Liver Resident Macrophages (Kupffer Cells) Share Several Functional Antigens in Common with Endothelial Cells.

The identification and specific functions of Kupffer cells (KCs), a liver resident macrophage subpopulation, are still unclear. We compared KCs with peritoneal macrophages using cDNA microarray analysis and found that these cells share some antigens with endothelial cells. KCs highly express VCAM-1 and VEGF receptors (VEGF-Rs) at transcriptional and protein levels. VCAM-1 mediates the functional binding of KCs with lymphocytes and induces KC activation. Among the VEGF receptors, VEGF-R2 and VEGF-R3 were expressed on the KCs, while VEGF-R1 was expressed on other tissue macrophage subsets. VEGF120, a ligand of both VEGF-R1 and VEGF-R2, transduced strong survival and chemotactic signals through the KCs, when compared to PIGF, a VEGF-R1 ligand, indicating that VEGF-R2 plays significant roles in regulating KC activities. Expression of the VEGF-Rs was regulated by TLR4 signalling. These results suggest that the function of KCs is partly regulated by the common antigens shared with endothelial cells.

Chondroprotective effect of the bioactive peptide prolyl-hydroxyproline in mouse articular cartilage in vitro and in vivo.

OBJECTIVE: To investigate the direct effect of prolyl-hydroxyproline (Pro-Hyp) on chondrocytes under in vivo and in vitro conditions in an attempt to identify Pro-Hyp as the bioactive peptide in collagen hydrolysate (CH). METHODS: The in vivo effects of CH and Pro-Hyp intake on articular cartilage were studied by microscopic examination of sections of dissected articular cartilage from treated C57BL/6J mice. In this study, mice that were fed diets containing excess phosphorus were used as an in vivo model. This mouse line showed loss of chondrocytes and reduced thickness of articular cartilage, with abnormality of the subchondral bone. The in vitro effects of CH, Pro-Hyp, amino acids and other peptides on proliferation, differentiation, glycosaminoglycan content and mineralization of chondrocytes were determined by MTT activity and staining with alkaline phosphatase, alcian blue and alizarin red. Expression of chondrogenesis-specific genes in ATDC5 cells was determined by semiquantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR). RESULTS: In vivo, CH and Pro-Hyp inhibited the loss of chondrocytes and thinning of the articular cartilage layer caused by phosphorus-induced degradation. In the in vitro study, CH and Pro-Hyp did not affect chondrocyte proliferation but inhibited their differentiation into mineralized chondrocytes. A combination of amino acids such as proline, hydroxyproline and prolyl-hydroxyprolyl-glycine did not affect chondrocyte proliferation or differentiation. Moreover, CH and Pro-Hyp caused two and threefold increases, respectively, in the staining area of glycosaminoglycan in the extracellular matrix of ATDC5 cells. RT-PCR indicated that Pro-Hyp increased the aggrecan mRNA level approximately twofold and decreased the Runx1 and osteocalcin mRNA levels by two-thirds and one-tenth, respectively. CONCLUSION: Pro-Hyp is the first bioactive edible peptide derived from CH to be shown to affect chondrocyte differentiation under pathological conditions.

Effects of changes in coronary stenosis on left ventricular diastolic filling assessed with pulsed Doppler echocardiography.

To determine the effects of changes in coronary stenosis on left ventricular diastolic filling, diastolic filling was serially examined before and after percutaneous transluminal coronary angioplasty using pulsed Doppler echocardiography in 50 patients with stable exertional angina pectoris. Peak rapid filling velocity and the ratio of peak atrial filling to peak rapid filling velocities were measured from the transmitral flow velocity pattern before and 2 and 9 days after coronary angioplasty. Peak rapid filling velocity increased and the ratio of peak atrial filling to peak rapid filling velocities decreased gradually after coronary angioplasty. The improvement in left ventricular diastolic filling was greater in patients with severe (greater than 90%) coronary stenosis than in patients with mild (less than or equal to 90%) coronary stenosis. In the long-term follow-up period, the improved left ventricular diastolic filling worsened in only 11 patients with marked progression to greater than 90% coronary stenosis. Thus, left ventricular diastolic filling improved gradually after coronary angioplasty, possibly reflecting post-ischemic "stunned" myocardium. Serial examinations of left ventricular diastolic filling with pulsed Doppler echocardiography may be a means of noninvasively assessing the temporal changes in the coronary stenosis and predicting the occurrence of coronary restenosis after coronary angioplasty.

