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Biomedical subjects

Joseph A Fisher

Publications and source records attributed to Joseph A Fisher.

15 recordsLinked to original sources

Novel methodology to comprehensively assess retinal arteriolar vascular reactivity to hypercapnia.

PURPOSE: (1) Describe a new methodology that permits the comprehensive assessment of retinal arteriolar vascular reactivity in response to a sustained and stable hypercapnic stimulus. (2) Determine the magnitude of the vascular reactivity response of the retinal arterioles to hypercapnic provocation in healthy, young subjects. METHODOLOGY: Eleven healthy subjects of mean age 27 years (SD 3.43) participated in the study and one eye was randomly selected. A mask attached to a sequential rebreathing circuit, and connected to a gas delivery system, was fitted to the face. To establish baseline values, subjects breathed bottled air for 15 min and at least 6 blood flow measurements of the supero-temporal arteriole were acquired using the Canon Laser Blood Flowmeter (CLBF). Air flow was then decreased until a stable increase in fractional end-tidal CO(2) concentration (F(ET)CO(2)) of 10-15% was achieved. CLBF measurements were acquired every minute (minimum of 6 measurements) during the 20-minute period of elevated F(ET)CO(2). F(et)CO(2) was then reduced to baseline levels, and 6 further CLBF measurements were acquired. Respiratory rate, blood pressure, pulse rate and oxygen saturation were monitored continuously. RESULTS: Retinal arteriolar diameter, blood velocity and blood flow increased during hypercapnia relative to baseline (p=0.0045, p<0.0001 and p<0.0001, respectively). Group mean F(ET)CO(2) showed an increase of 12.0% (SD 3.6) relative to baseline (p<0.0001). CONCLUSIONS: This study describes a new methodology that permits the comprehensive assessment of retinal arteriolar vascular reactivity in response to a sustained and stable hypercapnic stimulus. Retinal arteriolar diameter, blood velocity and blood flow increased significantly in response to a hypercapnic provocation in young, healthy subjects.

Adult↗

Vagal nerve activity contributes to improve the efficiency of pulmonary gas exchange in hypoxic humans.

The aim of this study was to test our hypothesis that both phasic cardiac vagal activity and tonic pulmonary vagal activity, estimated as respiratory sinus arrhythmia (RSA) and anatomical dead space volume, respectively, contribute to improve the efficiency of pulmonary gas exchange in humans. We examined the effect of blocking vagal nerve activity with atropine on pulmonary gas exchange. Ten healthy volunteers inhaled hypoxic gas with constant tidal volume and respiratory frequency through a respiratory circuit with a respiratory analyser. Arterial partial pressure of O(2) (P(aO(2))) and arterial oxygen saturation (S(pO(2))) were measured, and alveolar-to-arterial P(O(2)) difference (D(A-aO(2))) was calculated. Anatomical dead space (V(D,an)), alveolar dead space (V(D,alv)) and the ratio of physiological dead space to tidal volume (V(D,phys)/V(T)) were measured. Electrocardiogram was recorded, and the amplitude of R-R interval variability in the high-frequency component (RRIHF) was utilized as an index of RSA magnitude. These parameters of pulmonary function were measured before and after administration of atropine (0.02 mg kg(-1)). Decreased RRIHF (P < 0.01) was accompanied by decreases in P(aO(2)) and S(pO(2)) (P < 0.05 and P < 0.01, respectively) and an increase in D(A-aO(2)) (P < 0.05). Anatomical dead space, V(D,alv) and V(D,phys)/V(T) increased (P < 0.01, P < 0.05 and P < 0.01, respectively) after atropine administration. The blockade of the vagal nerve with atropine resulted in an increase in V(D,an) and V(D,alv) and a deterioration of pulmonary oxygenation, accompanied by attenuation of RSA. Our findings suggest that both phasic cardiac and tonic pulmonary vagal nerve activity contribute to improve the efficiency of pulmonary gas exchange in hypoxic conscious humans.

Adult↗

Modified N95 mask delivers high inspired oxygen concentrations while effectively filtering aerosolized microparticles.

