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Biomedical subjects

R A Klocke

Publications and source records attributed to R A Klocke.

At least 19 recordsLinked to original sources
PubMed1997

Oxidative stress and lung function.

It has been suggested that lung function can be altered by both free radical and oxidant exposure, while antioxidant vitamin intake is positively related to lung function. However, the information on the relation of blood levels of oxidants and antioxidants to lung function is sparse. The present cross-sectional study, conducted from September 1995 to May 1996, analyzes the association between lung function measured as forced expiratory volume in 1 second (FEV1) with 1) levels of thiobarbituric acid-reactive substances in plasma (p-TBARS) and in low and very low density lipoprotein cholesterol (LDL cholesterol/VLDL cholesterol-TBARS) as indicators of lipid peroxidation and 2) compounds with antioxidant activity, erythrocytic glutathione, plasma glutathione peroxidase, trolox equivalent antioxidant capacity, and serum bilirubin, which may protect against lipid peroxidation. The analysis was carried out in 132 nonsmoking subjects aged 37-73 years who were randomly selected from the residents of Erie and Niagara counties, New York. FEV1 in percent of the predicted value (FEV1%) was negatively and statistical significantly associated with p-TBARS (r = -0.19). A negative association with borderline statistical significance was observed between FEV1% with low density lipoprotein cholesterol/very low density lipoprotein cholesterol-TBARS (r = -0.16) and glutathione (r = -0.16), while FEV1% was positively related to serum bilirubin (r = 0.15). Participants in the lowest quartile of FEV1% showed significantly higher levels of p-TBARS (p = 0.02) and lower levels of bilirubin (p = 0.04) than did those in the highest quartile. Our results suggest that increased lipid peroxidation is associated with pulmonary airway narrowing in the general population.

Adult↗
PubMed1997

Variability of indices of hypoxemia in adult respiratory distress syndrome.

OBJECTIVE: To determine the usefulness of indices of hypoxemia in assessing patients with the adult respiratory distress syndrome (ARDS). DESIGN: Retrospective analysis of previously published data that describe the distributions of ventilation and pulmonary blood flow in ARDS. SETTING: University research laboratory. PATIENTS: Sixteen patients with ARDS. INTERVENTIONS: The FIO2 was varied between 0.21 and 1.0 in a computer model of gas exchange, based on a 50-compartment model of ventilation/perfusion inhomogeneity plus true shunt and deadspace. The indices of hypoxemia that were calculated as a function of inspired oxygen concentration included PaO2/FIO2, arterial/alveolar ratio (PaO2/alveolar PO2), the alveolar-arterial PO2 difference (P[A-a]O2), respiratory index (P[A-a]O2/PaO2), and venous admixture. MEASUREMENTS AND MAIN RESULTS: The PaO2/FIO2 ratio in patients with moderate shunts (< 30%) varied considerably with alteration in FIO2. At both extremes of FIO2, the PaO2/FIO2 in these patients was substantially greater than at intermediate FIO2. Patients with larger shunts (> 30%) had greater PaO2/FIO2 ratios at low FIO2, but the PaO2/FIO2 ratios decreased to relatively stable values at FIO2 values of > 0.5. In all patients, PaO2/FIO2 remained relatively stable at FIO2 values of > or = 0.5 and PaO2 values of < or = 100 torr (< or = 13.3 kPa). Other PO2-based indices exhibited less stability as FIO2 was varied. If hypoxemia resulted from true shunting, venous admixture was found to be stable at all FIO2 values. However, approximately one half of patients had clinically important hypoxemia resulting from mismatching of ventilation and blood flow. In these patients, venous admixture varied substantially with change in FIO2, and the degree of variation was proportional to the fraction of cardiac output perfusing gas exchange units with ventilation/perfusion ratios of < 0.1. CONCLUSIONS: All indices of hypoxemia are affected by changes in FIO2 in patients with ARDS. PaO2/FIO2 ratio exhibits the most stability at FIO2 values of > or = 0.5 and PaO2 values of < or = 100 torr (< or = 13.3 kPa), and is a useful estimation of the degree of gas exchange abnormality under usual clinical conditions. Venous admixture varies substantially with alteration of FIO2 in patients who have clinically important ventilation/perfusion abnormalities. Under these circumstances, venous admixture is a poor indicator of the efficiency of pulmonary oxygen exchange, even if venous admixture is calculated from measured arterial and venous oxygen content values. Estimated venous admixture, based on an assumed arterial-venous oxygen content difference, is even more unreliable.