Clinical application of transpulmonary contrast-enhanced Doppler technique in the assessment of severity of aortic stenosis.

OBJECTIVE: The aim of this study was to demonstrate the clinical usefulness of the transpulmonary contrast-enhanced Doppler technique by using it to assess the severity of aortic stenosis. BACKGROUND: Sonicated albumin microbubbles can pass through the pulmonary circulation after peripheral venous injection and have been reported to enhance Doppler signals from the left side of the heart. Therefore, their use to determine aortic flow velocity would facilitate the assessment of the severity of aortic stenosis. METHODS: Twenty-two patients with aortic stenosis and seven normal volunteers were examined. Aortic flow velocity was recorded with continuous wave Doppler technique from an apical window before and after injection of 2 ml of sonicated albumin. RESULTS: In 10 patients with aortic stenosis, the aortic velocity envelope was too indistinct to determine the peak velocity before sonicated albumin was injected. After injection, the aortic flow Doppler signal was enhanced in 9 of the 10 patients and the velocity envelope became clear enough to measure the peak velocity, enabling calculation of the transaortic pressure gradient. In the remaining 12 patients with aortic stenosis and in all 7 normal volunteers, the velocity envelope was clear before injection and became much clearer after injection. The calculated transaortic pressure gradient showed a good agreement with catheterization measurements (y = 1.1x-6.5, r = 0.88, p less than 0.001, SEE = 16 mm Hg, n = 13). Duration of Doppler signal enhancement was measured as the time during which the envelope was clearer than before injection throughout the ejection period. The duration was significantly shorter in patients with aortic stenosis than in normal volunteers (16 +/- 5 vs. 52 +/- 32 s, p less than 0.01). There was a significant correlation between left ventricular systolic pressure measured by catheterization and the duration of signal enhancement (r = -0.69), suggesting that albumin microbubbles were fragile at high pressure. CONCLUSIONS: The transpulmonary contrast-enhanced Doppler technique using sonicated albumin is useful for assessing the severity of aortic stenosis even in patients with poor Doppler recordings, although the duration of signal enhancement might be affected by left ventricular systolic pressure.

Long-term follow-up of atrial contraction after the maze procedure in patients with mitral valve disease.

OBJECTIVES: We sought to determine the effectiveness of the maze procedure for maintaining sinus rhythm and atrial contraction for a long period in patients with mitral valve disease. BACKGROUND: Although the maze procedure for atrial fibrillation (AF) has been effective in restoring sinus rhythm in patients with mitral valve disease, the long-term results of this procedure have not been determined. METHODS: We echocardiographically studied 94 consecutive patients with mitral valve disease before, as well as early (3.1 +/- 3.3 months) and late (2.2 +/- 0.9 years) after, the maze procedure. Peak velocity and the time-velocity integral of the left ventricular (LV) diastolic filling wave during atrial contraction (A wave), as well as the atrial filling fraction (calculated as the ratio of the time-velocity integral of the A wave to total diastolic filling), were obtained from transmitral flow recordings. Peak A wave velocity > or =10 cm/s was considered to indicate echocardiographic evidence of effective atrial contraction. RESULTS: Regular rhythm with P waves was restored in 70 patients (74%) in the early stage and in 59 patients (63%, p = 0.09) in the late stage after the maze procedure. Forty-seven patients (50%) in the early stage and 36 patients (38%, p = 0.14) in the late stage showed effective atrial contraction by Doppler echocardiography. Left atrial (LA) and LV end-diastolic diameters significantly decreased after the procedure (from 59 +/- 13 to 48 +/- 7 mm, p < 0.01; and from 54 +/- 9 to 47 +/- 5 mm, p < 0.01, respectively) and did not show significant changes during the follow-up period. Once atrial contraction was resumed, its degree did not change between the early and late stages after the maze procedure (17 +/- 6% vs. 17 +/- 6% for atrial filling fraction). CONCLUSIONS: Sinus rhythm and atrial contraction recovered early after the maze procedure in most patients and were maintained for more than two years. Once active atrial contraction was resumed, the degree of contraction did not change thereafter. These results demonstrate that the maze procedure is effective for a long period in patients with mitral valve disease.

