Motoaki Sugawara

Myocardial stiffness is determined by ventricular fibrosis, but not by compensatory or excessive hypertrophy in hypertensive heart.

OBJECTIVES Diastolic dysfunction that determines symptoms and prognosis in patients with systolic dysfunction causes heart failure even in the absence of systolic dysfunction. Our recent studies have suggested that myocardial stiffening is likely to play a crucial role in triggering deleterious cardiac disorder. This study investigated differential contribution of left ventricular (LV) hypertrophy and fibrosis to myocardial stiffening in the pressure-overloaded heart. METHODS Dahl-Iwai salt-sensitive rats fed on high-salt diet since 7 weeks transit to congestive heart failure at 20 weeks following development of hypertension, LV hypertrophy and fibrosis, and 20 such rats were divided into three groups: rats treated with angiotensin II type 1 receptor antagonist from 8 weeks (n=7), rats treated with calcineurin inhibitor from 8 weeks (n=6), and untreated rats (n=7). RESULTS Administration of angiotensin II type 1 receptor antagonist and calcineurin inhibitor did not affect blood pressure and allowed the development of compensatory hypertrophy. However, in contrast to the untreated rats, additive and excessive LV hypertrophy was not observed in either of the treated rats. The blockade of angiotensin II kept LV hydroxyproline content, a ratio of type I to type III collagen mRNA levels, collagen solubility and myocardial stiffness constant at the normal level; however, the calcineurin inhibition failed. CONCLUSIONS Myocardial stiffening may be attributed to progressive collagen accumulation, collagen phenotype shift and enhanced collagen cross-linking, but not to either compensatory LV hypertrophy or LV hypertrophy that progresses from the compensatory stage.

Relationship between the pressure and diameter of the carotid artery in humans.

Abstract The purpose of this study was to examine the assumption of similarity between pressure and diameter-change waveforms in humans. We measured carotid arterial pressure and diameter change, simultaneously, in six patients with heart disease. In all patients, the carotid arterial pressure–diameter relationship could, in practice, be regarded as being linear.

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.

A noninvasive method of measuring wave intensity, a new hemodynamic index: application to the carotid artery in patients with mitral regurgitation before and after surgery

SummaryWave intensity (WI) is a new hemodynamic index, which is defined as (dP/dt)(dU/dt) at any site of the circulation, where dP/dt and dU/dt are the time derivatives of blood pressure and velocity, respectively. Arterial WI in normal subjects has two positive sharp peaks. The first peak occurs during early systole when a forward-traveling compression wave is generated by the left ventricle. The magnitude of this peak increases markedly with an increase in cardiac contractility. The second peak, which occurs towards the end of systole, is caused by generation of a forward-traveling expansion wave by the ability of the left ventricle to actively stop aortic blood flow. The interval between the R wave of the ECG and the first peak of WI (R-lst peak interval) and the interval between the first and second peaks (lst–2nd interval) are approximately equal to the preejection period and left ventricular ejection time, respectively. Using a combined Doppler and echotracking system, we obtained carotid arterial WI non-invasively. We examined the characteristics of WI in 11 patients with mitral regurgitation (MR) before and after surgery, and 24 normal volunteers. In the MR group before surgery, the second peak was decreased and the (lst–2nd interval)/(R-R interval) ratio was reduced, compared with the normal group (140 ± 130 vs 750 ± 290mmHgm/s3, P < 0.0083; 20.7% ± 3.4% vs 26.7% ± 2.8%, P < 0.0083). There were no significant differences in the first peak between the normal group and the MR group before and after surgery. The second peak in the MR group was increased significantly (P < 0,016 vs before surgery) to 1150 ± 830mmHgm/s3 in the early period after surgery (stage I), and to 1090 ± 580mmHgm/s3 in the late period after surgery (stage II). These values did not differ significantly from that of the normal group. At stage I, the (R-1st peak interval)/(R-R interval) ratio was increased from 13.4% ± 2.7% to 2.6% ± 5.6% (P < 0.016 vs before surgery). At stage II, this ratio decreased to 16.2% ± 2.8% (P < 0.016 vs stage I), but was still significantly higher than that before surgery. The (1st–2nd inteval)/(R-R interval) ratio increased significantly after surgery (P < 0.016 vs before surgery) to values (27.0% ± 4.5% at stage I and 28.9% ± 2.6% at stage II) which did not differ significantly from that of the normal group. The recovery of the second peak after surgery suggests that the left ventricle had recovered the ability to actively stop aortic blood flow. Wave intensity is useful for analyzing changes in the working condition of the heart.

