the
recent development of a new ion selective electrode no method
existed for measuring the physiologically active form of
magnesium, free ions (iMg2+), in the blood. We investigated
the antiarrhythmic effect of magnesium sulfate administered to
critically ill patients with cardiac arrhythmias and reduced
iMg2+ as determined using the ion-selective electrode. Eight
patients with a low iMg2+ level (less than 0.40 mmol/L) were
given intravenous magnesium sulfate (group L). Magnesium
sulfate was also administered to patients with a normal iMg2+
level (more than 0.40 mmol/L) but who did not respond to
conventional antiarrhythmic drugs (group N). Intravenous
magnesium sulfate significantly increased the iMg2+ level in
patients in group L from 0.35plus or minus0.06 mmol/L (mean
plus or minus SD) to 0.54 plus or minus 0.09 mmol/L
(p<0.01), and had an antiarrhythmic effect in 7 of the 8
patients (88%). However, in group N patients, intravenous
magnesium sulfate had an antiarrhythmic effect in only 1 of
the 6 patients (17%) (p<0.05 vs group L). These results
suggest that intravenous magnesium sulfate may be effective in
the acute management of cardiac arrhythmias in patients with a
low serum iMg2+ level.
Ionic mechanisms of ischemia-related ventricular
arrhythmias
Ducceschi V.; Di Micco G.; Sarubbi B.; Russo B.; Santangelo
L.; Iacono A.
Facolta di Medicina e Chirurgia, Isto. Medico-Chirurgico
Cardiologia, Seconda Universita di Napoli, Piazza L. Miraglia,
80138 Naples Italy
Clinical Cardiology (USA), 1996, 19/4 (325-331)
The aim of this review is the utmost simplification of the
cellular electrophysiologic background of ischemia-related
arrhythmias. In the acute and subacute phase of myocardial
infarction, arrhythmias can be caused by an abnormal impulse
generation, abnormal automaticity or triggered activity caused
by early or delayed afterdepolarizations (EAD and DAD), or by
abnormalities of impulse conduction (i.e., reentry). This
paper addresses therapeutic intervention aimed at preventing
the depolarization of 'pathologic' slow fibers, counteracting
the inward calcium (Ca) influx that takes place through the
L-type channels (Ca antagonists), or hyperpolarizing the
diastolic membrane action potential increasing potassium (K)
efflux (K- channel openers) in arrhythmias generated by an
abnormal automaticity (ectopic tachycardias or accelerated
idioventricular rhythms). If the cause of enhanced impulse
generation is related to triggered activity, and since both
EAD and DAD are dependent on calcium currents that can appear
during a delayed repolarization, the therapeutic options are
to shorten the repolarization phase through K-channel openers
or Ca antagonists, or to suppress the inward currents directly
responsible for the afterdepolarization with Ca blockers.
Magnesium seems to represent a reasonable choice, as it is
able to shorten the action potential duration and to function
as a Ca antagonist. Abnormalities of impulse conduction
(reentry) account for the remainder of arryhythmias that occur
in the acute and subacute phase of ischemia and for most
dysrhythmias that develop during the chronic phase. Reentrant
circuits due to ischemia are usually Na channel-dependent.
During choice will depend on the length of the excitable gap:
in case of a short gap (ventricular fibrillation, polymorphic
ventricular tachycardia, etc.), the refractory period has been
identified as the most vulnerable parameter, and therefore a
correct therapeutic approach will be based on drugs able to
prolong the effective refractory period (K-channel blockers,
such as class III antiarrhythmic drugs); on the other hand,
for those arrhythmias characterized by a long excitable gap
(most of the monomorphic ventricular tachycardias), the most
appropriate therapeutic intervention consists of depressing
ventricular excitability and conduction by use of
sodium-channel blockers such as mexiletine and lidocaine.
Compared with other class I antiarrhythmic agents, these drugs
minimally affect refractoriness and exhibit a use-dependent
effect and a voltage dependent action (i.e., more pronounced
on the ischemic tissue because of its partial
depolarization).
Myocardial infarction: The first 24 hours
Gavagan T.; Reddy M.J.
Dept. of Family Practice, 1900 W. Polk St., Chicago, IL 60612
USA
American Family Physician (USA), 1996, 54/3
(921-938)
Myocardial infarction is the most common cause of death in
the United States. Rapid postinfarction intervention in the
first 24 hours decreases mortality. Treatment modalities are
rapidly evolving as new data from basic science research and
clinical trials become available. Rapid thrombolysis, accurate
criteria for diagnosis and administration of effective
adjunctive therapy are crucial in preventing complications of
myocardial infarction. Initial measures in the emergency
department include intravenous access, accurate history and
physical assessment, placement of oxygen, electrocardiography,
use of aspirin and nitrates, and consideration of thrombolysis
or angioplasty in appropriate candidates, optimally within one
to two hours of myocardial infarction. After hospital
admission, additional adjunctive treatment, including beta
blockers, angiotensin-converting enzyme inhibitors and
anticoagulation, can be instituted.