Computer Simulation↗
PubMed1995

Influence of cardiac action on gas mixing in closed-chest dogs.

We performed single-breath tests in closed-chest, paralyzed, and anesthetized dogs (6 with bilateral vagotomy and 6 with intact vagi) with the heart beating and during cardiac arrest. Repeated cardiac arrest was achieved by ventricular fibrillation and subsequent defibrillation. Twenty-four single-breath tests per dog were performed in combinations of three inspiratory volumes (VI; 0.2, 0.5, and 0.8 liter) and four postinspiratory pauses (0, 5, 10, and 30 s), either with or without cardiac arrest. The test gas contained four inert relatively insoluble gases (He, Ne, Ar, and SF6) with a sixfold range in diffusivity. Series dead space (VD) decreased with increasing postinspiratory pause, increasing gas diffusivity, or decreasing VI. In vagotomized animals, VD was smaller with the heart beating than during cardiac arrest, but this relationship was reversed in animals with intact vagi. The decrease in VD due to cardiogenic mixing accounted for only 10.8% of the total decrease in VD occurring during a 30-s postinspiratory pause. The slope of phase III decreased with increasing postinspiratory pause except at VI of 0.2 liter. No significant differences were noted in the slope of phase III between experiments performed with the heart beating or arrested. Tracer gas retained in the residual volume after expiration increased with increasing inspiratory pause. Gas retention was greater for He than for SF6 but was not affected by cardiac action. These findings indicate that cardiac action mainly affects the interface between inspired and alveolar gas and has little effect on mixing in the alveolar compartment.

Animals↗
PubMed1995

Distribution of pulmonary capillary transit times.

The length of time that blood remains in the pulmonary capillary is an important variable in gas exchange. We have investigated the distribution of capillary transit times in isolated rabbit lungs perfused with a bicarbonate-free buffer. The time course of gas exchange was monitored by enclosing the lungs in a plethysmograph. A bolus of buffer containing dissolved acetylene was injected into the perfusion system. Exchange of this inert gas occurred as soon as the bolus reached the capillary bed, thereby describing the input function into the bed. A separate bolus injection of bicarbonate solution resulted in production and excretion of CO2 as long as the bolus remained in the capillary bed. The rate of CO2 production was adjusted by partial inhibition of endothelial carbonic anhydrase. The distribution of capillary transit times was computed from a model of CO2 production in the capillary bed and the observed rates and volumes of acetylene and carbon dioxide excretion. The recovered distributions indicate that there is a fairly wide distribution of capillary transit times (relative dispersion, 0.45) around the mean value of 1.71 s (+/- 0.53 [SD]). Only 10% of capillary transit times are less than one half of mean transit time. It is likely that gas exchange reaches equilibrium in the capillary bed except possibly during strenuous exercise or exposure to high altitude or in disease.

Acetylene↗
PubMed1994

Transition.

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Critical Care↗
PubMed1993

Influence of carbon dioxide kinetics on pulmonary carbon dioxide exchange.

