Effect of mechanical power on mortality in invasively ventilated ICU patients without the acute respiratory distress syndrome: An analysis of three randomised clinical trials.

Background: The mechanical power of ventilation (MP) has an association with outcome in invasively ventilated patients with the acute respiratory distress syndrome (ARDS). Whether a similar association exists in invasively ventilated patients without ARDS is less certain.

Objective: To investigate the association of mechanical power with mortality in ICU patients without ARDS.

Associations of dynamic driving pressure and mechanical power with postoperative pulmonary complications-posthoc analysis of two randomised clinical trials in open abdominal surgery.

Background: While an association of the intraoperative driving pressure with postoperative pulmonary complications has been described before, it is uncertain whether the intraoperative mechanical power is associated with postoperative pulmonary complications.

Methods: Posthoc analysis of two international, multicentre randomised clinical trials (ISRCTN70332574 and NCT02148692) conducted between 2011-2013 and 2014-2018, in patients undergoing open abdominal surgery comparing the effect of two different positive end-expiratory pressure (PEEP) levels on postoperative pulmonary complications. Time-weighted average dynamic driving pressure and mechanical power were calculated for individual patients.

Association of Time-Varying Intensity of Ventilation With Mortality in Patients With COVID-19 ARDS: Secondary Analysis of the PRoVENT-COVID Study.

High intensity of ventilation has an association with mortality in patients with acute respiratory failure. It is uncertain whether similar associations exist in patients with acute respiratory distress syndrome (ARDS) patients due to coronavirus disease 2019 (COVID-19). We investigated the association of exposure to different levels of driving pressure (ΔP) and mechanical power (MP) with mortality in these patients.

Association of intensity of ventilation with 28-day mortality in COVID-19 patients with acute respiratory failure: insights from the PRoVENT-COVID study.

Background: The intensity of ventilation, reflected by driving pressure (ΔP) and mechanical power (MP), has an association with outcome in invasively ventilated patients with or without acute respiratory distress syndrome (ARDS). It is uncertain if a similar association exists in coronavirus disease 2019 (COVID-19) patients with acute respiratory failure.

Methods: We aimed to investigate the impact of intensity of ventilation on patient outcome.

Mortality associated with early changes in ARDS severity in COVID-19 patients - Insights from the PRoVENT-COVID study.

Purpose: We investigated changes in ARDS severity and associations with outcome in COVID-19 ARDS patients.

Methods: We compared outcomes in patients with ARDS classified as 'mild', 'moderate' or 'severe' at calendar day 1, and after reclassification at calendar day 2. The primary endpoint was 28-day mortality.

Validity of free testosterone calculation in pregnant women.

Objective Increased maternal testosterone concentration during pregnancy may affect the fetus. Therefore it is clinically relevant to have a quick and reliable method to determine free testosterone levels. Current calculators for free testosterone are suspected to perform poorly during pregnancy due to suggested competition between high levels of estradiol and free (bio-active) testosterone for sex hormone-binding globulin (SHBG) binding.

Diagnostic error as a result of drug-laboratory test interactions.

Background Knowledge of possible drug-laboratory test interactions (DLTIs) is important for the interpretation of laboratory test results. Test results may be affected by physiological or analytical drug effects. Failure to recognize these interactions may lead to misinterpretation of test results, a delayed or erroneous diagnosis or unnecessary extra tests or therapy, which may harm patients.

Impact of interactions between drugs and laboratory test results on diagnostic test interpretation - a systematic review.

Intake of drugs may influence the interpretation of laboratory test results. Knowledge and correct interpretation of possible drug-laboratory test interactions (DLTIs) is important for physicians, pharmacists and laboratory specialists. Laboratory results may be affected by analytical or physiological effects of medication.

Healthcare seeking behaviour of students living on their own compared to those living in the parental home: a cross-sectional study.

Objective This study aimed to investigate differences in healthcare seeking behaviour and barriers between students living in the parental home and those living on their own. Participants Five hundred and six second year students of the University of Amsterdam (UvA), interviewed in March and April 2015. Methods In a paper-and-pencil survey, questions were asked about the students' healthcare seeking behaviour and barriers.

