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1.
Neurol India ; 68(5): 989-993, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33109839

RESUMO

Background: A terrible pandemic, Covid-19, has captivated scientists to investigate if SARS-CoV-2 virus infects the central nervous system (CNS). A crucial question is if acute respiratory distress syndrome (ARDS), the main cause of death in this pandemic, and often refractory to treatments, can be explained by respiratory center dysfunction. Objective: To discuss that ARDS can be caused by SARS-CoV-2 infection of the respiratory center in the brainstem. Materials and Methods: I reviewed literature about SARS-CoV-2 mechanisms to infect the respiratory center in the brainstem. Results and Conclusions: An increasing amount of reports demonstrates that neurotropism is a common feature of coronavirus, which have been found in the brains of patients and experimental models, where the brainstem was severely infested. Recent studies have provided tremendous indication of the incidence of acute respiratory failure due to SARS-CoV-2 infection of the brainstem. SARS-CoV-2 might infect the CNS through the olfactory bulb, spreading from the olfactory nerves to the rhinencephalon, and finally reaching the brainstem. Hence, the virus infection causes respiratory center dysfunctions, leading to ARDS in COVID-19 patients. I conclude that acute ARDS in Covid-19 can be caused by SARS-CoV-2 invasion of brainstem respiratory center, suggesting the needs of more specific and aggressive treatments, with the direct participation of neurologists and neurointensivists.


Assuntos
Infecções por Coronavirus/fisiopatologia , Pneumonia Viral/fisiopatologia , Centro Respiratório/fisiopatologia , Síndrome do Desconforto Respiratório do Adulto/fisiopatologia , Betacoronavirus , Tronco Encefálico/fisiopatologia , Tronco Encefálico/virologia , Humanos , Hipóxia/fisiopatologia , Pandemias , Centro Respiratório/virologia , Tropismo Viral
2.
Nat Commun ; 11(1): 4883, 2020 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-32985528

RESUMO

Early stages of the novel coronavirus disease (COVID-19) are associated with silent hypoxia and poor oxygenation despite relatively minor parenchymal involvement. Although speculated that such paradoxical findings may be explained by impaired hypoxic pulmonary vasoconstriction in infected lung regions, no studies have determined whether such extreme degrees of perfusion redistribution are physiologically plausible, and increasing attention is directed towards thrombotic microembolism as the underlying cause of hypoxemia. Herein, a mathematical model demonstrates that the large amount of pulmonary venous admixture observed in patients with early COVID-19 can be reasonably explained by a combination of pulmonary embolism, ventilation-perfusion mismatching in the noninjured lung, and normal perfusion of the relatively small fraction of injured lung. Although underlying perfusion heterogeneity exacerbates existing shunt and ventilation-perfusion mismatch in the model, the reported hypoxemia severity in early COVID-19 patients is not replicated without either extensive perfusion defects, severe ventilation-perfusion mismatch, or hyperperfusion of nonoxygenated regions.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/fisiopatologia , Hipóxia/etiologia , Hipóxia/fisiopatologia , Pneumopatias/etiologia , Pneumopatias/fisiopatologia , Pulmão/irrigação sanguínea , Pulmão/fisiopatologia , Modelos Biológicos , Pneumonia Viral/complicações , Pneumonia Viral/fisiopatologia , Circulação Pulmonar/fisiologia , Simulação por Computador , Infecções por Coronavirus/epidemiologia , Humanos , Hipóxia/terapia , Pneumopatias/terapia , Conceitos Matemáticos , Modelos Cardiovasculares , Oxigenoterapia , Pandemias , Pneumonia Viral/epidemiologia , Fatores de Tempo , Vasoconstrição/fisiologia , Vasodilatação/fisiologia , Relação Ventilação-Perfusão/fisiologia
3.
BMJ Open Respir Res ; 7(1)2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32963028