Long-term administration of amlodipine prevents decompensation to diastolic heart failure in hypertensive rats

UNLABELLED OBJECTIVES; We assessed the effects of long-term amlodipine administration in a diastolic heart failure (DHF) rat model with preserved systolic function as well as the relationship between changes in left ventricular (LV) myocardial stiffening and alterations in extracellular matrix. BACKGROUND Although the effect of long-term administration of amlodipine has been shown to be disappointing in patients with systolic failure, the effect is unknown in those with DHF. METHODS Dahl salt-sensitive rats fed a high-salt diet for seven weeks were divided into three groups: eight untreated rats (DHF group), eight rats given high-dose amlodipine (10 mg/kg/day; HDA group) and seven rats given low-dose amlodipine (1 mg/kg/day; LDA group). RESULTS High-dose administration of amlodipine decreased systolic blood pressure and controlled excessive hypertrophy, without a decrease in the collagen content, and prevented the elevation of LV end-diastolic pressure at 19 weeks. Low-dose administration of amlodipine with subdeppressive effects did not control either hypertrophy or fibrosis; however, it prevented myocardial stiffening and, hence, the elevation of LV end-diastolic pressure. The ratio of type I to type III collagen messenger ribonucleic acid levels was significantly lower in both the HDA and LDA groups than in the DHF group. CONCLUSIONS Long-term administration of amlodipine prevented the transition to DHF both at the depressor and subdepressor doses. Amlodipine did not decrease the collagen content, but attenuated myocardial stiffness, with inhibition of the phenotype shift from type III to type I collagen. Thus, amlodipine may exert beneficial effects through amelioration of collagen remodeling in the treatment of DHF.

Development of a non-invasive real-time measurement system of wave intensity

Time-normalized wave intensity (WI) is a new hemodynamic index, which is defined as (dP/dt)(dU/dt) at any site of the circulation, where dP/dt and dU/dt are the time derivatives of blood pressure and velocity, respectively. WI provides information about the dynamic behavior of the heart and vascular system and their interaction. We have developed a new real-time measurement system for obtaining WI based on a conventional color Doppler system. The blood pressure waveforms were obtained non-invasively from the arterial diameter-change waveforms by an echo-tracking method. Using a 7.5 MHz linear array probe, we obtained carotid arterial WI, and analyzed the characteristics of the heart and vascular interactions. The results suggest that the system has great potential for clinical usefulness.

Spectrum analysis of turbulence in the canine ascending aorta measured with a hot-film anemometer

Abstract We measured turbulence velocity in the canine ascending aorta using a hot-film anemometer. Blood flow velocity was measured at various points across the ascending aorta approximately 1.5–2 times the diameter downstream from the aortic valve. The turbulence spectrum was calculated and its characteristics were examined in connection with the mean Reynolds number and/or measuring positions. In the higher wave number range the values of the turbulence spectra were higher at larger mean Reynolds number. In the higher wave number range, the values of the turbulence spectra were higher at points closer to the centerline of the aorta, when the mean Reynolds number was relatively large. The patterns of the turbulence spectra at various points outside the boundary layer on the aortic wall were similar.

Spectral Broadening in Ultrasonic Doppler Flowmeters Due to Unsteady Flow

It is shown that time-varying velocity produces frequency modulation of the backscattered signal in ultrasonic Doppler flowmeters. Further, for blood flow in the ascending aorta, it is estimated that the spectrum of the backscattered signal would have a very wide bandwidth in the acceleration phase.

Does repeated balloon inflation during coronary angioplasty induce ischemic tolerance? Analysis based on regional work

Abstract It has been reported that repeated brief balloon inflation during coronary angioplasty (PTCA) alleviates myocardial dysfunction. However, it has also been reported that PTCA does not induce ischemic tolerance. Six patients with stable angina pectoris were recruited for this study. They were scheduled for PTCA to a significant stenosis of the proximal left anterior descending artery (LAD). All patients had single-vessel coronary artery disease without angiographic evidence of collateral circulation and with normal wall motion. After the stenosis of LAD was dilated by a 30-s inflation, 60 s of balloon inflation was performed five times at 60-s intervals. Left ventricular regional work was determined in the first and fifth inflations, and the data were compared. Regional work of the interventricular septum decreased immediately after the balloon inflation (the first inflation: 5.3 ± 1.0 → 0.6 ± 0.2 mJ/cm3; fifth inflation: 5.3 ± 1.0 → 0.6 ± 0.3 mJ/cm3) and no statistically significant differences were found between the first and fifth inflations. After balloon deflation, the time required for the recovery of regional work was 30 s in the fifth inflation, compared with 40 s in the first inflation (at 30 s after deflation, first inflation: 3.6 ± 1.3 mJ/cm3; fifth inflation: 5.2 ± 1.2 mJ/cm3). Although repeated balloon inflation did not change the amount of reduction in regional work, it improved the postischemic recovery of regional work. These results suggest ischemic tolerance.

Facilitated diffusion of carbon dioxide in whole blood and hemoglobin solutions

The values of effective permeability (Kroghs diffusion coefficient) for carbon dioxide have been measured in horizontal stationary layers of whole blood and hemoglobin solutions in quasi-steady state, with the goal of understanding the specific nature of facilitated diffusion of carbon dioxide occurring in these media. The average partial pressure of carbon dioxide within the layer ranged from 0.74 kPa (5.6 mm Hg) to 15.7 kPa (118 mm Hg). Facilitation effects were significant in hemolysed blood and in hemoglobin solutions at low pCO2; the facilitation factor was up to 2.3. Facilitation effects were considerably less for intact blood; the facilitation factor of intact blood with hematocrit 45% was 0.3. The presence of the red cell membrane appears to have a negative effect on facilitation of carbon dioxide transport.