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PURPOSE: This study investigates whether positron emission tomography (PET) can be used to monitor the inflammatory response and its correlation with the later fibroproliferative phase in an experimental model of acute lung injury. METHODS: Hydrochloric acid (0.1 N, pH 1, 1.5 ml/kg) was instilled into the right bronchus of mice. A group of mice underwent a micro-computed tomography (CT) scan 1 h after lung injury and a series of 2-[(18)F]fluorine-2-deoxy-D: -glucose (FDG)-PET scans (6, 24 and 48 h and 7 days after surgery). After 21 days respiratory static compliance was assessed and lung tissue was collected in order to measure the hydroxy (OH)-proline content. Other groups of mice underwent micro-CT and micro-PET scans at the same time points, and then were immediately killed to assess arterial blood gases and histology. RESULTS: Histological analysis showed the recruitment of neutrophils and macrophages into the damaged lung, reaching the peak at 24 and 48 h, respectively. The time course of the [(18)F]FDG signal, used as a marker of inflammation, correlated with that of recruited inflammatory cells. In mice killed 21 days after the surgery, a correlation was found between reduced respiratory static compliance and high PET signal 7 days after lung injury. The PET signal also correlated with the OH-proline content. CONCLUSIONS: This study demonstrated that PET imaging is a valid means of tracking the inflammatory response, also in longitudinal studies. Moreover, a correlation was found between persistence of the inflammatory response and fibrotic evolution of the injury.

Aims Mitral regurgitation (MR) confers independent risk in patients with acute myocardial infarction. We utilized data from the VALsartan In Acute myocardial iNfarcTion echo study to relate baseline MR to left ventricular (LV) size, shape, and function, and to assess the relationship between baseline MR and progression of MR and cardiovascular (CV) outcomes. Methods and results We studied 496 patients with heart failure (HF) and/or systolic dysfunction after MI who underwent echocardiography at a median of 5 days after MI. MR severity, quantified as the regurgitant jet area/left atrial area ratio, was assessed at baseline, one and 20 months post-MI and related to LV size, shape, function, and clinical outcomes. Increased MR at baseline was associated with larger LV end-diastolic and end-systolic volumes, increased sphericity index, and reduced ejection fraction ( P trend < 0.001). Moderate–severe MR was an independent predictor of total mortality [adjusted hazard ratio (HR) 2.4 (1.1–5.3)], CV mortality [adjusted HR 2.7 (1.2–6.1)], hospitalization for HF [adjusted HR 2.5 (1.1–5.5)], or death or HF hospitalization [adjusted HR 2.5 (1.4–4.6)]. Patients with progression of MR during the first post-MI month were substantially more likely to die or develop HF (adjusted HR per increased MR grade 3.0, 95% CI 1.8–4.9). Progression of MR over 20 months in survivors was associated with increased hospitalizations for HF ( P < 0.001). Conclusion Following high-risk myocardial infarction, baseline mitral regurgitant severity is associated with larger LV volumes and worse LV function. Both baseline MR severity and progression of MR are associated with an increased likelihood of adverse outcomes.

Background Mitral regurgitation (MR) has been associated with adverse outcomes after myocardial infarction (MI). Without structural valve disease, functional MR has been related to left ventricular (LV) remodeling and geometric deformation of the mitral apparatus. The aims of this study were to elucidate the mechanistic components of MR after high-risk MI and to identify predictors of MR progression during follow-up. Methods The Valsartan in Acute Myocardial Infarction Echo substudy prospectively enrolled 610 patients with LV dysfunction, heart failure, or both after MI. MR at baseline, 1 month, and 20 months was quantified by mapping jet expansion in the left atrium in 341 patients with good-quality echocardiograms. Indices of LV remodeling, left atrial size, and diastolic function and parameters of mitral valve deformation, including tenting area, coaptation depth, anterior leaflet concavity, annular diameters, and contractility, were assessed and related to baseline MR. The progression of MR was further analyzed, and predictors of worsening among the baseline characteristics were identified. Results Tenting area, coaptation depth, annular dilatation, and left atrial size were all associated with the degree of baseline MR. Tenting area was the only significant and independent predictor of worsening MR; a tenting area of 4 cm 2 was a useful cutoff to identify worsening of MR after MI and moderate to severe MR after 20 months. Conclusions Increased mitral tenting and larger mitral annular area are determinants of MR degree at baseline, and tenting area is an independent predictor of progression of MR after MI. Although LV remodeling itself contributes to ischemic MR, this influence is directly dependent on alterations in mitral geometry.

Aspiration pneumonitis, a direct cause of acute lung injury, is associated to a severe deterioration of lung function due in part to endogenous surfactant system impairment. We evaluated the effects of selective exogenous surfactant administration in a murine model of acid-induced lung injury both at short and long term. Hydrochloric acid was instilled into the right bronchus of the mice (0.1 M, 1.5 ml/kg). Six hours from acid instillation, they received, in the injured lung, a 1 ml/kg bolus of porcine surfactant (Curosurf ®) 40 or 80 mg phospholipids/ml (Surf 40 or Surf 80), or saline (0.9% NaCl, vehicle) Functional, biochemical, histological and inflammatory results were obtained 24 h after injury. In the Surf 80 and vehicle group, lung mechanics and histology were assessed again after two weeks. Micro-Computed Tomography scans were performed at 24 h and two weeks. 24 h after injury in the Surf 80 group respiratory system compliance and oxygenation were significantly improved compared to the vehicle, while neutrophilic fraction in bronchoalveolar lavage was significantly lower. Surfactant-treated mice maintained a better compliance and a significantly reduced inflammatory infiltrate also two weeks after treatment compared to vehicle. Micro-Computed Tomography scan suggested a more pronounced reduction of injury in surfactant-treated animals two weeks after injury (p = 0.09). We showed a beneficial effect on lung function of a single bolus of exogenous surfactant in unilateral acid-induced lung injury up to two weeks after treatment. Our results may suggest a role of surfactant replacement in modulating spontaneous evolution of injury. © 2010 Elsevier Ltd.

