Aortic Aneurysm Clinical Trial
Official title:
Influence of Short AV Delay Pacing on Matrix Metalloproteinase Lives
As potential biomarkers of pressure-related aortic damage, matrix metalloproteinases (MMP) have been implicated in the pathogenesis of aortic aneurysm because of the important role they play in connective tissue homeostasis. In particular, a significant reduction in initially elevated serum MMP - 9 concentrations, compared with healthy controls, demonstrated after the aortic repair in patients with abdominal aortic aneurysm implies MMPs pivotal role in aortic aneurysms. Besides, due to an active degradation and repair processes taking place in the vascular wall governed by the balance between MMP enzymes and their inhibitors, MMP - 9, expression of which is predominantly associated with disruption of aortic elastic fibers, can also be detected in the serum of healthy subjects. Indeed, mechanical stress-induced upregulation of genes and their products stimulate MMP expression in the vascular wall, which is responsible for extracellular matrix degradation. Herein, it was hypothesized that reducing the acceleration rate of aortic pressure (aortic peak dP/dt) may decrease the mechanical stretch on the aortic wall which, may in turn, reduce the expression and serum levels of MMP-9.
The maximum value of acceleration rate of aortic pressure rise can be named as aortic peak
dP/dt. It, likewise, corresponds to the maximum value of first derivative of aortic pressure
curve with respect to time.Notably, aortic peak dP/dt would be one of the principal
determinants of mechanical stress applied to the aortic wall. Hence, interventions aiming to
reduce aortic peak dP/dt levels may open a new therapeutic avenue in the management of
pressure-related vascular damages such as aortic aneurisms.
Since it is the principle determining factor of aortic peak dP/dt, changing LV contractility,
thereby LV peak dP/dt, may be expected to lead to change aortic peak dP/dt values in the same
direction. Therefore, reduction of LV dP/dt can lead to a reduction in aortic dP/dt. Previous
finding strongly suggest that widening of the QRS complex could decrease LV contractility and
correspondingly LV peak dP/dt value which may eventually lead to a reduction in aortic peak
dP/dt.
From biomechanical point of view, as potential biomarkers of pressure-related aortic damage,
matrix metalloproteinases (MMP) have been implicated in the pathogenesis of aortic aneurysm
because of the important role they play in connective tissue homeostasis. In particular, a
significant reduction in initially elevated serum MMP - 9 concentrations, compared with
healthy controls, demonstrated after the aortic repair in patients with abdominal aortic
aneurysm implies MMPs pivotal role in aortic aneurysms. Besides, due to an active degradation
and repair processes taking place in the vascular wall governed by the balance between MMP
enzymes and their inhibitors, MMP - 9, expression of which is predominantly associated with
disruption of aortic elastic fibers, can also be detected in the serum of healthy subjects.
Indeed, mechanical stress-induced upregulation of genes and their products stimulate MMP
expression in the vascular wall, which is responsible for extracellular matrix degradation.
Herein, we hypothesized that reducing the acceleration rate of aortic pressure (aortic peak
dP/dt) may decrease the mechanical stretch on the aortic wall which, may in turn, reduce the
expression and serum levels of MMP-9.
To this end, in the current trial, effect of the prolongation of QRS duration over a certain
period of time by short AVD permanent pacing on the circulating levels of a vascular
extracellular matrix degradation marker, MMP-9, was examined.
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