Proarrhythmic and antiarrhythmic actions of ion
channel blockers on arrhythmias in the heart: Model
study
Chay T.R.
Department of Biological Sciences, University of Pittsburgh,
Pittsburgh, PA 15260 USA
American Journal of Physiology - Heart and Circulatory
Physiology (USA), 1996, 271/1 40-1 (H329-H356)
We explain why 1) some class I and IV antiarrhythmia drugs
could exert proarrhythmic action, 2) some class III drugs are
effective in controlling reentrant arrhythmias, and 3) cycle
length (CL) oscillation is involved in the termination or
initiation of reentry. To explain these phenomena, we employ
the following three means: bifurcation analysis, simulation,
and model construction. Antiarrhythmia drugs are modeled by
varying maximal conductances of Na+, Ca2+, and time-dependent
delayed rectifying and time- independent inward rectifying K
channels in the Beeler-Reuter model, where the model cells are
arranged in a ring. Bifurcation analysis predicts that there
is a critical ring size (CRS) at which infinite ring behavior
suddenly breaks down. Channel blockers can affect CRS in
different manners: Na+ and Ca2+ blockers shorten CRS, whereas
delayed rectifying K+ channel blockers and the inward K+
channel blockers lengthen CRS. This differential explains why
some antiarrhythmia drugs are proarrhythmic (i.e., shorten
CRS) whereas others are antiarrhythmic (i.e., lengthen CRS).
Simulation is then used to investigate how the drugs affect
reentrant rhythms in the neighborhood of the CRS. We find
that, in this region, CL, conduction velocity, and action
potential duration become oscillatory. As ring size shrinks,
the pattern of the oscillation becomes more complex. When the
ring shrinks to a certain size, reentry can no longer be
sustained, and it terminates after a few oscillatory cycles.
To explain the basic mechanism involved in CL oscillation, we
then construct a minimal model that contains a low-threshold
fast inward current and a high-threshold slow inward current.
With this model, we show that the two inward currents, with
vastly different activation and inactivation kinetics, cause
CL oscillations. Our results thus give theoretical
explanations for the experimental finding of Frame's group in
canine atrial tricuspid ring in vitro that class IC drugs can
bring about stable reentry from nonsustained transient
reentry, whereas class III drugs transform stable reentry to
complex oscillations in CL. Our results also support the
result of Frame's group, in that, in 'adjustable' tricuspid
rings, CL oscillation becomes more complex and its period
becomes shorter as an excitable gap is shortened.
Prophylactic effects of taurine and diltiazem,
alone or combined, on reperfusion arrhythmias in rats
Li P.; Kang Y.; Wang G.-X.
Department of Pharmacology, Tianjin Medical University,
Tianjin 300070 China
Acta Pharmacologica Sinica (China), 1996, 17/2
(122-124)
Aim: To study the effects of taurine (Tau) and diltiazem
(Dil), alone or in combination, on reperfusion arrhythmias in
anesthetized rats.
Methods: The arrhythmias were produced by coronary artery
ligation for 15 min followed by reperfusion. Malondialdehyde
(MDA) content and superoxide dismutase (SOD) activity were
measured by thiobarbituric acid fluorescence assay and
colorimetric determination.
Results: Taurine 70 mg . kg-1 in combination with Dil 1 mg
. kg-1 were more effective on prevention of the reperfusion
arrhythmias than each drug alone. The combination of both
drugs not only decreased the content of MDA, but also
increased the activity of SOD in reperfusion myocardium.
Conclusion: The inhibition of lipoperoxides formation as
well as the inhibition of the calcium influx was involved in
the anti-arrhythmic effect of both taurine and diltiazem.
The cardiovascular protective role of
docosahexaenoic acid
McLennan P.; Howe P.; Abeywardena M.; Muggli R.; Raederstorff
D.; Mano M. ; Rayner T.; Head R.
CSIRO, Division of Human Nutrition, Gouger Street, Adelaide,
SA 5000 Australia
European Journal of Pharmacology (Netherlands), 1996, 300/1-2
(83-89)
Dietary fish oils rich in n-3 polyunsaturated fatty acids
can modulate a diverse range of factors contributing to
cardiovascular disease. This study examined the relative roles
of eicosapentaenoic acid (20:5 n-3; EPA) and docosahexaenoic
acid (22:6 n-3; DHA) which are the principal n-3
polyunsaturated fatty acids regarded as candidates for
cardioprotective actions. At low dietary intakes (0.4-1.1% of
energy (%en)), docosahexaenoic acid but not eicosapentaenoic
acid inhibited ischaemia-induced cardiac a rrhythmias. At
intakes of 3.9-10.0%en, docosahexaenoic acid was more
effective than eicosapentaenoic acid at retarding hypertension
development in spontaneously hypertensive rats (SHR) and
inhibiting thromboxane-like vasoconstrictor responses in
aortas from SHR. In stroke-prone SHR with established
hypertension, docosahexaenoic acid (3.9-10.0%en) retarded the
development of salt-loading induced proteinuria but
eicosapentaenoic acid alone was ineffective. The results
demonstrate that purified n-3 polyunsaturated fatty acids
mimic the cardiovascular actions of fish oils and imply that
docosahexaenoic acid may be the principal active component
conferring cardiovascular protection.
