Progressive Hypoxia Research Articles

FETAL HYPOXIA AS A CAUSE OF UNVAFOURABLE PREGNANCY OUTCOMES: A SYSTEMATIC REVIEW OF ASSESSMENT METHODS

Hypoxia is one of the most frequent and serious types of stress for the human body. Hypoxia during pregnancy has adverse effects on fetal that may have implications not only for antenatal, but also postnatal period and even adulthood. Hypoxia usually occurs due to the placental insufficiency - a process in which there is a progressive decrease of the placental functions, when the transfer of oxygen and nutrients to the fetus through the placenta decreases, which leads to hypoxia and acidosis. Subsequent fetal hypoxemia stimulates the suppression of metabolic responses to preserve available nutrients, resulting in fetal growth restriction. This article presents an overview of modern scientific literature considering an etiology and pathophysiology of fetal hypoxia. Special attention is paid on the methods of evaluating fetal hypoxia in obstetric practice, such as Doppler, measuring lactate from fetal scalp blood testing, CTG monitoring, detection of RNA caused by hypoxia in maternal blood, measurement of the pH of the umbilical cord vessels, ECG-STan, fetal pulsoximetry. A new parameter for assessing the condition of the fetus, called the "non-reassuring fetal status" was observed, and the diagnostic criteria were described thoroughly. This systematic review presents a qualitative analysis of diagnostic methods and predictors of the outcome of pregnancies with acute and progressive fetal hypoxia. The study includes full-text publications in Russian and English on the methods of assessing the state of fetal hypoxia during pregnancy and childbirth, as well as their validity. In total, 548 sources were identified in PubMed, SCOPUS and eLIBRARY.RU databases. After screening, 53 articles were selected and included in the qualitative synthesis.

Hypoxia Performance Curve: Assess a Whole-Organism Metabolic Shift from a Maximum Aerobic Capacity towards a Glycolytic Capacity in Fish.

The utility of measuring whole-animal performance to frame the metabolic response to environmental hypoxia is well established. Progressively reducing ambient oxygen (O2) will initially limit maximum metabolic rate as a result of a hypoxemic state and ultimately lead to a time-limited, tolerance state supported by substrate-level phosphorylation when the O2 supply can no longer meet basic needs (standard metabolic rate, SMR). The metabolic consequences of declining ambient O2 were conceptually framed for fishes initially by Fry’s hypoxic performance curve, which characterizes the hypoxemic state and its consequences to absolute aerobic scope (AAS), and Hochachka’s concept of scope for hypoxic survival, which characterizes time-limited life when SMR cannot be supported by O2 supply. Yet, despite these two conceptual frameworks, the toolbox to assess whole-animal metabolic performance remains rather limited. Here, we briefly review the ongoing debate concerning the need to standardize the most commonly used assessments of respiratory performance in hypoxic fishes, namely critical O2 (the ambient O2 level below which maintenance metabolism cannot be sustained) and the incipient lethal O2 (the ambient O2 level at which a fish loses the ability to maintain upright equilibrium), and then we advance the idea that the most useful addition to the toolbox will be the limiting-O2 concentration (LOC) performance curve. Using Fry & Hart’s (1948) hypoxia performance curve concept, an LOC curve was subsequently developed as an eco-physiological framework by Neil et al. and derived for a group of fish during a progressive hypoxia trial by Claireaux and Lagardère (1999). In the present review, we show how only minor modifications to available respirometry tools and techniques are needed to generate an LOC curve for individual fish. This individual approach to the LOC curve determination then increases its statistical robustness and importantly opens up the possibility of examining individual variability. Moreover, if peak aerobic performance at a given ambient O2 level of each individual is expressed as a percentage of its AAS, the water dissolved O2 that supports 50% of the individual’s AAS (DOAAS-50) can be interpolated much like the P50 for an O2 hemoglobin dissociation curve (when hemoglobin is 50% saturated with O2). Thus, critical O2, incipient lethal O2, DOAAS-50 and P50 and can be directly compared within and across species. While an LOC curve for individual fish represents a start to an ongoing need to seamlessly integrate aerobic to anaerobic capacity assessments in a single, multiplexed respirometry trial, we close with a comparative exploration of some of the known whole-organism anaerobic and aerobic capacity traits to examine for correlations among them and guide the next steps.