Mortality in pulmonary arterial hypertension due to congenital heart disease: Serial changes improve prognostication.

Background: Adult patients with pulmonary arterial hypertension due to congenital heart disease (PAH-CHD) suffer from high mortality. This underlines the importance of adequate risk stratification to guide treatment decisions. Several baseline parameters are associated with mortality, however, their prognostic value may weaken after years of follow-up.

The influence of oral contraceptives on overnight 1 mg dexamethasone suppression test.

Background: In suspected hypercortisolism, the 1 mg dexamethasone suppression test is the usual initial test. In fertile women, false-positive test results are often due to the use of oral contraceptives. By elevating cortisol-binding globulin these contraceptives increase the total serum cortisol concentration.

The interaction of ibuprofen and diclofenac with aspirin in healthy volunteers.

Background And Purpose: Aspirin reduces the risk of myocardial infarction and stroke by inhibiting thromboxane production in platelets. This inhibition can be competitively antagonized by some non-steroidal anti-inflammatory drugs (NSAIDs).

Experimental Approach: By measuring thromboxane B(2) production in healthy volunteers, we investigated whether ibuprofen (800 mg three times daily for 7 days) or diclofenac (50 mg three times daily for 7 days) taken concurrently with aspirin 80 mg (once daily for 7 days) influenced the inhibitory effect of aspirin.

AT2 receptor-mediated vasodilation in the mouse heart depends on AT1A receptor activation.

Angiotensin (Ang) II type 2 (AT(2)) receptors are believed to counteract Ang II type 1 (AT(1)) receptor-mediated effects. Here, we investigated AT(2) receptor-mediated effects on coronary and cardiac contractility in C57BL/6 mice. Hearts were perfused according to Langendorff.

Angiotensin II type 2 receptor-mediated vasodilation. Focus on bradykinin, NO and endothelium-derived hyperpolarizing factor(s).

Angiotensin (Ang) II type 1 (AT(1)) receptors account for the majority of the cardiovascular effects Ang II, including vasoconstriction and growth stimulation. Recent evidence, mainly obtained in animals, suggests that Ang II type 2 (AT(2)) receptors counteract some or all of these effects. This review summarizes the current knowledge on the vasodilator effects induced by AT(2) receptors in humans and animals, focussing not only on the mediators of this effect, but also on the modulatory role of age, gender, and endothelial function.

Effects of the calcitonin gene-related peptide (CGRP) receptor antagonist BIBN4096BS on alpha-CGRP-induced regional haemodynamic changes in anaesthetised rats.

Several studies suggest that a calcitonin gene-related peptide (CGRP) receptor antagonist may have antimigraine properties, most probably via the inhibition of CGRP-induced cranial vasodilatation. We recently showed that the novel selective CGRP receptor antagonist, BIBN4096BS (1-piperidinecarboxamide, -N-[2-[[5-amino-1-[[4-(4-pyridinyl)-1-piperazinyl] carbonyl] pentyl]amino]-1-[(3,5-dibromo-4-hydroxyphenyl) methyl]-2-oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quinazolinyl)-, [[R-(R,(R*,S*)]), attenuated the CGRP-induced porcine carotid vasodilatation in a model predictive of antimigraine activity. In order to evaluate the potential safety of BIBN4096BS in migraine therapy, this study was designed to investigate the effects of intravenous BIBN4096BS on alpha-CGRP-induced systemic and regional haemodynamic changes in anaesthetised rats, using radioactive microspheres.

Superoxide does not mediate the acute vasoconstrictor effects of angiotensin II: a study in human and porcine arteries.

Objective: To investigate whether superoxide mediates angiotensin (Ang) II-induced vasoconstriction.

Methods: Human coronary arteries (HCAs), porcine femoral arteries (PFA) and porcine coronary arteries (PCAs) were mounted in organ baths and concentration-response curves to Ang II, the nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine (SNAP) and the NAD(P)H oxidase substrate NADH were constructed in the absence and presence of superoxide inhibiting and activating drugs. Extracellular superoxide was measured using cytochrome c reduction.