Enhancement of Doppler flow signals in the left heart chambers by intravenous injection of sonicated albumin.

OBJECTIVES: The objective of this study was to evaluate the effect of a transpulmonary contrast agent on Doppler flow signals in the left heart chambers. BACKGROUND: Echo contrast agents are good ultrasound reflectors and could be used as Doppler signal enhancers. Sonicated albumin microbubbles are transpulmonary echo contrast agents and could enhance left heart Doppler signals after peripheral venous injection. METHODS: Thirty-one patients with various heart diseases without intracardiac shunts were assessed with Doppler echocardiography before and after injection of sonicated albumin. RESULTS: After an intravenous injection, pulsed Doppler signals of transmitral flow became more intense in all 16 patients examined, although flow velocity itself was not changed. In Doppler color flow imaging, the maximal mitral regurgitant signal area increased from 312 +/- 405 mm2 to 434 +/- 465 mm2, an average increase of 59 +/- 40% in all 17 patients with mitral regurgitation (p < 0.01). These effects were considered to be due to improvement of signal to noise ratio by the enhancement of Doppler flow signals. The duration of enhancement of pulsed Doppler transmitral flow signals was significantly longer than that of the left ventricular echocardiographic opacification (44 +/- 11 s vs. 17 +/- 7 s, p < 0.01). CONCLUSIONS: Intravenous injection of sonicated albumin can enhance the Doppler flow signals in the left heart chambers. This effect may be useful to improve the sensitivity of the Doppler system for detecting abnormalities of left heart blood flow such as mitral regurgitation.

Comparative efficacy of the maze procedure for restoration of atrial contraction in patients with and without giant left atrium associated with mitral valve disease.

OBJECTIVES: We sought to determine the effectiveness of the maze procedure for restoring atrial contraction in patients with and without giant left atrium (GLA). BACKGROUND: Although the maze procedure has been reported to be effective for refractory atrial fibrillation, it is unknown whether this procedure can restore effective atrial contraction in patients with GLA. METHODS: Nineteen patients with and 32 patients without GLA were studied with Doppler echocardiography before and after the maze procedure. Peak velocity and the time-velocity integral of the left ventricular diastolic filling wave during atrial contraction (A wave) and the atrial filling fraction calculated as the ratio of the time-velocity integral of the A wave to that of total diastolic filling were compared between patients with and without GLA. A peak A wave velocity > or =10 cm/s was considered to indicate echocardiographic evidence of effective atrial contraction. RESULTS: Regular rhythm with P waves was restored in 10 patients (53%) with and 26 (81%, p < 0.05) without GLA. Four patients (21%) with and 21 patients (66%, p < 0.01) without GLA showed effective atrial contraction by echocardiography. Once atrial contraction was resumed, the degree of atrial contraction was comparable between patients with and without GLA (17+/-5% vs. 17+/-4% for atrial filling fraction at 12 months, respectively). CONCLUSIONS: Although most patients without GLA had restored atrial contraction by the maze procedure, it was resumed in fewer patients with GLA. However, once atrial contraction was resumed, the degree of atrial contraction was comparable between patients with and without GLA. Therefore, the maze procedure may be an option in selected patients with GLA.

Application of Doppler color flow imaging to determine valve area in mitral stenosis.

This study was undertaken to examine whether Doppler color flow imaging could accurately estimate the valve area in mitral stenosis. Doppler color flow assessments were performed in both an in vitro model and in 30 patients with mitral stenosis undergoing cardiac catheterization. In the experimental Doppler study using a circuit model, color jet width correlated well with actual orifice diameter (r = 0.99). In the clinical Doppler study, the mitral valve orifice was assumed to be elliptic and the mitral valve area was calculated from the following equation: (pi/4) (a x b), where a = color jet width at the mitral valve orifice in the apical long-axis view (short diameter) and b = the width in the 90 degrees rotated view (long diameter). Mitral valve area was also determined by two-dimensional echocardiography and the pressure half-time method, and the results for all three noninvasive methods were compared with those obtained at cardiac catheterization. By Doppler color flow imaging, mitral valve area could be determined in all patients and there was a significant correlation between the Doppler jet and catheterization estimates of mitral valve area (r = 0.93). Valve area determined by two-dimensional echocardiography correlated well with catheterization measurements in 26 patients (r = 0.84). However, the area could not be determined in 4 (13%) of the 30 patients because of technical problems. Although there was a fair correlation between the valve area determined by the pressure half-time method and catheterization (r = 0.79), this method tended to overestimate valve area in patients with aortic regurgitation.(ABSTRACT TRUNCATED AT 250 WORDS)

Validation of continuous wave Doppler-determined right ventricular peak positive and negative dP/dt: effect of right atrial pressure on measurement.