A Comparative Assessment of Effects of Major Mediators ofAcute Phase Response (IL-1, TNF-α, IL-6) on Breathing Pattern and Survival Rate in Rats with Acute Progressive Hypoxia.

A pressing issue of the day is the identification of therapeutic targets to suppress the “cytokine storm” in COVID-19 complicated by acute respiratory distress syndrome (ARDS) with concomitant hypoxemia. However, the key cytokine and its relative contribution to the pathogenesis of ARDS, which leads to high mortality, are unknown. A comparative assessment of the effect of elevated systemic levels of pro-inflammatory cytokines IL-1β, TNF-1α and IL-6 on the respiratory patterns and survival rate in rats was carried out under progressively increasing acute hypoxia. Increasing hypoxia was simulated by a rebreathing method (from normoxia to apnea). The recorded parameters were the breathing pattern components (tidal volume and respiratory rate), minute ventilation (MV), oxygen saturation, apnea onset time, and posthypoxic survival rate. A comparative analysis was carried out under mild, moderate and severe hypoxia (at FIO2 = 15, 12 and 8%, respectively). It was shown that increasing hypoxia was accompanied by an acute suppression of the compensatory elevation of MV in rats with increased systemic levels of IL-1β and TNF-1α. By contrast, IL-6 caused an intensive elevation of MV with increasing hypoxia. Acute hypoxia (FIO2 < 8%), in all experimental series, was accompanied by an impairment of the respiratory rhythm up to the development of apnea. Posthypoxic breathing restoration (survival rate) was 50% with IL-1β and TNF-1α and only 10% with IL-6. The obtained results indicate that the elevated IL-6 level, despite the absence of respiratory disorders at the initial stage of the developing pathologic process, leads to a higher mortality in rats compared to IL-1β and TNF-1α. This allows considering IL-6 as an early prognostic biomarker of a high risk of mortality under severe hypoxemia.

Oropharyngeal Dysphagia with Aspiration as a Provoking Factor for COPD Exacerbation

The most common provoking factors for chronic Obstructive Pulmonary Disease (COPD) exacerbation include viral and bacterial tracheobronchitis, pneumonia, and exposure to environmental irritants and air pollution. In many patients with COPD exacerbation, the underlying cause cannot be identified. In general, patients with COPD exacerbation get admitted to the hospital and treated with antibiotics, glucocorticoids and inhaled bronchodilators. Oropharyngeal dysphagia is an under-recognized provoking factor for COPD exacerbation. Patients with advanced COPD often have impaired coordination of respiration and deglutition which can lead to aspiration of liquids, food particles, and saliva into the airways. Aspiration events can lead to exacerbation of symptoms and cause further decline in lung function. We described a 69-year-old male with a history of COPD who presented with progressive dyspnea, productive cough and hypoxia which required intubation and mechanical ventilation. The patient underwent a bronchoscopy for airway inspection which showed pieces of meat in the right main bronchus which were removed. Reportedly, the patient was having difficulty swallowing solid food prior to admission to the hospital.

Improving outcomes in opioid-associated cardiac arrest

Improving outcomes in opioid-associated cardiac arrest

Altered physiological response and gill histology in black rockfish, Sebastes schlegelii, during progressive hypoxia and reoxygenation.