Cardiac angiotensin II: an intracrine hormone?

The beneficial effects of renin-angiotensin system blockers on cardiac structure and function are usually explained based on the capacity of these drugs to interfere with angiotensin II at cardiac tissue sites. This review addresses to what degree cardiac angiotensin II generation occurs independently of the circulating renin-angiotensin system, and in particular tries to unravel where such generation might take place, taking into consideration that many reports suggest that angiotensin II is an intracrine hormone (ie, a hormone that is synthesized and acts intracellularly). It concludes that angiotensin II generation in the heart depends on circulating (ie, kidney-derived) renin, and occurs in interstitial fluid and possibly, in view of the recent discovery of renin-binding sites, on the cell surface of cardiac cells.

The role of locally expressed angiotensin converting enzyme in cardiac remodeling after myocardial infarction in mice.

Objective: Angiotensin II, generated from angiotensin I by angiotensin converting enzyme (ACE), induces multiple effects including vasoconstriction, positive cardiac inotropy, hypertrophy of cardiomyocytes and proliferation of fibroblasts. ACE exists both in a tissue-bound (t-ACE) and a soluble form. The functional importance of locally produced angiotensin II is still unclear.

Vasoconstriction is determined by interstitial rather than circulating angiotensin II.

1. We investigated why angiotensin (Ang) I and II induce vasoconstriction with similar potencies, although Ang I-II conversion is limited. 2.

AT(2) receptor-mediated vasodilation in the heart: effect of myocardial infarction.

To investigate the functional consequences of postinfarct cardiac angiotensin (ANG) type 2 (AT(2)) receptor upregulation, rats underwent coronary artery ligation or sham operation and were infused with ANG II 3-4 wk later, when scar formation is complete. ANG II increased mean arterial pressure (MAP) more modestly in infarcted animals than in sham animals. The AT(1) receptor antagonist irbesartan, but not the AT(2) receptor antagonist PD123319, decreased MAP and antagonized the ANG II-mediated systemic hemodynamic effects.

Prostanoids, but not nitric oxide, counterregulate angiotensin II mediated vasoconstriction in vivo.

To evaluate the modulating effects of nitric oxide and prostanoids during angiotensin II-mediated vasoconstriction, male Wistar rats (n=25) were infused with increasing doses of angiotensin II following pretreatment with the cyclooxygenase inhibitor indomethacin, the nitric oxide-synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) plus sodium nitroprusside to restore mean arterial blood pressure, or saline. Hemodynamics were studied with the radioactive microsphere method. Indomethacin did not alter systemic or regional hemodynamics.

Angiotensin converting enzyme is the main contributor to angiotensin I-II conversion in the interstitium of the isolated perfused rat heart.

Objectives: Recent studies in homogenized hearts suggest that chymase rather than angiotensin converting enzyme (ACE) is responsible for cardiac angiotensin I to angiotensin II conversion. We investigated in intact rat hearts whether (i) enzymes other than ACE contribute to angiotensin I to angiotensin II conversion and (ii) the localization (endothelial/extra-endothelial) of converting enzymes.

Design And Methods: We used a modified version of the rat Langendorff heart, allowing separate collection of coronary effluent and interstitial fluid.

Angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade prevent cardiac remodeling in pigs after myocardial infarction: role of tissue angiotensin II.

Background: The mechanisms behind the beneficial effects of renin-angiotensin system blockade after myocardial infarction (MI) are not fully elucidated but may include interference with tissue angiotensin II (Ang II).

Methods And Results: Forty-nine pigs underwent coronary artery ligation or sham operation and were studied up to 6 weeks. To determine coronary angiotensin I (Ang I) to Ang II conversion and to distinguish plasma-derived Ang II from locally synthesized Ang II, (125)I-labeled and endogenous Ang I and II were measured in plasma and in infarcted and noninfarcted left ventricle (LV) during (125)I-Ang I infusion.