I. Pham

Pulmonary Pressure and Cardiac Function in Chronic Mountain Sickness Patients

BACKGROUND Chronic mountain sickness (CMS) is characterized by a loss of adaptation to hypoxia in high-altitude (HA) dwellers. Chronic hypoxemia, excessive erythrocytosis and frequently pulmonary hypertension (PH), which may lead to cardiac failure, develop in patients. We sought to assess the determinants of cardiac function in CMS patients with hypoxia-induced PH. METHODS Fifteen healthy men living at sea level (SL) were compared to 15 healthy men living at HA and 55 patients with CMS from Cerro de Pasco, Peru (altitude, 4,300 m). Pulmonary pressures and cardiac function were estimated by echocardiography. RESULTS None of the subjects had overt cardiac failure symptoms. CMS patients exhibited elevated mean pulmonary pressures as assessed by high-tricuspid pressure gradients (CMS patients, 34 +/- 10 mm Hg; HA subjects, 25 +/- 4 mm Hg [p = 0.002]; and SL subjects, 19 +/- 3 mm Hg [p < 0.001]). They also showed right ventricular (RV) dilation (mean end-diastolic RV area: CMS patients, 17 +/- 2 cm(2); HA subjects, 13 +/- 2 cm(2); SL subjects, 12 +/- 2 cm(2); p < 0.001) but did not display impaired systolic ventricular function. However, the RV Tei index was increased in CMS and HA subjects (CMS patients, 0.56 +/- 0.15; HA subjects, 0.52 +/- 0.12; SL subjects, 0.21 +/- 0.12; p < 0.001). CONCLUSION Despite obvious pulmonary arterial hypertension and right heart dilation, CMS patients did not show any symptom or echocardiographic parameter of heart failure. TRIAL REGISTRATION ClinicalTrials.gov. Identifier: NCT00424970.

Acetazolamide for Monge's Disease Efficiency and Tolerance of 6-Month Treatment

RATIONALE Monges disease is characterized by an excessive erythrocytosis, frequently associated with pulmonary hypertension, in high-altitude dwellers. It has a considerable impact on public health in high-altitude regions. A preliminary study demonstrated the efficiency of acetazolamide (Acz) (250 mg/d for 3 wk) in reducing serum erythropoietin and hematocrit. OBJECTIVES Evaluate the efficacy and tolerance of a 6-month treatment with 250 mg Acz that could be chronically implemented and its effects on pulmonary artery pressure and cardiac function. METHODS A two-phase study was performed in patients (hematocrit > or = 63%) from Cerro de Pasco, Peru (4,300 m). First phase: a double-blind, placebo-controlled study in 55 patients who received a single dose of either 250 mg Acz (n = 40) or placebo (n = 15) by daily oral administration for 12 weeks. Second phase (open label): after a 4-week washout period, all patients received 250 mg Acz for 12 weeks. Hematocrit, blood gases, clinical outcome, and pulmonary artery circulation were evaluated. MEASUREMENTS AND MAIN RESULTS First phase: Acz decreased by 44% the number of polycythemic subjects (P = 0.02), decreased hematocrit from 69 to 64% (P < 0.001), and increased arterial O(2) pressure from 42 to 45 mm Hg (P < 0.001). No severe adverse effect or hypokalemia was recorded. The second phase reproduced the effects observed during the first phase, without cumulative effects on hematocrit. A 4-week washout restored basal hematocrit. Only patients who received Acz for 6 months showed a clear reduction in pulmonary vascular resistance. CONCLUSIONS Acz reduces erythrocytosis and improves pulmonary circulation in Monges disease without adverse effects. Its implementation as a chronic treatment for this disease appears efficient and safe.

Postprandial endothelial dysfunction: role of glucose, lipids and insulin

Endothelium plays a key role in the regulation of vascular tone and development of atherosclerosis. Endothelial function is impaired early in patients with risk factors and endothelial dysfunction is a strong and independent predictor of cardiovascular events. Because in normal subjects blood concentrations of glucose, lipids and insulin are increased after each meals, and postprandial changes last a long time after the meals, these changes might be of importance in the process of atherosclerosis initiation and development. Experimental and human studies have shown that a transient increase of blood concentrations of glucose, triglycerides and fatty acids, and insulin are able to depress endothelium-dependent vasodilation in healthy subjects and that hyperglycemia, hypertriglyceridemia and hyperinsulinemia are generator of reactive oxygen species at the origin of a cascade of pathophysiological events resulting in the activation of nuclear factor-kappaB. Nuclear factor-kappaB is an ubiquitous transcription factor controlling the expression of numerous genes and is involved in immunity, inflammation, regulation of cell proliferation and growth and apoptosis. These mechanisms may be involved in the development of atherosclerosis in normal subjects when food intake is chronically modified towards glucids and lipids with cumulative effects both on depression of endothelium dependent dilation and oxidative stress.