Hypoxia has gradually become common in aquatic ecosystems and imposes a significant challenge for fish farming. The loss of equilibrium (LOE), 50% lethal time (LT50), plasma cortisol, glucose, red blood cells (RBC), hemoglobin (Hb), gill histological alteration, and related parameters (lamellar length [SLL] and width [SLW], interlamellar distance [ID], basal epithelial thickness [BET], lamellar surface area [LA], and gill surface area [GSA]); respiratory rate; the proportion of the secondary lamellae available for gas exchange (PAGE); and hypoxia-inducible factor (hif-1α, hif-2α) mRNA expression were determined during progressive hypoxia and reoxygenation (R-0, R-12, R-24h) to illustrate the underlying physiological response mechanisms in black rockfish Sebastes schlegelii. Results showed that the DO concentration significantly decreased during progressive hypoxia, while DO at LOE and LT50 were 2.42 ± 0.10mg L-1 and 1.67 ± 0.38mg L-1, respectively. Cortisol and glucose were significantly increased at LOE and LT50, with the highest levels observed at LT50, and then gradually recovered to normal within reoxygenation 24h. RBC number and Hb results were like those of glucose. Hypoxia stress resulted in lamellar clubbing, hypertrophy, and hyperplasia. Respiratory frequency significantly increased at LOE and decreased at LT50. Lamellar perimeters, SLL, ID, LA, GSA, and PAGE, significantly increased at LOE and LT50, with the highest values observed at LT50. However, SLW and BET significantly decreased at LOE, LT50, and R-0. These parameters recovered to nearly normal levels at R-24h. hif-1α mRNAs in gill and liver were significantly upregulated at LOE and LT50, and recovery to normal after reoxygenation 24h. hif-2α mRNAs in gill was similar to that of hif-1α, whereas hepatic hif-2α mRNAs remained unchanged during hypoxia-reoxygenation. These results indicated that progressive hypoxia stress elevated RBC number, Hb, cortisol, and glucose levels, induced the alteration of gill morphology, increased LA and GSA, stimulated respiratory frequency and PAGE, and upregulated the transcription of hif-1α and hif-2α in gill and liver. Reoxygenation treatment for 24h alleviated the stress mentioned above effects. These findings expand current knowledge on hypoxia tolerance in black rockfish Sebastes schlegelii.

Large Invasive Adrenal Cortical Carcinoma in a Patient With Neurofibromatosis Type I

Background: Adrenal cortical carcinoma is a rare neoplasm. Adrenal cortical carcinoma has previously been reported in less than 10 cases of patients with Neurofibromatosis Type I. Clinical Case: A 44-year-old Hispanic man with Neurofibromatosis Type I (NF1) presented with progressive hypoxia, tachypnea and abdominal pain. Intubation was required with 100% FiO2. CT angiogram of the chest and abdomen showed a 9.5 cm left adrenal mass with tumor thrombus in the left adrenal vein, distal left renal vein, IVC extending into the right atrium, suggestive of an adrenocortical carcinoma. Café-au-spots, neurofibromas and Lisch nodules were seen on physical exam but no signs suggestive of a functional adrenal cortical carcinoma. Transthoracic echocardiogram demonstrated a large well circumscribed echo-dense mass filling the right atrial cavity. Hemodynamically he was unstable with labile blood pressures due to right atrium thrombus burden. He was supported pending pheochromocytoma investigation. Biochemical work up revealed an elevated 24-hour free cortisol concentration of 95.9 ug/d (<=60ug/d) with a normal 24-hour urine metanephrine and normetanephrine [140ug/d (55-320ug/d) and 448 ug/d (114-865ug/d]. Plasma free metanephrine level was normal 0.43 (0.00-0.49nmol/L) and the normetanephrine levels was increased at 2.7 (0.00-0.89nmol/L) consistent with stress response. Serum aldosterone level and renin activity with potassium and DHEA-S levels were normal. Once pheochromocytoma was ruled out, he successfully underwent a left nephrectomy, left adrenalectomy, IVC thrombectomy, right atrium thrombectomy under a multidisciplinary team of surgeons. Surgery was well tolerated and he was discharged home 11 days later. Pathology confirmed adrenal cortical carcinoma, stage 4, with involvement of endocardium and left renal vein with mitotic count greater than 20/50 high-power fields, consistent with a high-grade tumor. Summary: Patients with NF1 have a higher predilection to develop tumors including pheochromocytoma, paraganglioma, gastrointestinal stromal tumor, and pancreatic neuroendocrine tumor. NF1 association with adrenal tumors is well known, most commonly pheochromocytomas which occur in 0.1–5.7% of patients with NF1. However, based on a literature search there have been less than 10 case reports which postulate an association between NF1 and ACC. Genetic analysis of these reported cases suggest a loss of heterozygosity at the NF1 locus as a possible explanation of development of ACC in patients with NF1. Conclusion: Adrenal cortical carcinoma is rare but should be considered in a patient with NF1 and adrenal mass when plasma/urine metanephrines are not suggestive of pheochromocytoma.