Trace elements in prognosis of myocardial
infarction and sudden coronary death
Kusleikaite M.; Masironi R.
Trace Element Institute for UNESCO, Lyon France
Journal of Trace Elements in Experimental Medicine (USA),
1996, 9/2 (57-62)
Ca, Cu, Mg, Mn, and Zn concentrates were measured in
plasma, RBC, and hair of 350 men aged 40-59 years with
myocardial infarction (MI) and/or who died from sudden cardiac
death (SCD), as compared with normal controls. Analyses were
done by flame atomic absorption spectrophotometry. Cu in
plasma of MI patients was significantly higher than the
controls'. Plasma Mn was significantly lower in SCD than in MI
subjects. No other consistent and significant changes were
observed. Past and present evidence indicates that high plasma
Cu levels may be associated with heart failure and rhythm
disorders. The low plasma Mn levels may be an indicator of
decreased parasympathetic tonus thus favouring myocardial
desynchronization and A-V block. Cu inhibits phosphodiesterase
activity and Mn inhibits andenylate cyclase activity thus
exerting an influence on the contractility of cardiomyocites
and of smooth muscle cells in coronary arteries. Cu and Mn
analyses may thus have a prognostic significance for MI and
SCD.
Prevention of cardiac arrhythmia by dietary (n-3)
polyunsaturated fatty acids and their mechanism of
action
Nair S.S.D.; Leitch J.W.; Falconer J.; Garg M.L.
Australia
Journal of Nutrition (USA), 1997, 127/3
(383-393)
The role of marine fish oil (n-3) polyunsaturated fatty
acids in the prevention of fatal ventricular arrhythmia has
been established in experimental animals. Prevention of
arrhythmias arising at the onset of ischemia and reperfusion
is important because if untreated, they result in sudden
cardiac death. Animals supplemented with fish oils in their
diet developed little or no ventricular fibrillation after
ischemia was induced. Similar effects have also been observed
in cultured neonatal cardiomyocytes. Several mechanisms have
been proposed and studied to explain the antiarrhythmic
effects of fish oil polyunsaturated fatty acids, but to date,
no definite mechanism has been validated. The sequence of
action of these mechanisms and whether more than one mechanism
is involved is also not clear. Some of the mechanisms
suggested to explain the antiarrhythmic action of fish oils
include the incorporation and modification of cell membrane
structure by (n-3) polyunsaturated fatty acids, their direct
effect on calcium channels and cardiomyocytes and their role
in eicosanoid metabolism. Other mechanisms that are currently
being investigated include the role of (n-3) polyunsaturated
fatty acids in cell signalling mediated through
phosphoinositides and their effect on various enzymes and
receptors. This article reviews these mechanisms and the
antiarrhythmic studies using (n-3) polyunsaturated fatty
acids.
Exposure to the n-3 polyunsaturated fatty acid
docosahexaenoic acid impairs alpha1-adrenoceptor-mediated
contractile responses and inositol phosphate formation in rat
cardiomyocytes
Reithmann C.; Scheininger C.; Bulgan T.; Werdan K.
Medizinische Klinik I, Klinikum Grosshadern, Universitat
Munchen, Marchioninistrasse 15, D-81377 Munchen Germany
Naunyn-Schmiedeberg's Archives of Pharmacology (Germany),
1996, 354/2 (109-119)
The beneficial effects of n-3 polyunsaturated fatty acids
of fish oil in the prevention of fatal arrhythmias in
myocardial ischemia were suggested to be at least in part
mediated by a modulation of dihydropyridine-sensitive L-type
calcium channels. As cardiac alpha1-adrenoceptor stimulation
has been suggested to have no significant effect on L-type
calcium channels, the aim of this study using cultured
neonatal rat cardiomyocytes was to investigate whether chronic
n-3 polyunsaturated fatty acid exposure may have an influence
on alpha1-adrenoceptor-induced positive inotropic effects and
induction of arrhythmias. Pretreatment of the rat
cardiomyocytes for 3 days in the presence of the n-3
polyunsaturated fish oil-derived fatty acid docosahexaenoic
acid (60 micromol/l) markedly decreased
alpha1-adrenoceptor-stimulated increase in contraction
velocity and induction of arrhythmias. The increase in
contraction velocity of the cardiomyocytes induced by the
beta-adrenoceptor agonist isoprenaline was also markedly
reduced by the n-3 fatty acid pretreatment. Basal contractile
amplitude and spontaneous beating frequency of the
cardiomyocytes were not significantly altered by the
docosahexaenoic acid exposure. The pretreatment of the rat
cardiomyocytes for 3 days in the presence of docosahexaenoic
acid (60 micromol/l) decreased alpha1-adrenoceptor-stimulat ed
formation of the calcium-mobilizing second messenger IP3 and
its metabolites IP2 and IP1 by 55%. The depression of IP3
formation by docosahexaenoic acid treatment was not mediated
by a decreased uptake of myo-inositol into the cardiomyocytes
nor by a decreased synthesis of phosphatidylinositol
bisphosphate (PIP2), the substrate of phospholipase C. The
level of glycerol-3-phosphate, an important substrate of the
phosphoinositide cycle, was unaltered by the docosahexaenoic
acid pretreatment. Receptor binding studies revealed that the
dissociation constant and maximal binding capacity of the
alpha1-adrenoceptor antagonist (3H)prazosin was unchanged by
the n-3 polyunsaturated fatty acid exposure.