Endothelin receptors blockade blunts hypoxia‐induced increase in PAP in humans

Eur J Clin Invest 2010; 40 (3): 195–202

Bosentan effects in hypoxic pulmonary vasoconstriction: Preliminary study in subjects with or without high altitude pulmonary edema-history.

Hypoxia-induced pulmonary vasoconstriction in patients with a medical history of high-altitude pulmonary edema (HAPE) may involve activation of the endothelin-1 (ET-1) pathway. We, therefore, compared the effect of the ETA/ETB receptor antagonist, bosentan, on pulmonary artery systolic pressure (PASP) in healthy subjects with (HS: HAPE subjects, n=5) or without a HAPE-history (CS: Control subjects, n=10). A double-blind, placebo-controlled, randomized, crossover design was performed in order to study the effects on PASP of a single oral dose of bosentan (250 mg) after 90 min exposure to normobaric hypoxia (FiO2=0.12). In normoxia, PASP, evaluated by echocardiography, was 23.4±2.7 mmHg in CS and 28±5.8 mmHg in HS (NS). During the placebo period, hypoxia induced a significant decrease in SaO2, PaO2 and PCO2 and increase in pH in both CS and HS. Pulmonary arterial systolic pressure was also significantly increased (+8.5±5.0 mmHg in CS; +13.4±3.1 mmHg in HS) and reached significantly higher levels in HS than in CS (P=0.02). Bosentan significantly but similarly blunted the hypoxia-induced increase in PASP in both CS (Bosentan: 27.0±3.3 mmHg; placebo: 32.1±3.5 mmHg; P<0.01) and HS (Bosentan: 35.0±2.9 mmHg; placebo: 41.4±7.6 mmHg; P<0.05), (CS 5.2±5.3 vs. HS −6.4±5.2 mmHg, NS). Bosentan did not have a major effect on the hypoxia-induced changes in blood gas, or on cardiac output (CO) and systemic blood pressure (SBP), which were not modified by hypoxia. Plasma ET-1 in hypoxia during the bosentan period was 2.8 times higher than during for both CS and HS. A single oral dose of bosentan similarly blunted the hypoxia-induced increase in PASP both in healthy and HAPE-susceptible subjects, without altering CO or SBP.

Rapidly progressive crescentic glomerulonephritis and aneurism with antineutrophil cytoplasmic antibody: Bartonella henselae endocarditis.

[3] Lavrov VF, Semenkov VF. The infection of mice with the influenza virus suppresses bone marrow precursor differentiation in the erythroid and granulocyte directions. Vopr Virusol 1991;36:284-6. [4] Likos AM, Kelvin DJ, Cameron CM et al. Influenza viremia and the potential for blood-borne transmission. Transfusion 2007;47:1080-8. [5] Calitri C, Gabiano C, Garazzino S et al. Clinical features of hospitalised children with 2009 H1N1 influenza virus infection. Eur J Pediatr Laboratory values showed: white blood cells 11,400/mm , hemoglobin 8 g/dL, creatininemia 195 mmol/L, blood urea nitrogen 22.8 mmol/L, albumin 30 Gr/L, proteinuria 6 Gr/24 h, Creactive protein 27 mg/L. Blood cultures were negative, as well as hepatitis B, hepatitis C, HIV and rickettsia serologies. Electro-

Transthoracic echocardiographic abnormalities in asymptomatic diabetic patients: association with microalbuminuria and silent coronary artery disease.