STUDY OBJECTIVE: In a pandemic, hypoxic patients will require an effective oxygen (O2) delivery mask that protects them from inhaling aerosolized particles produced by others, as well as protecting the health care provider from exposure from the patient. We modified an existing N95 mask to optimize O2 supplementation while maintaining respiratory isolation. METHODS: An N95 mask was modified to deliver O2 by inserting a plastic manifold consisting of a 1-way inspiratory valve, an O2 inlet and a gas reservoir. In a prospective repeated-measures study, we studied 10 healthy volunteers in each of 3 phases, investigating (1) the fractional inspiratory concentrations of O2 (F(I)O2) delivered by the N95 O2 mask, the Hi-Ox80 O2 mask, and the nonrebreathing mask during resting ventilation and hyperventilation, each at 3 O2 flow rates; (2) the ability of the N95 mask, the N95 O2 mask, and the nonrebreathing mask to filter microparticles from ambient air; and (3) to contain microparticles generated inside the mask. RESULTS: The F(I)O2s (median [range]) delivered by the Hi-Ox80 O2 mask, the N95 O2 mask, and the nonrebreathing mask during resting ventilation, at 8 L/minute O2 flow, were 0.90 (0.79 to 0.96), 0.68 (0.60 to 0.85), and 0.59 (0.52 to 0.68), respectively. During hyperventilation, the FiO2s of all 3 masks were clinically equivalent. The N95 O2 mask, but not the nonrebreathing mask, provided the same efficiency of filtration of internal and external particles as the original N95, regardless of O2 flow into the mask. CONCLUSION: An N95 mask can be modified to administer a clinically equivalent FiO2 to a nonrebreathing mask while maintaining its filtration and isolation capabilities.

Aerosols↗

Efficiency of oxygen administration: sequential gas delivery versus "flow into a cone" methods.

OBJECTIVE: Fio2 values of a new oxygen mask that exploits efficiencies afforded by sequential gas delivery (SGD) were compared to those of a nonrebreathing mask (NRM) and a Venturi oxygen mask. DESIGN: Prospective, single-blinded, randomized study. SETTING: Laboratory study. SUBJECTS: Eight healthy male volunteers. INTERVENTIONS: Volunteers breathed through each of the masks at various minute ventilations (VE). Oxygen flows were 2, 4, and 8 L/min to the SGD mask but only 8 L/min to the other masks. MEASUREMENTS AND MAIN RESULTS: Net FIO2 was calculated from end-tidal fractional concentrations of oxygen and CO2 with the alveolar gas equation. Only the SGD mask at an oxygen flow of 8 L/min consistently provided both FIO2>0.95 (at resting VE) and higher FIO2 than the other masks at all VE. The SGD mask delivered FIO2 comparable to other masks at only a fraction of the oxygen flow and was characterized by a consistent relation between FIO2 and oxygen flow for a given VE. CONCLUSION: We conclude that SGD can be exploited to provide FIO2>0.95 with oxygen flows as low as 8 L/min, as well as accurate and efficient dosing of oxygen even in the presence of hyperpnea.

Analysis of Variance↗

Changes in respiratory control after 5 days at altitude.

These experiments examined changes in the chemoreflex control of breathing and acid-base balance after 5 days at altitude (3480 m) in six healthy males. The partial pressures of carbon dioxide (P(CO2)) at which ventilation increased during isoxic hypoxic and hyperoxic modified rebreathing tests at sea level fell significantly at altitude by mean+/-S.E.M. of 12.8+/-2.51 mmHg and 9.5+/-1.77 mmHg, respectively, but response slopes above threshold were unchanged. Altitude exposure produced a respiratory alkalosis evidenced by a decrease in mean resting end-tidal P(CO2) from 41+/-0.84 mmHg at sea level to 32+/-2.04 mmHg at altitude, but pH did not increase significantly from its sea level value. Blood samples were analyzed to discover acid-base changes, using a modification of the equations for acid-base balance proposed by [Stewart, P.A., 1983. Modern quantitative acid-base chemistry. Can. J. Physiol. Pharmacol. 61, 1444-1461]. While strong ion difference at altitude was not significantly different from its sea level value, albumin concentration was increased significantly from 38.6+/-0.30 g L(-1) to 49.8+/-0.76 g L(-1). We suggest that the respiratory alkalosis was produced by a fall in the chemoreflex threshold and pH was corrected by an elevation in the concentration of weakly dissociated protein anions.

Acclimatization↗

The impact of hypercapnia on retinal capillary blood flow assessed by scanning laser Doppler flowmetry.

AIM: To determine the effect of hypercapnia on retinal capillary blood flow using scanning laser Doppler flowmetry (SLDF). METHODS: One randomly selected eye of each of 10 normal healthy subjects (mean age 25 years, SD 2.3) was studied. Subjects breathed unrestricted air for 15 min before (baseline) and after raising fractional (percent) end-tidal concentration of CO2 (FETCO2) for 15 min by adding low flows of CO2 to air entering a sequential gas delivery circuit attached to a nasal mask. Five good quality baseline SLDF images were acquired both of the optic nerve head (ONH) and of the macula. Subsequently, a minimum of 7 sequential images were acquired during hypercapnia. Five further images were acquired of the ONH, or of the macula, after returning to unlimited air breathing. The respiratory parameters of subjects were continually monitored. RESULTS: The group mean increase in end-tidal CO2 was 14.13% (SD 4.10) relative to baseline. The nasal macula (P = 0.028) and foveal (P = 0.042) areas showed a significant increase in retinal capillary blood flow in response to hypercapnia while no significant change was noted in the ONH or temporal macula areas. Change in blood flow significantly correlated with change of FETCO2 and/or end-tidal PO2 for 3 of the 4 locations. CONCLUSIONS: Hypercapnia provoked a significant increase in retinal capillary blood flow in 2 of 4 retinal locations. Hypercapnia also induced a change in respiratory parameters that significantly correlated with change in retinal capillary blood flow in 3 of the 4 locations.