OBJECTIVES: The present study aimed to validate the peak positive and negative values of the first derivative of right ventricular pressure (dP/dt) using Doppler echocardiography and to determine the impact of right atrial pressure on the measurements. BACKGROUND: A pressure gradient between the right ventricle and the right atrium can be obtained by continuous wave Doppler-derived tricuspid regurgitant velocity using the simplified Bernoulli equation. If right atrial pressure fluctuation during systole and isovolumic diastole were small compared with right ventricular pressure changes, right ventricular pressure could be evaluated, and maximal positive and negative dP/dt could also be determined with Doppler echocardiography. METHODS: We investigated 11 patients with a wide range of right atrial pressure with tricuspid regurgitation using simultaneous examination by Doppler ultrasound and catheterization. Hemodynamic conditions were altered by the Valsalva maneuver, and a total of 40 beats were analyzed. RESULTS: There was good correlation between Doppler-derived and catheterization-derived peak positive dP/dt (y = 1.0x - 15.4, r = 0.98, n = 40), irrespective of the level of right atrial pressure. Doppler-derived peak negative dP/dt also showed good correlation with that determined by catheterization (y = 0.9x + 58.2, r = 0.93, n = 40). However, in patients with high right atrial pressure (v wave pressure > or = 10 mm Hg), Doppler-derived peak negative dP/dt tended to show lower values than those from catheterization measurements, except in patients with pulmonary hypertension. CONCLUSIONS: We conclude that right ventricular dP/dt can be estimated by the Doppler method accurately and noninvasively. However, when right atrial pressure is relatively high compared with corresponding right ventricular pressure changes during isovolumic diastole, Doppler-derived peak negative dP/dt might underestimate catheter-derived measurements.

Intravascular ultrasound detection of atherosclerosis at the site of focal vasospasm in angiographically normal or minimally narrowed coronary segments.

OBJECTIVES: The purpose of this study was to use intravascular ultrasound imaging to examine the presence of occult atherosclerosis at the site of focal vasospasm in angiographically normal or minimally narrowed segments, testing the role of atherosclerosis in the development of vasospasm. BACKGROUND: Previous clinical and experimental studies have suggested that early atherosclerosis is present at the site of focal vasospasm. However, no clinical data exist demonstrating occult disease at the site of vasospasm at angiographically insignificant stenoses. METHODS: Twenty-two patients with chest pain at rest or during exertion, or both, were studied. Vasospasm was provoked by intracoronary administration of ergonovine maleate (0.01 to 0.04 mg). After relief of vasospasm by nitroglycerin administration, intravascular ultrasound imaging was performed with a 32- or 64-element, 20-MHz, synthetic aperture array ultrasound device. RESULTS: Focal vasospasm (arterial diameter reduction > or = 90%) with ST-T segment elevation was provoked in 15 patients: in the left anterior descending coronary artery in 8 patients and in the right coronary artery in 7. The remaining seven patients (control group) showed diffuse narrowing, averaging 22 +/- 12% (mean +/- SD) in diameter from the baseline angiograms after ergonovine administration. Atherosclerosis, defined as a significantly thickened intimal leading edge (0.42 +/- 0.07 mm) associated with an increased sonolucent zone (0.57 +/- 0.30 mm), was detected by ultrasound at all 15 sites with focal vasospasm, although these sites were normal or minimally narrowed by angiography. In contrast, seven segments from the control group exhibited a thin intimal leading edge (0.14 +/- 0.04 mm, p < 0.01) and sonolucent zone (0.10 +/- 0.07 mm, p < 0.01), indicating the absence of localized atherosclerotic lesions. CONCLUSIONS: These results indicate that atherosclerosis is present at the site of focal vasospasm, even in the absence of angiographically significant coronary disease. We suggest that the existence of such atherosclerotic lesions is related to the occurrence of focal vasospasm in the clinical settings.

