Neutrophil extracellular traps in patients with sepsis.

BACKGROUND: Release of neutrophil extracellular traps (NETs) has been identified as an important aspect of innate immunity. We examined whether sepsis had any influence on ex vivo generation of NETs by neutrophils. MATERIALS AND METHODS: We isolated neutrophils from consecutive patients with sepsis (n = 17) and without sepsis (n = 18) admitted to the intensive care unit. Neutrophils were activated by incubation with phorbol-12-myristate-13-acetate (PMA) to induce release of NETs, and NET formation was assessed by measuring the extracellular DNA level. Immunolabeling and fluorescence imaging were also performed. Extracellular killing of bacteria by NETs was studied by co-culture of Escherichia coli and neutrophils in the presence of a phagocytosis inhibitor. To assess in vivo NET formation, plasma levels of cell-free DNA and histones were measured. RESULTS: After stimulation with PMA, neutrophils isolated from septic patients released 4.08 ± 1.02% of their total DNA, whereas neutrophils from nonseptic patients released 29.06 ± 2.94% (P = <0.0001). Immunofluorescent staining of released DNA, elastase, and myeloperoxidase also revealed similar results. Neutrophils from nonseptic patients showed effective extracellular killing of E coli through NETs, whereas neutrophils from septic patients did not (P < 0.001). Plasma levels of cell-free DNA and histones were higher in septic patients than nonseptic patients (P < 0.001). CONCLUSIONS: The ex vivo generation of NETs is downregulated in neutrophils isolated from patients with sepsis. However, it is unclear whether in vivo NET formation is also impaired during sepsis, so further investigation is necessary.

Relationship between blood pressure obtained from the upper arm with a cuff-type sphygmomanometer and central blood pressure measured with a catheter-tipped micromanometer.

Recently, the importance of central blood pressure for cardiovascular risk stratification has been emphasized. Accordingly, the differences in peak systolic and bottom diastolic pressures between the ascending aorta and the brachial artery should be clarified. Study subjects consisted of 82 consecutive patients with suspected coronary artery disease who underwent cardiac catheterization, and in whom ascending aortic pressure waveform was obtained using a catheter-tipped micromanometer, and at the same time systolic and diastolic pressures were measured (single measurement) from the right upper arm with a cuff-type sphygmomanometer based on the oscillometric technique. No significant systematic difference (bias) was found between the peak pressure obtained in the ascending aorta and the systolic pressure from the right upper arm (133.6 +/- 25.1 vs 131.8 +/- 21.5 mmHg, not significant). Bland-Altman analysis showed only a small bias of +1.8 mmHg, and the limits of agreement were 25.4 mmHg and -21.8 mmHg. In contrast, the bottom pressure in the ascending aorta was significantly lower compared with the diastolic pressure from the upper arm (68.5 +/- 10.7 vs 73.0 +/- 12.4 mmHg, P < 0.0001). Bland-Altman analysis showed a small but significant bias of -4.5 mmHg, and the limits of agreement were 14.1 mmHg and -23.1 mmHg. The observed biases seemed to remain within practical range. However, random variation in the two measurements was rather large. This is considered to be caused by the random error in the single measurement with the cuff-type sphygmomanometer.

Lack of inertia force of late systolic aortic flow is a cause of left ventricular isolated diastolic dysfunction in patients with coronary artery disease.

OBJECTIVES: We investigated whether a lack of inertia force of late systolic aortic flow and/or apical asynergy provoke early diastolic dysfunction in patients with coronary artery disease (CAD). BACKGROUND: Left ventricular (LV) isolated diastolic dysfunction is a well-recognized cause of heart failure. METHODS: We evaluated LV apical wall motion and obtained left ventricular ejection fraction (LVEF) by left ventriculography in 101 patients who underwent cardiac catheterization to assess CAD. We also computed the LV relaxation time constant (Tp) and the inertia force of late systolic aortic flow from the LV pressure (P)-first derivative of left ventricular pressure (dP/dt) relation. Using color Doppler echocardiography, we measured the propagation velocity of LV early diastolic filling flow (Vp). Patients with LVEF > or =50% (preserved systolic function [PSF], n = 83) were divided into 2 subgroups: patients with inertia force (n = 53) and without inertia force (n = 30). No patient with systolic dysfunction (SDF) (LVEF <50%) had inertia force (n = 18). RESULTS: The Tp was significantly longer in patients with SDF (85.7 +/- 21.0 ms) and with PSF without inertia force (81.1 +/- 23.6 ms) than in those with PSF with inertia force (66.3 +/- 12.8 ms) (p< 0.001). The Vp was significantly less in the former 2 groups than in the last group. In patients with PSF, LV apical wall motion abnormality was less frequently observed in those with inertia force than in those without (p < 0.0001). CONCLUSIONS: An absence of inertia force in patients with PSF is one of the causes of isolated diastolic dysfunction in patients with CAD. Normal LV apical wall motion is substantial enough to give inertia to late systolic aortic flow.

