ABSTRACT
Transverse aortic constriction (TAC) is an effective technique for inducing left ventricular (LV) hypertrophy in mice. With the use of transthoracic echocardiography and Doppler measurements, we studied the effects of an acute increase in pressure overload on LV contractile performance and peak systolic wall stress index (WSI) at early time points after TAC and the time course of the development of LV hypertrophy in mice. The LV mass index was similar between TAC and sham-operated mice at postoperative day 1 but progressively increased in TAC mice by day 10. There was no further increase in the LV mass index between postoperative days 10 and 20. On day 1, whereas peak systolic WSI increased significantly, the LV ejection fraction (LVEF) and percent fractional shortening (%FS) decreased in TAC mice compared with sham-operated mice. By day 10, peak systolic WSI, LVEF, and %FS had recovered to baseline levels and were not significantly different between postoperative days 10 and 20. Thus LV systolic performance in mice declines immediately after TAC, associated with increased peak systolic WSI, but recovers to baseline levels with the development of compensatory LV hypertrophy over 10-20 days.
Subject(s)
Aorta/physiopathology , Cardiomegaly/physiopathology , Constriction, Pathologic/physiopathology , Systole , Ventricular Function, Left , Animals , Blood Flow Velocity , Blood Pressure , Cardiomegaly/etiology , Constriction, Pathologic/complications , Disease Models, Animal , Disease Progression , Echocardiography , Heart Rate , Male , Mice , Mice, Inbred C57BL , Myocardial Contraction , Observer VariationABSTRACT
A tubular injury characterized by intraluminal obstruction and transtubular backleak of glomerular filtrate occurs in experimental acute renal failure (ARF) in animals. To determine whether these alterations also occur in human ARF, we studied 44 patients developing nonoliguric ARF following cardiac surgery. The delay in appearance of i.v. administered inulin in urine (Tu) was used as a measure of tubular fluid flow rate. Tu was not longer in 13 ARF patients than it was in control subjects (7.2 vs 9.0 min), suggesting that at least a subpopulation of tubules was widely patent. The fractional urinary dextran clearance profile (thetaD; radii, 20 to 40 A) was then determined in 20 patients with sustained ARF in whom inulin clearance averaged 11 +/- 1 ml/min/1.73 m2. A mass conservation model, which assumes that thetaD in Bowman's space in ARF is the same as that measured in controls, when applied to the experimental observations revealed that, on the average, 42% of filtered inulin was lost by transtubular backleak. A similar fractional inulin backleak (38%) persisted in 11 additional patients in whom ARF had begun to recover and in whom inulin clearance averaged 26 +/- 3 ml/min/1.73 m2. These findings suggest that in hemodynamically-mediated and nonoliguric ARF, (1) tubular obstruction is not homogeneous, and (2) backleak of glomerular filtrate contributes to but does not fully account for depression of inulin clearance.