RESUMO

Reviews of COVID-19 CT imaging along with postmortem lung biopsies and autopsies indicate that the majority of patients with COVID-19 pulmonary involvement have secondary organising pneumonia (OP) or its histological variant, acute fibrinous and organising pneumonia, both well-known complications of viral infections. Further, many publications on COVID-19 have debated the puzzling clinical characteristics of 'silent hypoxemia', 'happy hypoxemics' and 'atypical ARDS', all features consistent with OP. The recent announcement that RECOVERY, a randomised controlled trial comparing dexamethasone to placebo in COVID-19, was terminated early due to excess deaths in the control group further suggests patients present with OP given that corticosteroid therapy is the first-line treatment. Although RECOVERY along with other cohort studies report positive effects with corticosteroids on morbidity and mortality of COVID-19, treatment approaches could be made more effective given that secondary OP often requires prolonged duration and/or careful and monitored tapering of corticosteroid dose, with 'pulse' doses needed for the well-described fulminant subtype. Increasing recognition of this diagnosis will thus lead to more appropriate and effective treatment strategies in COVID-19, which may lead to a further reduction of need for ventilatory support and improved survival.


Assuntos
Infecções por Coronavirus/fisiopatologia , Pneumonia em Organização Criptogênica/diagnóstico , Erros de Diagnóstico , Hipóxia/fisiopatologia , Pulmão/diagnóstico por imagem , Pneumonia Viral/fisiopatologia , Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Pneumonia em Organização Criptogênica/tratamento farmacológico , Pneumonia em Organização Criptogênica/etiologia , Pneumonia em Organização Criptogênica/fisiopatologia , Dexametasona/uso terapêutico , Glucocorticoides/uso terapêutico , Humanos , Hipóxia/etiologia , Pulmão/patologia , Pulmão/fisiopatologia , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/fisiopatologia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Tomografia Computadorizada por Raios X
4.
Respir Res ; 21(1): 249, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32972411

RESUMO

In the article "The pathophysiology of 'happy' hypoxemia in COVID-19," Dhont et al. (Respir Res 21:198, 2020) discuss pathophysiological mechanisms that may be responsible for the absence of dyspnea in patients with COVID-19 who exhibit severe hypoxemia. The authors review well-known mechanisms that contribute to development of hypoxemia in patients with pneumonia, but are less clear as to why patients should be free of respiratory discomfort despite arterial oxygen levels commonly regarded as life threatening. The authors propose a number of therapeutic measures for patients with COVID-19 and happy hypoxemia; we believe readers should be alerted to problems with the authors' interpretations and recommendations.


Assuntos
Infecções por Coronavirus/fisiopatologia , Dispneia/prevenção & controle , Hipóxia/fisiopatologia , Oxigênio/sangue , Pneumonia Viral/fisiopatologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Feminino , Humanos , Hipóxia/epidemiologia , Masculino , Oximetria/métodos , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Prognóstico , Medição de Risco , Resultado do Tratamento
5.
Life Sci ; 260: 118408, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32926931

RESUMO

AIMS: Baseline elevated B-type Natriuretic Peptide (BNP) has been found in high altitude pulmonary edema susceptible population. Exaggerated pulmonary vascular response to hypoxia may be related to endothelial dysfunction in hypoxia susceptible. We hypothesize that baseline BNP levels can predict hypoxia susceptibility in healthy individuals. MAIN METHODS: The pulmonary vascular response to hypoxia was compared in 35 male healthy individuals divided into two groups based on BNP levels (Group 1 ≤ 15 and Group 2 > 15 pg/ml). Acute normobaric hypoxia was administered to both the groups, to confirm hypoxia susceptibility in Group 2. KEY FINDINGS: Unlike Group 1, Group 2 had elevated post hypoxia BNP levels (26 vs 33.5 pg/ml, p = 0.002) while pulmonary artery pressure was comparable. A negative correlation with tissue oxygen consumption (delta pO2) and compartmental fluid shift was seen in Group 1 only. Endothelial dysfunction in Group 2 resulted in reduced vascular compliance leading to elevation of mean blood pressure on acute hypoxia exposure. BNP showed a positive correlation with endothelial dysfunction in Group 2 and has been linked to pre-diabetic disorder (HbA1c 6 ± 0.44%) and may additionally represent a lower cross-sectional area of vascular bed related to vascular remodeling mediated by chronic hypoxia. SIGNIFICANCE: Hypoxia susceptibility in healthy individuals may be related to endothelial dysfunction that limits vascular compliance during hypoxic stress. BNP level showed positive correlation with HbA1c (r = 0.49, p = 0.04) and negative correlation with delta pO2 (r = -0.52, p = 0.04) can predict reduced microvascular compliance due to endothelial dysfunction contributing to hypoxia susceptibility in healthy individuals. BNP levels≤15 pg/ml at sea level is indicative of hypoxia resistance.


