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Biomedical subjects

Alejandro C Arroliga

Publications and source records attributed to Alejandro C Arroliga.

At least 19 recordsLinked to original sources

Alterations of cellular bioenergetics in pulmonary artery endothelial cells.

Idiopathic pulmonary arterial hypertension (IPAH) is pathogenetically related to low levels of the vasodilator nitric oxide (NO). Because NO regulates cellular respiration and mitochondrial biogenesis, we hypothesized that abnormalities of bioenergetics may be present in IPAH. Evaluation of pulmonary artery endothelial cells from IPAH and control lungs in vitro revealed that oxygen consumption of IPAH cells was decreased, especially in state 3 respiration with substrates glutamate-malate or succinate, and this decrease paralleled reduction in Complex IV activity and IPAH cellular NO synthesis. IPAH pulmonary artery endothelial cells had decreased mitochondrial dehydrogenase activity and lowered mitochondrial numbers per cell and mitochondrial DNA content, all of which increased after exposure to NO donors. Although IPAH/pulmonary artery endothelial cells' ATP content was similar to control under normoxia, cellular ATP did not change significantly in IPAH cells under hypoxia, whereas ATP decreased 35% in control cells, identifying a greater dependence on cellular respiration for energy in control cells. Evidence that glucose metabolism was subserving the primary role for energy requirements of IPAH cells was provided by the approximately 3-fold greater glycolytic rate of IPAH cells. Positron emission tomography scan with [18F]fluoro-deoxy-D-glucose performed on IPAH patients and healthy controls revealed significantly higher uptake in IPAH lungs as compared with controls, confirming that the glycolytic rate was increased in vivo. Thus, there are substantial changes in bioenergetics of IPAH endothelial cells, which may have consequences for pulmonary hypertensive responses and potentially in development of novel imaging modalities for diagnosis and evaluation of treatment.

Adenosine Triphosphate↗

Predictors of nocturnal oxygen desaturation in pulmonary arterial hypertension.

BACKGROUND: Sleep may be associated with significant respiratory compromise in patients with lung disease and can result in hypoxia. In patients with pulmonary arterial hypertension (PAH), nocturnal desaturation may not be reflected in daytime evaluations of oxygenation and can lead to worsening pulmonary hemodynamics. The study was conducted to determine the prevalence and significance of nocturnal oxygen desaturation in patients with PAH. METHODS: A cross-sectional study conducted at the Cleveland Clinic. Patients were followed up at our institution except for the overnight oximetry study done at home. Data regarding degree of nocturnal desaturation, demographics, hemodynamics, pulmonary function, and functional capacity were collected. RESULTS: Forty-three patients (mean age, 47.9 +/- 13.5 years [+/- SD]; 36 women and 7 men) underwent nocturnal oximetry. The etiology of PAH included idiopathic PAH (88%) and PAH associated with connective tissue diseases (12%). The majority of patients were New York Heart Association functional class II (42%) or III (53%). Thirty patients (69.7%) spent > 10% of sleep time with oxygen saturation by pulse oximetry < 90%. Desaturators were older (p = 0.024) and had higher hemoglobin (p = 0.002). Sixteen of 27 patients (59%) without desaturation < 90% during a 6-min walk test were nocturnal desaturators. Nocturnal desaturators had higher brain natriuretic protein (p = 0.004), lower cardiac index (p = 0.03), and higher mean right atrial pressure (p = 0.09), mean pulmonary artery pressure, and pulmonary vascular resistance. On echocardiography, desaturators were more likely to have moderate or severe right ventricular dilation (p = 0.04) and pericardial effusion. Only one patient had significant sleep apnea. CONCLUSIONS: Nocturnal hypoxemia is common in PAH patients and correlates with advanced pulmonary hypertension and right ventricular dysfunction. Approximately 60% patients without exertional hypoxia had nocturnal desaturation. Overnight oximetry should be considered in the routine workup of PAH patients who do not demonstrate exertional desaturation.