beta-Adrenoceptor- and forskolin-stimulated adenylyl cyclase
activities were not diminished by the docosahexaenoic acid
pretreatment. Chronic exposure of the cardiomyocytes to the
n-6 polyunsaturated fatty acid arachidon ic acid (60
micromol/l) did neither significantly alter
alpha1-adrenoceptor-induced inositol phosphate formation nor
alpha1-adrenoceptor-stimulated increase in contraction
velocity. The results presented show that chronic n-3
polyunsaturated fatty acid pretreatment of rat cardiomyocytes
leads to a marked impairment of alpha1-adrenoceptor-induced
positive inotropic effects and induction of arrhythmias
concomitant with a n-3 fatty acid-induced decrease in IP3
formation. This derangement of the phosphoinositide pathway by
chronic n-3 fatty acid exposure may, thus, contribute to the
beneficial effects of fish oil-derived fatty acids in the
prevention of fatal arrhythmias in myocardial ischemia.
Selenium deficiency associated with cardiac
dysfunction in three patients with chronic respiratory
failure
To Y.; Koshino T.; Kubo M.; Yoshizawa A.; Kudo K.; Kabe
J.
Japan
Japanese Journal of Thoracic Diseases (Japan), 1996, 34/12
(1406-1410)
We encountered three patients with chronic respiratory
failure who had heart failure of cardiac arrhythmias and low
levels of serum selenium. All three had tracheostomies and had
received long-term parenteral nutrition that had not included
selenium. All three also had refractory cardiac dysfunction,
which was manifested in edema, heart failure, and various
tachycardias. We suspected that selenium deficiency had caused
their cardiac dysfunction. Serum selenium concentrations were
found to be much lower than normal in all three, so 100
microg/day of selenium was administered in addition to their
tube feedings. Cardiac function improved after replacement of
selenium. These cases show the need for preventing selenium
deficiency in patients with chronic respiratory failure during
long-term administration of parenteral nutrition.
Fish oil and other nutritional adjuvants for
treatment of congestive heart failure
McCarty M.F.
Medical Hypotheses (United Kingdom), 1996, 46/4
(400-406)
Published clinical research, as well as various theoretical
considerations, suggest that supplemental intakes of the
'metavitamins' taurine, coenzyme Q10, and L-carnitine, as well
as of the minerals magnesium, potassium, and chromium, may be
of therapeutic benefit in congestive heart failure. High
intakes of fish oil may likewise be beneficial in this
syndrome. Fish oil may decrease cardiac afterload by an
antivasopressor action and by reducing blood viscosity, may
reduce arrhythmic risk despite supporting the heart's
beta-adrenergic responsiveness, may decrease fibrotic cardiac
remodeling by impeding the action of angiotensin II and, in
patients with coronary disease, may reduce the risk of
atherothrombotic ischemic complications. Since the measures
recommended here are nutritional and carry little if any toxic
risk, there is no reason why their joint application should
not be studied as a comprehensive nutritional therapy for
congestive heart failure.
Evidence on the participation of the 3',5'-cyclic
AMP pathway in the non-genomic action of
1,25-dihydroxy-vitamin D3 in cardiac muscle.
Selles J; Boland R
Mol Cell Endocrinol (Netherlands) Dec 1991, 82 (2-3)
p229-35
Several studies have suggested that vitamin D plays a role
in cardiovascular function. It has been recently shown that in
vitro treatment of vitamin D-deficient chick cardiac muscle
with physiological concentrations of 1,25-dihydroxy-vitamin D3
(1,25(OH)2D3) induces a rapid (1-10 min) increase of tissue
45Ca uptake which can be suppressed by Ca channel blockers.
The hormone simultaneously stimulated heart microsomal
membrane protein phosphorylation. Experiments were performed
to investigate the existence of a relationship between these
changes and to obtain information about the mechanism involved
in 1,25(OH)2D3-induced modifications in cardiac protein
phosphorylation. Dibutyryl cyclic AMP (10 microM) and
forskolin (10 microM), known activators of the cAMP pathway,
produced time courses of changes in 45Ca uptake by chick heart
tissue similar to 1,25(OH)2D3 (10(-10) M). Analogously to the
hormone, the effects of both compounds were abolished by
nifedipine (30 microM) and verapamil (10 microM). In agreement
with these observations, 1,25(OH)2D3 significantly increased
(34-70%) heart muscle cAMP levels within 1-10 min of
treatment. In addition, 1,25(OH)2D3 and forskolin caused
similar changes in cardiac microsomal membrane protein
phosphorylation (e.g. stimulation in 43 kDa and 55 kDa
proteins). These changes were also evidenced by direct
exposure of isolated heart microsomes to 1,25(OH)2D3,
suggesting a direct membrane action of the hormone. The fast
effects of 1,25(OH)2D3 on dihydropyridine-sensitive cardiac
muscle Ca uptake could be reproduced in primary-cultured
myocytes isolated from chick embryonic heart. Furthermore, the
effects of the hormone could be suppressed by a specific
protein kinase A inhibitor. These results suggest that
1,25(OH)2D3 affect s heart cell calcium metabolism through
regulation of Ca channel activity mediated by the cAMP
pathway.
