The integration of cerebral oximetry into cardiac arrest resuscitation provides a novel noninvasive method to determine the quality of cerebral perfusion and oxygen delivery to the brain. The use of automated mechanical chest compression device during in-hospital cardiac arrest may lead to improved oxygen delivery and organ perfusion.
Rationale Cardiovascular disease is the leading cause of death world-wide. Macrophages are crucial in regulating the plaque environment, especially the lipid content. However, current characterisation of macrophage phenotypes lipoprotein handling capacity is conflicting and incomplete. We hypothesised that lipoprotein handling differed among distinct macrophage phenotypes due to differential gene and protein expression. We tested this using a range of functional, gene and protein expression assays. Methodology Monocytes were isolated from healthy donor blood by gradient centrifugation and magnetic selection, then differentiated into macrophages over 7 days using M-CSF. Macrophages were polarised over 24 hour by IFNg+LPS, IL-4, IL-10, oxPAPC (oxidised phospholipid) and CXCL4, respectively. Unpolarised macrophages were used as controls.Foam cell formation was determined by Oil-Red-O staining and acLDL uptake was detected by flow cytometry. Cholesterol content and efflux were measured using colorimetric and fluorescent assays. RNA expression was determined by RNAseq and qRT-PCR and cell surface protein expression was measured by flow cytometry. Results IFNÃ□³+LPS macrophages did not readily form foam cells (0.23 compared to unpolarised) or process lipoprotein particles, whereas IL-4 and IL-10 polarised macrophages displayed the highest capacity in foam cell formation (1.02 and 1.08 compared to unpolarised) and lipoprotein handling. OxPAPC macrophages exhibited lipoprotein processing capabilities similar to IL-4 and IL-10 macrophages, but did not readily form foam cells (0.22 compared to unpolarised Heterozygous germline mutations in the gene encoding type II bone morphogenetic protein receptor (BMPRII) underlie the majority (~80%) of the familial form of pulmonary arterial hypertension (HPAH).1 PAH is a devastating cardiovascular disorder caused by narrowing of blood vessels in the lungs. We earlier demonstrated that mutations in BMPR2 impinge upon the BMP signalling pathway and potentiate the TGF-b² signalling leading to abnormal proliferation and apoptosis resistance of endothelial and pulmonary arterial smooth muscle cells (PASMCs). 2,3 No cure for this disorder is known. Traditional therapies aim to improve cardiopulmonary function and were established before recognising the involvement of substantial genetic components of PAH. Hence, there is an urgent need to identify novel compounds capable of providing therapeutic intervention prior to or following the onset of disease.High-throughput cell based BMP-responsive screens were carried out, which identified several natural compounds as hits. The hit compounds were optimised through a medicinal chemistry programme. These compounds were tested in a number of cell based experiments including reporter assays, gene expression studies and western blot analyses. The compounds CRT-01, CRT-02 and CRT-03 enhanced BMP signalling in BMP responsive reporter assays. Moreover, these compounds were able to induce BMP responsive id1 gene expression and increased the phosphoryla...
Introduction:
Over 15,000 incidences of Calcium Channel Blocker (CCB) overdose were reported by the American Association of Position Control Centers (AAPCC) in 2020, resulting in 45 deaths from pure CCB overdose and 176 deaths from multidrug overdose involving CCBs. We present a single-center experience on the use of VA ECMO in the management of refractory hypotension due to CCB toxicity.
Hypothesis:
VA ECMO is effective and can be life-saving in vasoplegic shock from drug overdose
Methods:
We retrospectively reviewed our ECMO registry in the last 5 years to identify patients who were started on ECMO support for refractory hypotension due to drug overdose.
Results:
We found 5 patients who were started on VA-ECMO for drug overdose, all involving CCBs. Mean age was 60. They had persistent lactic acidosis and hypotension after fluid resuscitation, requiring escalating doses of vasopressors until they were on or near the maximum. All patients were started on hyperinsulinemia euglycemic protocol and 3 patients received methylene blue. The mean time to intubation was 11.2 ± 4.14 hours. An echocardiogram demonstrated intact systolic function in all patients. VA-ECMO was started within 11.2 ± 4.5 hours of admission. Pressor requirements quickly improved on ECMO support. Average time on ECMO was 69 ± 48.6 hours. 4 of 5 patients improved quickly and were extubated within 10 days (mean: 4.88 ± 2.95). In these 4 patients, the length of ICU stay was 8.5 ± 3.87 days, and hospital stay was 11.75 ± 2.06 days. One patient had a protracted course due to renal failure, pneumonia, and concern for North-South Syndrome. Cannulation was switched to subclavian/axillary approach, but that was complicated by left arm ischemia and switch to VV-ECMO after 44 hours of VA-ECMO. She was discharged after a 46-day hospital stay.
Conclusions:
VA-ECMO support is effective and lifesaving in patients with refractory shock from CCB toxicity. Early referral to ECMO capable center should be considered in these patients.
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