Hypoxia, not pulmonary vascular pressure induces blood flow through intrapulmonary arteriovenous anastomoses

Blood flow through intrapulmonary arteriovenous anastomoses (IPAVA) is increased with exposure to acute hypoxia and has been associated with pulmonary artery systolic pressure (PASP). We aimed to determine the direct relationship between blood flow through IPAVA and PASP in 10 participants with no detectable intracardiac shunt by comparing: (1) isocapnic hypoxia (control); (2) isocapnic hypoxia with oral administration of acetazolamide (AZ; 250 mg, three times-a-day for 48 h) to prevent increases in PASP, and (3) isocapnic hypoxia with AZ and 8.4% NaHCO3 infusion (AZ+HCO3-) to control for AZ-induced acidosis. Isocapnic hypoxia (20 min) was maintained by end-tidal forcing, blood flow through IPAVA was determined by agitated saline contrast echocardiography and PASP was estimated by Doppler ultrasound. Arterial blood samples were collected at rest before each isocapnic-hypoxia condition to determine pH, [HCO3-], and PaCO2. AZ decreased pH (-0.08 ± 0.01), [HCO3-] (-7.1 ± 0.7 mmol/l), and PaCO2 (-4.5 ± 1.4 mmHg; p<0.01), while intravenous NaHCO3 restored arterial blood gas parameters to control levels. Although PASP increased from baseline in all three hypoxic conditions (p<0.05), a main effect of condition expressed an 11 ± 2% reduction in PASP from control (p<0.001) following AZ administration while intravenous NaHCO3 partially restored the PASP response to isocapnic hypoxia. Blood flow through IPAVA increased during exposure to isocapnic hypoxia (p<0.01) and was unrelated to PASP, cardiac output and pulmonary vascular resistance for all conditions. In conclusion, isocapnic hypoxia induces blood flow through IPAVA independent of changes in PASP and the influence of AZ on the PASP response to isocapnic hypoxia is dependent upon the H+ concentration or PaCO2. Abbreviations list: AZ, acetazolamide; FEV1, forced expiratory volume in 1 second; FIO2, fraction of inspired oxygen; FVC, forced vital capacity; Hb, total haemoglobin; HPV, hypoxic pulmonary vasoconstriction; HR, heart rate; IPAVA, intrapulmonary arteriovenous anastomoses; MAP, mean arterial pressure; PASP, pulmonary artery systolic pressure; PETCO2, end-tidal partial pressure of carbon dioxide; PETO2, end-tidal partial pressure of oxygen; PFO, patent foramen ovale; PVR, pulmonary vascular resistance; Q̇c, cardiac output; RVOT, right ventricular outflow tract; SpO2, oxyhaemoglobin saturation; SV, stroke volume; TRV, tricuspid regurgitant velocity; V̇E, minute ventilation; VTI, velocity-time integra

Tracheal Epstein-Barr Virus-Associated Smooth Muscle Tumour in an Hiv-Positive Patient

Epstein-Barr virus-related smooth muscle tumours (EBV-SMTs) are a rare but well recognized non-AIDS-defining malignancy that can also be found in several other immunosuppressed states. Pulmonary involvement of EBVSMTs is not uncommon, but it can present with multifocal lesions in any anatomical site. The present article describes an HIV-positive woman with dyspnea who was found to have a large tracheal EBV-SMT. The authors discuss their approach to diagnosis and management, and present unique follow-up bronchoscopic imaging

Dyspnea due to Pulmonary Vessel Arteritis

Pulmonary arteritis is a rare cause of pulmonary hypertension. Causes of pulmonary arteritis can be divided into primary and secondary, as well as classified according to vessel size. Only large vessel vasculitis is associated with pulmonary hypertension; primary forms include Takayasu arteritis and giant cell arteritis. The diagnosis of pulmonary arteritis can be challenging and the associated morbidity is serious without prompt, directed treatment. The authors present a case involving a 48-year-old First Nations man presenting with a six-month history of exertional dyspnea and severe stenosis of the left pulmonary artery, who was ultimately diagnosed with pulmonary arteritis related to large vessel vasculitis

Influence of methazolamide on the human control of breathing : a comparison to acetazolamide

Acetazolamide is used to prevent/treat acute mountain sickness and both central and obstructive sleep apnoea. Methazolamide, like acetazolamide reduces hypoxic pulmonary vasoconstriction, but has fewer side effects including less skeletal muscle function impairment. Since methazolamide’s effects on respiratory control in humans are unknown, we (1) compared the effects of oral methazolamide and acetazolamide on ventilatory control, and (2) determined the ventilation-log PO₂ relationship in humans. In a double blind, placebo-controlled, randomized cross-over design, we studied the effects of acetazolamide (250 mg tid), methazolamide (100 mg bid) and placebo in fourteen young male subjects who were exposed to 7 minutes of normoxic hypercapnia and to three levels of eucapnia and hypercapnic hypoxia. With placebo, methazolamide, and acetazolamide, the CO₂ sensitivities were 2.39 ± 1.29, 3.27 ± 1.82 and 2.62 ± 1.79 l/min/mmHg (NS) and estimated apnoeic thresholds were 32 ± 3, 28 ± 3 and 26 ± 3 mmHg, respectively (P < 0.001, placebo vs methazolamide and acetazolamide). The relationship between ventilation (V̇ I) and log PO₂ (using arterialized venous PO₂ in hypoxia) was linear, while neither agent influenced the relationship between hypoxic sensitivity (ΔV̇ I/Δlog PO₂) and arterial [H⁺]. Using ΔV̇ I/Δlog PO₂ rather than ΔV̇ I/ΔSaO₂ enables a more accurate estimation of oxygenation and ventilatory control in metabolic acidosis/alkalosis when right- or left-ward shifts of the oxyhaemoglobin saturation curve occur. Since acetazolamide and methazolamide has similar effects on ventilatory control, methazolamide may be preferred for indications requiring the use of a carbonic anhydrase inhibitor, avoiding some of the negative side-effects of acetazolamide.Health and Social Development, Faculty of (Okanagan)Medicine, Faculty ofOther UBCNon UBCHealth and Exercise Sciences, School of (Okanagan)Southern Medical Program (Okanagan)ReviewedFacult