Jeffrey Mazer

Activation of endothelial BKCa channels causes pulmonary vasodilation.

BACKGROUND Large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels cause hyperpolarization and can regulate vascular tone. In this study, we evaluated the effect of endothelial BK(Ca) activation on pulmonary vascular tone. METHODS The presence of BK(Ca) channels in lung microvascular endothelial cells (LMVEC) and rat lung tissue was confirmed by RT-PCR, immunoblotting and immunohistochemistry. Isolated pulmonary artery (PA) rings and isolated ventilated-perfused rat lungs were used to assay the effects of BK(Ca) channel activation on endothelium-dependent vasodilation. RESULTS Immunoblotting and RT-PCR revealed the presence of BK(Ca) channel alpha- and beta(4)-subunits in LMVEC. Immunohistochemical staining showed BK(Ca) channel alpha-subunit expression in vascular endothelium in rat lungs. In arterial ring studies, BK(Ca) channel activation by NS1619 enhanced endothelium-dependent vasodilation that was attenuated by tetraethylammonium and iberiotoxin. In addition, activation of BK(Ca) channels by C-type natriuretic peptide caused endothelial-dependent vasodilation that was blocked by iberiotoxin, L-NAME, and lanthanum. Furthermore, BK(Ca) activation by NS1619 caused a dose-dependent reduction in PA pressures that was attenuated by L-NAME. In vitro, BK(Ca) channel activation in LMVEC caused hyperpolarization and increased NO production. CONCLUSIONS Pulmonary endothelium expresses BK(Ca) channels. Activation of endothelial BK(Ca) channels causes hyperpolarization and NO mediated endothelium-dependent vasodilation in micro- and macrovasculature in the lung.

Outcomes of Sleep Disordered Breathing in Pregnancy

Sleep disordered breathing has been linked to adverse cardiovascular outcomes in the general population. In pregnancy, sleep disordered breathing has also been linked to pathologic disorders that have been associated with long term cardiovascular and metabolic outcomes such as gestational hypertensive disorders and gestational diabetes mellitus. Endothelial dysfunction, sympathetic stimulation and inflammation are among the mechanisms proposed to explain the association with adverse outcomes. In addition to mechanistic research, future efforts need to focus on the effect of therapy on such outcomes.

C-type natriuretic peptide does not attenuate the development of pulmonary hypertension caused by hypoxia and VEGF receptor blockade.

AIMS C-type natriuretic peptide (CNP) is a local regulator of vascular tone and remodeling in many vascular beds. However, the role of CNP in modulating pulmonary arterial hypertensive and vascular remodeling responses is unclear. The purpose of this study was to determine if CNP is capable of preventing the development of pulmonary hypertension (PH). MAIN METHODS We used animal models of PH caused by chronic hypoxia alone or in combination with the vascular endothelial growth factor (VEGF) receptor blocker SU5416. We measured pulmonary hemodynamics, right ventricular hypertrophy and vascular remodeling effects in response to a continuous infusion of low dose or high dose CNP or vehicle placebo. KEY FINDINGS Right ventricular hypertrophy and a marked elevation in right ventricular systolic pressure (RVSP) were seen in both models of PH. Rats treated with the combination of SU5416 and chronic hypoxia also developed pulmonary endothelial hyperproliferative lesions. Continuous intravenous infusion of CNP at either dose did not attenuate the development of PH, right ventricular hypertrophy or vascular remodeling in either of the models of PH despite a three-fold increase in serum CNP levels. SIGNIFICANCE CNP does not prevent the development of PH in the chronic hypoxia or SU5416 plus hypoxia models of pulmonary hypertension suggesting that CNP may not play an important modulatory role in human PH.