Hypoxia: Progressive Multiple Myeloma and Its Therapy Resistance

This study critically reviews the role of hypoxia in the progression of Multiple Myeloma (MM) and its therapy resistance. It explains the existence and role played by Hypoxia Inducible Factors (HIF) including HIF-1α and HIF-β in tumor (MM) progression. These HIF are key transcription factors of hypoxia and they aid the cellular adaptation of both normal and cancer cells to reduction in oxygen concentration. At initial stage of MM, the bone marrow environment sufficiently supports the growth and survival of the MM cells, but as the disease progresses and the plasma cells goes deeper into the bone marrow, they experience a more hypoxic condition. This then activates HIF1 and HIF-2 which ultimately stimulates angiogenic factors. This is a description of the step by step approaches through which a review of Hypoxia: progressive multiple myeloma and its drug resistance was conducted using Google scholar and PubMed search engines to search articles published from 2000 to May 2020 using the following key words: hypoxia, progressive multiple myeloma, treatment resistance, hypoxia and multiple myeloma. This review suggests that agents capable of inhibiting the action of HIF’s, as well as those that would act specifically on the hypoxic zones will be helpful in minimizing/eliminating drug resistance and relapses in MM patients and would invariably improves the patient life expectancy.

Determinants of response to hypercapnia and to progressive and transient hypoxia in obstructive sleep apnea patients.

The knowledge regarding the control of breathing during wakefulness in patients affected by obstructive sleep apnea (OSAS) is still challenging. The aim of this study is firstly to analyze hypoxic and hypercapnic ventilatory response in OSA patients in comparison to controls and secondly, to investigate correlations between chemosensivity and both lung function tests, such as arterial blood gas analysis and spirometric parameters, and clinical characteristics, such as age and BMI. Seventeen never treated OSA patients (16M; 53±13.2 years; BMI=34.5±8.1; AHI=45±14.7) underwent nocturnal cardiopulmonary monitoring test, complete lung function tests (spirometry, lung volumes and arterial blood gas analysis on room air). Read's rebreathing test was used to evaluate hypercapnic ventilatory response (HVR<inf>CO2</inf>); hypoxic ventilatory response (HVR<inf>O2</inf>) was studied through progressive and transient methods. The response was expressed in terms of slope of linear regression for HVR<inf>CO2</inf> and of hyperbolic curve for HVR<inf>O2</inf> between minute ventilation (VE) or mean inspiratory flow (VT/Ti) and PetCO<inf>2</inf> or PetO<inf>2</inf>. The OSA group showed increased transient, but not progressive, HVR<inf>O2</inf> and a lower HVR<inf>CO2</inf>. A lower HVR<inf>CO2</inf> was predicted by greater values of BMI (P<0.01). Progressive HVR<inf>O2</inf> increased with age and lower FEV<inf>1</inf>/VC, while transient HVR<inf>O2</inf> (P<0.05) was inversely correlated with the nocturnal lowest SaO<inf>2</inf> (P<0.01). Nocturnal intermittent hypoxic stimuli increases daytime glomic reactivity to transient hypoxia, while BMI is the main independent determinants of the bulbar response to hypercapnia in normocapnic OSAS patients.

Mechanical Ventilation and Coronavirus Disease 2019: A Case-Control Analysis of Clinical Characteristics, Lung Mechanics, and Mortality.

Objectives:To investigate the differences in clinical course, ventilator mechanics, and outcomes of patients with coronavirus disease 2019 secondary to acute respiratory distress syndrome infection compared with a historical cohort of acute respiratory distress syndrome.Design:Comparative case-control study.Setting:Multicenter, comprehensive tertiary healthcare facility in Detroit, MI.Patients/Subjects:Adult patients hospitalized with coronavirus disease 2019 secondary to acute respiratory distress syndrome infection were compared with patients hospitalized with acute respiratory distress syndrome prior to the coronavirus disease 2019 pandemic (control).Interventions:None.MEASUREMENTS AND Main Results:We included 384 patients in the analysis. Inpatient mortality was significantly higher in patients with coronavirus disease 2019 secondary to acute respiratory distress syndrome infection compared with controls (64% vs 49%; p = 0.007). Despite both groups demonstrating similar ventilatory function and Sequential Organ Failure Assessment score on day 1 of intubation, with similar lung compliance throughout the study period, patients with coronavirus disease 2019 secondary to acute respiratory distress syndrome infection demonstrated progressive hypoxia compared with controls across the study period. Similarly, higher positive end-expiratory pressure levels and increased use of paralytics were observed in the patients with coronavirus disease 2019 secondary to acute respiratory distress syndrome infection group. On univariate analysis of the entire cohort, significant risk factors for inpatient mortality included coronavirus disease 2019 infection (p = 0.007), older age (p < 0.001), high Sequential Organ Failure Assessment score (p = 0.003), vasopressor use (p = 0.039), paralytic use (p < 0.001), higher positive end-expiratory pressure levels on day 3 (p = 0.027) and day 7 (p < 0.001), in addition to acute respiratory distress syndrome severity on both days 3 (p = 0.008) and 7 (p < 0.001). Multivariate analysis identified coronavirus disease 2019 infection (odds ratio, 1.939; p = 0.021), older age (odds ratio, 1.042; p < 0.001), paralytic use (odds ratio, 3.366; p < 0.001), and higher Sequential Organ Failure Assessment score (odds ratio, 1.152; p = 0.027) as significant predictors of mortality across the entire cohort.Conclusions:Patients with coronavirus disease 2019 secondary to acute respiratory distress syndrome infection demonstrated higher mortality compared with control patients hospitalized with acute respiratory distress syndrome prior to the pandemic, with progressive hypoxia throughout the study period, despite similar lung mechanics and initial Sequential Organ Failure Assessment score. Coronavirus disease 2019 infection, older age, paralytic use, and higher Sequential Organ Failure Assessment scores were independent risk factors for 28-day mortality across the entire cohort.