Evaluation of fatty acid beta-oxidation in patients with prior myocardial infarction in relation to myocardial blood flow, total oxidative metabolism, and left ventricular wall motion.

BACKGROUND: Fatty acid metabolism in patients with myocardial infarction (MI) who undergo coronary reperfusion has not been fully elucidated and was investigated in the present study using positron emission tomography. METHODS AND RESULTS: The clearance rate constant of 11C-acetate (acetate-Kmono) and that of 11C-palmitate (palmitate-Kmono) from the myocardium were calculated using a monoexponential equation in 14 patients with MI. A total of 155 regions of interest were classified based on coefficient of determination (R2) values of monoexponential curves for 11C-palmitate clearance: well fitted regions (R2>or=0.5) and poorly fitted regions (R2<0.5). Regional relative myocardial blood flow calculated from the initial distribution of 11C-acetate and left ventricular (LV) wall motion were also evaluated. Peak 11C-palmitate uptake (14,434+/-3,052 vs 12,016+/-3,088 counts/s, p<0.001) and percent clearance during acquisition (38.2+/-10.1 vs 23.6+/-11.4%, p<0.001) were significantly greater in the well fitted regions (n=111) than in the poorly fitted regions (n=44). Acetate-Kmono was significantly higher in the former than in the latter (0.0641+/-0.0099 vs 0.0476+/-0.0103 min-1, p<0.001). LV wall motion and regional relative blood flow were also significantly greater in the former regions. Palmitate-Kmono in the well fitted regions was significantly higher in normal LV wall motion areas than in hypokinesis areas (0.0363+/-0.0062 vs 0.0274+/-0.0057 min-1, p<0.001) CONCLUSIONS: Maintenance of myocardial fatty acid beta-oxidation with better myocardial blood flow is substantial in the preservation of total myocardial oxidative metabolism and LV wall motion in patients with MI. The finding that the early-phase clearance of 11C-palmitate is fitted with a monoexponential curve may provide important information in the evaluation of myocardial fatty acid beta-oxidation.

Usefulness of plasma brain-type natriuretic peptide level to differentiate left ventricular diastolic dysfunction from preserved diastolic function in patients with systolic dysfunction.

The extent of left ventricular (LV) diastolic dysfunction is related to the finding that some patients with cardiomegaly due to LV systolic dysfunction have good exercise tolerance, although others have limited tolerance. A brain-type natriuretic peptide level of >/=104 pg/ml reliably enables the detection of relatively worse LV diastolic function in patients with systolic dysfunction, and this value may provide clinically useful information for the management of patients with cardiomegaly.

Tl-201 washout rate in remote normal regions in patients with prior myocardial infarction and left ventricular remodeling.

BACKGROUND: Myocardial characteristics of remote normal regions in patients with myocardial infarction (MI) and left ventricular (LV) remodeling have not been fully elucidated. Thus, we investigated this issue from the viewpoint of myocardial Tl-201 dynamics. METHODS AND RESULTS: In 14 patients with prior anterior MI, 10 with inferior MI, and 14 age-matched patients with atypical chest pain served as controls; exercise stress Tl-201 SPECT and cardiac catheterization were performed. Tl-201 washout rate was calculated for 8 myocardial segments, and LV end-diastolic volume index was obtained as a parameter of LV remodeling. LV end-diastolic volume index was greater in anterior MI patients than in control patients; in contrast, no significant difference was observed between inferior MI patients and control patients. The washout rate in remote normal regions was significantly less in anterior MI patients than in the corresponding segments in control patients (39.8% +/- 8.7% vs 48.4% +/- 4.4%, P < .01). There was no significant difference between inferior MI patients and control patients (43.6% +/- 6.9% vs 47.8% +/- 4.5%). CONCLUSIONS: Reduced Tl-201 washout rates in remote normal regions are found in patients with anterior MI and LV remodeling. Subclinical myocardial ischemia during exercise in remote normal regions exists and may be related to the pathologic condition of such LV walls.

Evaluation of whole left ventricular systolic performance and local myocardial systolic function in patients with prior myocardial infarction using global long-axis myocardial strain.

Left ventricular (LV) global strain along its long axis during systole, which is obtained by dividing mitral annular excursion by the distance from the mitral annulus to the LV apex at end-diastole, can be used to assess whole LV systolic performance. The evaluation of LV wall function using this parameter suggests that previous myocardial infarction (MI) causes long-axis myocardial function in remote normal LV walls, as well as in walls with MI, to deteriorate.

Paradoxical brain embolism caused by pulmonary arteriovenous fistula and coincident pulmonary embolism--a case report.