Assuntos
Altitude , Endotélio Vascular/fisiopatologia , Hipóxia/fisiopatologia , Pulmão/fisiopatologia , Peptídeo Natriurético Encefálico/metabolismo , Artéria Pulmonar/fisiopatologia , Edema Pulmonar/fisiopatologia , Adulto , Feminino , Humanos , Masculino , Testes de Função Respiratória
6.
PLoS One ; 15(9): e0239194, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32966320

RESUMO

BACKGROUND: Aircrew members are required to attend hypoxia awareness training regularly to strengthen their memory of their personal hypoxia symptoms by undergoing training inside a hypobaric chamber. The aim of this study was to examine the association between hypoxia symptoms experienced during two training sessions that were 4 years apart. METHODS: This was a crossover study to compare hypoxia symptoms and self-reported physiological effects of trapped gas between a previous training session and a current training session in an altitude chamber. The subjects were military crew members who undertook a 25,000-feet refresher training course in 2018. We used a structured questionnaire to obtain the target information before and during hypoxia exposure. Data were analyzed using SPSS software. RESULTS: A total of 341 trainees participated in this survey and completely filled out the questionnaire. Gastrointestinal tract discomfort caused by the expansion of trapped gas was the main physiological reaction during the previous and current training sessions. Frequently reported symptoms were poor concentration (30.5%), impaired cognitive function (20.5%), visual disturbances (16.4%), hot flashes (15.8%), and paresthesia (12.6%) during both exposures. However, the proportions of participants reporting poor concentration (P = 0.378) and visual disturbances (P = 0.594) were not significantly different between the recalled and current training sessions. The five most common symptoms among the subjects with less than 1,000 flight hours were poor concentration (29.8%), visual disturbance (27.3%), impaired cognitive function (14.9%), dizziness/lightheadedness (11.6%), and hot flashes (9.9%), which overlapped substantially with the symptoms reported by other subjects. The occurrence of those five most common symptoms in the group with more than 1,000 flight hours did not significantly differ between the recalled training session and the current training session. CONCLUSIONS: The most common hypoxia symptoms reported were similar between the recalled and current training sessions in an environment with a low oxygen concentration. This finding was also clearly affected by the duration of flight experience. Moreover, GI effects of the expansion of trapped gas were commonly observed at low atmospheric pressure.


Assuntos
Hipóxia , Rememoração Mental , Adulto , Medicina Aeroespacial , Altitude , Pressão Atmosférica , Estudos Cross-Over , Feminino , Humanos , Hipóxia/fisiopatologia , Hipóxia/psicologia , Masculino , Pessoa de Meia-Idade , Militares , Inquéritos e Questionários
7.
PLoS One ; 15(9): e0238857, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32898195

RESUMO

BACKGROUND: Hypoxia-induced oxidative stress is one of the main mechanisms of myocardial injury, which frequently results in cardiomyocyte death and precipitates life-threatening heart failure. Propofol (2,6-diisopropylphenol), which is used to sedate patients during surgery, was shown to strongly affect the regulation of physiological processes, including hypoxia-induced oxidative stress. However, the exact mechanism is still unclear. METHODS: Expression of LRPPRC, SLIRP, and Bcl-2 after propofol treatment was measured by RT-qPCR and western blot analyses. The effects of propofol under hypoxia were determine by assessing mitochondrial homeostasis and mitochondrial function, including the ATP level and mitochondrial mass. Autophagy/mitophagy was measured by detecting the presence of LC3B, and autophagosomes were observed by transmission microscopy. RESULTS: Propofol treatment inhibited cleaved caspase-9 and caspase-3, indicating its inhibitory roles in mitochondrial-related apoptosis. Propofol treatment also transcriptionally activated LRPPRC, a mitochondrial-associated protein that exerts multiple functions by maintaining mitochondrial homeostasis, in a manner dependent on the presence of hypoxia-induced factor (HIF)-1α transcriptional activity in H9C2 and primary rat cardiomyocytes. LRPPRC induced by propofol maintained the mitochondrial membrane potential (MMP) and promoted mitochondrial function, including ATP synthesis and transcriptional activity. Furthermore, LRPPRC induced by propofol contributes, at least partially, to the inhibition of apoptotic cell death induced by hypoxia. CONCLUSION: Taken together, our results indicate that LRPPRC may have a protective antioxidant effect by maintaining mitochondrial homoeostasis induced by propofol and provide new insight into the protective mechanism of propofol against oxidative stress.


Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Hipóxia/fisiopatologia , Mitocôndrias/efeitos dos fármacos , Proteínas Mitocondriais/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Propofol/farmacologia , Substâncias Protetoras/farmacologia , Anestésicos Intravenosos/farmacologia , Animais , Apoptose , Células Cultivadas , Potencial da Membrana Mitocondrial , Mitocôndrias/genética , Mitocôndrias/metabolismo , Proteínas Mitocondriais/genética , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-bcl-2 , Ratos , Espécies Reativas de Oxigênio
8.
PLoS One ; 15(8): e0237673, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790747

RESUMO

PURPOSE: This study investigated the acute changes in full spectrum differential blood cell count including reticulocytes and immature reticulocytes after a voluntary maximal dry apnea in non-elite divers. Aim of the present study is to obtain information on important regulatory compensation mechanisms and to provide insights into apneic regulatory processes. METHODS: Ten apnea divers performed a voluntary dry mean apnea time of 317 sec [SD ±111 sec]. Differential blood cell count including reticulocytes was measured before and immediately after a single maximal breath-hold. To evaluate kinetics, blood samples were also taken after 30 min and 4 h. Value distributions are presented with dot plots. P-values were calculated using a mixed linear model for time dependency. Four difference values were compared to baseline values with Dunnett's procedure. RESULTS: Significant changes were found in red blood cell parameters for erythrocytes, red cell distribution width, hematocrit, hemoglobin, MCV, reticulocytes and immature reticulocytes, and in white blood cell parameters for leucocytes, lymphocytes, immature granulocytes, monocytes, basophile granulocytes, neutrophil granulocytes and eosinophil granulocytes and for thrombocytes. CONCLUSION: Adaptive mechanisms regarding cell counts in elite apnea divers are not readily transferable to non-elite recreational sportspersons. Divers and physicians should be aware of the limited adaptive performance of humans in the case of extended apnea.


Assuntos
Adaptação Fisiológica/fisiologia , Suspensão da Respiração , Mergulho/fisiologia , Hipóxia/sangue , Adulto , Contagem de Células Sanguíneas , Hematócrito , Hemoglobinas/análise , Humanos , Hipóxia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
9.
Hum Cell ; 33(4): 1036-1045, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32779153

RESUMO

The obstructive sleep apnea syndrome (OSAS) is a common sleep-related breathing disorder and an important cause of refractory hypertension. MicroRNAs (miRNAs) are involved in the development of hypertension, but their role in OSAS with hypertension (OSAS-hypertension) has been little studied. Evidence indicates that miR-126a-3p expression is lower in patients with OSAS-hypertension compared with the patients with OSAS alone. However, its role in the pathogenesis of OSAS-hypertension remains unclear. Therefore, this study aims to investigate the role of miR-126a-3p in OSAS-hypertension and to determine whether HIF-1α is involved in this process. Sprague Dawley rats were exposed to chronic intermittent hypoxia (CIH) for 8 weeks to induce OSAS-hypertension. Rat aortic smooth muscle cells (A7r5) were cultured under hypoxia as an in vitro model. Our results showed that rats exposed to 8 week CIH exhibited decreased miR-126a-3p and increased HIF-1α expression. Furthermore, administration of recombinant adeno-associated virus expressing miR-126a-3p (rAAV-miR-126a) counteracted the CIH-induced systolic blood pressure upregulation, oxidase stress, inflammation, and heart and abdominal aorta vascular remodeling. Moreover, the mechanism was associated with its targeted suppression of HIF-1α. These findings suggest that miR-126a-3p might be a novel potential therapeutic target for the treatment of OSAS-hypertension.