PO2 of the metathoracic ganglion in response to progressive hypoxia in an insect: PO2 of the insect central nervous system

PO2 of the metathoracic ganglion in response to progressive hypoxia in an insect: PO2 of the insect central nervous system

656 Fetal hypoxia induced by partial maternal aortic occlusion is tolerated in a lamb model

Hemorrhage is a leading cause of maternal mortality. Resuscitative endovascular balloon occlusion of the aorta (REBOA) has been used for hemorrhage control in obstetrical patients, however the fetal effects are unknown. Preliminary data from a pregnant ewe model showed that fetal physiologic changes from partial aortic occlusion (pREBOA) first occur at mean placental arterial pressure (pMAP) 40mmHg, however data are lacking on fetal neurological outcomes. We aimed to further evaluate the effects of decreased pMAP on the fetus in a sheep model. A REBOA catheter was placed in the infrarenal aorta of four gravid term ewes. pMAP was approximated by maternal femoral MAP. The REBOA balloon was inflated to decrease pMAP to 40mmHg, then decreased in 5mmHg increments to a fetal SaO2 of 15%. Fetal hemodynamics, SaO2, pH, and lactate were monitored via right fetal carotid arterial lines. At fetal SaO2 15%, the REBOA was deflated followed by a recovery period. pREBOA was then repeated twice as part of a separate study. Data from the first round are presented here. Post-mortem fetal brain magnetic resonance imaging (MRI) was performed to evaluate for ischemia. Mean baseline pMAP was 57.5±6.2mmHg and it was decreased to 40mmHg (n=1), 30mmHg (n=2), and 25mmHg (n=1) prior to recovery. Fetal SaO2 was significantly lower than baseline (58.5±7.4%) at each decreased pMAP (p<0.0001, Fig 1A). Fetal heart rate did not significantly increase until pMAP 25mmHg (baseline 133.5±8.8 vs. 156±14.1, p=0.001, Fig 1B). Fetal pH and lactate did not significantly change until pMAP 30mmHg (pH 7.22±0.02 vs. 7.14±0.1, p=0.01; lactate 1.9±0.4 vs. 3.5±2.8, p=0.004). After 3 rounds of hypoxia, there was no evidence of ischemia on fetal brain MRIs (Fig 2). Fetal SaO2, heart rate, pH, and lactate did not change significantly until a relatively low pMAP. After three rounds of progressive hypoxia from pREBOA, there was no evidence of fetal brain ischemia on MRI. Future studies in a survival model are needed to evaluate neurologic function after maternal pREBOA.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Fatal outcome of congenital aortopulmonary window with patent ductus arteriosus complicating pregnancy

ABSTRACTAortopulmonary window (APW) is a rare congenital heart defect with abnormal communication between the ascending aorta and the pulmonary trunk with two separate semilunar valves. We present an autopsy case report wherein a young primigravida woman presented with progressive breathlessness and central cyanosis at 21 weeks of gestation. Echocardiography performed in the emergency room revealed elevated right-sided cardiac pressures suggestive of severe pulmonary hypertension; however, no structural cardiac defect was discernible. The patient succumbed to congestive cardiac failure and progressive hypoxia within 5 days of hospitalization. The autopsy revealed a Type I aortopulmonary window (2 cm) with patent ductus arteriosus. The lungs showed changes of severe pulmonary hypertension with superadded bronchopneumonia. This report underscores a rare presentation of APW, undiagnosed until pregnancy, leading to the Eisenmenger syndrome and death.

