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Biomedical subjects

B E Shykoff

Publications and source records attributed to B E Shykoff.

At least 19 recordsLinked to original sources

Revised one-step method for determination of cardiac output.

Cardiac output (Q) is a determinant of blood pressure and O(2) delivery and is critical in the maintenance of homeostasis, particularly during environmental stress and exercise. Cardiac output can be determined invasively in patients; however, indirect methods are required for other situations. Soluble gas techniques are widely used to determine (Q). Historically, measurements during a breathhold, prolonged expiration and rebreathing to CO(2) equilibrium have been used; however, with limitations, especially during stress. Farhi and co-workers developed a single-step CO(2) rebreathing method, which was subsequently revised by his group, and has been shown to be reliable and compared closely to direct, invasive measures. V(CO2), P(ACO2), and P(VCO2) are determined during a 12-25s rebreathing, using the appropriate tidal volume, and (Q) is calculated. This method can provide accurate data in laboratory and field experiments during exercise, increased or decreased gravity, water immersion, lower body pressure, head-down tilt, altered ambient pressure or changes in inspired gas composition.

Algorithms↗

Cardiac output: a view from Buffalo.

Cardiac output (Q) is a primary determinant of blood pressure and O2 delivery and is critical in the maintenance of homeostasis, particularly during environmental stress. Cardiac output can be determined invasively in patients; however, indirect methods are required for other situations. Soluble gas techniques are widely used to determine Q. Historically, measurements during a breathhold, prolonged expiration and rebreathing to CO2 equilibrium have been used; however, with limitations, especially during stress. Farhi and co-workers developed a single-step CO2 rebreathing method, which was subsequently revised by his group, and has been shown to be valid (compared to direct measures) and reliable. Carbon dioxide output (VCO2), partial pressure of arterial CO2 (PaCO2), and partial pressure of mixed venous CO2 (Pv(CO2)) are determined during 12-25 s of rebreathing, using the appropriate tidal volume, and Q is calculated. This method has the utility to provide accurate data in laboratory and field experiments during exercise, increased and micro-gravity, water immersion, lower body pressure, head-down tilt, and changes in gas composition and pressure. Utilizing the Buffalo CO2 rebreathing method it has been shown that the Q can adjust to a wide range of changes in environments maintaining blood pressure and O2 delivery at rest and during exercise.

Algorithms↗

Office blood pressures, arterial compliance characteristics, and estimated cardiac load.

Because of rising interest in new methods to detect arterial diseases, we compared data from 3 different compliance-related techniques to measure arterial stiffness: systolic pulse contour analysis, diastolic pulse contour analysis (modified Windkessel model), and muscular (brachial) artery compliance by cuff plethysmography. Variables measured in the sitting position were compared with each other, with clinic blood pressures (BPs), and with the cardiac time-tension integral (CTTI) in 63 established hypertensive and 28 age-matched normotensive subjects. Hypertensives demonstrated marginal reductions in C(1) (thought to represent reduced large vessel compliance) and increased central systolic BP augmentation. In contrast, muscular artery compliance tended to be greater in the hypertensives despite normal brachial arterial diameters. C(2), suggested to be an indicator of small artery properties, was similar in both groups. CTTI was strongly related to systolic pressure (r=0.81), integrated mean arterial pressure (r=0.83), and systolic pressure-heart rate product (r=0.85) and was less strongly related to diastolic (r=0.71) or pulse pressure (r=0.57). Weak correlations were observed between CTTI and measured compliance-related variables, which also showed absent or weak correlations among themselves. We conclude that the weak relationships among BP and compliance-related variables could be due to intrinsic differences in the properties of large and small arteries, theoretical methodological weaknesses, measurement artifacts, or intrinsic hemodynamic differences of the sitting position. At present, compliance-related variables provide little additional advantage over cuff BP in the office estimation of cardiac work.

Arteries↗

Diameter, pressure and compliance relationships in dorsal hand veins.