1,25(OH)2 vitamin D3, and retinoic acid antagonize
endothelin-stimulated hypertrophy of neonatal rat cardiac
myocytes.
Wu J; Garami M; Cheng T; Gardner DG
Department of Medicine, University of California, San
Francisco, 94143, USA.
J Clin Invest (United States) Apr 1 1996, 97 (7)
p1577-88
1,25(OH)2 Vitamin D3 (VD3) and retinoic acid (RA) function
as ligands for nuclear receptors which regulate transcription.
Though the cardiovascular system is not thought to represent a
classical target for these ligands, it is clear that both
cardiac myocytes and vascular smooth muscle cells respond to
these agents with changes in growth characteristics and gene
expression. In this study we demonstrate that each of these
ligands suppresses many of the phenotypic correlates of
endothelin-induced hypertrophy in a cultured neonatal rat
cardiac ventriculocyte model. Each of these agents reduced
endothelin-stimulated ANP secretion in a dose-dependent
fashion and the two in combination proved to be more effective
than either agent used alone (VD3: 49%; RA:52%; VD3 + RA:80%
inhibition). RA, at concentrations known to activate the
retinoid X receptor, and, to a lesser extent, VD3 effected a
reduction in atrial natriuretic peptide, brain natriuretic
peptide, and alpha-skeletal actin mRNA levels. Similar
inhibition (VD3:30%; RA:33%; VD3 + RA:59% inhibition) was
demonstrated when cells transfected with reporter constructs
harboring the relevant promoter sequences were treated with
VD3 and/or RA for 48 h. These effects were not accompanied by
alterations in endothelin-induced c-fos, c-jun, or c-myc gene
expression, suggesting either that the inhibitory locus
responsible for the reduction in the mRNA levels lies distal
to the activation of the immediate early gene response or that
the two are not mechanistically coupled. Both VD3 and RA also
reduced [3H]leucine incorporation (VD3:30%; RA:33%; VD3 +
RA:45% inhibition) in endothelin-stimulated ventriculocytes
and, once again, the combination of the two was more effective
than either agent used in isolation. Finally, 1,25(OH)2
vitamin D3 abrogated the increase in cell size seen after
endothelin treatment. These findings suggest that the liganded
vitamin D and retinoid receptors are capable of modulating the
hypertrophic process in vitro and that agents acting through
these or similar signaling pathways may be of value in probing
the molecular mechanisms underlying hypertrophy.
[Effect of vitamin E deficiency on the development
of cardiac arrhythmias as affected by acute ischemia]
Belkina LM; Arkhipenko IuV; Dzhaparidze LM; Saltykova VA;
Meerson FZ
Biull Eksp Biol Med (USSR) Nov 1986, 102 (11)
p530-2
Malonic dialdehyde content was increased by 53% in the
myocardium of male Wistar rats (250-300 g) devoid of vitamin E
for 2 months, as compared to the control rats (animals
receiving an optimal amount of vitamin E). Transitory ischemia
(10 min) with subsequent reoxygenation (5 min) was induced
during open heart surgery under urethan anesthesia. Ischemia
was induced by the occlusion of the descending branch of the
left coronary artery. In ischemic rats with vitamin E
deficiency the incidence of ventricular fibrillation,
tachycardia, extrasystoles and the additive duration of
arrhythmias were significantly increased as compared to the
control.
Antioxidant protection against adrenaline-induced
arrhythmias in rats with chronic heart hypertrophy.
Kirshenbaum LA; Gupta M; Thomas TP; Singal PK
Division of Cardiovascular Sciences, St Boniface General
Hospital Research Centre, Winnipeg, Manitoba.
Can J Cardiol (Canada) Mar 1990, 6 (2) p71-4
Effects of vitamin E on adrenaline-induced arrhythmias were
examined in rats with chronic heart hypertrophy subsequent to
narrowing of the abdominal aorta. After 60 weeks of pressure
overload, the rats showed an increase of about 21% in
heart/body weight ratio and a small but significant rise in
left ventricular end diastolic pressure (LVEDP) (sham control
1.7 +/- 0.67 mmHg; hypertrophy 7.1 +/- 2.7 mmHg) without any
change in left ventricular peak systolic pressure (LVSP).