Assuntos
Expressão Gênica , Hipertensão/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Apneia Obstrutiva do Sono/genética , Animais , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/genética , Células Cultivadas , Hipertensão/etiologia , Hipertensão/terapia , Hipóxia/complicações , Hipóxia/fisiopatologia , Masculino , MicroRNAs/administração & dosagem , MicroRNAs/farmacologia , Terapia de Alvo Molecular , Ratos Sprague-Dawley , Apneia Obstrutiva do Sono/etiologia , Apneia Obstrutiva do Sono/terapia , Remodelação Vascular/efeitos dos fármacos , Remodelação Vascular/genética
10.
BMJ Case Rep ; 13(8)2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32859618

RESUMO

During the previous months, we have seen the rapid pandemic spread of SARS-CoV-2. Despite being considered a respiratory virus, it has become clear that other clinical presentations are possible and some of these are quite frequent. In this paper, a case of a man in his late 70s showing atypical symptoms in general practice is presented. Apart from fever, the patient complained of diarrhoea, borborygmus, loss of appetite and nausea. He developed no respiratory symptoms during his disease. Due to his symptoms, malignant disease was suspected, and he was referred for further testing which revealed typical COVID-19 findings on a chest CT scan. The occurrence of atypical symptoms is discussed, including the importance of recognising these in an ongoing pandemic.


Assuntos
Anorexia/fisiopatologia , Infecções por Coronavirus/fisiopatologia , Diarreia/fisiopatologia , Hipóxia/fisiopatologia , Pulmão/diagnóstico por imagem , Náusea/fisiopatologia , Pneumonia Viral/fisiopatologia , Idoso , Betacoronavirus , Proteína C-Reativa/metabolismo , Infecções por Coronavirus/diagnóstico , Medicina Geral , Humanos , Masculino , Pandemias , Pneumonia Viral/diagnóstico , Tomografia Computadorizada por Raios X
13.
Am J Physiol Regul Integr Comp Physiol ; 319(2): R211-R222, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32609532

RESUMO

Although severe intermittent hypoxia (IH) is well known to induce deleterious cardiometabolic consequences, moderate IH may induce positive effects in obese individuals. The present study aimed to evaluate the effect of two hypoxic conditioning programs on cardiovascular and metabolic health status of overweight or obese individuals. In this randomized single-blind controlled study, 35 subjects (54 ± 9.3 yr, 31.7 ± 3.5 kg/m2) were randomized into three 8-wk interventions (three 1-h sessions per week): sustained hypoxia (SH), arterial oxygen saturation ([Formula: see text]) = 75%; IH, 5 min [Formula: see text] = 75% - 3 min normoxia; normoxia. Ventilation, heart rate, blood pressure, and tissue oxygenation were measured during the first and last hypoxic conditioning sessions. Vascular function, blood glucose and insulin, lipid profile, nitric oxide metabolites, and oxidative stress were evaluated before and after the interventions. Both SH and IH increased ventilation in hypoxia (+1.8 ± 2.1 and +2.3 ± 3.6 L/min, respectively; P < 0.05) and reduced normoxic diastolic blood pressure (-12 ± 15 and -13 ± 10 mmHg, respectively; P < 0.05), whereas changes in normoxic systolic blood pressure were not significant (+3 ± 9 and -6 ± 13 mmHg, respectively; P > 0.05). IH only reduced heart rate variability (e.g., root-mean-square difference of successive normal R-R intervals in normoxia -21 ± 35%; P < 0.05). Both SH and IH induced no significant change in body mass index, vascular function, blood glucose, insulin and lipid profile, nitric oxide metabolites, or oxidative stress, except for an increase in superoxide dismutase activity following SH. This study indicates that passive hypoxic conditioning in obese individuals induces some positive cardiovascular and respiratory improvements despite no change in anthropometric data and even a reduction in heart rate variability during IH exposure.


Assuntos
Glicemia/metabolismo , Pressão Sanguínea/fisiologia , Sistema Cardiovascular/fisiopatologia , Frequência Cardíaca/fisiologia , Hipóxia/fisiopatologia , Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Adulto , Sistema Cardiovascular/metabolismo , Colesterol/sangue , Feminino , Humanos , Hipóxia/metabolismo , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Sobrepeso/metabolismo , Método Simples-Cego , Triglicerídeos/sangue
14.
Respir Res ; 21(1): 198, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32723327