Adult↗

Efficient breathing circuit for use at altitude.

We describe a case report of a subject suffering high-altitude cerebral and pulmonary edema successfully treated with low flow rates of supplemental oxygen administered with a breathing system designed to conserve oxygen supplies at high altitude.

Altitude Sickness↗

Preoperative and postoperative mapping of cerebrovascular reactivity in moyamoya disease by using blood oxygen level-dependent magnetic resonance imaging.

OBJECT: The ability to map cerebrovascular reactivity (CVR) at the tissue level in patients with moyamoya disease could have considerable impact on patient management, especially in guiding surgical intervention and assessing the effectiveness of surgical revascularization. This paper introduces a new noninvasive magnetic resonance (MR) imaging-based method to map CVR. Preoperative and postoperative results are reported in three cases to demonstrate the efficacy of this technique in assessing vascular reserve at the microvascular level. METHODS: Three patients with angiographically confirmed moyamoya disease were evaluated before and after surgical revascularization. Measurements of CVR were obtained by rapidly manipulating end-tidal PCO2 between hypercapnic and hypocapnic states during MR imaging. The CVR maps were then calculated by comparing the percentage of changes in MR signal with changes in end-tidal PCO2. Presurgical CVR maps showed distinct regions of positive and negative reactivity that correlated precisely with the vascular territories supplied by severely narrowed vessels. Postsurgical reactivity maps demonstrated improvement in the two patients with positive clinical outcome and no change in the patient in whom a failed superficial temporal artery-middle cerebral artery bypass was performed. CONCLUSIONS: Magnetic imaging-based CVR mapping during rapid manipulation of end-tidal PCO2 is an exciting new method for determining the location and extent of abnormal vascular reactivity secondary to proximal large-vessel stenoses in moyamoya disease. Although the study group is small, there seems to be considerable potential for guiding preoperative decisions and monitoring efficacy of surgical revascularization.

Adult↗

Calculation of O2 consumption during low-flow anesthesia from tidal gas concentrations, flowmeter, and minute ventilation.

We present the principles of a new method to calculate O2 consumption (V*O2) during low-flow anesthesia with a circle circuit when the source gas flows, end-tidal O2 concentrations and patient inspired minute ventilation are known. This method was tested in a model with simulated O2 uptake and CO2 production. The difference between calculated V*O2 and simulated V*O2 was 0.01 +/- 0.02 L/min. A similar approach can be used to calculate uptake of inhaled anesthetics. At present, with this method, the limiting factor in precision of measurement of V*O2 and uptake of anesthetic is the precision of measurement of gas flow and gas concentration (especially O2 concentration in end-tidal gas, FETO2) available in clinical anesthetic units.

Anesthesia, Inhalation↗

The effects of carbon monoxide on respiratory chemoreflexes in humans.

As protection against low-oxygen and high-carbon-dioxide environments, the respiratory chemoreceptors reflexly increase breathing. Since CO is also frequently present in such environments, it is important to know whether CO affects the respiratory chemoreflexes responsiveness. Although the peripheral chemoreceptors fail to detect hypoxia produced by CO poisoning, whether CO affects the respiratory chemoreflex responsiveness to carbon dioxide is unknown. The responsiveness of 10 healthy male volunteers were assessed before and after inhalation of approximately 1200 ppm CO in air using two iso-oxic rebreathing tests; hypoxic, to emphasize the peripheral chemoreflex, and hyperoxic, to emphasize the central chemoreflex. Although mean (SEM) COHb values of 10.2 (0.2)% were achieved, no statistically significant effects of CO were observed. The average differences between pre- and post-CO values for ventilation response threshold and sensitivity were -0.5 (0.9) mmHg and 0.8 (0.3) L/min/mmHg, respectively, for hyperoxia, and 0.7 (1.1) mmHg and 1.2 (0.8) L/min/mmHg, respectively, for hypoxia. The 95% confidence intervals for the effect of CO were small. We conclude that environments with low levels of CO do not have a clinically significant effect acutely on either the central or the peripheral chemoreflex responsiveness to carbon dioxide.

Adult↗

Rescuer position for tracheal intubation on the ground.

