|
Current Cardiology Reviews
ISSN: 1573-403X
Current Cardiology Reviews
Volume 2, Number 4, November 2006
Contents
Preconditioning and Shear Stress in the Microcirculation
in Ischemia-Reperfusion Injury Pp. 237-245
Silvia Bertuglia
[Abstract]
Oxidative Stress and the Pathogenesis of Atrial Fibrillation
Pp. 247-254
Shahriar Iravanian and Samuel C. Dudley Jr.
[Abstract]
Fetal Arterial Changes in Response to Maternal
Cigarette Smoking: Revisiting the Natural History of the Earliest
Stage of Atherosclerosis Pp. 255-259
Luigi Matturri and Anna Maria Lavezzi
[Abstract]
NADPH Oxidases in the Heart Pp. 261-270
Christof Meischl, Dirk Roos and Hans W.M. Niessen
[Abstract]
Assessment of Cardiac Performance with Magnetic
Resonance Imaging Pp. 271-282
Alistair A. Young
[Abstract]
Dynamic Ventricular Repolarisation: From Physiology
to Prognosis Pp. 283-288
Olivier Xhaet, Philippe van de Borne and Atul Pathak
[Abstract]
The Coronary Circulation in Cyanotic Congenital
Heart Disease Pp. 287-292
Joseph K. Perloff
[Abstract]
Why is Inhibition of the Renin-Angiotensin System
Effective for Preventing Cardiac Events in Patients With Coronary
Risk Factors or Coronary Artery Disease? Pp. 293-316
Isabelle and Alain Nitenberg
[Abstract]
Abstracts
[Back to top]
Preconditioning and Shear Stress in the Microcirculation
in Ischemia-Reperfusion Injury
Silvia Bertuglia
Postischemic reperfusion causes microvascular endothelial
cell dysfunction characterized by low shear stress, excessive
oxidative stress and a reduced nitric oxide (NO) release.
Recent studies have demonstrated that reduced shear forces
are responsible for the impairment of endothelium-dependent
vasodilation after ischemia reperfusion (I/R) injury. Preconditioning
is an endogenous phenomenon whereby intermittent periods of
ischemia provide protection against subsequent periods of
I/R. Several models show that intermittent hypoxia (IH, brief
periods of systemic hypoxia and reoxygenation), treatment
with erythropoietin (EPO) and ultrasound exposure are methods
of preconditioning. This chapter explores the hypothesis that
these procedures that improve tolerance to subsequent I/R
are directly related to shear stress. It acts as a biochemical
mechanotransducer by modulating the production of vasoactive
substances by endothelial cells. The adaptation of endothelial
cells to high shear stress during the preconditioning period
is crucial to ensure vasodilation and capillary perfusion
during subsequent periods of I/R. Both IH and EPO treatment
increase blood viscosity thus increasing shear stress associated
with a reduced oxidative stress during postischemic reperfusion.
Ultrasound treatment can also improve tolerance to I/R and
normale shear stress during postischemic reperfusion by pulsatile
mechanism acting on endothelial cells.
[Back to top]
Oxidative Stress and the Pathogenesis of Atrial Fibrillation
Shahriar Iravanian and Samuel C. Dudley Jr.
There is growing evidence that oxidative stress is involved
in the pathogenesis of atrial fibrillation. Many known triggers
of oxidative stress, such as age, diabetes, smoking, inflammation,
and renin angiotensin system activation are linked with an
increased risk of the arrhythmia. Blockers of angiotensin
II signaling and other drugs with anti-oxidant properties
can reduce the incidence of atrial fibrillation. Now, studies
in animal models and human tissue have shown directly that
atrial fibrillation is associated with increased atrial oxidative
stress. We review the evidence for a role of oxidative stress
in causing atrial fibrillation and propose a unifying hypothesis
that multiple triggers elicit oxidative stress which acts
to enhance the risk of atrial fibrillation through ion channel
dysregulation.
[Back to top]
Fetal Arterial Changes in Response to Maternal
Cigarette Smoking: Revisiting the Natural History of the Earliest
Stage of Atherosclerosis
Luigi Matturri and Anna Maria Lavezzi
The current knowledge of the development and progression
of atherosclerotic lesions is largely owed to experimental
studies carried out in animals fed a high cholesterol diet.