Intravenous infusion of adrenaline caused rhythm disorders in
a dose-dependent manner and pathological arrhythmias
(occurrence of six premature ventricular complexes/min) were
observed at doses of 2.9 +/- 0.6 and 3.8 +/- 1.0 micrograms/kg
of the drug in control and hypertrophy animals, respectively.
Administration of two doses of vitamin E (50 mg/kg
intraperitoneally), given 24 h and 1 h before adrenaline
infusion, significantly increased the amount of adrenaline
required to produce pathological arrhythmias (control 8.0 +/-
3.0; hypertrophy 7.7 +/- 2.0 micrograms/kg). Vitamin E
pretreatment did not have any detrimental effect on the
pressure readings nor did it have any influence on
adrenaline-induced pressure changes. The data suggest that a
combination therapy with vitamin E may allow therapeutic use
of higher concentrations of adrenaline required to improve
function in failing hearts with a reduced risk of
arrhythmias
The antiarrhythmic effects of taurine alone and in
combination with magnesium sulfate on ischemia/reperfusion
arrhythmia
Yi K.-M.; Wang G.-X.
Dept. of Pharmacology, Tianjin Medical College, Tianjin
300070 China
Chinese Pharmacological Bulletin (China), 1994, 10/5
(358-362)
The effect of tauring (Taur) alone and in combination with
magnesium sulfate (MgSO4) on ischemia/reperfusion arrhythmia
was investigated. The arrhythmia as produced by coronary
artery occlusion for 10 min followed by reperfusion. In
addition, the present study also observed the effect of MgSO4
alone and in combination with Taur on hemodynamics. The
results showed that Taur (50 mg . kg-1) and MgSO4 (25 mg .
kg-1) had partly antiarrhythmic effect. Taur (100, 150mg.
kg-1) MgSO4 (50, 100mg. kg-1) had significantly antiarrhythmic
effect. Taur (50 mg. kg-1) combined with MgSO4 (25 mg. kg-1)
shortened the duration of ventricular tachycardia (VT) more
than that either drug did alone. The hypotensive effect of
MgSO4 (25 mg. kg-1) was not increased by coadministration of
Taur, but the myocardial oxygen consumption was reduced. These
findings indicate that Taur in combination with MgSO4 is more
effect on reperfusion arrhythmia, and that the mechanism of
antiarrhythmic effect of Taur and MgSO4 may be involved in the
effect of defence on myocardium.
The effects of antioxidants on reperfusion
dysrhythmias
Kovacs P.; Baricova L.; Kovalova M.; Dostal J.; Stankovicova
T.; Svec P.
Katedra Farmakologie a Toxikologie, Farmaceuticka Fakulta,
Univerzita Komenskeho, Kalinciakova 8, 832 32 Bratislava
Slovak Republic
Ceska a Slovenska Farmacie (Czech Republic), 1995, 44/5
(257-260)
The present study aims to investigate the effects of the
lipophilic antioxidant Trolox C (a vitamin E analogue) and
stobadine, a scavenger of free oxygen radicals, on reperfusion
dysrhythmias. Experiments were performed on isolated perfused
rat hearts subjected to global stop-flow ischaemia followed by
reperfusion. Trolox C (10-4 mol.l-1) and stobadine (10-5
mol.l-1) were infused immediately prior to ischaemia. Trolox C
(10-4 mol.l-1) and stobadine (10-5 mol.l-1) decreased the
incidence and duration of reperfusion-induced dysrhythmias
(quantified by the dysrhythmia score) in comparison to the
ischaemic-reperfusion damaged hearts. There was an improvement
in the recovery of contraction force and left ventricular
diastolic pressure in Trolox or stobadine pretreated hearts.
No significant changes in coronary flow resistance were
observed. The results suggest that both substances protect the
myocardium during ischaemic-reperfusion injury probably by
affecting the generation and activity of reactive oxygen
species.
Protective effects of all-trans-retinoic acid
against cardiac arrhythmias induced by isoproterenol,
lysophosphatidylcholine or ischemia and reperfusion
Kang JX; Leaf A
Department of Medicine, Harvard Medical School, Boston,
Massachusetts, USA.
J Cardiovasc Pharmacol (United States) Dec 1995, 26 (6)
p943-8
Previous studies have shown that free polyunsaturated fatty
acids (PUFA) reduce the excitability of cardiac myocytes and
exert antiarrhythmic effects. Therefore, we hypothesized that
retinoic acid (RA, vitamin A acid), which has structural
characteristics similar to those of PUFA, may have similar
antiarrhythmic effects. To test this hypothesis, we used an
isolated, spontaneously beating, neonatal rat cardiac myocyte
preparation to examine the effects of RA, added to the
perfusion solution, on the cell contraction and arrhythmias
induced by isoproterenol (ISO) or lysophosphatidylcholine
(LPC). All-trans-RA (10-20 microM) induced a marked and
reversible reduction in the contraction rate of the cell in
2-5 min without changing the amplitude of the contractions.
