Quantification of shunt fraction using contrast ultrasound and indicator dilution in an in vitro model.

Transthoracic saline contrast echocardiography is commonly used to assess intrathoracic shunt flow in vivo. Though the technique has many advantages (safe, simple, repeatable), the measurement technique lacks specificity, and the contrast agent has limited stability. This study sought to determine if the indicator dilution modeling technique could be applied to ultrasound contrast data to quantify shunt fraction and to determine if buoyant force has a significant effect on microbubble pathway determination at a "vascular" bifurcation.

Acute hyperglycemia does not affect central respiratory chemoreflex responsiveness to CO in healthy humans.

The central respiratory chemoreceptor complex (CCRC) is comprised of brainstem neurons and surrounding interoceptors, which collectively increase ventilation in response to elevated brainstem tissue CO/[H] (i.e., central chemoreflex; CCR).

Regional differences in cerebrovascular reactivity in response to acute isocapnic hypoxia in healthy humans: Methodological considerations.

The cerebrovasculature responds to blood gas challenges. Regional differences (anterior vs. posterior) in cerebrovascular responses to increases in CO have been extensively studied.

Cardiorespiratory plasticity in humans following two patterns of acute intermittent hypoxia.

New Findings: What is the central question of this study? Do cardiorespiratory experience-dependent effects (EDEs) differ between two different stimulus durations of acute isocapnic intermittent hypoxia (IHx; 5-min vs. 90-s cycles between hypoxia and normoxia)? What is the main finding and its importance? There was long-term facilitation in ventilation and blood pressure in both IHx protocols, but there was no evidence of progressive augmentation or post-hypoxia frequency decline. Not all EDEs described in animal models translate to acute isocapnic IHx responses in humans, and cardiorespiratory responses to 5-min versus 90-s on/off IHx protocols are largely similar.

The influence of increased venous return on right ventricular dyssynchrony during acute and sustained hypoxaemia.

New Findings: What is the central question of this study? Right ventricular dyssynchrony is a marker of function that is elevated in healthy individuals exposed to acute hypoxia, but does it remain elevated during sustained exposure to high altitude hypoxia, and can it be normalised by augmenting venous return? What is the main finding and its importance? For the first time it is demonstrated that (i) increasing venous return in acute hypoxia restores the synchrony of right ventricular contraction and (ii) dyssynchrony is evident after acclimatisation to high altitude, and remains sensitive to changes in venous return. Therefore, the interpretation of right ventricular dyssynchrony requires consideration the prevailing haemodynamic state.

Abstract: Regional heterogeneity in timing of right ventricular (RV) contraction (RV dyssynchrony; RVD) occurs when pulmonary artery systolic pressure (PASP) is increased during acute hypoxia.

Influence of blood Po on the stability of agitated saline contrast.

The utility of transthoracic saline contrast echocardiography (TTSCE) to assess blood flow through intrapulmonary arteriovenous anastomoses (Q̇) in humans is limited due to the potential destabilizing effects of the gas concentration gradients established in varied blood-gas environments. This study assessed the specific effect of a hyperoxic and mixed venous blood-gas environment on the stability of saline contrast. We hypothesized that the rate of contrast mass lost in hyperoxic blood would be similar to mixed venous due to the establishment of equal and opposing gas gradients (O, N, CO) created when the partial pressure of dissolved gases is manipulated.

Angiotensin II-Type I Receptor Antagonism Does Not Influence the Chemoreceptor Reflex or Hypoxia-Induced Central Sleep Apnea in Men.

Components of the renin-angiotensin system (RAS) situated within the carotid body or central nervous system may promote hypoxia-induced chemoreceptor reflex sensitization or central sleep apnea (CSA). We determined if losartan, an angiotensin-II type-I receptor (ATR) antagonist, would attenuate chemoreceptor reflex sensitivity before or after 8 h of nocturnal hypoxia, and consequently CSA severity. In a double-blind, randomized, placebo-controlled, crossover protocol, 14 men (age: 25 ± 2 years; BMI: 24.

Acute intermittent hypercapnic hypoxia and sympathetic neurovascular transduction in men.

Key Points: Intermittent hypoxia leads to long-lasting increases in muscle sympathetic nerve activity and blood pressure, contributing to increased risk for hypertension in obstructive sleep apnoea patients. We determined whether augmented vascular responses to increasing sympathetic vasomotor outflow, termed sympathetic neurovascular transduction (sNVT), accompanied changes in blood pressure following acute intermittent hypercapnic hypoxia in men. Lower body negative pressure was utilized to induce a range of sympathetic vasoconstrictor firing while measuring beat-by-beat blood pressure and forearm vascular conductance.

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

New Findings: What is the central question of this study? Acetazolamide and methazolamide both reduce hypoxic pulmonary vasoconstriction equally, but methazolamide does not impair skeletal muscle function. The effect of methazolamide on respiratory control in humans is not yet known. What is the main finding and its importance? Similar to acetazolamide after chronic oral administration, methazolamide causes a metabolic acidosis and shifts the ventilatory CO response curve leftwards without reducing O sensitivity.

UBC-Nepal expedition: phenotypical evidence for evolutionary adaptation in the control of cerebral blood flow and oxygen delivery at high altitude.

Key Points: Sherpa have lived in the Nepal Himalaya for 25-40 thousand years and display positive physiological adaptations to hypoxia. Sherpa have previously been demonstrated to suffer less negative cerebral side effects of ascent to extreme altitude, yet little is known as to whether or not they display differential regulation of oxygen delivery to the brain compared to lowland natives. We demonstrate that Sherpa have lower brain blood flow during ascent to and acclimatization at high altitude compared to lowlanders and that this difference in flow is not attributable to factors such as mean arterial pressure, blood viscosity and pH.