Adult↗

Predictors of long-term mortality in patients with ventilator-associated pneumonia.

PURPOSE: To determine the long-term outcome of ventilator-associated pneumonia (VAP) and identify factors associated with increased mortality. METHODS: We retrospectively studied 671 patients with VAP admitted to an intensive care unit between 1994 and 2000. We determined long-term and out-of-hospital mortality for these patients. RESULTS: The in-hospital mortality was 42.3%; 19.8% of patients had concomitant bacteremia, the mortality was 59.7% versus 38.0% for those without bacteremia (P <.001). The factors associated with increased hospital mortality by univariable analysis were: diagnosis on admission, the need of vasopressors during the stay in the intensive care unit, not undergoing a tracheostomy, the absence of fever, the presence of concomitant bacteremia, and renal failure or the need for dialysis. Patients transferred from an outside hospital and patients with normal serum bicarbonate, serum total bilirubin <2 mg/dL, and platelets >120x4> 10(3)/microL had a lower in-hospital mortality. All of these factors except bilirubin level, platelet count, transfer from outside hospital, and serum bicarbonate remained significant on multivariable analysis. The estimated mortality at 1, 3 and 5 years is 25.9% (95% confidence interval [CI], 20.2-30.1%), 33.6% (95% CI, 27.4-39.2%) and 44.7% (95% CI, 38.1-50.6%), respectively. CONCLUSIONS: VAP is associated with a high rate of hospital and long-term mortality. The presence of bacteremia is associated with a high mortality. The 5-year estimated mortality of the survivors is less than 50%.

Aged↗

Clinical epidemiology of acute lung injury and acute respiratory distress syndrome: incidence, diagnosis, and outcomes.

Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are clinical syndromes characterized by the sudden onset of severe hypoxemia and diffuse bilateral pulmonary infiltrates in the absence of left atrial hypertension. Although advances have been made in the understanding of the etiology, pathophysiology, and epidemiology of both entities, many questions remain regarding their incidence, diagnosis, and outcomes. This article reviews the currently used definition of ARDS and ALI, different studies that have advanced the understanding of the epidemiology and outcomes of these entities, and several diagnostic issues that are important for both clinicians and researchers.

Biopsy↗

Pulmonary artery catheter and fluid management in acute lung injury and the acute respiratory distress syndrome.

The PAC provides a wealth of information about circulatory and respiratory systems and intravascular fluid volume over time. Specifically, the PAC allows measurement of central venous and pulmonary arterial pressure, pulmonary artery occlusion pressure, mixed venous blood gases, and indicator-dilution cardiac output. Based on these quantitative date, systemic and pulmonary vascular resistance can be derived. The PAC is frequently used in patients with ALI and ARDS, both to confirm the diagnosis and to optimize hemodynamic management. In this article, we review the evidence on the use of the PAC in patients with ALI/ARDS, paying particular attention to the recently published fluid and catheter treatment trial by the ARDS Clinical Trials Network.

Body Fluids↗

Tracheostomy after cardiovascular surgery: an assessment of long-term outcome.

OBJECTIVE: To ascertain long-term survival, identify risk factors for death, and document complications of tracheostomy after cardiovascular surgery. METHODS: Between January 1, 1998, and September 1, 2001, 188 (1.4%) of 13,191 patients undergoing cardiovascular surgery had tracheostomy for respiratory failure 5 to 79 days (median, 14 days) after surgery. Factors associated with mortality were identified in the hazard function domain, and mode of death and complications of tracheostomy were determined by follow-up. RESULTS: Survival was 75%, 50%, and 31% at 30 days, 3 months, and 2 years, respectively. The most important risk factors for death were older age (P = .004) and variables representing deteriorating hemodynamic (P < .0001), respiratory (P < .0001), and renal (P = .0001) function between the index cardiovascular operation and tracheostomy. The mode of death was isolated respiratory failure in only 21 (16%) of 130 patients, but multisystem organ failure in 71 (55%). Follow-up of 58 survivors identified voice complaints in 13 (24%), tracheal stenosis in 5 (9.2%), and permanent tracheostomy in 3 (6%). CONCLUSIONS: Only one third of patients undergoing tracheostomy after cardiovascular surgery survive, because it is used primarily in those with deteriorating function of multiple organ systems. Although tracheostomy may enhance patient comfort and simplify nursing care, selection algorithms need to be developed if survival is the goal of the intervention.