The diameter-pressure characteristics of dorsal hand veins previously have not been characterized. In this study, the effects of distending pressure with and without infused norepinephrine on diameter and compliance were observed. The elevation needed for venous collapse was measured, and the effects of baseline constriction on venous reactivity were assessed. In seven supine subjects, a brachial cuff on an elevated arm was used to generate distending pressures while a linear variable displacement transformer (LVDT) measured changes in venous diameter. Arctangent functions of distending pressure were fitted to the normalized diameter, then compliance functions were calculated. In supine subjects, 5-15 cm of elevation emptied dorsal hand veins. Norepinephrine decreased the venous diameter at any distending pressure by increasing the P50 without significantly changing the midpoint slope. Compliance was a nearly single-valued function of the normalized diameter with a maximum value at about 60% distention. Reactivity depends on distending pressure and baseline P50. Percentage constriction is a function of initial and final P50 and of distending pressure.

Blood Pressure↗

Pet ownership, but not ace inhibitor therapy, blunts home blood pressure responses to mental stress.

In the present study, we evaluated the effect of a nonevaluative social support intervention (pet ownership) on blood pressure response to mental stress before and during ACE inhibitor therapy. Forty-eight hypertensive individuals participated in an experiment at home and in the physician's office. Participants were randomized to an experimental group with assignment of pet ownership in addition to lisinopril (20 mg/d) or to a control group with only lisinopril (20 mg/d). On each study day, blood pressure, heart rate, and plasma renin activity were recorded at baseline and after each mental stressor (serial subtraction and speech). Before drug therapy, mean responses to mental stress did not differ significantly between experimental and control groups in heart rate (94 [SD 6.8] versus 93 [6.8] bpm), systolic blood pressure (182 [8.0] versus 181 [8.3] mm Hg), diastolic blood pressure (120 [6.6] versus 119 [7.9] mm Hg), or plasma renin activity (9.4 [0.59] versus 9.3 [0.57] ng. mL(-1). h(-1)). Lisinopril therapy lowered resting blood pressure by approximately 35/20 mm Hg in both groups, but responses to mental stress were significantly lower among pet owners relative to those who only received lisinopril (P<0.0001; heart rate 81 [6.3] versus 91 [6.5] bpm, systolic blood pressure 131 [6.8] versus 141 [7.8] mm Hg, diastolic blood pressure 92 [6.3] versus 100 [6.8] mm Hg, and plasma renin activity 13.9 [0.92] versus 16.1 [0.58] ng. mL(-1). h(-1)). We conclude that ACE inhibitor therapy alone lowers resting blood pressure, whereas increased social support through pet ownership lowers blood pressure response to mental stress.

Analysis of Variance↗

Arterial stiffness: clinical relevance, measurement, and treatment.

Hardening of the pulse, first described thousands of years ago by Chinese healers, was known even then to be an adverse prognostic sign. In Western medicine, the association of aging, increased large-arterial stiffness, and systolic hypertension has been recognized for more than a century. Yet the adverse consequences of age-related arterial stiffness still receive little attention in everyday clinical practice, perhaps because clinicians assume that nothing can be done about the process. Recent developments, however, suggest that improved clinical recognition of age-related vascular stiffening will lead to better therapy and improved outcomes for patients with hypertension.

Aging↗

Heparin attenuates norepinephrine-induced venoconstriction.

Reversal by heparin of norepinephrine-induced constriction of normal hand veins was studied. Venous size was measured using a linear variable differential transformer (LVDT) during infusions of saline, norepinephrine, insulin and norepinephrine, and graded doses of heparin with norepinephrine. Heparin reduced the venoconstrictive effects of norepinephrine (p < 0.01), with the effects beginning at 18.5 nmol/min (0.05 U/min) and reaching a maximum between 185 nmol/min and 1.85 mumol/min (0.5 and 5 U/min). Maximal heparin-induced venorelaxation correlated with the maximal insulin effect within individuals (r = 0.8, p < 0.01) and was unchanged by the addition of insulin. Methylene blue, a non-specific inhibitor of the nitric oxide cGMP cascade, reduced heparin-induced venorelaxation. In conclusion, heparin in either physiologic or pharmacologic concentration attenuated norepinephrine-induced venoconstriction. A common mechanism of venorelaxation by heparin and insulin is not excluded given the correlation and lack of additivity of maximum effects and their inhibition by methylene blue.

Adult↗

Cardiovascular response to submaximal exercise in sustained microgravity.