Only a few studies have addressed the atherogenic effects
of other important exogenous risk factor, namely cigarette
smoking. The results of our research into the effects of cigarette
smoking on the fetal arterial wall have demonstrated that
the first reactive event is a severe alteration of the architecture
of the tunica media, forming perpendicularly oriented columns
of smooth muscle cells (SMCs), infiltrating the intima. These
histopathological alterations go hand in hand with a marked
change in the biological homeostasis of the SMCs. Our molecular
biology research has shown that the first reaction of these
cells to the nicotine is an intense activation of the c-fos
proto-oncogene, followed by the transformation of the SMCs
to “myofibroblasts”, characterized by the presence
of β-actin
and acquisition of both synthetic and ameboid activity. If
the harmful effects of passive smoke persist, the myofibroblasts
start to proliferate, as demonstrated by positivity of the
PCNA, together with the onset of chromosomal alterations.
These peculiar changes of the tunica media are the prerequisites
for lipid accumulation that thereafter over-whelm the myofibroblast
reaction.
[Back to top]
NADPH Oxidases in the Heart
Christof Meischl, Dirk Roos and Hans W.M. Niessen
The recently discovered protein family of NADPH oxidases
(NOX) is a group of transmembrane proteins that generate reactive
oxygen species (ROS) by transferring electrons from NADPH
onto molecular oxygen. The NOX proteins are the catalytic
subunits that assemble with several regulatory subunits to
form the catalytically active enzyme complex. Of the regulatory
subunits exist several isoforms that are differentially expressed
in a wide range of tissues.
In relation to the heart, low NOX1 expression has been described
in the coronary vascular system, NOX2 expression in cardiomyocytes,
vascular smooth muscle (VSMCs) and endothelial cells, and
NOX4 seems to be present in VSMCs, fibroblasts and endothelial
cells. While the prototypical NOX2 in phagocytes generates
high bursts of superoxide that are needed to kill off invading
pathogens, the other members of this family, as well as NOX2
in nonphagocytic tissues, are responsible for the generation
of lower levels of ROS that are essential for cell signalling.
Since the first demonstration of the basic principle of NADPH-oxidase-dependent
redox signalling some ten years ago, NADPH-oxidase-derived
ROS have been implicated in all major signalling pathways
in most, if not all, tissue types.
In the heart, ROS have been shown to play a role in cell proliferation,
hypertrophy, apoptosis, differentiation and endothelial activation
and adhesivity. Not surprisingly, therefore, NADPH oxidases
have been implicated in the pathophysiologies of diabetes,
hypertension, atherosclerosis, cardiac hypertrophy, heart
failure, preconditioning and acute myocardial infarction,
both by dysregulation of redox-based signalling pathways and
by oxidative modification of a wide range of bio-molecules.
This review will briefly present the different NOX-family
members and summarize our current knowledge concerning their
regulation. Thereafter, we will give an overview of the expression
patterns of the NOX-family members in the heart, both in health
and disease, and will review their role in the (patho)physiology
of the heart. Finally the present-day therapeutic opportunities
in the form of the 3-hydroxyl-3-methylglutaryl coenzyme A
(HMG-CoA) reductase inhibitors, or statins, will be critically
assessed.
[Back to top]
Assessment of Cardiac Performance with Magnetic
Resonance Imaging
Alistair A. Young
A quantitative assessment of regional cardiac performance
is required for the diagnosis of disease, evaluation of severity
and the quantification of treatment effect. MRI allows the
noninvasive quantification of motion and deformation in the
heart, including the precise assessment of all components
of deformation in all regions of the heart throughout the
cardiac cycle. In recent years, these imaging protocols have
become standardized in both the research and clinical settings.
However, adoption in the routine clinical environment has
been hindered by the complex and time-consuming nature of
the image post-processing. Model-based image analysis procedures
provide a powerful mechanism for the fast, accurate assessment
of cardiac MRI data and lend themselves to biophysical analysis
and standardized functional mapping procedures. This paper
reviews the current state of the art in MRI assessment of
cardiac performance with an emphasis on mathematical modeling
analysis procedures. Firstly, fast and accurate evaluation
of mass and volume is discussed using interactive 4D modeling
techniques. Analysis of tissue function, strain and strain
rate is then reviewed. Mathematical models of regional tissue
function and wall motion allow registration between cases
and across groups, enabling quantification of multidimensional
patterns of wall motion between disease and treatment groups.
Finally, information on myocardial tissue kinematics can be
incorporated into biophysical models of cardiac mechanics
and used to gain an understanding of how physiological tissue
parameters such as contractility, ventricular compliance and
electrical activation combine to effect whole heart function.