Inhaled β-agonist therapy and respiratory muscle fatigue as under-recognised causes of lactic acidosis

A 49-year-old man with chronic obstructive pulmonary disease (COPD) presented with significant tachypnoea, fevers, productive cough and increased work of breathing for the previous 4 days. Laboratory data showed elevated lactate of 3.2 mEq/L. Continuous inhaled ipratropium and albuterol nebuliser treatments were administered. Lactate levels increased to 5.5 and 3.9 mEq/L, at 6 and 12 h, respectively. No infectious source was found and the lactic acidosis cleared as the patient improved. The lactic acidosis was determined to be secondary to respiratory muscle fatigue and inhaled β-agonist therapy, two under-recognised causes of lactic acidosis in patients presenting with respiratory distress. Lactic acidosis is commonly used as a clinical marker for sepsis and shock, but in the absence of tissue hypoperfusion and severe hypoxia, alternative aetiologies for elevated levels should be sought to avoid unnecessary and potentially harmful medical interventions.

Arterial Catheter Use in the ICU: A National Survey of Antiseptic Technique and Perceived Infectious Risk.

Objectives: Recent studies have shown that the occurrence rate of bloodstream infections associated with arterial catheters is 0.9–3.4/1,000 catheter-days, which is comparable to that of central venous catheters. In 2011, the Centers for Disease Control and Prevention published new guidelines recommending the use of limited barrier precautions during arterial catheter insertion, consisting of sterile gloves, a surgical cap, a surgical mask, and a small sterile drape. The goal of this study was to assess the attitudes and current infection prevention practices used by clinicians during insertion of arterial catheters in ICUs in the United States. Design: An anonymous, 22-question web-based survey of infection prevention practices during arterial catheter insertion. Setting: Clinician members of the Society of Critical Care Medicine. Subjects: Eleven thousand three hundred sixty-one physicians, nurse practitioners, physician assistants, respiratory therapists, and registered nurses who elect to receive e-mails from the Society of Critical Care Medicine. Interventions: None. Measurements and Main Results: There were 1,265 responses (11% response rate), with 1,029 eligible participants after exclusions were applied. Only 44% of participants reported using the Centers for Disease Control and Prevention–recommended barrier precautions during arterial catheter insertion, and only 15% reported using full barrier precautions. The mean and median estimates of the incidence density of bloodstream infections associated with arterial catheters were 0.3/1,000 catheter-days and 0.1/1,000 catheter-days, respectively. Thirty-nine percent of participants reported that they would support mandatory use of full barrier precautions during arterial catheter insertion. Conclusions: Barrier precautions are used inconsistently by critical care clinicians during arterial catheter insertion in the ICU setting. Less than half of clinicians surveyed were in compliance with current Centers for Disease Control and Prevention guidelines. Clinicians significantly underestimated the infectious risk posed by arterial catheters, and support for mandatory use of full barrier precautions was low. Further studies are warranted to determine the optimal preventive strategies for reducing bloodstream infections associated with arterial catheters.

A prophylactic fresh frozen plasma transfusion leads to a possible case of transfusion-related acute lung injury

A 39-year-old man with cholangiocarcinoma presented with fever and abdominal pain. He was hypotensive, jaundiced and had right upper quadrant tenderness. Laboratory testing showed a leucocytosis, elevated liver function tests, total bilirubin and International Normalised Ratio (INR). Given the concern for cholangitis, the patient was given antibiotics and three units of fresh frozen plasma (FFP) before biliary drain placement. After drain placement, and within 3 h of receiving blood products, the patient became tachypnoeic and hypoxic with a chest X-ray revealing new bilateral airspace disease. The rapid development of respiratory distress was determined to most likely be transfusion-related acute lung injury (TRALI). He rapidly progressed to intubation and required 100% FiO2, high positive-end expiratory pressure (PEEP) and intermittent-prone ventilation for 48 h but eventually recovered and was extubated. TRALI is an under-recognised aetiology for respiratory distress in the critically ill. Adopting a conservative transfusion strategy may prevent TRALI.

1057: Survey of intensivists shows variability in the use of steroids in septic shock

Introduction: Contradictory evidence regarding the use of low dose steroids in septic shock is a challenge for physicians. Recent published guidelines attempt to address this, yet leave clinicians with recommendations that are subject to interpretation. Methods: The purpose of this study was to pilo