Hypoxic Pulmonary Vasoconstriction in Humans: Tale or Myth

Hussain, Azar; Suleiman, M‐Saadeh; George, Sarah J.; Loubani, Mahmoud; Morice, AH

doi:10.2174/1874192401711010001

Cited by 22 publications

(19 citation statements)

References 96 publications

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“…We considered that stenosis of the airway decreases volume of ventilation and pulmonary perfusion due to hypoxic pulmonary vasoconstriction (HPV). HPV is fundamental physiological mechanism to optimize the ventilation perfusion matching [11]. In the present study, the F/M ratio correlated with the decreased accumulation on ventilation SPECT/CT and perfusion SPECT/CT images.…”

Section: Discussionsupporting

confidence: 61%

Diagnostic value of ventilation/perfusion single-photon emission computed tomography/computed tomography for bronchiolitis obliterans syndrome in patients after lung transplantation

Nakashima

Shinya²,

Oto

et al. 2019

Nuclear Medicine Communications

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To evaluate the diagnostic value of function volume/morphological volume ratio calculated from ventilation/perfusion single-photon emission computed tomography/computed tomography in distinguishing the lungs with bronchiolitis unilateral lungs were significantly lower in lungs with bronchiolitis obliterans syndrome (each P < 0.0001). The area under the curve values of ventilation and perfusion images were 0.97 and 0.99, respectively. Significant correlations were identified between the function volume/morphological volume ratios of ventilation and perfusion images and forced expiratory volume in 1 second (r = 0.54, P < 0.0001 and r = 0.45, P < 0.0001, respectively). The function volume/morphological volume ratio of ventilation image had a significantly weak correlation with forced vital capacity. Conclusions The function volume/morphological volume ratio enables a semi-quantitative assessment of ventilation and perfusion lung functions and is useful for diagnosing bronchiolitis obliterans syndrome after lung transplantation.

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Section: Discussionsupporting

confidence: 61%

Diagnostic value of ventilation/perfusion single-photon emission computed tomography/computed tomography for bronchiolitis obliterans syndrome in patients after lung transplantation

Nakashima

Shinya²,

Oto

et al. 2019

Nuclear Medicine Communications

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“…HPV is a rapid and reversible contraction of pulmonary arteries, whose intensity is proportional to the degree of hypoxia and it occurs independently of neural or humoral factors ( Sylvester et al, 2012 ). HPV contributes to the physiologically high PVR state during fetal life, while it allows to optimize the ratio between ventilation and perfusion during the postnatal life ( Dunham-Snary et al, 2017 ; Hussain et al, 2017 ). Pulmonary arteries also mount a maladaptive response to chronic hypoxia, known as pathological pulmonary arterial remodeling, characterized by the hyperplasic and hypertrophic thickening of medial layer and later thickening of adventitia and intima, with increased extracellular matrix deposition.…”

Section: Introductionmentioning

confidence: 99%

Revisiting the Role of TRP, Orai, and ASIC Channels in the Pulmonary Arterial Response to Hypoxia

et al. 2018

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The pulmonary arteries are exquisitely responsive to oxygen changes. They rapidly and proportionally contract as arterial PO2 decrease, and they relax as arterial PO2 is re-established. The hypoxic pulmonary vasoconstriction (HPV) is intrinsic since it does not require neural or endocrine factors, as evidenced in isolated vessels. On the other hand, pulmonary arteries also respond to sustained hypoxia with structural and functional remodeling, involving growth of smooth muscle medial layer and later recruitment of adventitial fibroblasts, secreted mitogens from endothelium and changes in the response to vasoconstrictor and vasodilator stimuli. Hypoxic pulmonary arterial vasoconstriction and remodeling are relevant biological responses both under physiological and pathological conditions, to explain matching between ventilation and perfusion, fetal to neonatal transition of pulmonary circulation and pulmonary artery over-constriction and thickening in pulmonary hypertension. Store operated channels (SOC) and receptor operated channels (ROC) are plasma membrane cationic channels that mediate calcium influx in response to depletion of internal calcium stores or receptor activation, respectively. They are involved in both HPV and pathological remodeling since their pharmacological blockade or genetic suppression of several of the Stim, Orai, TRP, or ASIC proteins in SOC or ROC complexes attenuate the calcium increase, the tension development, the pulmonary artery smooth muscle proliferation, and pulmonary arterial hypertension. In this Mini Review, we discussed the evidence obtained in in vivo animal models, at the level of isolated organ or cells of pulmonary arteries, and we identified and discussed the questions for future research needed to validate these signaling complexes as targets against pulmonary hypertension.