Exposure to Nitrate Increases Susceptibility to Hypoxia in Fish.

AbstractAquatic hypoxic events are increasing in frequency and intensity as concentrations of nutrients, such as nitrate, continue to rise from human activities. Many fish species can alter their behavior and physiology to cope with drops in oxygen, but these compensatory strategies may be compromised under high levels of nitrate pollution. Hence, we investigated whether exposure to elevated nitrate concentrations affects key behavioral (avoidance and aquatic surface respiration [ASR]) and physiological (hemoglobin and hematocrit levels, ventilation frequency, and burst and prolonged swimming performance) responses of fish to mitigate the impacts of acute hypoxia. Juvenile silver perch (Bidyanus bidyanus) were exposed to one of three nitrate concentrations (0, 50, or 100 mg NO3- L-1) for 3 wk, after which behavioral and physiological responses of fish to progressive hypoxia were assessed. Fish exposed to nitrate utilized ASR at a higher threshold of partial pressure of oxygen during progressive hypoxia compared with control animals but did not alter behavioral avoidance of low oxygen levels. In these nitrate-exposed fish, the early onset of ASR behaviors is likely a behavioral, compensatory strategy to cope with nitrate-induced physiological disruptions, namely, increases in ventilation frequency and lower levels of hemoglobin and hematocrit. The physiological constraints placed by nitrate and acute hypoxia exposures manifested to lower the swimming performance of silver perch. Collectively, these data suggest that exposure to elevated nitrate is likely to disrupt key behavioral and physiological strategies used by fish to cope with short-term hypoxia.

PO2 of the metathoracic ganglion in response to progressive hypoxia in an insect.

Mammals regulate their brain tissue PO2 tightly, and only small changes in brain PO2 are required to elicit compensatory ventilation. However, unlike the flow-through cardiovascular system of vertebrates, insect tissues exchange gases through blind-ended tracheoles, which may involve a more prominent role for diffusive gas exchange. We tested the effect of progressive hypoxia on ventilation and the PO2 of the metathoracic ganglion (neural site of control of ventilation) using microelectrodes in the American locust, Schistocerca americana. In normal air (21 kPa), PO2 of the metathoracic ganglion was 12 kPa. The PO2 of the ganglion dropped as air PO2 dropped, with ventilatory responses occurring when ganglion PO2 reached 3 kPa. Unlike vertebrates, insects tolerate relatively high resting tissue PO2 levels and allow tissue PO2 to drop during hypoxia, activity and discontinuous gas exchange before activating convective or spiracular gas exchange. Tracheated animals, and possibly pancrustaceans in general, seem likely to generally experience wide spatial and temporal variation in tissue PO2 compared with vertebrates, with important implications for physiological function and the evolution of oxygen-using proteins.

Progressive Hypoxia: A Pivotal Pathophysiologic Mechanism of COVID-19 Pneumonia

Progressive Hypoxia: A Pivotal Pathophysiologic Mechanism of COVID-19 Pneumonia

Oxygen-dependence of upper thermal limits in crustaceans from different thermal habitats.