Superfusion of the myocytes with either ISO (3 microM) or LPC
(5 microM) induced sustained tachyarrhythmias characterized by
spasmodic contractures and fibrillation. Addition of 15-20
microM all-trans-RA to the perfusion solution effectively
prevented as well as terminated the arrhythmias induced by ISO
and LPC. Furthermore, in a whole-animal model of arrhythmia in
which the left anterior descending coronary artery (LAD) of
the anesthetized rat was occluded for 15 min followed by
reperfusion, both the incidence and severity of ventricular
tachycardia and fibrillation (VT, VF) were significantly
reduced during the ischemic and reperfusion periods by
intravenous infusion of all-trans-RA. In contrast, other
analogues, including retinol and retinal, and other
fat-soluble vitamins, including vitamin D, E, and K, did not
have such effects. Our results demonstrate that all-trans-RA
can produce antiarrhythmic effects similar to those of PUFA,
suggesting a novel role of RA as a potential antiarrhythmic
agent.
Effects of dietary supplementation with
alpha-tocopherol on myocardial infarct size and ventricular
arrhythmias in a dog model of ischemia-reperfusion
Sebbag L; Forrat R; Canet E; Renaud S; Delaye J; de Lorgeril
M
Institut National pour la Sante et la Recherche Medicale
(INSERM), Unit 63, Lyon, France.
J. Am. Coll. Cardiol. (USA), 1994, 24/6
(1580-1585)
Objectives. We investigated whether dietary supplementation
with the antioxidant vitamin alpha-tocopherol (500 mg daily)
might reduce lethal ventricular arrhythmias and infarct
size.
Background. Previous studies suggested that dietary
supplementation with alpha-tocopherol may be associated with a
reduced risk of ischemic heart disease. However, the mechanism
of this protection remains unknown.
Methods. Beagle dogs were randomized to either a
supplemented or a control group. Because of the low mortality
rate in the supplemented group, five dogs were added to the
control group. After 2 months, dogs were anesthetized and
underwent a 2-h coronary artery occlusion and 6-h reperfusion.
Plasma vitamin E, retinol and malondialdehyde concentrations
were assessed in all dogs.
Results. Fourteen dogs (11 of 25 control vs. 3 of 19
supplemented dogs, p < 0.05) developed ventricular
fibrillation during either ischemia or reperfusion.
Malondialdehyde concentrations were higher in dogs that
subsequently developed arrhythmias (2.7 plus or minus 0.2
micromol/liter, mean plus or minus SEM) compared with dogs
that did not (2.1 plus or minus 0.2 micromol/liter, p = 0.03).
Among survivors with significant ischemia, infarct size was
larger in supplemented (n = 12, 58.5 plus or minus 3.3% of
area at risk) than in control (n = 11, 41.9 plus or minus
6.5%, p < 0.04) dogs. In addition, for a given collateral
flow, supplemented dogs (n = 16) developed larger infarct size
than control dogs (n = 15, p < 0.001, analysis of
covariance).
Conclusions. The data suggest that dietary alpha-tocopherol
supplementation prevented lethal ventricular arrhythmias
associated with ischemia and reperfusion. However, its
influence on infarct size and long-term prognosis warrants
further inve stigation.
Magnesium flux during and after open heart
operations in children.
Satur CM, Stubington SR, Jennings A, Newton K, Martin PG,
Gebitekin C, Walker DR
Department of Cardiothoracic Surgery, Killingbeck Hospital,
Leeds, United Kingdom.
Ann Thorac Surg (United States) Apr 1995, 59 (4)
p921-7
Hypomagnesemia and depletion of the body's magnesium stores
is known to be associated with an increased incidence of both
cardiac arrhythmias and neurological irritability. In a
two-part prospective study we have evaluated whether magnesium
deficiency is a significant occurrence in children treated in
the intensive care unit after open heart operations, and
subsequently have sought to identify how intraoperative
metabolic changes were related to the resultant findings. In
41 children studied after operation the plasma magnesium
concentration showed a significant decrease from 0.92 mmol/L
(10th to 90th centile, 0.71 to 1.15 mmol/L) immediately after
operation to 0.77 mmol/L (0.65 to 0.91 mmol/L) on the
following morning. The subsequent change in grouped values was
not significant but 14 (34.2%) and 7 (17.1%) possessed values
of less than 0.7 mmol/L and 0.6 mmol/L, respectively. The
occurrence of cardiac arrhythmias was not statistically
related to the occurrence of hypomagnesemia. In 21 children
perioperative changes in extracellular and tissue magnesium,
potassium, and calcium content were measured. It was found
that hemodilution with a prime low in magnesium caused a
reduction from a median of 0.81 mmol/L to 0.61 mmol/L (p <
0.01). Plasma potassium level, however, was elevated from 3.7
mmol/L to 4.15 mmol/L (p < 0.05) and the ionized calcium
content from 1.17 mmol/L (1.07 to 1.25 mmol/L) to 1.49 mmol/L
(1.25 to 2.56 mmol/L) (p = 0.0009). The myocardial content of
magnesium did not change significantly but skeletal muscle
content was depleted from 6.75 mumol/g (2.85 to 8.35 mumol/g)
to 5.65 mumol/g (2.45 to 7.2 mumol/g) (p < 0.01)
Sino-atrial Wenckebach conduction in thyrotoxic
periodic paralysis: a case report.