Cardiovascular Diseases↗

Long-term results after addition of sildenafil in idiopathic PAH patients on bosentan.

Idiopathic pulmonary arterial hypertension is a disease involving small muscular pulmonary arteries and arterioles. Treatment with prostacyclin analogs and endothelin receptor antagonists is the cornerstone of therapy in these patients. Recent evidence suggests that phosphodiesterase-5 inhibitors such as sildenafil may improve functional capacity and hemodynamics in patients with pulmonary arterial hypertension. Despite these advances, pulmonary arterial hypertension remains a deadly and progressive disease and it has been suggested that combination therapy aimed at multiple targets may produce a greater improvement while minimizing adverse effects. We report three patients who declined after initial improvement on bosentan and subsequently showed an improvement in their functional capacity and brain natriuretic peptide (BNP) with the addition of sildenafil. This benefit has been sustained over a mean follow-up period of 19 (range 12-24) months.

3',5'-Cyclic-GMP Phosphodiesterases↗

Update in ARDS management: recent randomized controlled trials that changed our practice.

In the last 7 years, 14 randomized controlled trials in patients with acute respiratory distress syndrome (ARDS) have shown that: Mechanical ventilation with a tidal volume of 6 mL/kg of predicted body weight is better than mechanical ventilation with a tidal volume of 12 mL/kg of predicted body weight. Prone positioning improves oxygenation but poses safety concerns. A high level of positive end-expiratory pressure does not improve survival. High-frequency oscillatory ventilation is in theory the ideal "lung-protective" method, but its benefits have not been proven. No drug therapy has been shown to improve survival in patients with ARDS. Exogenous surfactant may improve oxygenation but has no significant effect on the death rate or length of use of mechanical ventilation. Low-dose inhaled nitric oxide has no substantial impact on the duration of ventilatory support or on the death rate. Partial liquid ventilation may be beneficial in young patients with acute lung injury or ARDS, although further study is needed to confirm this.

Glycine↗

Surgical intervention in patients with moderate to severe pulmonary arterial hypertension.

BACKGROUND: Patients with pulmonary arterial hypertension are believed to experience severe postoperative complications after major surgery. METHODS: We retrospectively analyzed the data of 21 patients with pulmonary arterial hypertension who underwent 28 surgical procedures at our institution between 1996 and 2002. RESULTS: The average mean pulmonary arterial pressure was 53 +/- 14.4 mm Hg. Twenty-two procedures were performed under general anesthesia. Extubation occurred within 24 hours of surgery in 72% and an intensive care unit stay was not required after 43% of the procedures. Perioperative morbidity and mortality were typically related to the surgical procedure or underlying disease. CONCLUSIONS: In our study, patients with moderate to severe pulmonary arterial hypertension had an 18% per procedure mortality and a 19% rate of right heart failure after surgical intervention.

Adult↗

Lung cancer: Preoperative pulmonary evaluation of the lung resection candidate.

Lung resection provides the best chance of cure for individuals with early stage non-small cell lung cancer. Naturally, lung resection will lead to a decrease in lung function. The population that develops lung cancer often has concomitant lung disease and a reduced ability to tolerate further losses in lung function. The goal of the preoperative pulmonary assessment of individuals with resectable lung cancer is to identify those individuals whose short- and long-term morbidity and mortality would be unacceptably high if surgical resection were to occur. Pulmonary function measures such as the forced expiratory volume in 1 second and the diffusing capacity for carbon monoxide are useful predictors of postoperative outcome. In situations in which lung function is not normal, the prediction of postoperative lung function from preoperative results and the assessment of exercise capacity can be performed to further clarify risks. Published guidelines help to direct the order of testing, permitting us to offer resection to as many patients as possible.

