The manner in which the left atrium adapts to chronic mitral regurgitation and the role of the adapted left atrium as a modulator of excessive central blood volume were analyzed in seven conscious dogs, instrumented with high-fidelity pressure transducers and ultrasonic dimension gauges for measurement of left atrial and left ventricular pressure and cavity size. After obtaining data in a control situation, mitral regurgitation was produced by transventricular chordal sectioning. Heart rate was matched by right atrial pacing. In the "early" stage (7-14 days), left ventricular end-diastolic and mean left atrial pressures increased from 6 to 16 mm Hg and from 4 to 12 mm Hg, respectively. Both left ventricular end-diastolic segment length and left atrial diameter prior to atrial contraction increased by 7%. In the "late" stage (20-35 days), despite significant decreases in left ventricular filling pressure (11 mm Hg) and left atrial pressure (8 mm Hg), there was a continuous increase in left ventricular end-diastolic dimension (10%) and atrial end-diastolic diameter (10%). After the onset of mitral regurgitation, the left atrium performed greater work with a more enlarged cavity. Left atrial chamber stiffness was progressively decreased. These changes were associated with progressive increase in the left atrial diameter at zero stress, and there was a significant increase in the diameter of the left atrial myocyte. These results indicate that during chronic mitral regurgitation, the left atrium enlarges in size and mass, with a more potent booster action. The left atrial chamber becomes more compliant. Thus, the enlarged left atrium appears to exert an important compensatory mechanism in the case of T he left atrium, a muscular contractile chamber located in the inflow path to the left ventricle, functions both as a pump and as a reservoir for blood.1 During mitral regurgitation, the left ventricle decompresses into the left atrium as the mitral orifice, in parallel with the aortic valve, acts as a pressuredependent outlet for the ventricle. The physiological consequences to the left atrium are characterized by increases in left atrial size and pressure; however, the magnitude of these changes depends chiefly on the rapidity and severity with which the regurgitation develops. In animal experiments, we observed that the atrial diameter suddenly increased following the onset of acute mitral regurgitation. Hence, atrial shortening was initially augmented, in accord with the FrankStarling mechanism in atrial muscle. However, progressive increase in regurgitation was associated with further increases in atrial size but diminished atrial stroke; hence, the atrial chamber was rendered less compliant.2 These changes in left atrial compliance were postulated as follows: the atrium subjected to From the Third Division, Department of Internal Medicine, Faculty of Medicine, Kyoto University, Kyoto, Japan, and the Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan.Presented in pa...

Abstract-Progression to failure in hypertension is associated with ventricular dilation, excessive myocyte lengthening, and an increase in myocyte length/width ratio. The temporal development of these changes in relation to impaired pump performance is unknown. We examined isolated myocytes from 1-to 12-month-old spontaneously hypertensive heart failure (SHHF) rats who develop heart failure at approximately 24 months of age. Left ventricular myocyte cross-sectional area reached a maximum of Ϸ350 to 400 m 2 at 3 months of age and did not change significantly thereafter. Nonetheless, LV systolic wall stress, a known stimulus for myocyte transverse growth, increased progressively between 3 and 12 months of age. Unlike the situation in normally aging rats with stable body mass, myocyte length in SHHF rats continued to increase with aging (PϽ0.05 from 9 to 12 months of age). In summary, (1) left ventricular myocyte transverse growth reaches an upper limit by 3 months of age although systolic wall stress continues to rise; and (2) cell length is significantly increased by 12 months of age. This study suggests that maladaptive remodeling of cardiac myocyte shape begins long before pump failure in hypertension. Additionally, it appears that the left ventricle may be robbed of an important adaptive mechanism to normalize wall stress (eg, myocyte transverse growth) early in the progression to failure. (Hypertension. 1998;32:753-757.)

Regional changes in cardiac myocyte shape during the progression to failure with hypertension have not been clearly established. To address this issue, we examined left and right ventricular myocytes from lean, female spontaneously hypertensive/heart failure rats with compensated hypertrophy (approximately 12 months of age) and congestive heart failure (approximately 24 months of age). During this period, body weight did not change, but heart weight increased 59% and lung weight increased 93%. Left ventricular function declined with the onset of failure. Left ventricular myocyte volume increased 27% exclusively because of myocyte lengthening (29% increase). The onset of left ventricular failure resulted in a 72% increase in right ventricular myocyte volume. Right ventricular myocyte growth, however, was proportional, with a 23% increase in myocyte length and 18% increase in myocyte width. Changes in left ventricular myocyte shape were virtually identical to data collected previously from patients with similar disease, suggesting that this is a relevant animal model. Evidence suggests that left ventricular myocyte transverse growth is defective because dilation and failure were associated with cell lengthening, without a change in myocyte diameter. Although severe hypertrophy was present in the right ventricle as a result of left ventricular failure, myocyte growth was proportional, suggesting that cell shape was properly regulated in this chamber.

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