RESUMO

The novel coronavirus disease 2019 (COVID-19) pandemic is a global crisis, challenging healthcare systems worldwide. Many patients present with a remarkable disconnect in rest between profound hypoxemia yet without proportional signs of respiratory distress (i.e. happy hypoxemia) and rapid deterioration can occur. This particular clinical presentation in COVID-19 patients contrasts with the experience of physicians usually treating critically ill patients in respiratory failure and ensuring timely referral to the intensive care unit can, therefore, be challenging. A thorough understanding of the pathophysiological determinants of respiratory drive and hypoxemia may promote a more complete comprehension of a patient's clinical presentation and management. Preserved oxygen saturation despite low partial pressure of oxygen in arterial blood samples occur, due to leftward shift of the oxyhemoglobin dissociation curve induced by hypoxemia-driven hyperventilation as well as possible direct viral interactions with hemoglobin. Ventilation-perfusion mismatch, ranging from shunts to alveolar dead space ventilation, is the central hallmark and offers various therapeutic targets.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Hipóxia/etiologia , Pulmão/fisiopatologia , Consumo de Oxigênio/fisiologia , Pandemias , Pneumonia Viral/complicações , Insuficiência Respiratória/complicações , Infecções por Coronavirus/epidemiologia , Estado Terminal , Humanos , Hipóxia/metabolismo , Hipóxia/fisiopatologia , Pneumonia Viral/epidemiologia , Insuficiência Respiratória/metabolismo , Insuficiência Respiratória/fisiopatologia
15.
Med Hypotheses ; 143: 110022, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32634734

RESUMO

The current SARS-Cov-2 virus pandemic challenges critical care physicians and other caregivers to find effective treatment for desperately ill patients - especially those with sudden and extreme hypoxemia. Unlike patients with other forms of Acute Respiratory Distress Syndrome, these patients do not exhibit increased lung stiffness or dramatic dyspnea., even in the presence of arterial blood oxygen levels lower than that seen normally in mixed venous blood. Urgent intubation and mechanical ventilation with high inflation pressures and raised inhaled oxygen concentration have proved unhelpful or worse, but why? Our Hypothesis is that sudden opening of a previously undetected probe-patent foramen ovale (PPFO) may explain this mystery. As hypoxemia without acidosis is a rather weak stimulus of dyspnea or increased ventilation, and opening of such an intracardiac shunt would not worsen lung mechanical properties, the absence of dramatic symptom changes would not be surprising. We point out the high frequency of PFO both in life and at autopsy, and the physiological evidence of large shunt fractions found in Covid-19 patients. Published evidence of hypercoagulability and abundant evidence of pulmonary emboli found at autopsy are in accord with our hypothesis, as they would contribute to raised pressure in the pulmonary arteries and right heart chambers, potentially causing a shunt to open. We review the interaction between viral corona spike protein and ACE-2 receptors present on the surface of alveolar lining cells, and contribution to hypercoagulabilty caused by the spike protein. Search for an open PFO after a large drop in arterial oxygen saturation can be performed at the bedside with a variety of well-established techniques including bedside echocardiography, nitrogen washout test, and imaging studies. Potential treatments might include balloon or patch closure of the shunt, and various drug treatments to lower pulmonary vascular resistance.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Forame Oval Patente/complicações , Hipóxia/etiologia , Pneumonia Viral/complicações , Betacoronavirus/patogenicidade , Betacoronavirus/fisiologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/fisiopatologia , Forame Oval Patente/sangue , Forame Oval Patente/fisiopatologia , Humanos , Hipóxia/sangue , Hipóxia/fisiopatologia , Modelos Biológicos , Pandemias , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/sangue , Pneumonia Viral/fisiopatologia , Circulação Pulmonar , Receptores Virais/fisiologia , Mecânica Respiratória , Glicoproteína da Espícula de Coronavírus/fisiologia , Trombofilia/etiologia
16.
Am J Physiol Regul Integr Comp Physiol ; 319(3): R243-R254, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32639864

