Diastolic Mitral Regurgitation in 2:1 Atrioventricular Block: Insight of the Diastolic Pressure

The aim of the study was to assess the impact of mitral regurgitation (MR) on left ventricular (LV) anatomic and molecular remodeling and function and to determine whether early LV remodeling and function predict long-term outcome in experimental organic MR. A new rodent model of chronic MR was created. Twenty-eight rats had surgically induced MR, twelve rats had a sham operation, and twelve rats had no operation. LV diameters, volume, and mass and LV ejection fraction (LVEF) and LV fractional shortening (LVFS) were assessed using echocardiography in the early stage of MR (6 and 12 wk after induction of MR). LV hemodynamics was assessed invasively. Cardiac α- and β-myosin heavy chains and sarco(endo)plasmic reticulum Ca2+-ATPase 2 (SERCA2) were measured to assess molecular remodeling and contractility. Cox's proportional hazard ratios (HR) were used to identify outcome predictors. Early LV dilation was demonstrated in rats with MR when LVEF and LVFS were still normal. LV remodeling was associated with an increase in LV end-diastolic pressure and decrease in maximal change in pressure over time. Shifting of α- to β-myosin and reduced SERCA2 were observed in rats with MR. Cox's proportional hazard analysis showed that LV end-diastolic diameters (HR, 1.2–2.4; P = 0.007) and LV end-diastolic volume (HR, 1.1–1.4; P = 0.005) at 6 wk and LV mass index (HR, 1.1–2.0; P = 0.004) at 12 wk after induction of MR were significantly associated with 1-yr mortality. However, LVEF (HR, 0.7–6.8 for the 6 wk, P > 0.05; and HR, 0.4–3.2 for the 12 wk, P > 0.05) and LVFS (HR, 0.4–1.4 for the 6 wk; and 0.4–3.1 for the 12 wk, P > 0.05) did not predict late death. Chronic MR leads to LV anatomic and cellular remodeling and impaired contractility. The time course of LV remodeling and function changes in the rat model of MR is similar to humans. Prediction of outcome may be achieved by assessments of early LV remodeling.

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Volume overload hypertrophy in a closed-chest model of mitral regurgitation

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1988.254.6.h1034 ◽

1988 ◽

Vol 254 (6) ◽

pp. H1034-H1041 ◽

Cited By ~ 11

Author(s):

J. P. Kleaveland ◽

W. G. Kussmaul ◽

T. Vinciguerra ◽

R. Diters ◽

B. A. Carabello

Keyword(s):

Cardiac Output ◽

Mitral Regurgitation ◽

Diastolic Pressure ◽

Volume Ratio ◽

Volume Overload ◽

Canine Model ◽

Left Ventricular ◽

Closed Chest ◽

Cardiac Decompensation ◽

End Diastolic Volume

Chronic volume overload hypertrophy as seen in mitral regurgitation in humans eventually may cause left ventricular dysfunction. Longitudinal study of the mechanisms leading to such dysfunction is difficult in humans and more easily performed in an animal model. In this study, we describe a canine model of volume overload hypertrophy produced by mitral regurgitation. An arterially placed grasping forceps was used to disrupt mitral chordae or leaflets; thus mitral regurgitation was produced without the need for thoracotomy. Eleven of 22 dogs had severe mitral regurgitation (regurgitant fraction greater than 0.50) and survived for greater than or equal to 3 mo (average 9.2 +/- 6 mo) after the production of mitral regurgitation. At 3 mo, end-diastolic volume increased from 48 +/- 9 to 85 +/- 19 ml, P less than 0.01. Left ventricular mass increased from 71 +/- 13 to 90 +/- 10 g, P less than 0.01. Left ventricular end-diastolic pressure increased from 9 +/- 3 to 19 +/- 6 mmHg, P less than 0.01. Cardiac output decreased from 2.3 +/- 0.61 to 1.80 +/- 0.64 l/min, P less than 0.05. The mass-to-volume ratio decreased from 1.44 +/- 0.17 to 1.09 +/- 0.13, P less than 0.01. We conclude that this closed-chest model of chronic mitral regurgitation produces significant eccentric cardiac hypertrophy. Despite a doubling of end-diastolic volume, there was a fall in cardiac output and a rise in left ventricular end-diastolic pressure, suggesting cardiac decompensation.

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