In the absence of erythrocytes, carbonic anhydrase (CA) localized to the pulmonary capillary endothelium catalyzes the dehydration of bicarbonate to CO2. We studied the effects of lung CA and the reactions of CO2 on CO2 excretion in isolated lungs perfused with buffer. In indicator-dilution experiments, recoveries of dissolved CO2 and acetylene (C2H2) in the venous effluent were delayed significantly compared with a vascular indicator because the gases were distributed in both the vascular and alveolar volumes. In a second group of experiments, the kinetics of CO2 excretion were monitored with a plethysmographic method after injection of a bolus containing dissolved CO2 or bicarbonate. Exchange was compared with excretion of dissolved C2H2. The rate of excretion of dissolved CO2 and C2H2 was identical, indicating that CO2 is exchanged in the same manner as an inert gas. When bicarbonate was injected, CO2 excretion lagged behind C2H2 excretion by approximately 0.3 s. Inhibition of lung CA with acetazolamide reduced the quantity of CO2 exchanged to one-fourth of control and decreased the delay in exchange by one-half.

Acetazolamide↗
PubMed1993

State of the ARRD.

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Periodicals as Topic↗
PubMed1993

Detection and correction of hypoxemia associated with air travel.

Hypoxemia occurs during air travel because the pressure in aircraft cabins is not maintained equal to barometric pressure at sea level. Identification of patients who will develop significant arterial hypoxemia is most conveniently achieved by exposing these individuals to inspired oxygen tensions similar to those experienced during air travel. We utilized commercial Venturi devices with nitrogen as a source gas to lower inspired oxygen tensions (114 and 99 mm Hg) to simulate exposure to altitude (6,700 and 10,000 feet) that occurs with air travel. Oxygen was administered by nasal cannulas to correct the induced hypoxemia. Eleven normal subjects had baseline oxygen saturations of 97.3% as determined by ear oximetry. Exposure to reduced oxygen tensions for 20 min using 35 and 40% Venturi devices caused minimal O2 desaturation (94.8 and 93.8%, respectively). Mean baseline arterial oxygen saturation was 93.2% in 11 patients with chronic obstructive lung disease. Oxygen saturation fell to 89.5 and 87.5%, respectively, with exposure to the two levels of reduced oxygen tensions. Hypoxemia was corrected with administration of O2 by nasal cannulas at rates of 1.2 and 1.5 L/min, respectively. We conclude that individual patients can be evaluated conveniently for possible development of hypoxemia associated with air travel using available Venturi devices. This approach also permits determination of the oxygen therapy needed to correct hypoxemia.

Air Pressure↗
PubMed1992

Pulmonary hypoxic vasoconstriction: how strong? How fast?

We have developed a minimally invasive technique for studying regional blood flow in conscious sheep, bypassing the complications of open-chest surgery, flow probes and tracer infusion. We quantitate regional perfusion continuously on the basis of regional clearance of methane (methane is produced in the sheep rumen, enters the circulation and is eliminated nearly completely (greater than 95%) in the lung). Tracheal intubation with a dual-lumen catheter isolates the gas exchange of the right apical lobe (RAL; less than 15% of the lung) from that of the remainder of the lung, which serves as a control (CL). We measure RAL and CL methane elimination by entraining expirates in constant flows, sampled continuously for methane. Results obtained with this technique and from regional oxygen uptake are in excellent agreement. We have found that hypoxic vasoconstriction is far more potent and stable during eucapnic hypoxia than during hypocapnic hypoxia. The time course of the vasoconstriction suggests that many of the data in the literature may have been obtained prior to steady state.

Analysis of Variance↗
PubMed1991

Kinetic measurements of gas exchange in the intact pulmonary microcirculation.

The kinetics of gas exchange are monitored in an isolated perfused lung preparation contained within a plethysmograph. The lungs are perfused with buffer, and there is no gas exchange until a 2.0-ml bolus of reactant is injected into the perfusion system. Subsequent gas exchange produces a pressure transient that is related to the corresponding volume of exchanged gas. The observed rate of volume change is the result of two separate processes: 1) the rate of gas exchange during transit through the capillary bed and 2) the distribution of vascular transit times between the point of injection and the capillary bed. The latter is assessed by a control injection containing a dissolved inert gas that is liberated in the alveoli as the bolus enters the capillary bed. Analysis of the experimental curves permits the separation of these two processes. A model of exchange kinetics indicates that this method has the capability of measuring kinetic events occurring during gas exchange in the microcirculation under physiological conditions.

