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Current Cardiology Reviews
ISSN: 1573-403X
Current Cardiology Reviews
Volume 3, Number 2, May 2007
Contents
The Pathophysiology of Uric Acid in Relation to Cardiovascular
Disease Pp. 99-103
Matiullah Naqibullah, Maiken J. Calberg and Erik Kjoller
[Abstract]
Towards a Better Understanding of Cardiac and
Vascular Disease in Patients with Chronic Kidney Disease
Pp. 105-109
Andrew D. Booth and Adeera Levin
[Abstract]
The Coronary Collateral Circulation in Man
Pp. 111-119
Christian Seiler
[Abstract]
Cellular Therapy for Myocardial Repair Pp.
121-135
Julia Feygin, Abner M. Mhashilkar, Robert Deans and Jianyi
Zhang
[Abstract]
Tako-tsubo Cardiomyopathy: A Review of the Literature
Pp. 137-142
Todd A. Dorfman, Raed Aqel, Marc Mayhew and Ami E. Iskandrian
[Abstract]
Heat Shock Proteins – Two Sides of a Coin
Pp. 143-148
Se-Chan Kim, Bum-Soo Kim, Li Lin and Anne A. Knowlton
[Abstract]
From Anrep’s Phenomenon to Myocardial Hypertrophy:
Role of the Na+/H+ Exchanger
Pp. 149-164
Irene L. Ennis, Horacio E. Cingolani, Carolina D. Garciarena,
María C. Camilión de Hurtado, María C.
Villa-Abrille, Ernesto A. Aiello and Néstor G. Pérez
[Abstract]
Abstracts
[Back to top]
The Pathophysiology of Uric Acid in Relation to Cardiovascular
Disease
Matiullah Naqibullah, Maiken J. Calberg and Erik Kjoller
Uric acid is produced by the degradation of purines,
a process catalysed by xanthine oxidase, which is also responsible
for the production of toxic free radicals. This provides a
central link to the association between serum uric acid and
myocardial ischemia, myocardial dysfunction and also non-cardiac
dysfunction in patients with heart disease, mainly due to
an impaired peripheral circulation. Uric acid can thus be
considered a marker for pathophysiological mechanisms in patients
with heart disease, and thus an explanation for S-uric acid’s
prognostic importance. Inhibition of xanthine oxidase by allopurinol
may possibly be used as a therapy for patients with heart
disease in the future.
[Back to top]
Towards a Better Understanding of Cardiac and
Vascular Disease in Patients with Chronic Kidney Disease
Andrew D. Booth and Adeera Levin
Cardiovascular disease is the major cause of morbidity and
mortality in patients with chronic kidney disease (CKD). Cardiac
event rate rises as the glomerular filtration rate decreases,
particularly below 60 ml/min/1.73m2. This risk remains even
after adjustment for traditional risk factors. In patients
with end stage renal failure (ESRF), death rates from cardiovascular
disease are 20 to 40 times higher than in the general population
and make up 40% of all-cause mortality. Furthermore, 72% patients
with ESRF who suffer an acute myocardial infarction are dead
within 2 years. Interestingly, whilst coronary artery atherosclerosis
is more common in patients with CKD and risk of plaque rupture
greater, only a third of the cardiac events in dialysis patients
are associated with myocardial infarction; two thirds are
due to sudden cardiac death or cardiac failure. Taken together,
these observations suggest there is a more complex pattern
of cardiovascular injury in patients with kidney disease.
We propose to review the current understanding of vascular
disease in CKD, the relation of vascular disease to cardiac
disease and outcomes, using accumulating data regarding both
acute and chronic inflammation. We postulate that the complex
pattern of cardiovascular injury is due to these processes,
which are understudied and under-recognized and are likely
to be modified in the context of CKD. We suggest a direction
of study, which may help to identify the nature of the vascular
injury in CKD, understand the impact of this on cellular and
clinical events, and ultimately help to design interventional
studies targeted at specific patient groups.
[Back to top]
The Coronary Collateral Circulation in Man
Christian Seiler
Well developed coronary collateral arteries in patients with
coronary artery disease (CAD) mitigate myocardial infarcts
with less ventricular aneurysm formation and improved ventricular
function, they reduce future cardiovascular events, and improve
survival. Myocardial infarct size is a product of coronary
artery occlusion time, area at risk for infarction and the
inverse of collateral supply. Collateral arteries preventing
myocardial ischemia during brief vascular occlusion are present
in 1/3 of patients with CAD. Collateral flow sufficient to
prevent myocardial ischemia during coronary occlusion amounts
to ≥25% of the normal flow through the open vessel.
Among individuals without relevant coronary stenoses, there
are preformed collateral arteries preventing myocardial ischemia
in 20-25%.
Coronary collateral flow can be assessed only during vascular
occlusion of the collateral-receiving artery. Presently, the
gold standard for clinical coronary collateral assessment
is the measurement of intracoronary occlusive pressure- or
velocity-derived collateral flow index which expresses collateral
as a fraction of flow during vessel patency.
Clinical variables predicting the development of collateral
arteries are the hemodynamic severity of coronary stenoses
and the duration of myocardial ischemic symptoms.