Ventilatory responses to acute hypoxia and hypercapnia in humans with a patent foramen ovale.

Subjects with a patent foramen ovale (PFO) have blunted ventilatory acclimatization to high altitude compared with subjects without PFO. The blunted response observed could be because of differences in central and/or peripheral respiratory chemoreflexes. We hypothesized that compared with subjects without a PFO (PFO-), subjects with a PFO (PFO+) would have blunted ventilatory responses to acute hypoxia and hypercapnia.

Attenuation of human hypoxic pulmonary vasoconstriction by acetazolamide and methazolamide.

Acetazolamide (AZ), a carbonic anhydrase inhibitor used for preventing altitude illness attenuates hypoxic pulmonary vasoconstriction (HPV) while improving oxygenation. Methazolamide (MZ), an analog of acetazolamide, is more lipophilic, has a longer half-life, and activates a major antioxidant transcription factor. However, its influence on the hypoxic pulmonary response in humans is unknown.

The independent effects of hypovolaemia and pulmonary vasoconstriction on ventricular function and exercise capacity during acclimatisation to 3800 m.

Key Points: We sought to determine the isolated and combined influence of hypovolaemia and hypoxic pulmonary vasoconstriction on the decrease in left ventricular (LV) function and maximal exercise capacity observed under hypobaric hypoxia. We performed echocardiography and maximal exercise tests at sea level (344 m), and following 5-10 days at the Barcroft Laboratory (3800 m; White Mountain, California) with and without (i) plasma volume expansion to sea level values and (ii) administration of the pulmonary vasodilatator sildenafil in a double-blinded and placebo-controlled trial. The high altitude-induced reduction in LV filling and ejection was abolished by plasma volume expansion but to a lesser extent by sildenafil administration; however, neither intervention had a positive effect on maximal exercise capacity.

Influence of myocardial oxygen demand on the coronary vascular response to arterial blood gas changes in humans.

It remains unclear if the human coronary vasculature is inherently sensitive to changes in arterial Po and Pco or if coronary vascular responses are the result of concomitant increases in myocardial O consumption/demand ([Formula: see text]). We hypothesized that the coronary vascular response to Po and Pco would be attenuated in healthy men when [Formula: see text] was attenuated with β-adrenergic receptor blockade. Healthy men (age: 25 ± 1 yr, n = 11) received intravenous esmolol (β-adrenergic receptor antagonist) or volume-matched saline in a double-blind, randomized crossover study and were exposed to poikilocapnic hypoxia, isocapnic hypoxia, and hypercapnic hypoxia.

Reduced blood flow through intrapulmonary arteriovenous anastomoses during exercise in lowlanders acclimatizing to high altitude.

What is the central question of this study? The aim was to determine, using the technique of agitated saline contrast echocardiography, whether exercise after 4-7 days at 5050 m would affect blood flow through intrapulmonary arteriovenous anastomoses (Q̇IPAVA) compared with exercise at sea level. What is the main finding and its importance? Despite a significant increase in both cardiac output and pulmonary pressure during exercise at high altitude, there is very little Q̇IPAVA at rest or during exercise after 4-7 days of acclimatization. Mathematical modelling suggests that bubble instability at high altitude is an unlikely explanation for the reduced Q̇IPAVA.

Intra-individual variability in cerebrovascular and respiratory chemosensitivity: Can we characterize a chemoreflex "reactivity profile"?

Intra-individual variability in the magnitude of human cerebrovascular and respiratory chemoreflex responses is largely unexplored. By comparing response magnitudes of cerebrovascular CO reactivity (CVR; middle and posterior cerebral arteries; MCA, PCA), central (CCR; CO) and peripheral respiratory chemoreflexes (PCR; CO and O), we tested the hypothesis that a within-individual reactivity magnitude profile could be characterized. The magnitudes of CVR and CCR were tested with hyperoxic rebreathing and PCR magnitudes were tested through transient respiratory tests (TT-CO, hypercapnia; TT-N, hypoxia).

Intermittent hypoxia and arterial blood pressure control in humans: role of the peripheral vasculature and carotid baroreflex.

Intermittent hypoxia (IH) occurs in association with obstructive sleep apnea and likely contributes to the pathogenesis of hypertension. The purpose of this study was to examine the putative early adaptations at the level of the peripheral vasculature and carotid baroreflex (CBR) that may promote the development of hypertension. Ten healthy male participants (26 ± 1 yr, BMI = 24 ± 1 kg/m(2)) were exposed to 6 h of IH (1-min cycles of normoxia and hypoxia) and SHAM in a single-blinded, counterbalanced crossover study design.

A methodological approach for quantifying and characterizing the stability of agitated saline contrast: implications for quantifying intrapulmonary shunt.

Agitated saline contrast echocardiography is often used to determine blood flow through intrapulmonary arteriovenous anastomoses (Q̇IPAVA). We applied indicator dilution theory to time-acoustic intensity curves obtained from a bolus injection of hand-agitated saline contrast to acquire a quantitative index of contrast mass. Using this methodology and an in vitro model of the pulmonary circulation, the purpose of this study was to determine the effect of transit time and gas composition [air vs.

The effects of graded changes in oxygen and carbon dioxide tension on coronary blood velocity independent of myocardial energy demand.

In humans, coronary blood flow is tightly regulated by microvessels within the myocardium to match myocardial energy demand. However, evidence regarding inherent sensitivity of the microvessels to changes in arterial partial pressure of carbon dioxide and oxygen is conflicting because of the accompanied changes in myocardial energy requirements. This study aimed to investigate the changes in coronary blood velocity while manipulating partial pressures of end-tidal CO2 (Petco2) and O2 (Peto2).