Intraoperative Ventilator Management of the Critically Ill Patient.

Strategies for the intraoperative ventilator management of the critically ill patient focus on parameters used for lung protective ventilation with acute respiratory distress syndrome, preventing or limiting the deleterious effects of mechanical ventilation, and optimizing anesthetic and surgical conditions to limit postoperative pulmonary complications for patients at risk. Patient conditions such as obesity, sepsis, the need for laparoscopic surgery, or one-lung ventilation may benefit from intraoperative lung protective ventilation strategies. Anesthesiologists can use risk evaluation and prediction tools, monitor advanced physiologic targets, and incorporate new innovative monitoring techniques to develop an individualized approach for patients.

HIMF (Hypoxia-Induced Mitogenic Factor) Signaling Mediates the HMGB1 (High Mobility Group Box 1)-Dependent Endothelial and Smooth Muscle Cell Crosstalk in Pulmonary Hypertension.

Objective: HIMF (hypoxia-induced mitogenic factor; also known as FIZZ1 [found in inflammatory zone-1] or RELM [resistin-like molecule-α]) is an etiological factor of pulmonary hypertension (PH) in rodents, but its underlying mechanism is unclear. We investigated the immunomodulatory properties of HIMF signaling in PH pathogenesis. Approach and Results: Gene-modified mice that lacked HIMF (KO [knockout]) or overexpressed HIMF human homolog resistin (hResistin) were used for in vivo experiments.

Hypoxia-Inducible Factor 1α Is a Critical Downstream Mediator for Hypoxia-Induced Mitogenic Factor (FIZZ1/RELMα)-Induced Pulmonary Hypertension.

Objective: Pulmonary hypertension (PH) is characterized by progressive elevation of pulmonary vascular resistance, right ventricular failure, and ultimately death. We have shown that in rodents, hypoxia-induced mitogenic factor (HIMF; also known as FIZZ1 or resistin-like molecule-β) causes PH by initiating lung vascular inflammation. We hypothesized that hypoxia-inducible factor-1 (HIF-1) is a critical downstream signal mediator of HIMF during PH development.

Resistin-Like Molecule α in Allergen-Induced Pulmonary Vascular Remodeling.

Resistin-like molecule α (RELMα) has mitogenic, angiogenic, vasoconstrictive, and chemokine-like properties and is highly relevant in lung pathology. Here, we used RELMα knockout (Retnla(-/-)) mice to investigate the role of RELMα in pulmonary vascular remodeling after intermittent ovalbumin (OVA) challenge. We compared saline- and OVA-exposed wild-type (WT) mice and found that OVA induced significant increases in right ventricular systolic pressure, cardiac hypertrophy, pulmonary vascular remodeling of intra-alveolar arteries, goblet cell hyperplasia in airway epithelium, and intensive lung inflammation, especially perivascular inflammation.

Hypoxia-induced mitogenic factor (FIZZ1/RELMα) induces endothelial cell apoptosis and subsequent interleukin-4-dependent pulmonary hypertension.

Pulmonary hypertension (PH) is characterized by elevated pulmonary artery pressure that leads to progressive right heart failure and ultimately death. Injury to endothelium and consequent wound repair cascades have been suggested to trigger pulmonary vascular remodeling, such as that observed during PH. The relationship between injury to endothelium and disease pathogenesis in this disorder remains poorly understood.

Caveolin-1 knockout mice exhibit airway hyperreactivity.

Caveolae are flask-shaped plasma membrane invaginations expressing the scaffolding caveolin proteins. Although caveolins have been found in endothelium and epithelium (where they regulate nitric oxide synthase activity), their role in smooth muscle is still under investigation. We and others have previously shown that caveolae of human airway smooth muscle (ASM), which express caveolin-1, contain Ca(2+) and force regulatory proteins and are involved in mediating the effects of inflammatory cytokines such as TNF-α on intracellular Ca(2+) concentration responses to agonist.

Estrogen increases nitric-oxide production in human bronchial epithelium.

Although sex differences in asthma severity are recognized, the mechanisms by which sex steroids such as estrogen influence the airway are still under investigation. Airway tone, a key aspect of asthma, represents a balance between bronchoconstriction and dilation. Nitric oxide (NO) from the bronchial epithelium is an endogenous bronchodilator.

Neurokinin-neurotrophin interactions in airway smooth muscle.

Neurally derived tachykinins such as substance P (SP) play a key role in modulating airway contractility (especially with inflammation). Separately, the neurotrophin brain-derived neurotrophic factor (BDNF; potentially derived from nerves as well as airway smooth muscle; ASM) and its tropomyosin-related kinase receptor, TrkB, are involved in enhanced airway contractility. In this study, we hypothesized that neurokinins and neurotrophins are linked in enhancing intracellular Ca(2+) concentration ([Ca(2+)](i)) regulation in ASM.

Neurotrophins induce nitric oxide generation in human pulmonary artery endothelial cells.

Aims: Members of the growth factor family of neurotrophins [NTs; e.g. brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT3)] and their high-affinity receptors (tropomyosin-related kinase; Trk) and low-affinity receptors p75 neurotrophin receptor (p75NTR) have been localized to pulmonary artery (PA) in humans.

Caveolin-1 and force regulation in porcine airway smooth muscle.

Caveolae are specialized membrane microdomains expressing the scaffolding protein caveolin-1. We recently demonstrated the presence of caveolae in human airway smooth muscle (ASM) and the contribution of caveolin-1 to intracellular calcium ([Ca(2+)](i)) regulation. In the present study, we tested the hypothesis that caveolin-1 regulates ASM contractility.

Cutaneous sympathetic neural responses to body cooling in type 2 diabetes mellitus.

In humans, sympathetic vasoconstrictor nerves in the skin contribute to resting vascular tone and mediate reflex vasoconstrictor responses to body cooling. Although it is well recognized that type 2 diabetes mellitus (T2DM) is associated with peripheral neurovascular changes, it is unclear to what extent the thermal responsiveness of the cutaneous vasoconstrictor system is altered in individuals with relatively uncomplicated T2DM. We tested the hypothesis that skin sympathetic nerve activity (SSNA) is decreased at baseline and during body cooling in individuals with T2DM compared to healthy controls (C) of similar age and body size.

Neurotrophins in lung health and disease.

Neurotrophins (NTs) are a family of growth factors that are well-known in the nervous system. There is increasing recognition that NTs (nerve growth factor, brain-derived neurotrophic factor and NT3) and their receptors (high-affinity TrkA, TrkB and TrkC, and low-affinity p75NTR) are expressed in lung components including the nasal and bronchial epithelium, smooth muscle, nerves and immune cells. NT signaling may be important in normal lung development, developmental lung disease, allergy and inflammation (e.