The authors encountered a very rare case of paradoxical brain embolism resulting from pulmonary arteriovenous fistula and coincident pulmonary embolism. Enhanced computed tomography was useful for diagnosing this infrequent condition.

Two cases with renal infarction diagnosed in the early course using contrast-enhanced CT.

We experienced two cases of renal infarction with atrial fibrillation who presented with acute abdominal pain. On initial urinalysis, both patients showed no hematuria, but the plasma lactate dehydrogenase level was markedly elevated with little or no rise in plasma transaminases. Their diagnosis was confirmed by contrast-enhanced CT of the abdomen on the second and third days of the crisis. We immediately initiated anticoagulant therapy, resulting in successful prevention of new embolism. Contrast-enhanced CT should be considered if abdominal symptoms develop in patients with atrial fibrillation. Renal infarction could be diagnosed in the early course, even in cases with incomplete occlusion of the renal arteries and normal renal function.

The role of apically directed intraventricular isovolumic relaxation flow in speeding early diastolic left ventricular filling.

Left ventricular (LV) systolic performance has been acknowledged to have a close relation to LV early diastolic filling and LV relaxation. However, the mechanism showing how good LV systolic function enhances the LV early diastolic filling has not been fully elucidated from the viewpoint of intraventricular flow dynamics. Thus, we investigated this issue in 82 patients with suggested coronary artery disease who underwent cardiac catheterization. Apically directed intraventricular isovolumic relaxation flow (IRF) and the propagation velocity of early diastolic filling flow were measured using pulsed and color Doppler echocardiography. LV ejection fraction and LV relaxation time constant tau were obtained in cardiac catheterization. As we were not able to measure the IRF velocity less than 14 cm/s that was limited by a Doppler low-cut filter, we analyzed the data collected from 78 patients with measurable IRF velocity. The IRF velocity significantly correlated with LV ejection fraction (r = 0.74, P <.001) and with LV relaxation time constant tau (r = -0.31, P <.01). The propagation velocity of early diastolic filling flow significantly correlated with the IRF velocity (r = 0.73, P <.001) and also significantly correlated with LV ejection fraction (r = 0.70, P <.001). Good LV systolic performance augments LV early diastolic filling directly, mediated by IRF. A faster IRF velocity may play a role in delivering good LV systolic performance to LV early diastolic filling.

Reverse redistribution phenomenon on rest (99m)Tc-tetrofosmin myocardial single photon emission computed tomography involves impaired left ventricular contraction in patients with acute myocardial infarction.

The purpose of this study was to investigate the clinical significance of the reverse redistribution (RR) phenomenon on technetium-99m ((99m)Tc)-tetrofosmin myocardial single photon emission computed tomography (SPECT) performed at rest. Twenty-five patients underwent myocardial SPECT 3 weeks after the onset of acute myocardial infarction. Myocardial images were acquired at 40 min (early) and 4 h (delayed) after the injection of 740 MBq of (99m)Tc-tetrofosmin. The regional myocardial uptake of the tracer in 26 segments of the left ventricular (LV) wall was visually scored from 0 (no activity) to 3 (normal activity), and then the RR was defined as a decrease of more than 1 point in the activity score on the delayed image compared with that on the early image. Regions with an activity score of 3 on both the early and delayed images were defined as normal, and those with a score of 0 or 1 on the early image were considered to have a fixed defect. The regional myocardial (99m)Tc-tetrofosmin uptake and washout rate were also quantitatively assessed in each region. In addition, exercise stress electrocardiograph-gated SPECT with (99m)Tc-tetrofosmin was performed within 1 week of the rest study, and the percent count increase (%CI) during myocardial contraction in each corresponding region was studied. RR was observed in 18 of the 25 patients. The regional washout rate of (99m)Tc-tetrofosmin was significantly higher in the RR regions (45.0+/-3.8%) than in either the normal regions (36.4+/-4.1%, p<0.001) or in those with a fixed defect (39.7+/-3.9%, p<0.001). The %CI in the RR regions (10.4+/-10.4%) was significantly less than that in the normal regions (23.5+/-10.1%, p<0.001); however, no significant difference was found between the RR regions and those with a fixed defect (8.0+/-7.2%). In patients with acute myocardial infarction, the regions showing the RR phenomenon on (99m)Tc-tetrofosmin SPECT have severely impaired LV wall contraction after exercise.

Increased serum triglyceride clearance and elevated high-density lipoprotein 2 and 3 cholesterol during treatment of primary hypertriglyceridemia with bezafibrate.