Salutary effect of disopyramide on left ventricular diastolic function in hypertrophic obstructive cardiomyopathy.

OBJECTIVES: The purpose of this study was to estimate the effect of disopyramide on left ventricular diastolic function in patients with hypertrophic obstructive cardiomyopathy. BACKGROUND: Although disopyramide has been reported to lessen clinical symptoms in patients with hypertrophic obstructive cardiomyopathy, few data exist regarding its effect on diastolic function in these patients. METHODS: Thirteen patients with hypertrophic cardiomyopathy (six with and seven without left ventricular outflow obstruction) were examined. Before and after intravenous disopyramide, hemodynamic and angiographic studies were performed. RESULTS: In patients with outflow obstruction, pressure gradient at the outflow tract decreased from a mean +/- SD of 100 +/- 45 to 26 +/- 33 mm Hg (p < 0.01). Although systolic function was similarly impaired in both groups, the time constant of left ventricular pressure decay (tau) shortened from 56 +/- 10 to 44 +/- 8 ms (p < 0.01) and the constant of left ventricular chamber stiffness (kc) decreased from 0.049 +/- 0.017 to 0.038 +/- 0.014 m2/ml (p < 0.01) only in patients with outflow obstruction. Shortening in tau correlated best with decrease in left ventricular systolic pressure (r = 0.84, p < 0.01). In contrast, tau was prolonged from 52 +/- 10 to 64 +/- 11 ms (p < 0.01) and kc was unchanged in patients without outflow obstruction. CONCLUSIONS: The primary effects of disopyramide on the hypertrophied left ventricle were negative inotropic and negative lusitropic. However, left ventricular diastolic properties in patients with outflow obstruction were improved with a decrease in outflow pressure gradient. Relief of clinical symptoms in hypertrophic obstructive cardiomyopathy with disopyramide might be due in part to improvement of diastolic function, which appears secondary to the reduction in ventricular afterload.

Morphology of vulnerable coronary plaque: insights from follow-up of patients examined by intravascular ultrasound before an acute coronary syndrome.

OBJECTIVES: To determine the morphologic features of coronary plaques associated with acute coronary syndrome, we prospectively followed patients with atherosclerotic disease identified by intravascular ultrasound (IVUS). BACKGROUND: Although clinical evaluation of the vulnerable atherosclerotic plaque is important, few data exist regarding the morphology of the vulnerable plaque in clinical settings. METHODS: We examined 114 coronary sites without significant stenosis by angiography (<50% diameter stenosis) in 106 patients. All the sites exhibited atherosclerotic lesions by IVUS. These lesions consisted of 22 concentric and 92 eccentric plaques with a percent plaque area averaging 59 +/- 12%. RESULTS: During the follow-up period of 21.8 +/- 6.4 months (range 1 to 24), 12 patients had an acute coronary event at a previously examined coronary site at an average of 4.0 +/- 3.4 months after the initial IVUS study. All the preexisting plaques related to the acute events exhibited an eccentric pattern and the mean percent plaque area was 67 +/- 9%, which was greater than plaque area in the other 90 patients without acute events (57 +/- 12%, p < 0.05). There was no statistically significant difference in lumen area between two patient groups (6.7 +/- 3.0 vs. 7.5 +/- 3.7 mm2). Among 12 coronary sites with an acute occlusion, 10 sites contained the echolucent zones, eight of these shallow and two deep, likely representing a lipid-rich core. In 90 sites without acute events, an echolucent zone in the shallow portion was seen at only four sites (p < 0.05). CONCLUSIONS: Large eccentric plaque containing an echolucent zone by IVUS can be at increased risk for instability even though the lumen area is preserved at the time of initial study. Compensatory enlargement of vessel wall due to remodeling may contribute to the relatively small degree of stenosis by angiography.

Early changes in left ventricular function in chronic asymptomatic alcoholics: relation to the duration of heavy drinking.