Cardiac output (Q), heart rate (HR), blood pressure, and oxygen consumption (VO2) were measured repeatedly both at rest and at two levels of exercise in six subjects during microgravity exposure. Exercise was at 30 and 60% of the workload producing the individual's maximal VO2 in 1 G. Three of the subjects were on a 9-day flight, Spacelab Life Sciences-1, and three were on a 15-day flight, Spacelab Life Sciences-2. We found no temporal differences during the flights. Thus we have combined all microgravity measurements to compare in-flight values with erect or supine control values. At rest, Q in flight was 126% of Q erect (P < 0.01) but was not different from Q supine, and HR in flight was 81% of HR erect (P < 0.01) and 91% of HR supine (P < 0.05). Thus resting stroke volume (SV) in flight was 155% of SV erect (P < 0.01) and 109% SV supine (P < 0.05). Resting mean arterial blood pressure and diastolic pressure were lower in flight than erect (P < 0.05). Exercise values were considered as functions of VO2. The increase in Q with VO2 in flight was less than that at 1 G (slope 3.5 vs. 6.1 x min-1.l-1.min-1). SV in flight fell with increasing VO2, whereas SV erect rose and SV supine remained constant. The blood pressure response to exercise was not different in flight from erect or supine. We conclude that true microgravity causes a cardiovascular response different from that seen during any of its putative simulations.

Adult↗

Phrenic neural output during hypoxia in dogs: constant-flow ventilation vs. spontaneous breathing.

We studied the effects of removing cyclic pulmonary afferent neural information on respiratory pattern generation in anesthetized dogs. Phrenic neural output during spontaneous breathing (SB) was compared with that occurring during constant-flow ventilation (CFV) at several levels of eucapnic hypoxemia. Hypoxia caused an increase in both the frequency and the amplitude of the moving time average (MTA) phrenic neurogram during both SB and CFV. The change in frequency as arterial saturation was reduced from 90 to 60% during SB was significantly higher than that during CFV [SB, 32.3 +/- 10.9 (SD) breaths/min; CFV, 10.3 +/- 5.8 breaths/min; P = 0.001]. By contrast, the increase in the amplitude of the MTA phrenic neurogram was smaller (SB, 0.62 +/- 0.68 units; CFV, 1.35 +/- 0.81 units; P = 0.01). The changes in frequency with hypoxia during both modes of ventilation resulted primarily from a shortening of expiratory time. Both inspiratory time and expiratory time were greater during CFV than during SB, but their change in response to hypoxia was not significantly different. We conclude that the amplitude response of the MTA phrenic neurogram to hypoxia is similar to that seen during hypercapnia; in the presence of phasic afferent feedback the MTA amplitude response is decreased and the frequency response is increased relative to the response observed in the absence of phasic afferents.

Afferent Pathways↗

Respiratory sinus arrhythmia in dogs. Effects of phasic afferents and chemostimulation.

We examined the hypothesis that respiratory sinus arrhythmia (RSA) is primarily a central phenomenon and thus that RSA is directly correlated with respiratory controller output. RSA was measured in nine anesthetized dogs, first during spontaneous breathing (SB) and then during constant flow ventilation (CFV), a technique whereby phasic chest wall movements and thoracic pressure swings are eliminated. Measurements of the heart rate and of the moving time averaged (MTA) phrenic neurogram during these two ventilatory modes were made during progressive hypercapnia and progressive hypoxia. RSA divided by the MTA phrenic amplitude (RSAa) showed a power-law relationship with both arterial carbon dioxide partial pressure (PaCO2) and oxygen saturation (SaO2), but with different exponents for different conditions. However, the power-law relation between RSAa and respiratory frequency had an exponent indistinguishable from -2 whether hypoxia or hypercapnia was the stimulus for increased respiratory drive, and during both CFV and spontaneous breathing (-1.9 +/- 0.4, hypoxia, SB; -1.8 +/- 0.7, hypoxia, CFV; -2.1 +/- 0.8, hypercapnia, SB; -1.9 +/- 0.7, hypercapnia, CFV). We conclude that respiratory sinus arrhythmia is centrally mediated and directly related to respiratory drive, and that changes in blood gases and phasic afferent signals affect RSA primarily by influencing respiratory drive.

Afferent Pathways↗

Interpretation of the krypton-81m dynamic series: the distribution of a tidal breath.

