Lindsey M. Boulet

Measuring the human ventilatory and cerebral blood flow response to CO2: a technical consideration for the end-tidal-to-arterial gas gradient.

Our aim was to quantify the end-tidal-to-arterial gas gradients for O2 (PET-PaO2) and CO2 (Pa-PETCO2) during a CO2 reactivity test to determine their influence on the cerebrovascular (CVR) and ventilatory (HCVR) response in subjects with (PFO+, n = 8) and without (PFO-, n = 7) a patent foramen ovale (PFO). We hypothesized that 1) the Pa-PETCO2 would be greater in hypoxia compared with normoxia, 2) the Pa-PETCO2 would be similar, whereas the PET-PaO2 gradient would be greater in those with a PFO, 3) the HCVR and CVR would be underestimated when plotted against PETCO2 compared with PaCO2, and 4) previously derived prediction algorithms will accurately target PaCO2. PETCO2 was controlled by dynamic end-tidal forcing in steady-state steps of -8, -4, 0, +4, and +8 mmHg from baseline in normoxia and hypoxia. Minute ventilation (V̇E), internal carotid artery blood flow (Q̇ICA), middle cerebral artery blood velocity (MCAv), and temperature corrected end-tidal and arterial blood gases were measured throughout experimentation. HCVR and CVR were calculated using linear regression analysis by indexing V̇E and relative changes in Q̇ICA, and MCAv against PETCO2, predicted PaCO2, and measured PaCO2. The Pa-PETCO2 was similar between hypoxia and normoxia and PFO+ and PFO-. The PET-PaO2 was greater in PFO+ by 2.1 mmHg during normoxia (P = 0.003). HCVR and CVR plotted against PETCO2 underestimated HCVR and CVR indexed against PaCO2 in normoxia and hypoxia. Our PaCO2 prediction equation modestly improved estimates of HCVR and CVR. In summary, care must be taken when indexing reactivity measures to PETCO2 compared with PaCO2.

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. Ambulatory blood pressure was measured during each condition and the following night. Vascular strain of the carotid and femoral artery, a measure of localized arterial stiffness, and hemodynamic shear patterns in the brachial and femoral arteries were measured during each condition. Brachial artery reactive hyperemia flow-mediated vasodilation was assessed before and after each condition as a measure of endothelial function. CBR function and its control over leg vascular conductance (LVC) were measured after each condition with a variable-pressure neck chamber. Intermittent hypoxia 1) increased nighttime pulse pressure by 3.2 ± 1.3 mmHg, 2) altered femoral but not brachial artery hemodynamics, 3) did not affect brachial artery endothelial function, 4) reduced vascular strain in the carotid and possibly femoral artery, and 5) shifted CBR mean arterial pressure (MAP) to higher MAP while blunting LVC responses to CBR loading. These results suggest limb-specific vascular impairments, reduced vascular strain, and CBR resetting combined with blunted LVC responses are factors in the early pathogenesis of IH-induced development of hypertension.

Comparing and characterizing transient and steady‐state tests of the peripheral chemoreflex in humans

What is the central question of this study? We aimed to characterize the cardiorespiratory and cerebrovascular responses to transient and steady‐state tests of the peripheral chemoreflex and to compare the hypoxic ventilatory responses (HVRs) between these tests. What is the main finding and its importance? The cardiovascular and cerebrovascular responses to transient tests were small in magnitude and short in duration. The steady‐state isocapnic hypoxia test elicited a larger HVR than the transient 100% N2 test, but the response magnitudes were correlated within individuals. The transient test of the HVR elicits fewer systemic effects than steady‐state techniques and may have greater experimental utility than previously appreciated.

Changes in left ventricular function and coronary blood flow velocity during isocapnic hypoxia: A cardiac magnetic resonance imaging study

Background Cardiac stress testing is the standard of care for diagnosing ischemic heart disease. Traditional stress testing involves physical or pharmacological stress to induce hyperemia and/or increase myocardial oxygen demand. Physical stress is not possible in 100% of cases however, and pharmacological stress carries rare but serious risk. We asked whether acute isocapnic hypoxia could be utilized as an alternative cardiovascular stress test.

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. sulphur hexafluoride (SF6)] on contrast conservation between two detection sites separated by a convoluted network of vessels. We hypothesized that the contrast lost between the detection sites would increase with transit times and be reduced by using contrast bubbles composed of SF6 Changing the flow and/or reducing the volume of the circulatory network manipulated transit time. Contrast conservation was measured as the ratio of outflow and inflow contrast masses. For air, 53.2 ± 3.4% (SE) of contrast was conserved at a transit time of 9.25 ± 0.02 s but dropped to 16.0 ± 1.0% at a transit time of 10.17 ± 0.06 s. Compared with air, SF6 contrast conservation was significantly greater (P < 0.05) with 114.3 ± 2.9% and 73.7 ± 3.3% of contrast conserved at a transit time of 10.39 ± 0.02 s and 13.46 ± 0.04 s, respectively. In summary, time-acoustic intensity curves can quantify agitated saline contrast, but loss of contrast due to bubble dissolution makes measuring Q̇IPAVA across varying transit time difficult. Agitated saline composed of SF6 is stabilized and may be a suitable alternative for Q̇IPAVA measurement.

Influence of prior hyperventilation duration on respiratory chemosensitivity and cerebrovascular reactivity during modified hyperoxic rebreathing

What is the central question of this study? We characterized and compared the cardiorespiratory and cerebrovascular responses to the ‘Duffin’ modified hyperoxic CO2 rebreathing test by randomly altering the prior hyperventilation duration. What is the main finding and its importance? Our main finding was that prior hyperventilation duration (1, 3 or 5 min) had no effect on cardiorespiratory and cerebrovascular responses to the hyperoxic rebreathing test, within individuals. These findings suggest that the standard 5 min prior hyperventilation duration used to clear body CO2 stores is unnecessary and can reasonably be shortened to 1 min, reducing protocol times and improving participant comfort.

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). It was hypothesized that an increase in Petco2 (hypercapnia) or decrease in Peto2 (hypoxia) would result in a significant increase in mean blood velocity in the left anterior descending artery (LADVmean) due to an increase in both blood gases and energy demand associated with the concomitant cardiovascular response. Cardiac energy demand was assessed through noninvasive measurement of the total left ventricular mechanical energy. Healthy subjects (n = 13) underwent a euoxic CO2 test (Petco2 = -8, -4, 0, +4, and +8 mmHg from baseline) and an isocapnic hypoxia test (Peto2 = 64, 52, and 45 mmHg). LADVmean was assessed using transthoracic Doppler echocardiography. Hypercapnia evoked a 34.6 ± 8.5% (mean ± SE; P < 0.01) increase in mean LADVmean, whereas hypoxia increased LADVmean by 51.4 ± 8.8% (P < 0.05). Multiple stepwise regressions revealed that both mechanical energy and changes in arterial blood gases are important contributors to the observed changes in LADVmean (P < 0.01). In summary, regulation of the coronary vasculature in humans is mediated by metabolic changes within the heart and an inherent sensitivity to arterial blood gases.

Reduced blood flow through intrapulmonary arteriovenous anastomoses at rest and during exercise in lowlanders during acclimatization 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 .

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 .

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

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. Both hypovolaemia and hypoxic pulmonary vasoconstriction play a role in the reduction of LV filling at 3800 m, but the increase in LV filling does not influence exercise capacity at this moderate altitude.