Animals↗
PubMed1990

High-frequency oscillation during simulated altitude exposure.

Ventilatory requirements using high-frequency oscillation (HFO) during simulated altitude exposure were investigated in control dogs and animals with oleic acid-induced lung injury. FIO2 values of 0.21 and 1.0 were supplied by bias flow to the normal and injured dogs, respectively. After a control period, animals were exposed to a simulated altitude of 8,000 ft (barometric pressure 564 torr), followed by a second control period at ground level. Both experimental groups had similar values of PaCO2 at ground level and during exposure to reduced barometric pressure. The tidal volume necessary to maintain eucapnia was higher in oleic acid-injured animals compared with the control group; cardiac output and functional residual capacity were lower. The alveolar-arterial oxygen difference was substantially larger in the oleic acid group. Adequate gas exchange can be maintained with HFO during exposure to altitude provided that ventilation and inspired PO2 are not reduced below normobaric levels.

Altitude↗
PubMed1990

Role of molecular diffusion in conventional and high frequency ventilation.

The influence of molecular diffusion on gas-mixing during conventional mechanical ventilation (CMV) and high frequency ventilation (HFV) was studied by observing the wash-in of six poorly soluble, inert gases in arterial blood. Anesthetized dogs were ventilated either with CMV or HFV. Following a step change in inspired gas composition, the increase in arterial concentrations of hydrogen, helium, methane, ethane, isobutane, and sulfur hexafluoride was determined by gas chromatography. The relative gas diffusivities encompassed a range of almost one order of magnitude. Propane, present in inspired gas during both the control and wash-in phases, served as an internal reference for calculation of blood tracer concentrations. The wash-in of all six inert gases followed a single exponential time course during both CMV and HFV. The rate of wash-in of each gas decreased with increasing molecular weight (MW). The relationship of rate constants to a measure of relative diffusivity (MW-0.5) was significantly different than zero for both types of ventilation. The slope of this relationship was three times larger for CMV than HFV, indicating that molecular diffusion has a greater role in gas mixing during ventilation with large tidal volumes. Diffusion has a minor role in gas mixing during high frequency ventilation with small tidal volumes. Demonstration of the presence of gas separation secondary to molecular diffusion during HFV is enhanced by measuring wash-in, rather than wash-out, of inert gases because gas separation is likely to be obscured as exhaled gases pass through the well-mixed central airways during gas wash-out.

Animals↗
PubMed1987

Air transportation of patients with acute respiratory failure: theory.

Adult respiratory distress syndrome (ARDS) that results from severe trauma often occurs in remote places, making it necessary to transport the patients to tertiary medical facilities by air. Since these severely hypoxic patients are exposed to additional risk of reduced inspired oxygen tension due to decreased barometric pressure, the feasibility of transportation of these patients was investigated by computer analysis. Mathematical models of pulmonary gas exchange in patients with ARDS were developed to calculate arterial and mixed venous blood tensions while breathing room air and oxygen at sea level, 8,000 ft, and 40,000 ft. Under each condition the following parameters were varied: alveolar ventilation (VA), cardiac output (Q), metabolic rate (VO2), hematocrit (Hcrit), and membrane diffusing capacity for oxygen (DmO2). Most of the gas exchange problems at altitude could be overcome by breathing oxygen as long as cardiac output and hematocrit were adequate. Hypoxemia in ARDS patients will not be greatly affected by the reduced inspired oxygen tensions at altitude in much the same way that hypoxemia in ARDS is poorly responsive to increased inspired oxygen tensions at sea level.

Aerospace Medicine↗