OBJECTIVES: This study sought to assess preclinical cardiac abnormalities in chronic alcoholic patients and possible differences among alcoholics related to the duration of heavy drinking. BACKGROUND: Chronic excessive alcohol intake has been reported as a possible cause of dilated cardiomyopathy. However, before the appearance of severe cardiac dysfunction, subtle signs of cardiac abnormalities may be identified. METHODS: We studied 30 healthy subjects (age 44 +/- 8 years) and 89 asymptomatic alcoholics (age 45 +/- 8 years, p = NS) divided into three groups, with short (S, 5-9 years, n = 31), intermediate (I, 10-15 years, n = 31) and long (L, 16-28 years, n = 27) duration of alcoholism. Transmitral early (E) and late (A) Doppler flow velocities, E/A ratio, deceleration time of E (DT) and isovolumic relaxation time (IVRT) were obtained. Left ventricular (LV) wall thickness and volumes were also determined by echocardiography, and LV mass and ejection fraction (EF) were calculated. RESULTS: The alcoholics had prolonged IVRT (92 +/- 11 vs. 83 +/- 7 ms, p < 0.001), longer DT (180 +/- 20 vs. 170 +/- 10 ms, p < 0.01), smaller E/A (1.25 +/- 0.34 vs. 1.40 +/- 0.32, p < 0.05), larger LV volumes (73 +/- 8 vs. 65 +/- 7 ml/m2, p < 0.001 for end-diastolic volume index; 25 +/- 4 vs. 21 +/- 2 ml/m2, p < 0.001 for end-systolic volume index), higher LV mass index (92 +/- 14 vs. 78 +/- 8 g/m2, p < 0.001) and thicker posterior wall (9 +/- 1 vs. 8 +/- 1 mm, p < 0.001). Ejection fraction did not differ between the two groups (66 +/- 4 vs. 67 +/- 2%). Deceleration time of the early transmitral flow velocity was longer in groups L (187 +/- 18 ms) and I (185 +/- 16 ms) compared with group S (168 +/- 17 ms, p < 0.001 for L and I vs. S), whereas A was higher in group L compared with S (43 +/- 10 vs. 51 +/- 10 cm/s, p < 0.005). Multiple regression analysis identified duration of heavy drinking as the most important variable affecting DT and A. CONCLUSIONS: Left ventricular dilation with preserved EF and impaired LV relaxation characterized LV function in chronic asymptomatic alcoholic patients. It appeared that the progression of abnormalities in LV diastolic filling related to the duration of alcoholism.

Left ventricular diastolic filling with an implantable ventricular assist device: beat to beat variability with overall improvement.

OBJECTIVES: We studied the effects of left ventricular (LV) unloading by an implantable ventricular assist device on LV diastolic filling. BACKGROUND: Although many investigators have reported reliable systemic and peripheral circulatory support with implantable LV assist devices, little is known about their effect on cardiac performance. METHODS: Peak velocities of early diastolic filling, late diastolic filling, late to early filling ratio, deceleration time of early filling, diastolic filling period and atrial filling fraction were measured by intraoperative transesophageal Doppler echocardiography before and after insertion of an LV assist device in eight patients. A numerical model was developed to simulate this situation. RESULTS: Before device insertion, all patients showed either a restrictive or a monophasic transmitral flow pattern. After device insertion, transmitral flow showed rapid beat to beat variation in each patient, from abnormal relaxation to restrictive patterns. However, when the average values obtained from 10 consecutive beats were considered, overall filling was significantly normalized from baseline, with early filling velocity falling from 87 +/- 31 to 64 +/- 26 cm/s (p < 0.01) and late filling velocity rising from 8 +/- 11 to 32 +/- 23 cm/s (p < 0.05), resulting in an increase in the late to early filling ratio from 0.13 +/- 0.18 to 0.59 +/- 0.38 (p < 0.01) and a rise in the atrial filling fraction from 8 +/- 10% to 26 +/- 17% (p < 0.01). The deceleration time (from 112 +/- 40 to 160 +/- 44 ms, p < 0.05) and the filling period corrected by the RR interval (from 39 +/- 8% to 54 +/- 10%, p < 0.005) were also significantly prolonged. In the computer model, asynchronous LV assistance produced significant beat to beat variation in filling indexes, but overall a normalization of deceleration time as well as other variables. CONCLUSIONS: With LV assistance, transmitral flow showed rapidly varying patterns beat by beat in each patient, but overall diastolic filling tended to normalize with an increase of atrial contribution to the filling. Because of the variable nature of the transmitral flow pattern with the assist device, the timing of the device cycle must be considered when inferring diastolic function from transmitral flow pattern.

Left ventricular echocardiographic and histologic changes: impact of chronic unloading by an implantable ventricular assist device.