Background High dosage anthracyclines in pediatric patients with acute lymphoblastic leukemia (ALL) is associated with cardiotoxicity. However, data on the cardiac effects of lower cumulative doses of these drugs are not conclusive. The aim of this study was to assess the cardiac effects of low cumulative anthracycline doses in long-term survivors of ALL. Procedure Echocardiograms were performed on 62 long-term ALL survivors, without any overt or sub-clinical signs or symptoms of heart failure. The interval after stopping therapy was 12.6 ± 4.3 years; the mean cumulative dose of anthracyclines was 228.2 ± 42.3 mg/m2. Left ventricular (LV) structure and function were studied by echocolor-Doppler. An age, gender and body surface area (BSA) matched group of healthy subjects was used as controls. Cardiac data were analyzed before and after BSA normalization. Results Long term survivors of ALL, showed a lower LV mass index, interventricular septal and posterior wall thickness, which were independently related to gender and to age at which the ALL diagnosis was made. Data analyzed according to gender showed that abnormalities were confined to the female group. No alterations were observed in the ALL male group versus the corresponding control group. No relationship was observed between the echocardiografic abnormalities and the duration of follow-up or the anthracycline mean dose employed. Conclusions In the absence of any signs or symptoms of heart failure, female ALL survivors treated with low cumulative anthracycline doses, showed a reduced LV mass and wall thickness. This suggests that in female ALL survivors an echocardyographic follow-up should be recommended. Pediatr Blood Cancer. 2010;55:1343–1347. © 2010 Wiley-Liss, Inc.

Aims To assess the relationship between left atrial (LA) size and outcome after high-risk myocardial infarction (MI) and to study dynamic changes in LA size during long-term follow-up. Methods and results The VALIANT Echocardiography study prospectively enrolled 610 patients with left ventricular (LV) dysfunction, heart failure (HF), or both following MI. We assessed LA volume indexed to body surface area (LAVi) at baseline, 1 month, and 20 months after MI. Baseline LAVi was an independent predictor of all-cause death or HF hospitalization ( P = 0.004). In patients who survived to 20 months, LAVi increased a mean of 3.00 ± 7.08 mL/m2 from baseline. Hypertension, lower estimated glomerular filtration rate, and LV mass were the only baseline independent predictors of LA remodelling. Changes in LA size were related to worsening in MR and increasing in LV volumes. LA enlargement during the first month was significantly greater in patients who subsequently died or were hospitalized for HF than in patients without events. Conclusion Baseline LA size is an independent predictor of death or HF hospitalization following high-risk MI. Moreover, LA remodelling during the first month after infarction is associated with adverse outcome.

Use of local arterial distensibility measurements by change in carotid artery diameter divided by pulse pressure has limitations because blood pressure is often taken in a vessel distant or at a time different from where and when change in diameter is taken. In 92 subjects (23 to 91 years of age), carotid artery diameter was continuously measured ecographically, whereas blood pressure was continuously measured simultaneously tonometrically on the contralateral artery, the 2 signals being synchronized via 2 EKGs. Within each cardiac cycle, there was a linear relationship between the changes in vessel diameter and the changes in blood pressure during either the protomesosystole or the diastole after the dicrotic notch. The diastolic slope was displaced upward and steeper than the systolic slope, the pressure-diameter loop showing a hysteresis. Both slopes showed a high reproducibility when data were averaged over a several-second period. There were small differences between consecutive cardiac cycles, suggesting that modulation of arterial mechanical response to continuous changes in intravascular pressure may undergo physiological variations. In the 92 subjects, systolic and diastolic slopes correlated significantly with distensibility values obtained by Reneman formula and exhibited a close inverse relationship with each subject's age and systolic blood pressure, thereby showing the ability to reflect age- and pressure-dependent large artery stiffening. This method may allow precise assessment of man's arterial mechanical properties within each cardiac cycle. This highly dynamic assessment may help to collect information on properties of normal and altered large elastic arteries and the mechanisms involved in disease. © 2008 American Heart Association, Inc.

Diabetes is associated with a reduction of arterial distensibility. Limited information exists regarding whether or how early this appears in the course of the disease. We studied 54 normoglycemic, normotensive, healthy offspring of 2 parents with type 2 diabetes mellitus and 55 age- and sex-matched healthy control subjects. Carotid diastolic diameter and systodiastolic change were measured by echo tracking (Wall Track System) and wall thickness by echocolor Doppler (Sonos 5500, Philips). Pulse pressure was measured by a semiautomatic device positioned on the brachial artery and arterial distensibility calculated by Reneman formula. Blood pressure, blood glucose, glycohemoglobin, and insulin sensitivity (homeostasis model assessment index) were normal or only slightly elevated and by and large similar in the 2 groups. Compared with control subjects, offspring of diabetic parents showed similar carotid diameters at diastole and a reduced increase in carotid diameter at systole (−16%), a reduced carotid artery distensibility (−30%), and an increased pulse pressure (+21.8%), all differences being statistically significant ( P 2 ). Carotid artery wall thickness was not different between the 2 groups. Thus, subjects with predisposition to diabetes show carotid artery stiffening even in the absence of blood pressure alterations, as well as substantial alterations of glucose metabolism, body mass index, and changes in carotid wall thickness. This suggests that, in diabetes, alterations in arterial mechanical properties represent an early phenomenon, which may occur in the absence of metabolic and blood pressure alterations.