Keiko Ono

Development of different phenotypes of hypertensive heart failure: systolic versus diastolic failure in Dahl salt-sensitive rats.

Objective There are two phenotypes of heart failure, systolic failure and isolated diastolic heart failure with preserved left ventricular systolic function. Although isolated diastolic heart failure frequently occurs, there are only models for diastolic dysfunction unassociated with heart failure and models with overt diastolic heart failure have not been established. We attempted to develop two different models, i.e. diastolic and systolic failure models, based on hypertension. Materials and methods Dahl salt-sensitive rats were placed on 8% NaCl diet from 7 weeks old (7-week starting group) or 8 weeks old (8-week starting group). As an age-matched control, Dahl salt-sensitive rats were consistently placed on normal chow. In these rats, echocardiogram was serially recorded, followed by hemodynamic and histological studies. Results The 7-week starting rats showed a steep elevation in blood pressure and progressive left ventricular hypertrophy, and fell into overt heart failure at approximately 19 weeks. The development of heart failure was not associated with a decrease in left ventricular midwall fractional shortening or an increase in left ventricular end-diastolic dimension as compared with the age-matched control, which mimics the characteristics of clinically observed isolated diastolic heart failure. The 8-week starting rats showed a gradual rise in blood pressure and less progressive left ventricular hypertrophy, and fell into heart failure at approximately 26 weeks with a decrease in mid-wall fractional shortening and an increase in left ventricular end-diastolic dimension. Hemodynamic and histological studies at failing stage revealed comparable elevation of left ventricular end-diastolic pressure and comparable left ventricular fibrosis in both groups. Conclusion These two different models of overt heart failure may be useful as models of isolated diastolic heart failure and systolic heart failure based on the same hypertensive heart disease, respectively, and may contribute to discrimination of the mechanisms of the development of the two different phenotypes of heart failure.

Evolving changes in Doppler Mitral flow velocity pattern in rats with hypertensive hypertrophy

OBJECTIVES The aim of our study was to explore evolving changes in a mitral flow velocity pattern (MFVP) and its hemodynamic and pathological correlates in hypertensive rats in an isolated diastolic heart failure model. BACKGROUND Development of left ventricular (LV) hypertrophy and concomitant diastolic dysfunction cause heart failure in hypertensive hearts even with normal systolic function; however, associated evolving change in MFVP is still unclear. METHODS Mitral flow velocity pattern was recorded every 2 weeks from 7 to 19 weeks in six hypertensive rats. Hemodynamic and pathological correlates of Doppler mitral flow indexes were examined as an additional part of the study using the hypertensive rats at the age of 13 weeks (compensatory stage, n = 7) and at 19 weeks (heart failure stage, n = 8). RESULTS Initial development of pressure overload LV hypertrophy resulted in a decrease in early diastolic filling wave (E), a reciprocal increase in the filling wave due to atrial contraction (A) and prolongation of deceleration time of E wave (relaxation abnormality pattern). These changes were associated with an increase in tau, an index of LV relaxation, but without a change in LV end-diastolic pressure. Transition to congestive heart failure caused an increase in E, a decrease in A and shortening of deceleration time. These changes were not associated with further increase in tau but with elevation of LV end-diastolic pressure, reflecting marked LV hypertrophy and myocardial fibrosis. CONCLUSIONS Development of pressure overload LV hypertrophy is associated with evolving changes in MFVP from normal to relaxation abnormality pattern and, in turn, to pseudonormalized to restrictive pattern. Analysis of MFVP may be useful to follow not only functional but also constitutional changes of the myocardium in hypertensive hearts.

Calcineurin Inhibitor Attenuates Left Ventricular Hypertrophy, Leading to Prevention of Heart Failure in Hypertensive Rats

BackgroundThere is controversy regarding the contribution of calcineurin activation to the development of pressure-overload left ventricular (LV) hypertrophy and heart failure. The aim of this study was to explore whether the inhibition of calcineurin may prevent the transition to heart failure in hypertensive rats and, if so, to clarify in which developmental stage of LV hypertrophy calcineurin plays a key role. Methods and ResultsDahl salt-sensitive rats placed on an 8% NaCl diet from the age of 7 weeks (hypertensive rats) were randomized to no treatment (n=6) or treatment with the calcineurin inhibitor FK506 (1 mg · kg−1 · d−1) from 8 weeks (FKE, n=7) or from 17 weeks (FKL, n=7). Rats placed on a 0.3% NaCl diet were defined as control rats (n=6). The administration of FK506 from 8 weeks attenuated, although it did not block, LV hypertrophy observed in the untreated rats and prevented the transition to heart failure. The development of LV fibrosis, however, was not attenuated by the administration of FK506 from 8 weeks. The administration of FK506 from 17 weeks brought no benefit for cardiac remodeling or LV function and failed to prevent heart failure. ConclusionsCalcineurin inhibition, if started from the initial stage of pressure overload, attenuated the development of LV hypertrophy without any effect on LV fibrosis and prevented the transition to heart failure. The activation of calcineurin is involved in the development of LV hypertrophy but not of LV fibrosis, and this involvement may be crucial at the initial stage.

Structural changes in the thermochromic solid-state phase transition of poly(3-alkylthiophene

Abstract In order to clarify the structural changes in the thermocrhomic phase transition, the temperature dependence of the X-ray diffraction and Fourier-transform infrared spectra was measured for the oriented and unoriented poly(3-dodecylthiophene)[P3DT]and poly(3-hexylthiophene)[P3HT]. The detailed analysis of these data lead us to support the structural model proposed before: as the temperature increases, the trans-type side chains begin to disorder by an introduction of gauche bonds. This disordering affects the regularity in the main chain conformation and decreases the effective length of the polythiophene conjugate system.

Case of hemorrhagic pancreatic pseudocyst in which ultrasound imaging was useful.

A 50-year-old man was admitted to our institution for upper abdominal pain. The diagnosis was chronic pancreatitis. A pseudocyst 3 cm in diameter had been detected in the head of the pancreas by ultrasonography a year and a half earlier. At the current hospitalization, ultrasound examination showed a mass 5 cm in diameter where the pseudocyst had been seen. This mass comprised an external hypoechoic lesion, a middle movable hyperechoic lesion, and an internal cystic lesion showing an arterial signal on Doppler ultrasound examination. Computed tomography showed a high-density area thought to be a hematoma in the head of the pancreas, and extravasation in the mass was demonstrated by rapid injection of a contrast medium. Our diagnosis was a bleeding pseudocyst. The patient suddenly vomited fresh blood and went into hypovolemic shock on the 11th hospital day. Emergency angiography and transcatheter embolization with steel coils was accomplished under a diagnosis of rupture of the bleeding pseudocyst into the duodenum. Ultrasonographic examination showed that the mass had decreased in size and the cystic lesion, showing an arterial signal, had disappeared after embolization. Although bleeding pseudocysts occur infrequently, they are a life-threatening complication of chronic pancreatitis. Early diagnosis and treatment are thus essential. Ultrasound examination with Doppler ultrasonography is strongly indicated when diagnosing bleeding pseudocysts and examining patients with chronic pancreatitis accompanied by abdominal pain, gastrointestinal bleeding, or both. Early treatment by transcatheter embolization should be used to avoid this potentially lethal complication.