RESUMO

We hypothesized that the physiological adaptations of the fetus in response to chronic intrauterine hypoxia depend on its sex and the gestational age of exposure. Pregnant guinea pigs were exposed to room air (normoxia, NMX) or 10.5% O2 (hypoxia, HPX) at either 25 days (early onset) or 50 days (late onset) of gestation until term (~65 days). We evaluated the effects of HPX on hemodynamic and cardiac function indices using Doppler ultrasound and determined sex-related differences in near-term fetuses. Indices of uterine/umbilical artery pulsatility (PI index) and fetal heart systolic and diastolic function [Tei index and passive filling (E-wave) to filling due to atrial contraction (A-wave) (E/A ratios), respectively] were measured in utero and fetal body (FBW) and organ weights measured from extracted fetuses. Both early- and late-onset HPX decreased FBW in both males and females, had no effect on placenta weights, and increased placenta weight-to-FBW ratios. Early- but not late-onset HPX increased uterine artery PI, but neither HPX condition affected umbilical artery PI. Early-onset HPX increased left ventricle E/A ratios in both males and females, whereas late-onset HPX increased the right ventricle E/A ratio in females only. Hypoxia had no effect on the Tei index in either sex. Early- and late-onset HPX induce placental insufficiency and fetal growth restriction and increase diastolic filling depending on the sex, with female fetuses having a greater capacity than males to compensate for intrauterine hypoxia.


Assuntos
Retardo do Crescimento Fetal/fisiopatologia , Coração Fetal/fisiopatologia , Caracteres Sexuais , Artérias Umbilicais/diagnóstico por imagem , Animais , Feminino , Cobaias , Humanos , Hipóxia/fisiopatologia , Masculino , Insuficiência Placentária/fisiopatologia , Gravidez
17.
J Thorac Cardiovasc Surg ; 160(2): e55-e66, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32689704

RESUMO

OBJECTIVES: This study aims to evaluate the protective effects of progesterone on white matter injury and brain immaturity in neonatal rats with chronic hypoxia. METHODS: Three-day old Sprague-Dawley rats were randomly divided into 3 groups: (1) control (n = 48), rats were exposed to normoxia (fraction of inspired oxygen: 21% ± 0%); (2) chronic hypoxia (n = 48), rats were exposed to hypoxia (fraction of inspired oxygen: 10.5% ± 1.0%); and (3) progesterone (n = 48), rats were exposed to hypoxia and administrated with progesterone (8 mg/kg/d). Hematoxylin-eosin staining, immunohistochemistry, real-time quantitative polymerase chain reaction, and Western blot analyses were compared on postnatal day 14 in different groups. Motor skill and coordination abilities of rats were assessed via rotation experiments. RESULTS: Increased brain weights (P < .05), narrowed ventricular sizes (P < .01), and rotarod experiment scores (P < .01) were better in the progesterone group than in the chronic hypoxia group. The number of mature oligodendrocytes and myelin basic protein expression increased in the progesterone group compared with the chronic hypoxia group (P < .01). The polarization of M1 microglia cells in the corpus callosum of chronic hypoxia-induced hypomyelination rats was significantly increased, whereas there were fewer M2 microglia cells. Conversely, progesterone therapy had an opposite effect and caused an increase in M2 microglia polarization versus a reduction in M1 microglia cells. CONCLUSIONS: Progesterone could prevent white matter injury and improve brain maturation in a neonatal hypoxic rat model; this may be associated with inducing a switch from M1 to M2 in microglia.


Assuntos
Encéfalo/efeitos dos fármacos , Hipóxia/tratamento farmacológico , Leucoencefalopatias/prevenção & controle , Fármacos Neuroprotetores/farmacologia , Progesterona/farmacologia , Substância Branca/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Comportamento Animal/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Plasticidade Celular/efeitos dos fármacos , Doença Crônica , Modelos Animais de Doenças , Feminino , Hipóxia/metabolismo , Hipóxia/patologia , Hipóxia/fisiopatologia , Leucoencefalopatias/metabolismo , Leucoencefalopatias/patologia , Leucoencefalopatias/fisiopatologia , Masculino , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/patologia , Atividade Motora/efeitos dos fármacos , Proteína Básica da Mielina/metabolismo , Oligodendroglia/efeitos dos fármacos , Oligodendroglia/metabolismo , Oligodendroglia/patologia , Ratos Sprague-Dawley , Substância Branca/metabolismo , Substância Branca/patologia , Substância Branca/fisiopatologia
18.
ACS Chem Neurosci ; 11(16): 2416-2421, 2020 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-32600045