[Back to top]
Dynamic Ventricular Repolarisation: From Physiology
to Prognosis
Olivier Xhaet, Philippe van de Borne and Atul Pathak
Identification of high-risk patients for sudden cardiac
death (SCD) remains difficult. Non-invasive markers evaluating
changes in heart rate and ventricular repolarisation (VR)
have been developed to stratify this risk. Most studies using
VR analysis rely on static analysis of the QT interval which
is poorly reproducible and heart rate dependent.
Dynamic VR analysis assesses QT interval modification according
to RR duration of the precedent heart cycle. This relation
is characterized by the linear regression QT/RR (y = ax+b)
thus defined by its slope (a) and the value of the QT for
a virtual null RR cycle (b). Analysis can be made for QTa
(apex) and QTe (end).
In healthy subjects, the difference of QT/RR slopes observed
between day and night highly suggest that the QT/RR slope
is influenced by the autonomic tone. The QT/RR slope is also
influenced by clinical, physiological, pharmacological and
various diseases associated with an increased risk of SCD.
The prognostic value of the QT/RR slope for SCD has been demonstrated
after myocardial infarction and in chronic heart failure.
These results suggest that QT dynamicity is a promising tool
able to identify patients at risk of SCD.
[Back to top]
The Coronary Circulation in Cyanotic Congenital
Heart Disease
Joseph K. Perloff
Background: The coronary circulation in cyanotic congenital
heart disease (CCHD) encompasses extramural coronary arteries,
basal coronary blood flow, flow reserve, the coronary microcirculation,
and coronary atherogenesis.
Methods: Coronary arteriograms were analyzed in 59
adults with CCHD. Dilated extramural coronaries were examined
histologically in 6 patients. Basal coronary blood flow was
determined with N-13 positron emission tomography in 14 patients
and in 10 controls. Hyperemic flow was induced by intravenous
dipyridamole pharmacologic stress. Immunostaining of coronary
arterioles against SM alpha-actin permitted microcirculatory
morphometric analysis. Non-fasting total cholesterols were
retrieved in 279 patients in four categories: Group A—143
cyanotic unoperated, Group B—47 acyanotic after reparative
surgery, Group C---41 acyanotic unoperated, Group D---48 acyanotic
before and after operation.
Results: Extramural coronary arteries were mildly
or moderately dilated to ectatic in 49/59 angiograms. Histologic
examination disclosed loss of medial smooth muscle, increased
medial collagen, and duplication of internal elastic lamina.
Basal coronary flow was appreciably increased. Hyperemic flow
was comparable to controls. Alterations in coronary arteriolar
length, volume and surface densities indicated remodeling
of the microcirculation. Coronary Atherosclerosis was not
detected in the either arteriograms or necropsy specimens.
Conclusions: Extramural coronary arteries dilate
in CCHD in response to endothelial vasodilator substances
coupled with mural attenuation caused by medial abnormalities.
Basal coronary flow was appreciably increased, but hyperemic
flow was normal. Remodeling of the microcirculation was the
key mechanism for preservation of flow reserve. The coronaries
were atheroma-free because of hypocholesterolemia, hypoxemia,
upregulated nitric oxide, low platelet counts, and hyper-bilirubinrmia.
[Back to top]
Why is Inhibition of the Renin-Angiotensin System
Effective for Preventing Cardiac Events in Patients With Coronary
Risk Factors or Coronary Artery Disease?
Isabelle and Alain Nitenberg
Primary and secondary strategies for preventing cardiac events
remain a major challenge in cardiovascular diseases. To date,
there is robust evidence that inhibition of the renin-angiotensin
system by angiotensin-converting enzyme inhibitors or angiotensin
II receptor antagonists significantly improves the outcome
and prevents cardiac events in patients with coronary risk
factors. This beneficial effect may be explained both by the
reduction of arterial pressure, and by arterial pressure non-dependent
effects. This observation raises at least one question: why
does inhibition of the renin-angiotensin system improve cardiac
outcome of patients with risk factors? One answer could be
that the renin-angiotensin system is up-regulated in these
patients. Then one may ask another question: why and how is
the renin-angiotensin system stimulated by markedly different
conditions such as hypertension, diabetes, dyslipidemia, cigarette
smoking and obesity? In these conditions, is there a common
pathway that leads to stimulation of the renin-angiotensin
system and explains the beneficial effect of inhibiting this
system?
On the basis of previous experimental and clinical studies,
this review proposes an integrative pathophysiological representation
of the path leading from major coronary risk factors to renin-angiotensin
system activation and cardiac events mainly due to complications
of coronary artery disease. This allows us to understand how
the renin-angiotensin system is involved in coronary artery
disease, and why inhibition of this system has such beneficial
effects in patients with cardiovascular risk factors.
|