AIMS This study aimed to assess, on routine echocardiography, cardiac left ventricular (LV) disorders, their determinants and their role in the screening process of silent myocardial ischaemia (SMI) in asymptomatic diabetic patients. METHODS A total of 586 asymptomatic diabetic patients with one or more additional cardiovascular risk factors, but no history of heart failure or myocardial infarction, prospectively underwent rest echocardiography and myocardial scintigraphy. Those with SMI (abnormal scintigraphy) were subsequently screened for angiographic coronary artery disease (CAD). RESULTS LV hypertrophy, LV dilatation, systolic dysfunction and hypokinesia were found in 33.6, 8.6, 3.2 and 6.1%, respectively, of the study population. SMI was found in 156 (26.6%) patients, 55 of whom had silent CAD. On multivariate analysis, age (OR: 1.03 [1.00-1.05], P=0.02), microalbuminuria (OR: 2.2 [1.4-3.2], P<0.0001) and silent CAD (OR: 2.4 [1.3-4.6], P=0.007) were predictive of LV hypertrophy. Creatinine clearance (OR: 0.97 [0.96-0.99], P=0.002) and silent CAD (OR: 3.7 [1.3-10.0]) were associated with LV dilatation. LV systolic dysfunction was associated with microalbuminuria (OR: 3.8 [1.3-11.4], P=0.02) and silent CAD (OR: 3.8 [1.1-12.6], P=0.03). Hypokinesia was associated with retinopathy (OR: 2.4 [1.1-5.4], P=0.04), microalbuminuria (OR: 2.3 [1.1-5.0], P=0.04) and LV dilatation (OR: 3.0 [1.1-8.1], P=0.03). In patients with SMI, the positive predictive value of LV hypertrophy associated with another echocardiographic abnormality (n=19) for CAD was 63.2%. CONCLUSION LV hypertrophy was found in one-third of asymptomatic diabetic patients, while LV dilatation, systolic dysfunction or hypokinesia was seen in<10%. The main predictors of LV abnormalities were microalbuminuria and silent CAD. The presence of LV hypertrophy with another abnormality should raise the possibility of the presence of silent CAD.

Epo deficiency alters cardiac adaptation to chronic hypoxia.

The involvement of erythropoietin in cardiac adaptation to acute and chronic (CHx) hypoxia was investigated in erythropoietin deficient transgenic (Epo-TAg(h)) and wild-type (WT) mice. Left (LV) and right ventricular functions were assessed by echocardiography and hemodynamics. HIF-1α, VEGF and Epo pathways were explored through RT-PCR, ELISA, Western blot and immunocytochemistry. Epo gene and protein were expressed in cardiomyocytes of WT mice in normoxia and hypoxia. Increase in blood hemoglobin, angiogenesis and functional cardiac adaptation occurred in CHx in WT mice, allowing a normal oxygen delivery (O2T). Epo deficiency induced LV hypertrophy, increased cardiac output (CO) and angiogenesis, but O2T remained lower than in WT mice. In CHx Epo-TAg(h) mice, LV hypertrophy, CO and O2T decreased. HIF-1α and Epo receptor pathways were depressed, suggesting that Epo-TAg(h) mice could not adapt to CHx despite activation of cardioprotective pathways (increased P-STAT-5/STAT-5). HIF/Epo pathway is activated in the heart of WT mice in hypoxia. Chronic hypoxia induced cardiac adaptive responses that were altered with Epo deficiency, failing to maintain oxygen delivery to tissues.

Evidence for a Specific Diabetic Cardiomyopathy: An Observational Retrospective Echocardiographic Study in 656 Asymptomatic Type 2 Diabetic Patients

Aim. Our aim was to assess the prevalence of subclinical diabetic cardiomyopathy, occurring among diabetic patients without hypertension or coronary artery disease (CAD). Methods. 656 asymptomatic patients with type 2 diabetes for 14 ± 8 years (359 men, 59.7 ± 8.7 years old, HbA1c 8.7 ± 2.1%) and at least one cardiovascular risk factor had a cardiac echography at rest, a stress cardiac scintigraphy to screen for silent myocardial ischemia (SMI), and, in case of SMI, a coronary angiography to screen for silent CAD. Results. SMI was diagnosed in 206 patients, and 71 of them had CAD. In the 157 patients without hypertension or CAD, left ventricular hypertrophy (LVH: 24.1%) was the most frequent abnormality, followed by left ventricular dilation (8.6%), hypokinesia (5.3%), and systolic dysfunction (3.8%). SMI was independently associated with hypokinesia (odds ratio 14.7 [2.7–81.7], p < 0.01) and systolic dysfunction (OR 114.6 [1.7–7907], p < 0.01), while HbA1c (OR 1.9 [1.1–3.2], p < 0.05) and body mass index (OR 1.6 [1.1–2.4], p < 0.05) were associated with systolic dysfunction. LVH was more prevalent among hypertensive patients and hypokinesia in the patients with CAD. Conclusion. In asymptomatic type 2 diabetic patients, diabetic cardiomyopathy is highly prevalent and is predominantly characterized by LVH. SMI, obesity, and poor glycemic control contribute to structural and functional LV abnormalities.

Amebic Liver Abscess, Extensive Thrombosis, and Patent Cardiac Foramen Ovale

Extensive venous thrombosis is usually seen postmortem in amebic liver abscess because of its dismal prognosis. Herein, we describe amebic liver abscess, whose late diagnosis led to multiple deep thromboses, pulmonary embolism, and right atrial thrombosis, in this patient with patent foramen ovale.