Chia BL, Lee KH, Cheah JS
Department of Medicine, National University Hospital,
National University of Singapore.
Int J Cardiol (Ireland) Jan 6 1995, 47 (3)
p285-9
A 28-year-old male presented with thyrotoxic periodic
paralysis. On admission to hospital the serum potassium level
was 1.4 mmol/l. The ECG showed classical features of
hypokalaemia. In addition, sino-atrial block with Wenckebach
conduction was also present. With the normalization of the
serum potassium, the ECG became completely normal and showed
no evidence of any arrhythmia .
A possible beneficial effect of selenium
administration in antiarrhythmic therapy.
Lehr D
New York Medical College, N.Y. 10025-6421.
J Am Coll Nutr (United States) Oct 1994, 13 (5)
p496-8
OBJECTIVE: The following review of the literature on the
importance of Selenium (Se) in myocardial homeostasis and of
the pharmacology of this trace metal, represents an attempt to
search, without prejudice to other possible explanations, for
a rationale of a beneficial effect of Se substitution as an
adjuvant to antiarrhythmic therapy.
BACKGROUND: For several years, in the early 1980s, I had to
deal with the problem of a serious ventricular arrhythmia
(non-sustained and sustained ventricular tachycardia) which
was remarkably resistant to a battery of the most potent
antiarrhythmic agents. Eventually, dramatic improvement,
lasting for a period of 8 years, was achieved with Flecainide,
which, however, left unsolved the episodic occurrence of
disabling ventricular bigemini. Over the most recent period of
1 year and 8 months, there was a sudden and unexplained return
to unbroken normal sinus rhythm. Among the multiplicity of
possible reasons for this fortunate development, the
concurrent introduction of Se substitution appeared as the
most obvious, though very tentative explanation. Substitution
of this trace metal preceded the extinction of ventricular
bigemini by 1 week and actually represented the sole
modification of otherwise reasonably standardized conditions
of antiarrhythmic therapy, life style and diet. (25 Refs.)
Omega-3 fatty acids and prevention of ventricular
fibrillation.
Leaf A
Medical Services, Massachusetts General Hospital,
Charlestown, MA 02129, USA.
Prostaglandins Leukot Essent Fatty Acids 1995
Feb-Mar;52(2-3):197-8
Interest in the potential cardiovascular benefits of
omega-3 long chain polyunsaturated fatty acids has been
largely focused on possible antiatherothrombotic effects. In
addition, however, definitive antiarrhythmic effects of these
dietary omega-3 fatty acids have been reported by Charnock
& McLennan. Our studies commenced with the observation
that two of these fatty acids, eicosapentaenoic (C20:5n-3,
EPA) and docosahexaenoic acid (C22:6n-3, DHA) prevented
contracture and fibrillation of isolated neonatal cardiac
myocytes when exposed to toxic levels of ouabain (0.1 mM).
This protection was associated with prevention of excessively
high intracellular calcium concentrations in the myocyte.
Further, it was shown that these fatty acids modulate calcium
currents through L-type calcium channels and that the effect
occurs within a few minutes of adding EPA or DHA to the medium
perfusing the cultured cardiac myocytes. Infusing an emulsion
of the omega-3 fatty acids intravenously just prior to
compression of a coronary artery in a conscious, prepared dog
will prevent the expected subsequent ischemia-induced
ventricular fibrillation. (9 Refs.)
[Effect of anti-arrhythmia drugs on the beta2
receptor-dependent adenyl cyclase system of lymphocytes in
patients with cardiac rhythm disorders]
Krasnikova TL, Iurkova VB, Ku'zmina MM, Ku'lginskaia IV,
Sokolov SF, Golitsyn SI, Chernousova TV, Svet EA, Mazaev
AV
Kardiologiia (USSR) Jul 1989, 29 (7) p25-9
The authors analyzed the density of beta 2-adrenoreceptors,
their affinity for catecholamines and activity of peripheral
lymphocyte adenylate cyclase in healthy donors and patients
with frequent ventricular premature contraction (VPC) in their
pretreatment state and during short-term ethmosine or
allapinine therapy. The density of beta 2-adrenoreceptors was
increased by 43%, whereas guanylimidodiphosphate- or
forskolin-induced stimulation of adenylate cyclase was
decreased in the lymphocytes of VPC patients as compared to
those of healthy donors. Ethmosine therapy failed to produce
any changes in the density and affinity of the receptors for
catecholamines. Allapinine caused a 47% reduction in beta
2-adrenoreceptor density and a 10(2)-10(3)-fold decrease in
receptor affinity for 1-isoproterenol. After discontinuation
of allapinine, the changes in beta 2-adrenoreceptor density
and affinity for catecholamines remained on days 3 and 7,
respectively. The clinical effect of both ethmosine and
allapinine was accompanied by an increase in lymphocyte
adenylate cyclase activity.
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