BACKGROUND: Emergency oral tracheal intubations in the pre-hospital setting can be more difficult because the rescuer's position with respect to a patient lying on the ground may not provide optimal conditions for intubation. Since optimal visualisation of the larynx often depends on the force generated during laryngoscopy, we measured the pressure required for intubation (P(i)) as well as the maximum pressure (P(max)) that can be generated with the laryngoscopy blade in seven intubator positions. METHODS: Nineteen hospital personnel with intubation experience participated in this study. A modified #3 Macintosh laryngoscope blade was used to measure the pressure exerted on the tongue of a manikin placed on the ground during intubation. The following positions were studied: standard, sitting, prone, kneeling, left and right lateral decubitus and straddling. RESULTS: Intubating in the straddling position required the lowest P(i), as a percent of P(max) (68+/-14%). This was significantly less than the prone, right lateral decubitus and sitting positions. (Tukey's W procedure, P<0.05) CONCLUSION: The straddling position affords the intubator significantly more reserve force than the prone, right lateral decubitus or sitting position. We suggest that the straddling position may be an advantageous position for pre-hospital intubations especially when visualisation of the glottis is difficult.

Adult↗

A simple breathing circuit to maintain isocapnia during measurements of the hypoxic ventilatory response.

We report the development and testing of a simple breathing circuit that maintains isocapnia in human subjects during hypoxic hyperpnea. In addition, the circuit permits rapid switching between two gas mixtures with different partial pressures of oxygen. Eleven volunteers breathed repeated cycles of exposure to air (2 min of 21% O(2), balance N(2)) and hypoxia (2 min of 8.3+/-0.1% O(2), balance N(2)). Hypoxia induced significant increases in minute ventilation, breathing frequency and tidal volume (P < 0.05) that were consistent over repeated cycles of hypoxia (P > 0.1, one-way ANOVA). The system successfully maintained isocapnia in all subjects, with an average change in end-tidal CO(2) of only -0.2 mmHg during hyperventilation in hypoxia (range 0.4 to -0.8 mmHg). This system may be suitable for repeated tests of the hypoxic ventilatory response (HVR) and may prove useful for exploring intra- and inter-individual variability of HVR in humans.

Adult↗

Normocapnia improves cerebral oxygen delivery during conventional oxygen therapy in carbon monoxide-exposed research subjects.

STUDY OBJECTIVE: We determine whether maintaining normocapnia during hyperoxic treatment of carbon monoxide-exposed research subjects improves cerebral oxygen delivery. METHODS: This experiment used a randomized, single-blinded, crossover design. We exposed 14 human research subjects to carbon monoxide until their carboxyhemoglobin levels reached 10% to 12%. We then treated each research subject with 60 minutes of hyperoxia with or without normocapnia. Research subjects returned after at least 24 hours, were reexposed to carbon monoxide, and were given the alternate treatment. Relative changes in cerebral oxygen delivery were calculated as the product of blood oxygen content and middle cerebral artery velocity (an index of cerebral blood flow) as measured by transcranial Doppler ultrasonography. RESULTS: Maintaining normocapnia during hyperoxic treatment resulted in significantly higher cerebral oxygen delivery compared with standard oxygen treatment (P <.05; 95% confidence interval at 60 minutes 2.8% to 16.7%) as a result of the prevention of hypocapnia-induced cerebral vasoconstriction and more rapid elimination of carbon monoxide due to increased minute ventilation. CONCLUSION: If severely poisoned patients respond like our research subjects, maintaining normocapnia during initial hyperoxic treatment of carbon monoxide poisoning may lead to increased oxygen delivery to the brain. Determining the effect of such a change in conventional treatment on outcome requires clinical studies.

Adult↗

Direct effect of Pa(CO2) on respiratory sinus arrhythmia in conscious humans.

Respiratory sinus arrhythmia (RSA) may improve the efficiency of pulmonary gas exchange by matching the pulmonary blood flow to lung volume during each respiratory cycle. If so, an increased demand for pulmonary gas exchange may enhance RSA magnitude. We therefore tested the hypothesis that CO2 directly affects RSA in conscious humans even when changes in tidal volume (V(T)) and breathing frequency (F(B)), which indirectly affect RSA, are prevented. In seven healthy subjects, we adjusted end-tidal PCO2 (PET(CO2)) to 30, 40, or 50 mmHg in random order at constant V(T) and F(B). The mean amplitude of the high-frequency component of R-R interval variation was used as a quantitative assessment of RSA magnitude. RSA magnitude increased progressively with PET(CO2) (P < 0.001). Mean R-R interval did not differ at PET(CO2) of 40 and 50 mmHg but was less at 30 mmHg (P < 0.05). Because V(T) and F(B) were constant, these results support our hypothesis that increased CO2 directly increases RSA magnitude, probably via a direct effect on medullary mechanisms generating RSA.

Adult↗