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“…Intratracheal instillation is more direct and consistently results in better reproducibility of virus delivery [64, 67], and depending on the GEM will produce fewer adenomas and lung carcinomas in 84 to 421 days [68]. While adenomas are benign, they still occupy space that obstructs ventilation in large [69] and smaller [70] airways leading to impairment of oxygen diffusion [71–74]. Subcutaneous tumor model (injection of cancer cells into the mouse’s flank) is another common approach to study cancer, but this approach has two disadvantages.…”

Section: Discussionmentioning

confidence: 99%

Effect of cyclical intermittent hypoxia on Ad5CMVCre induced solitary lung cancer progression and spontaneous metastases in the KrasG12D+; p53fl/fl; myristolated p110fl/fl ROSA-gfp mouse

et al. 2019

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Background Epidemiological data suggests that obstructive sleep apnea (OSA) is associated with increased cancer incidence and mortality. We investigate the effects of cyclical intermittent hypoxia (CIH), akin to the underlying pathophysiology of OSA, on lung cancer progression and metastatic profile in a mouse model. Methods Intrathoracic injection of Ad5CMVCre virus into a genetically engineered mouse (GEM) Kras G12D+/- ; p53 fl/fl ; myristolated-p110α fl/fl -ROSA-gfp was utilized to induce a solitary lung cancer. Male mice were then exposed to either CIH or Sham for 40–41 days until harvest. To monitor malignant progression, serial micro CT scans with respiratory gating (no contrast) was performed. To detect spontaneous metastases in distant organs, H&E and immunohistochemistry were performed. Results Eighty-eight percent of injected Ad5CMVCre virus was recovered from left lung tissue, indicating reliable and accurate injections. Serial micro CT demonstrated that CIH increases primary lung tumor volume progression compared to Sham on days 33 (p = 0.004) and 40 (p<0.001) post-injection. In addition, CIH increases variability in tumor volume on day 19 (p<0.0001), day 26 (p<0.0001), day 33 (p = 0.025) and day 40 (p = 0.004). Finally, metastases are frequently detected in heart, mediastinal lymph nodes, and right lung using H&E and immunohistochemistry. Conclusions Using a GEM mouse model of metastatic lung cancer, we report that male mice with solitary lung cancer have accelerated malignant progression and increased variability in tumor growth when exposed to cyclical intermittent hypoxia. Our results indicate that cyclical intermittent hypoxia is a pathogenic factor in non-small cell lung cancer that promotes the more rapid growth of developing tumors.

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Hypoxic Pulmonary Vasoconstriction in Humans: Tale or Myth

Cited by 22 publications

References 96 publications

Diagnostic value of ventilation/perfusion single-photon emission computed tomography/computed tomography for bronchiolitis obliterans syndrome in patients after lung transplantation

Diagnostic value of ventilation/perfusion single-photon emission computed tomography/computed tomography for bronchiolitis obliterans syndrome in patients after lung transplantation

Revisiting the Role of TRP, Orai, and ASIC Channels in the Pulmonary Arterial Response to Hypoxia

Effect of cyclical intermittent hypoxia on Ad5CMVCre induced solitary lung cancer progression and spontaneous metastases in the KrasG12D+; p53fl/fl; myristolated p110fl/fl ROSA-gfp mouse

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