Lung scans during cyclic breathing of krypton-81m, an isotope with a 13-s half-life, were acquired in "list mode," where both temporal and spatial information are preserved. Subjects in the left lateral decubitus position breathed with two tidal volumes at each of two frequencies. Profiles of total activity over the acquisition period were examined. They showed little effect of frequency or tidal volume on the distribution of air between dependent and non-dependent regions. Dynamic series for ensemble-averaged breaths were constructed. The regional flow per unit volume was shown to correspond to the time derivative of the regional activity of the dynamic series divided by the corresponding activity. Both the relative timing of the gas flow to different lung regions and the flow per unit volume as a function of time were obtained from the dynamic series. The dependent lung was seen to be better ventilated throughout the respiratory cycle except for brief periods at the start of inspiration and the end of expiration. Most of the dead-space gas can be construed to enter and leave the dependent lung.

Female↗

Airflow and normal lung sounds.

The relationship between total air flow and normal breath sounds recorded at 2 sites on the chest was investigated. Sounds were measured during rhythmic breathing, during flow rate tracking, and during flow rate tracking against an external resistance by subjects seated and in the left lateral decubitus position. The sound amplitude during inspiration varied directly with the square of the air flow at the mouth. Changes in subject position and breathing pattern altered the gain between the square of the flow and the sound amplitude but not the functional relationship.

Adult↗

A model-free method for mass spectrometer response correction.

A new method for correction of mass spectrometer output signals is described. Response-time distortion is reduced independently of any model of mass spectrometer behavior. The delay of the system is found first from the cross-correlation function of a step change and its response. A two-sided time-domain digital correction filter (deconvolution filter) is generated next from the same step response data using a regression procedure. Other data are corrected using the filter and delay. The mean squared error between a step response and a step is reduced considerably more after the use of a deconvolution filter than after the application of a second-order model correction. O2 consumption and CO2 production values calculated from data corrupted by a simulated dynamic process return to near the uncorrupted values after correction. Although a clean step response or the ensemble average of several responses contaminated with noise is needed for the generation of the filter, random noise of magnitude less than or equal to 0.5% added to the response to be corrected does not impair the correction severely.

Cardiac Output↗

Effects of unequal pressure swings and different waveforms on distribution of ventilation: a non-linear model simulation.

In an attempt to understand the role of unequal pleural pressure swings and of different waveforms of pleural pressure variation in the distribution of ventilation during cyclic breathing, a mathematical model simulation was performed. The computer model which incorporates non-linear resistances and compliances as well as sinusoidal, square, and triangular waveforms of pleural pressure variations indicates that the distribution of ventilation is insensitive to the waveform of the pleural pressure. The distribution is also little changed by the depth of breathing (amplitude), but it is affected significantly by the pattern of different pressures over the regions of the model. For sinusoidal, triangular, and low amplitude square wave pleural pressures with equal amplitudes on both compartments, air was distributed preferentially to the lower compartment under the influence of the static pressure difference. With unequal amplitudes, more air flowed to the compartment experiencing the larger pressure swing. This was virtually independent of the waveform and of the amplitudes of the pleural pressure variation. Comparison of the present results with a constant flow model reveals that the overall distribution of tidal air during cyclic breathing is very different from the results obtained in constant rate inspiration experiments or in bolus distribution experiments. New experiments performed under cyclic breathing conditions are thus indicated.

Humans↗

Pulmonary effects of submerged oxygen breathing: 4-, 6-, and 8-hour dives at 140 kPa.

Elevated inspired oxygen partial pressures (PO2) may cause pulmonary oxygen toxicity (PO2T). However, normal variability and water immersion also cause pulmonary function (PF) changes. In 21 subjects, we measured the variability of flow-volume parameters and diffusing capacity for carbon monoxide (DLCO) for six weeks without diving. In 24 divers, we compared the effects of air (P(I)O2 = 0.3 atm = 30 kPa) and oxygen (P(I)O2 = 1.4 atm = 140 kPa) during paired resting dives of 4, 6, or 8 hours in a freshwater pool 4.6 m deep. Without diving, median coefficients of variation (CV) were: vital capacity, 3.2%; FEV1, 3.5%; peak flow, 7.0%; and DLCO, 5.9%. Measurements within 2.4.CV of baseline were considered unchanged. After 4-, 6-, and 8- hour air dives, PF decreased in one, one, and four subjects, respectively, and three, one, and two, respectively, reported symptoms. After the oxygen dives, PF decreased in two, three, and four subjects, respectively, and two, four, and seven, respectively, reported symptoms. PO2T persisted for several days after 8-hour oxygen dives.

Adult↗