OBJECTIVES: We studied the effects of chronic left ventricular unloading by a ventricular assist device and assessed left ventricular morphologic and histologic changes. BACKGROUND: The implantable left ventricular assist device has been effective as a "bridge" to cardiac transplantation. Although there are reports documenting its circulatory support, little is known about the effects of chronic left ventricular unloading on the heart itself. METHODS: We performed intraoperative transesophageal echocardiography at the insertion and explanation of a HeartMate left ventricular assist device in 19 patients with end-stage heart failure. They were supported by the assist device for 3 to 153 days (mean [+/-SD] 68 +/- 33). Measurements were taken retrospectively to obtain left atrial and ventricular diameters and interventricular septal and posterior wall thicknesses. Histologic examinations were made from the left ventricular myocardial specimens of 15 patients at the times of insertion and explanation for heart transplantation. Insertion and explanation specimens were compared qualitatively (0 to 3 scale) for wavy fibers, contraction band necrosis and fibrosis, with quantitative measurement of minimal myocyte diameter across the nucleus. RESULTS: Left atrial and left ventricular diastolic and systolic diameters decreased immediately after insertion of the left ventricular assist device (from 46 to 35, 63 to 41 and 59 to 36 mm, respectively, all p < 0.001). Left ventricular wall thickness increased from 10 to 14 mm (p < 0.001) for the interventricular septum and from 10 to 13 mm for the posterior wall (p<0.001). No echocardiographic measurements showed significant subsequent changes at the chronic stage. Myocardial histologic findings demonstrated a reduction in myocyte damage (from 1.9 to 0.5, p<0.001, for wavy fiber and from 1.3 to 0.2, p<0.01, for contraction band necrosis) and an increase in fibrosis (from 1.3 to 1.9, p<0.05), but without significant change in myocyte diameter (from 15.6 to 16.8 micrometer, p=0.065). CONCLUSIONS: Left ventricular unloading with the implantable assist device induces an immediate increase in wall thickness, consistent with the reduction in chamber size, thereby decreasing wall stress. Chronic unloading allows myocardial healing and fibrosis without evidence for ongoing myocyte damage or atrophy. Left ventricular assist device insertion may have a role in "resting" the ventricle for selected patients with heart failure.

Noninvasive assessment of left atrial maximum dP/dt by a combination of transmitral and pulmonary venous flow.

OBJECTIVES: The study assessed whether hemodynamic parameters of left atrial (LA) systolic function could be estimated noninvasively using Doppler echocardiography. BACKGROUND: Left atrial systolic function is an important aspect of cardiac function. Doppler echocardiography can measure changes in LA volume, but has not been shown to relate to hemodynamic parameters such as the maximal value of the first derivative of the pressure (LA dP/dt(max)). METHODS: Eighteen patients in sinus rhythm were studied immediately before and after open heart surgery using simultaneous LA pressure measurements and intraoperative transesophageal echocardiography. Left atrial pressure was measured with a micromanometer catheter, and LA dP/dt(max) during atrial contraction was obtained. Transmitral and pulmonary venous flow were recorded by pulsed Doppler echocardiography. Peak velocity, and mean acceleration and deceleration, and the time-velocity integral of each flow during atrial contraction was measured. The initial eight patients served as the study group to derive a multilinear regression equation to estimate LA dP/dt(max) from Doppler parameters, and the latter 10 patients served as the test group to validate the equation. A previously validated numeric model was used to confirm these results. RESULTS: In the study group, LA dP/dt(max) showed a linear relation with LA pressure before atrial contraction (r = 0.80, p < 0.005), confirming the presence of the Frank-Starling mechanism in the LA. Among transmitral flow parameters, mean acceleration showed the strongest correlation with LA dP/dt(max) (r = 0.78, p < 0.001). Among pulmonary venous flow parameters, no single parameter was sufficient to estimate LA dP/dt(max) with an r2 > 0.30. By stepwise and multiple linear regression analysis, LA dP/dt(max) was best described as follows: LA dP/dt(max) = 0.1 M-AC +/- 1.8 P-V - 4.1; r = 0.88, p < 0.0001, where M-AC is the mean acceleration of transmitral flow and P-V is the peak velocity of pulmonary venous flow during atrial contraction. This equation was tested in the latter 10 patients of the test group. Predicted and measured LA dP/dt(max) correlated well (r = 0.90, p < 0.0001). Numerical simulation verified that this relationship held across a wide range of atrial elastance, ventricular relaxation and systolic function, with LA dP/dt(max) predicted by the above equation with r = 0.94. CONCLUSIONS: A combination of transmitral and pulmonary venous flow parameters can provide a hemodynamic assessment of LA systolic function.