BACKGROUND: Hypertriglyceridemia accompanied by low levels of high-density lipoprotein cholesterol (HDL-C) is a risk factor for coronary artery disease. High-density lipoprotein 2 (HDL2) and 3 (HDL3) are believed to suppress the progress of atherosclerosis through reverse cholesterol transport. As a result, peripheral tissues can be protected against excessive accumulation of cholesterol. Although bezafibrate is known to accelerate the increase of HDL-C, results are not standardized regarding increases of HDL3 and HDL2 subfractions. OBJECTIVE: This study assessed the effects of bezafibrate on serum triglyceride (TG) fractional clearance rate (K2) and HDL2 and HDL3 cholesterol (HDL2-C and HDL3-C, respectively) levels in patients with primary hypertriglyceridemia (serum TG ≥150 mg/dL). METHODS: Outpatients with primary hypertriglyceridemia were enrolled in this 8-week study conducted at the Third Department of Internal Medicine, Nagoya City University Hospital (Nagoya, Japan). Oral bezafibrate was administered at a dose of 400 mg/d (200-mg tablet BID, morning and evening) for 8 weeks. After 8 weeks, serum levels of total cholesterol (TC), TG, HDL-C, HDL2-C, and HDL3-C were measured. A fat emulsion tolerance test to assess K2 and measurements of plasma lipoprotein lipase (LPL) mass, LPL activity, and hepatic triglyceride lipase (HTGL) activity in postheparin plasma were performed before bezafibrate administration and after the course of treatment. RESULTS: Sixteen patients (10 men, 6 women; mean [SD] age, 54 [12] years [range, 30-69 years]; mean [SD] body mass index, 23 [2] kg/m(2)) entered the study. The following findings were observed in male and female patients after 8 weeks of treatment. A statistically significant reduction was observed in mean serum TG level (P<0.01). Significant increases were seen in HDL-C, HDL2-C, and HDL3-C (all P<0.01), K2 (P<0.01), and in plasma LPL mass (P<0.01) and LPL activity (P<0.05). TC level and HTGL activity did not change significantly. No adverse effects related to the use of bezafibrate were documented. CONCLUSIONS: In this study, bezafibrate treatment resulted in significant decreases in serum TG level and significant increases in HDL2-C and HDL3-C levels and plasma LPL mass and activity. We hypothesize that bezafibrate may increase HDL3-C by promoting TG-rich lipoprotein catabolism and may increase HDL2-C by promoting the conversion of HDL3 to HDL2.

Myocardial oxidative metabolism in remote normal regions in the left ventricles with remodeling after myocardial infarction: effect of beta-adrenoceptor blockers.

UNLABELLED: In patients with myocardial infarction (MI), an expansion of the remote normal regions of the left ventricle is often observed. However, the characteristics of such regions are not fully understood. Thus, we investigated this issue from the standpoint of myocardial oxidative metabolism using (11)C-acetate PET. METHODS: In 33 patients with recent MI (24 not receiving beta-blockers, 9 receiving beta-blockers) and 12 age-matched normal control subjects, (11)C-acetate dynamic myocardial PET scanning was performed at rest. Time-activity curves of (11)C-acetate in 5-7 regions of interest (ROIs) on the midventricular transaxial image in each subject were generated, and the clearance rate constant (K(mono)) in each ROI was calculated by monoexponential fitting as an index of myocardial oxidative metabolism. The left ventricular (LV) end-diastolic volume index as an index of LV remodeling and the heart rate. pressure product were obtained in all subjects. RESULTS: The LV end-diastolic volume index was significantly larger in patients with MI without beta-blockers than in normal control subjects (101 +/- 22.5 vs. 61.6 +/- 12.8 mL x m(-2); P < 0.001). There was no significant difference in the heart rate x pressure product between the patients with MI without beta-blockers and the normal control subjects (8,229 +/- 1,503 vs. 8,311 +/- 1,311 mm Hg x min(-1)). The K(mono) in remote normal regions was significantly greater in patients with MI without beta-blockers even when compared with the highest K(mono) on the anteroseptal wall of the left ventricle in normal control subjects (0.078 +/- 0.022 vs. 0.065 +/- 0.007 min(-1); P < 0.01). In contrast, the heart rate. pressure product (6,911 +/- 1,135 mm Hg x min(-1)) and the K(mono) (0.054 +/- 0.009 min(-1)) in remote normal regions were significantly less in patients with beta-blockers than in those without beta-blockers (P < 0.001). No significant difference in the LV end-diastolic volume index was found between the MI patients with and without beta-blockers. Multivariate regression analysis showed that beta-blockers significantly and directly decreased the K(mono) in remote normal regions after adjusting the effect of the heart rate x pressure product, although the prime determinant of the K(mono) in such regions was the heart rate x pressure product. CONCLUSION: Myocardial oxidative metabolism in remote normal regions is accelerated in the left ventricles with remodeling after acute MI. Therapy using beta-blockers normalizes the myocardial oxidative metabolism in such regions through the reduction of the heart rate x pressure product and their direct effect on the myocardium.