The critical thermal maximum (CTMAX) is the temperature at which animals exhibit loss of motor response because of a temperature-induced collapse of vital physiological systems. A central mechanism hypothesised to underlie the CTMAX of water-breathing ectotherms is insufficient tissue oxygen supply for vital maintenance functions because of a temperature-induced collapse of the cardiorespiratory system. The CTMAX of species conforming to this hypothesis should decrease with declining water oxygen tension (PO2) because they have oxygen-dependent upper thermal limits. However, recent studies have identified a number of fishes and crustaceans with oxygen-independent upper thermal limits, their CTMAX unchanged in progressive aquatic hypoxia. The previous studies, which were performed separately on cold-water, temperate and tropical species, suggest the oxygen-dependence of upper thermal limits and the acute thermal sensitivity of the cardiorespiratory system increases with decreasing habitat temperature. Here we directly test this hypothesis by assessing the oxygen-dependence of CTMAX in the polar Antarctic krill (Euphausia superba), as well as the temperate Baltic prawn (Palaemon adspersus) and brown shrimp (Crangon crangon). We found that P. adspersus and C. crangon maintain CTMAX in progressive hypoxia down to 40mmHg, and that only E. superba have oxygen-dependent upper thermal limits at normoxia. In E. superba, the observed decline in CTMAX with water PO2 is further supported by heart-rate measurements showing a plateauing, and subsequent decline and collapse of heart performance at CTMAX. Our results support the hypothesis that the oxygen-dependence of upper thermal limits in water-breathing ectotherms and the acute thermal sensitivity of their cardiorespiratory system increases with decreasing habitat temperature.

Treatment Options for Coronavirus Disease 2019 in Patients With Reduced or Absent Kidney Function.

Coronavirus disease 2019, the disease caused by the severe acute respiratory syndrome coronavirus 2 virus, was first identified in the Hubei Province of China in late 2019. Currently, the only role for therapy is treatment of the disease, as opposed to postexposure prophylaxis, however multiple clinical trials are currently ongoing for both treatment and prophylaxis. Treating coronavirus disease 2019 relies on two components; the first is inhibition of the viral entrance and replication within the body and the second is inhibition of an exacerbated immune response which can be seen in patients with severe disease. Many drugs have shown in vitro antiviral activity; however, clinical trials have not been as promising. This review summarizes the current data for the most commonly used drugs for coronavirus disease 2019 and will cover the unique factors that may affect the dosing of these medications in patients with CKD. While clinical trials are ongoing, most are in patients with normal kidney function. During a pandemic, when patients with CKD are at higher risk of both infection and death, it is imperative to include patients these patients in the clinical trials.

Pulmonary toxicity of systemic lung cancer therapy

Lung cancer is the leading cause of cancer-related deaths worldwide. As new therapies are developed, it is important to understand the pulmonary toxicities associated with systemic lung cancer therapies. Cytotoxic chemotherapy regimens for NSCLC often include taxanes. Pulmonary toxicity from taxanes presents as an ILD-type reaction characterized by increasing dyspnoea, dry cough, fever and bilateral pulmonary interstitial infiltrates. The incidence of taxane-induced pneumonitis is rare, and many patients respond to steroid therapy; however, fatal cases have been reported. Patients with NSCLC are routinely tested for the presence of tumour oncogenes to determine their candidacy for targeted therapies, such as TKI. EGFR-TKI can cause pneumonitis characterized by progressive dyspnoea and hypoxia. EGFR-TKI-associated ILD rarely presents as an AIP with rapidly progressive respiratory failure and high mortality rates. The most recent development in lung cancer therapy has been the discovery of immune checkpoint inhibitor (ICI). ICI pneumonitis has been increasingly recognized as a common complication of ICI therapy, with reported incidence as high as 19% in some clinical settings. Early-grade ICI pneumonitis may be asymptomatic; however, high-grade ICI pneumonitis can result in progressive dyspnoea, hypoxia and respiratory failure. ICI pneumonitis is unique in that only half of the patients will improve with steroid treatment, and mortality rates are high. As treatment of NSCLC evolves, providers must be able to recognize and respond to the development of drug-induced pulmonary toxicities.

The role of the cardiac lymphatic system in the development and progression of heart failure and novel therapeutic approaches for its management in post-infarction cardiac remodeling

Cardiac lymphatic vessels play a vital role in maintaining homeostasis in both physiological and pathological conditions, providing outflow of metabolites. It has been shown that myocardial infarction and postinfarction cardiac remodeling is accompanied by the lymphatic remodeling, which entails functional disorders and is of great importance in heart failure pathogenesis. As a result of progressive myocardial edema, hypoxia and fibrosis of the interstitial space increase, aggravating edema. Other pathways of additional myocardial damage and contractility reduction are triggered. Lymphatic efflux is associated with arrhythmias. Experimental models showed the positive effect of exogenous activation of lymphangiogenesis in relation to the prevention and treatment of heart failure, which can be further used to improve treatment regimens. This review discusses cardiac lymphatic remodeling after myocardial infarction, as well as the pathogenesis of related complications.