Prevalence of Mycobacterium avium and Mycobacterium tuberculosis in blood cultures of Brazilian AIDS patients after introduction of highly active retroviral therapy.

The use of highly active antiretroviral therapy (HAART) for the treatment of HIV infection has been associated with a marked reduction in the incidence of most opportunistic infections. From April 2001 to February 2002, 80 blood samples from patients who were suspected to have disseminated mycobacterial infection, presenting fever and (preferably) a CD4 T cell count < 100.0 cell/mL were investigated. Twelve (15%) of the 80 blood cultures were positive for mycobacteria, with Mycobacterium avium being identified in 7 (8.8%) samples and M. tuberculosis in 5 (6.2%). The TCD4+ count at the time of M. avium bacteremia ranged from 7 cells/microL (average of 48.5 cell/microL), while in M. tuberculosis bacteremia it ranged from 50.0 cells/microL (average of 80.0 cell/microL). The prevalence of M. avium bacteremia in our study follows the expected decline in opportunistic infections observed after the introduction of HAART; however, mycobacteremia by M. tuberculosis still indicates a high prevalence of tuberculosis infection in AIDS patients.

Effects of atrioventricular interval on left ventricular diastolic filling assessed with pulsed Doppler echocardiography.

Effects of changes in atrioventricular interval on left ventricular diastolic filling were studied using pulsed Doppler echocardiography in 14 patients with programmable dual chamber pacemakers. Peak early diastolic filling velocity (E) and peak atrial filling velocity (A) were measured from the transmitral flow velocity pattern at three different atrioventricular intervals under the same pacing rate of 80 beats.min-1 in each patient. When the atrioventricular interval was switched from intermediate [148(SD10) ms] to short [68(11) ms], stroke volume did not change significantly [60(14) to 58(13) ml], but E increased from 39(12) to 44(11) cm.s-1 (p less than 0.05), and A decreased from 48(8) to 38(9) cm.s-1 (p less than 0.05). At the short atrioventricular interval, incomplete atrial emptying by the atrial contraction seemed to cause a reciprocal increase in the early diastolic filling. When the atrioventricular interval was switched from intermediate to long [234(16) ms], stroke volume, E and A did not change significantly [57(14) ml, 37(13) cm.s-1, 51(8) cm.s-1 respectively]. At the short and long atrioventricular intervals, atrial filling always changed in the direction opposite to that of early diastolic filling. Changes in stroke volume as well as peak early diastolic filling velocity caused by altering atrioventricular interval were pronounced in aged patients and patients with decreased early diastolic filling. In conclusion, left ventricular diastolic filling patterns can be affected by atrioventricular interval even without any concomitant pathological changes in the left atrial or ventricular function. These effects should not be taken lightly, especially in patients with decreased left ventricular early diastolic filling.

Left ventricular function and the relationship between left atrial pressure and peak early diastolic filling velocity in dog.

OBJECTIVE: The aim was to clarify the roles of left atrial pressure and ventricular function in the determination of early diastolic filling. METHODS: Various grades of ventricular dysfunction were made in 12 mongrel dogs by coronary microembolization under pentobarbitone anaesthesia. Left atrial pressure was altered by volume loading. Peak early diastolic filling velocity was measured using pulsed Doppler echocardiography. Ventricular fractional shortening was measured using M mode echocardiography. RESULTS: Peak early filling velocity increased as left atrial pressure increased. There was a direct relationship between mean left atrial pressure and the velocity before and after induction of ventricular dysfunction. The slope of the regression line between mean left atrial pressure and peak early filling velocity decreased as the grade of the dysfunction increased. There was a significant correlation between the slope of the regression line and mean left ventricular fractional shortening (r = 0.65, n = 31, p less than 0.01). CONCLUSIONS: Early diastolic filling was affected by both left atrial pressure and left ventricular function. These facts are useful in interpreting the various transmitral flow patterns observed clinically.