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been established as a cause of severe alveolar damage and pneumonia in patients with advanced Coronavirus disease (COVID-19). The consolidation of lung parenchyma precipitates the alterations in blood gases in COVID-19 patients that are known to complicate and cause hypoxemic respiratory failure. With SARS-CoV-2 damaging multiple organs in COVID-19, including the central nervous system that regulates the breathing process, it is a daunting task to compute the extent to which the failure of the central regulation of the breathing process contributes to the mortality of COVID-19 affected patients. Emerging data on COVID-19 cases from hospitals and autopsies in the last few months have helped in the understanding of the pathogenesis of respiratory failures in COVID-19. Recent reports have provided overwhelming evidence of the occurrence of acute respiratory failures in COVID-19 due to neurotropism of the brainstem by SARS-CoV-2. In this review, a cascade of events that may follow the alterations in blood gases and possible neurological damage to the respiratory regulation centers in the central nervous system (CNS) in COVID-19 are related to the basic mechanism of respiratory regulation in order to understand the acute respiratory failure reported in this disease. Though a complex metabolic and respiratory dysregulation also occurs with infections caused by SARS-CoV-1 and MERS that are known to contribute toward deaths of the patients in the past, we highlight here the role of systemic dysregulation and the CNS respiratory regulation mechanisms in the causation of mortalities seen in COVID-19. The invasion of the CNS by SARS-CoV-2, as shown recently in areas like the brainstem that control the normal breathing process with nuclei like the pre-Bötzinger complex (pre-BÖTC), may explain why some of the patients with COVID-19, who have been reported to have recovered from pneumonia, could not be weaned from invasive mechanical ventilation and the occurrences of acute respiratory arrests seen in COVID-19. This debate is important for many reasons, one of which is the fact that permanent damage to the medullary respiratory centers by SARS-CoV-2 would not benefit from mechanical ventilators, as is possibly occurring during the management of COVID-19 patients.


Assuntos
Infecções por Coronavirus/fisiopatologia , Hipóxia/fisiopatologia , Pneumonia Viral/fisiopatologia , Centro Respiratório/fisiopatologia , Insuficiência Respiratória/fisiopatologia , Betacoronavirus , Gasometria , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/mortalidade , Humanos , Hipóxia/metabolismo , Pandemias , Pneumonia Viral/metabolismo , Pneumonia Viral/mortalidade , Centro Respiratório/metabolismo , Centro Respiratório/virologia , Insuficiência Respiratória/metabolismo , Insuficiência Respiratória/mortalidade , Tropismo Viral
19.
Artigo em Inglês | MEDLINE | ID: mdl-32698542

RESUMO

The literature suggests that acute hypobaric (HH) and normobaric (NH) hypoxia exposure elicits different physiological responses. Only limited information is available on whether maximal cardiorespiratory exercise test outcomes, performed on either the treadmill or the cycle ergometer, are affected differently by NH and HH. A focused literature review was performed to identify relevant studies reporting cardiorespiratory responses in well-trained male athletes (individuals with a maximal oxygen uptake, VO2max > 50 mL/min/kg at sea level) to cycling or treadmill running in simulated acute HH or NH. Twenty-one studies were selected. The exercise tests in these studies were performed in HH (n = 90) or NH (n = 151) conditions, on a bicycle ergometer (n = 178) or on a treadmill (n = 63). Altitudes (simulated and terrestrial) varied between 2182 and 5400 m. Analyses (based on weighted group means) revealed that the decline in VO2max per 1000 m gain in altitude was more pronounced in acute NH vs. HH (-7.0 ± 1.4% vs. -5.6 ± 0.9%). Maximal minute ventilation (VEmax) increased in acute HH but decreased in NH with increasing simulated altitude (+1.9 ± 0.9% vs. -1.4 ± 1.8% per 1000 m gain in altitude). Treadmill running in HH caused larger decreases in arterial oxygen saturation and heart rate than ergometer cycling in acute HH, which was not the case in NH. These results indicate distinct differences between maximal cardiorespiratory responses to cycling and treadmill running in acute NH or HH. Such differences should be considered when interpreting exercise test results and/or monitoring athletic training.


Assuntos
Altitude , Exercício Físico/fisiologia , Hipóxia/fisiopatologia , Consumo de Oxigênio/fisiologia , Oxigênio/metabolismo , Teste de Esforço , Humanos , Masculino , Respiração
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