One fifth to one third of patients with CAD cannot be revascularized
by percutaneous coronary intervention or coronary artery bypass
grafting; therapeutic promotion of collateral growth appears
to be a valuable treatment strategy in those patients. Promotion
of collateral growth should aim at inducing the development
of large conductive collateral arteries (i.e. arteriogenesis)
and not so much the sprouting of capillary like vessels (i.e.
angiogenesis). So far, the largest, controlled clinical angiogenesis
trials on the efficacy of VEGF and basic FGF have been negative
with regard to treadmill exercise time and myocardial scintigraphic
data. Large conductive collateral arteries (i.e. arteriogenesis)
appear to be effectively promoted via the activation
of monocytes / macrophages, which release VEGF, FGF, tumor
necrosis factor alpha, granulocyte colony stimulating factors
and other growth and remodelling-associated factors.
[Back to top]
Cellular Therapy for Myocardial Repair
Julia Feygin, Abner M. Mhashilkar, Robert Deans and Jianyi
Zhang
Post infarction left ventricular remodeling is a compensatory
response to an acute myocardial infarction that is characterized
by left ventricular dilation and myocardial hypertrophy. Although
stable left ventricular remodeling may be achieved for a period
of time, progressive myocardial dysfunction usually develops
and ultimately leads to overt congestive heart failure. Heart
failure is considered an end-stage, irreversible clinical
condition for which current medical management strategies
merely relieve symptoms, slow deterioration, and prolong life
modestly.
In recent years, stem cell transplantation has emerged as
a potential “preventive” therapy for detrimental
ventricular remodeling and progression to heart failure. The
therapeutic approach is based on the notion that stem or progenitor
cells can be delivered to the site of injury to directly or
indirectly instigate repair of the damaged myocardium. This
novel approach offers an unprecedented opportunity to treat
the underlying loss of myocytes, restore function to the scar
tissue in the infarct region and inhibit the cascade of events
leading to congestive heart failure.
This review focuses on recent research in the field of adult
stem cell-based cellular therapy. In addition, stem cell mobilization
with cytokines and growth factors to initiate endogenous repair
of the infarct region is briefly discussed. Although cellular
therapy shows great clinical promise, many hurdles remain
before the possibility of widespread clinical use. However,
the intense research efforts will likely lead to the development
of effective cellular therapies against cardiovascular and
other degenerative diseases.
[Back to top]
Tako-tsubo Cardiomyopathy: A Review of the Literature
Todd A. Dorfman, Raed Aqel, Marc Mayhew and Ami E. Iskandrian
The diagnosis of Takotsubo cardiomyopathy (TC) must be considered
in all patients who develop transient left ventricular apical
(or mid ventricular) ballooning in the absence of obstructive
coronary artery disease (CAD). Although the prevalence of
TC remains unknown, approximately 2% of all patients presenting
with a presumed diagnosis of ST elevation myocardial infarction
have been found to have this syndrome. TC usually occurs in
the setting of physical or emotional stress associated with
excessive sympathetic stimulation and catecholamine release.
A literature review and illustrative case report are provided.
[Back to top]
Heat Shock Proteins – Two Sides of a Coin
Se-Chan Kim, Bum-Soo Kim, Li Lin and Anne A. Knowlton
Heat Shock Proteins (HSPs) are intracellular molecular chaperones,
which preserve protein folding and protect cells from injury.
Intracellularly, their normal location, HSPs are protective.
HSPs can also be found in the extracellular compartment, either
after necrotic cell death or independent of cell death. The
physiologic function of exogenous HSPs remains elusive. However,
extracellular as well as membrane- localized HSPs have been
implicated in the pathogenesis of a number of diseases including
type I diabetes, Crohn´s, atherosclerosis and juvenile
chronic arthritis. It is thought that HSPs can provoke an
immune response either by directly activating the innate immune
system, or through the adaptive immune response leading to
production of antibodies, possibly as a result of prior exposure
to the bacterial HSPs, which have great sequence similarity.
Extracellular HSPs can activate Toll-like receptors (TLR),
and induce the production of cytokines; but, intracellular
HSPs can downregulate cytokine production and mediate myocardial
protection. Production of nitric oxide may trigger HSPs, ameliorating
cardiotoxic effects of cytokines. Apoptosis has come into
focus as a contributing factor for ischemia/reperfusion injury,
and conflicting data exist about a potentially beneficial
or deleterious role of HSPs. Although novel therapeutic strategies
include elevation of specific HSPs, the interplay of HSPs
in the clinical setting is poorly understood.
[Back to top]
From Anrep’s Phenomenon to Myocardial Hypertrophy:
Role of the Na+/H+ Exchanger
Irene L. Ennis, Horacio E. Cingolani, Carolina D. Garciarena,
María C. Camilión de Hurtado, María C.
Villa-Abrille, Ernesto A. Aiello and Néstor G. Pérez
In this review, the enhanced activity of the cardiac
Na+/H+
exchanger is considered to be a key step in the intracellular
signaling pathway leading to cardiac hypertrophy, and the
inhibition of the exchanger is a pharmacological tool to prevent
or regress it. This enhanced activity has been demonstrated
after stretching neonatal rat cardiomyocytes and cat papillary
muscles. In the latter preparation, the activation of the
exchanger results in a mechanical counterpart, the slow force
response to stretch. The chain of events triggered by a stretch
begins with the release of angiotensin II (Ang II), which
in turn releases endothelin (ET) and ends with the increase
in [Ca2+]i through the Na+/Ca2+
exchanger (NCX) in its reverse mode and the activation of
the calcineurin/NFAT pathway. It should be emphasized that
the link proposed herein between myocardial stretch and Ang
II/ET relies upon the release of small amounts of these peptides.
Higher concentrations of either of them may trigger Ca2+
influx through mechanisms other than NCX, and induce cardiac
hypertrophy by the activation of widely recognized intracellular
signaling pathways.
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