Exercise Test↗

Exacerbation of underlying pulmonary disease in pregnancy.

OBJECTIVE: The presence of underlying pulmonary disease in women of childbearing potential can present a significant challenge during pregnancy and the postpartum period. Management of the underlying disease, recognizing and preventing disease progression, and, most important, managing and minimizing toxic side effects of various therapies require the expertise of an interdisciplinary team. This team must involve close collaboration between intensive care physicians, pulmonary physicians, and high-risk obstetricians familiar with these disease states in an effort to minimize fetal and maternal morbidity and mortality. We will review the impact of the pregnant state in lung transplant recipients, patients with pulmonary arterial hypertension, and patients with underlying cystic fibrosis. DESIGN: Review of the literature in regards to pregnancy outcomes and issues for patients with cystic fibrosis, pulmonary hypertension, and lung transplants. METHODS: A review of the epidemiology, pathophysiology, risk factors, classification, clinical features, and outcomes for pregnant patients with underlying pulmonary diseases. CONCLUSIONS: Safety of pregnancy in the female lung transplant recipient concerns three outcomes: maternal outcome, fetal outcome, and transplanted graft outcome.

Critical Care↗

Ovarian hyperstimulation syndrome.

OBJECTIVE: Ovarian hyperstimulation syndrome (OHSS) is a rare iatrogenic complication of ovarian stimulation usually occurring during the luteal phase or during the early part of pregnancy. OHSS is a potential complication of ovarian induction by almost every agent used for ovarian stimulation. Today, due to aggressive treatment protocols including the development of in vitro fertilization and cryopreservation with the goal of obtaining sufficient numbers of oocytes and embryos, an increased risk of developing OHSS is present. OHSS is now becoming increasingly more recognized due to the higher number of women undergoing assisted reproductive techniques. DESIGN: Review of the literature regarding ovarian hyperstimulation syndrome. METHODS: A review of the epidemiology, pathophysiology, risk factors, classification, clinical features, and treatment and prevention of OHSS. CONCLUSION: OHSS can be thought of as the loss of control over the hyperstimulation of the ovaries. Although the prevalence of the severe form of OHSS is small, it is important to remember that OHSS is usually an iatrogenic complication of a nonvital treatment that has the potential for a fatal outcome. Therefore, critical care physicians play an integral part in the care of these patients and therefore should be familiar with and recognize the various clinical manifestations and potential outcomes of this entity.

Critical Care↗

Auto-positive end-expiratory pressure: mechanisms and treatment.

Auto-positive end-expiratory pressure (auto-PEEP) is a common problem in patients receiving full or partial ventilatory support, as well as in those ready to be weaned from the ventilator. Physicians should be alert for it and take measures to reduce it, as it can have serious consequences.

Humans↗

Nitric oxide and pulmonary arterial pressures in pulmonary hypertension.

Decreased production of vasodilator substances such as nitric oxide (NO) has been proposed as important in development of pulmonary arterial hypertension (PAH). We hypothesize that NO measured over time serves as a non invasive marker of severity of PAH and response to therapy. We prospectively and serially measured exhaled NO and carbon monoxide (CO), a vasodilator and anti-inflammatory product of heme oxygenases, in 17 PAH patients in conjunction with hemodynamic parameters over 2 years. Although pulmonary artery pressures and NO were similar in all patients at entry to the study, NO increased in the 12 individuals who survived to complete the study, and correlated with change in pulmonary artery pressures. In contrast, CO did not change or correlate with hemodynamic parameters. Investigation of NO-oxidant reaction products in PAH in comparison to controls suggests that NO synthesis is impaired in the lung and that reactive oxygen species may be involved in the pathophysiology of pulmonary hypertension. Endogenous NO is inversely related to pulmonary artery pressure in PAH, with successful therapy of PAH associated with increase in NO.

Blood Pressure↗