Alveolar macrophage activation is a key initiation signal for acute lung ischemia-reperfusion injury.

Lung ischemia-reperfusion (I/R) injury is a biphasic inflammatory process. Previous studies indicate that the later phase is neutrophil-dependent and that alveolar macrophages (AMs) likely contribute to the acute phase of lung I/R injury. However, the mechanism is unclear. AMs become activated and produce various cytokines and chemokines in many inflammatory responses, including transplantation. We hypothesize that AMs respond to I/R by producing key cytokines and chemokines and that depletion of AMs would reduce cytokine/chemokine expression and lung injury after I/R. To test this, using a buffer-perfused, isolated mouse lung model, we studied the impact of AM depletion by liposome-clodronate on I/R-induced lung dysfunction/injury and expression of cytokines/chemokines. I/R caused a significant increase in pulmonary artery pressure, wet-to-dry weight ratio, vascular permeability, tumor necrosis factor (TNF)-alpha, monocyte chemoattractant protein (MCP)-1, and macrophage inflammatory protein (MIP)-2 expression, as well as decreased pulmonary compliance, when compared with sham lungs. After AM depletion, the changes in each of these parameters between I/R and sham groups were significantly attenuated. Thus AM depletion protects the lungs from I/R-induced dysfunction and injury and significantly reduces cytokine/chemokine production. Protein expression of TNF-alpha and MCP-1 are positively correlated to I/R-induced lung injury, and AMs are a major producer/initiator of TNF-alpha, MCP-1, and MIP-2. We conclude that AMs are an essential player in the initiation of acute lung I/R injury.

[Clinical, functional and hemodynamic features of patients with pulmonary arterial hypertension]. / Caracterización clínica, funcional y hemodinámica de la población con hipertensión pulmonar arterial evaluada en el Instituto Nacional del Tórax.

BACKGROUND: Pulmonary Arterial Hypertension is a rare, progressive and devastating disease with severe consequences in quality of life and survival. AIM: A clinical, functional and hemodynamic assessment of patients with pulmonary arterial hypertension and categorization according to severity. MATERIAL AND METHODS: Prospective registry of patients with arterial pulmonary hypertension, hemodynamically defined. Clinical evaluation was performed using World Health Organization functional score (I to IV) and Borg dyspnea scale. Six minute walking test, echocardiography and right heart catheterization were used for functional and hemodynamic assessment. Intravenous Adenosine was used to assess vascular reactivity during the hemodynamic evaluation. RESULTS: Twenty nine patients were included (25 women, age range 16-72 years). Pulmonary hypertension was idiopathic in 11, associated to connective tissue disease in seven, associated to congenital heart disease in nine and associated to chronic thromboembolism in two. The mean lapse of symptoms before assessment was 2.9 years and 100% had dyspnea (Borg 5.1). Functional class I, II, III and IV was observed in 0, 5, 21 and 3 patients respectively. Six minutes walking test was 378+/-113 m. Mean pulmonary pressure was 59.4+/-12.2 mmHg, cardiac index was 2.57+/-0.88 and pulmonary vascular resistance index: 1798.4+/-855 (dyne.sec)/cm5. Nine patients had a mean pulmonary arterial pressure >55 mmHg and a cardiac index <2.1, considered as bad prognosis criteria. Adenosine test was positive in 17%. CONCLUSIONS: This group of patients with Pulmonary Arterial Hypertension was mainly conformed by young females, with a moderate to severe disease.

Caracterización clínica, funcional y hemodinámica de la población con hipertensión pulmonar arterial evaluada en el Instituto Nacional del Tórax / Clinical, functional and hemodynamic features of patients with pulmonary arterial hypertension

Background: Pulmonary Arterial Hypertension is a rare, progressive and devastating disease with severe consequences in quality of life and survival. Aim: A clinical, functional and hemodynamic assessment of patients with pulmonary arterial hypertension and categorization according to severity. Material and methods: Prospective registry of patients with arterial pulmonary hypertension, hemodynamically defined. Clinical evaluation was performed using World Health Organization functional score (I to IV) and Borg dyspnea scale. Six minute walking test, echocardiography and right heart catheterization were used for functional and hemodynamic assessment. Intravenous Adenosine was used to assess vascular reactivity during the hemodynamic evaluation. Results: Twenty nine patients were included (25 women, age range 16-72 years). Pulmonary hypertension was idiopathic in 11, associated to connective tissue disease in seven, associated to congenital heart disease in nine and associated to chronic thromboembolism in two. The mean lapse of symptoms before assessment was 2.9 years and 100% had dyspnea (Borg 5.1). Functional class I, II, III and IV was observed in 0, 5, 21 and 3 patients respectively. Six minutes walking test was 378±113 m. Mean pulmonary pressure was 59.4±12.2 mmHg, cardiac index was 2.57±0.88 and pulmonary vascular resistance index: 1798.4±855 (dyne.sec)/cm5. Nine patients had a mean pulmonary arterial pressure >55 mmHg and a cardiac index <2.1, considered as bad prognosis criteria. Adenosine test was positive in 17%. Conclusions: This group of patients with Pulmonary Arterial Hypertension was mainly conformed by young females, with a moderate to severe disease.