Circadian rhythms in pump parameters of patients on contemporary left ventricular assist device support

Background: Algorithms to monitor pump parameters are needed to further improve outcomes after left ventricular assist device (LVAD) implantation. Previous research showed a restored circadian rhythm in pump parameters in patients on HeartWare (HVAD) support. Circadian patterns in HeartMate3 (HM3) were not studied before, but this is important for the development of LVAD monitoring algorithms. Hence, we aimed to describe circadian patterns in HM3 parameters and their relation to patterns in heart rate (HR). Methods: 18 HM3 patients were included in this study. HM3 data were retrieved at a high frequency (one sample per 1 or 2 h) for 1–2 weeks. HR was measured using a wearable biosensor. To study overall patterns in HM3 parameters and HR, a heatmap was created. A 24-h cosine was fitted on power and HR separately. The relationship between the amplitude of the fitted cosines of power and HR was calculated using Spearman correlation. Results: A lower between patient variability was found in power compared with flow and PI. 83% of the patients showed a significant circadian rhythmicity in power (p < 0.001–0.04), with a clear morning increase. All patients showed significant circadian rhythmicity in HR (p < 0.001–0.02). The amplitudes of the circadian rhythm in power and HR were not correlated (Spearman correlation of 0.32, p = 0.19). Conclusions: A circadian rhythm of pump parameters is present in the majority of HM3 patients. Higher frequency pump parameter data should be collected, to enable early detection of complications in the future development of predictive algorithms

Cohort profile: the Utrecht Cardiovascular Cohort-Second Manifestations of Arterial Disease (UCC-SMART) Study-an ongoing prospective cohort study of patients at high cardiovascular risk in the Netherlands

PURPOSE: The Utrecht Cardiovascular Cohort-Second Manifestations of Arterial Disease (UCC-SMART) Study is an ongoing prospective single-centre cohort study with the aim to assess important determinants and the prognosis of cardiovascular disease progression. This article provides an update of the rationale, design, included patients, measurements and findings from the start in 1996 to date. PARTICIPANTS: The UCC-SMART Study includes patients aged 18-90 years referred to the University Medical Center Utrecht, the Netherlands, for management of cardiovascular disease (CVD) or severe cardiovascular risk factors. Since September 1996, a total of 14 830 patients have been included. Upon inclusion, patients undergo a standardised screening programme, including questionnaires, vital signs, laboratory measurements, an ECG, vascular ultrasound of carotid arteries and aorta, ankle-brachial index and ultrasound measurements of adipose tissue, kidney size and intima-media thickness. Outcomes of interest are collected through annual questionnaires and adjudicated by an endpoint committee. FINDINGS TO DATE: By May 2022, the included patients contributed to a total follow-up time of over 134 000 person-years. During follow-up, 2259 patients suffered a vascular endpoint (including non-fatal myocardial infarction, non-fatal stroke and vascular death) and 2794 all-cause deaths, 943 incident cases of diabetes and 2139 incident cases of cancer were observed up until January 2020. The UCC-SMART cohort contributed to over 350 articles published in peer-reviewed journals, including prediction models recommended by the 2021 European Society of Cardiology CVD prevention guidelines. FUTURE PLANS: The UCC-SMART Study guarantees an infrastructure for research in patients at high cardiovascular risk. The cohort will continue to include about 600 patients yearly and follow-up will be ongoing to ensure an up-to-date cohort in accordance with current healthcare and scientific knowledge. In the near future, UCC-SMART will be enriched by echocardiography, and a food frequency questionnaire at baseline enabling the assessment of associations between nutrition and CVD and diabetes

Activation of TRPC6 channels is essential for lung ischaemia–reperfusion induced oedema in mice

Lung ischaemia–reperfusion-induced oedema (LIRE) is a life-threatening condition that causes pulmonary oedema induced by endothelial dysfunction. Here we show that lungs from mice lacking nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox2y/−) or the classical transient receptor potential channel 6 (TRPC6−/−) are protected from LIR-induced oedema (LIRE). Generation of chimeric mice by bone marrow cell transplantation and endothelial-specific Nox2 deletion showed that endothelial Nox2, but not leukocytic Nox2 or TRPC6, are responsible for LIRE. Lung endothelial cells from Nox2- or TRPC6-deficient mice showed attenuated ischaemia-induced Ca2+ influx, cellular shape changes and impaired barrier function. Production of reactive oxygen species was completely abolished in Nox2y/− cells. A novel mechanistic model comprising endothelial Nox2-derived production of superoxide, activation of phospholipase C-γ, inhibition of diacylglycerol (DAG) kinase, DAG-mediated activation of TRPC6 and ensuing LIRE is supported by pharmacological and molecular evidence. This mechanism highlights novel pharmacological targets for the treatment of LIRE

Exogenous surfactant application in a rat lung ischemia reperfusion injury model: effects on edema formation and alveolar type II cells

<p>Abstract</p> <p>Background</p> <p>Prophylactic exogenous surfactant therapy is a promising way to attenuate the ischemia and reperfusion (I/R) injury associated with lung transplantation and thereby to decrease the clinical occurrence of acute lung injury and acute respiratory distress syndrome. However, there is little information on the mode by which exogenous surfactant attenuates I/R injury of the lung. We hypothesized that exogenous surfactant may act by limiting pulmonary edema formation and by enhancing alveolar type II cell and lamellar body preservation. Therefore, we investigated the effect of exogenous surfactant therapy on the formation of pulmonary edema in different lung compartments and on the ultrastructure of the surfactant producing alveolar epithelial type II cells.</p> <p>Methods</p> <p>Rats were randomly assigned to a control, Celsior (CE) or Celsior + surfactant (CE+S) group (n = 5 each). In both Celsior groups, the lungs were flush-perfused with Celsior and subsequently exposed to 4 h of extracorporeal ischemia at 4°C and 50 min of reperfusion at 37°C. The CE+S group received an intratracheal bolus of a modified natural bovine surfactant at a dosage of 50 mg/kg body weight before flush perfusion. After reperfusion (Celsior groups) or immediately after sacrifice (Control), the lungs were fixed by vascular perfusion and processed for light and electron microscopy. Stereology was used to quantify edematous changes as well as alterations of the alveolar epithelial type II cells.</p> <p>Results</p> <p>Surfactant treatment decreased the intraalveolar edema formation (mean (coefficient of variation): CE: 160 mm³(0.61) vs. CE+S: 4 mm³(0.75); p < 0.05) and the development of atelectases (CE: 342 mm³(0.90) vs. CE+S: 0 mm³; p < 0.05) but led to a higher degree of peribronchovascular edema (CE: 89 mm³(0.39) vs. CE+S: 268 mm³(0.43); p < 0.05). Alveolar type II cells were similarly swollen in CE (423 μm³(0.10)) and CE+S (481 μm³(0.10)) compared with controls (323 μm³(0.07); p < 0.05 vs. CE and CE+S). The number of lamellar bodies was increased and the mean lamellar body volume was decreased in both CE groups compared with the control group (p < 0.05).</p> <p>Conclusion</p> <p>Intratracheal surfactant application before I/R significantly reduces the intraalveolar edema formation and development of atelectases but leads to an increased development of peribronchovascular edema. Morphological changes of alveolar type II cells due to I/R are not affected by surfactant treatment. The beneficial effects of exogenous surfactant therapy are related to the intraalveolar activity of the exogenous surfactant.</p