Cellular and ventricular contractile dysfunction in experimental canine mitral regurgitation.
Key result
Experimental mitral regurgitation in dogs led to intrinsic cardiocyte contractile defects that correlated strongly with a size-independent measure of active ventricular stiffness (r=0.88).
Why the study?
Does left ventricular volume overload from mitral regurgitation cause intrinsic cellular contractile dysfunction in a canine model?
Population
17 dogs (10 with induced mitral regurgitation, 7 controls)
Comparison
Left ventricular volume overload produced by… vs Control dogs without induced mitral regurgitation
Design
Preclinical, Investigators characterizing cellular contractile performance…
Follow-up
3 months
Authors
Discussion
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Member takes
Implication
Caution against clinical extrapolation from this canine model; leaves open translation of cardiocyte defects to human mitral regurgitation.
Key Points
- To determine whether left ventricular contractile dysfunction in chronic mitral regurgitation originates from primary cellular defects within cardiocytes and to identify the underlying structural basis.
- Induced chronic left ventricular volume overload via catheter transection of mitral chordae tendineae in 10 dogs, comparing them with 7 control dogs after 3 months.
- Assessed left ventricular function using the end-ejection stress-volume relation (EESVR) and measured isolated cardiocyte contractile performance (viscosity-velocity relation) under blinded conditions.
- Performed morphometric analyses of left ventricular tissue to evaluate interstitial volume fraction and cardiocyte myofibril volume fraction.
- Left ventricles and isolated cardiocytes exhibited significant contractile abnormalities, with ventricular EESVR correlating with cardiocyte peak sarcomere shortening velocity (SSV, r = 0.63; r = 0.88 for active ventricular stiffness vs. SSV).
- Ventricular and cellular contractile dysfunction strongly correlated with a reduced volume fraction of cardiocyte myofibrils, with no observed changes in interstitial volume fraction.
- Left ventricular mass in dogs with mitral regurgitation did not significantly correlate with either cellular or ventricular contractile indices, indicating inadequate compensatory hypertrophy.
Structured PICO
Does left ventricular volume overload from mitral regurgitation cause intrinsic cellular contractile dysfunction in a canine model?
P
Population
17 dogs (10 with induced mitral regurgitation, 7 controls)
I
Intervention
Left ventricular volume overload produced by catheter transection of mitral chordae tendineae
C
Comparator
Control dogs without induced mitral regurgitation
O
Outcome
Left ventricular contractile function (end-ejection stress-volume relation) and cellular contractile performance (viscosity-velocity relation)surrogate
Chronic left ventricular volume overload from mitral regurgitation leads to intrinsic cardiocyte contractile defects, likely driven by myofibrillar loss and failure of compensatory hypertrophy.
Cite This Study
Urabe et al. (1992) studied Mitral regurgitation (n=17). Catheter transection of mitral chordae tendineae (experimental MR) vs. Control dogs was evaluated on Left ventricular contractile function (end-ejection stress-volume relation) and cardiocyte contractile performance. Experimental mitral regurgitation in dogs led to intrinsic cardiocyte contractile defects that correlated strongly with a size-independent measure of active ventricular stiffness (r=0.88).