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Biomedical subjects

J C Denniston

Publications and source records attributed to J C Denniston.

At least 19 recordsLinked to original sources

Ventilatory acclimatization to high altitude is prevented by CO2 breathing.

The hypoxia of high altitude stimulates ventilation. If the resultant respiratory alkalosis inhibits the initial increase in ventilation, then with prevention of alkalosis, ventilation should rise immediately to a stable plateau. 4 subjects inspired CO2 (3.77%) from ambient air in a hypobaric chamber (PB = 440-455 Torr) during 100 h at high altitude. Ventilation (for given oxygen uptakes at rest and during exercise) increased promptly and remained stable. 4 control subjects exposed to high altitude without CO2 supplementation showed the expected progressive increases in ventilation with time. The hyperoxic CO2 ventilatory response curve shifted progressively to the left with time in the control subjects, but not in those given supplemental CO2. The latter group also failed to increase the ventilatory response to isocapnic hypoxia. Thus, CO2 supplementation at high altitude prevented the so-called "ventilatory acclimatization' from occurring. Prevention of respiratory alkalosis at high altitude probably permitted maintenance of [H+] at some central nervous system locus, thus allowing an uninhibited hypoxic stimulation of ventilation.

Acclimatization

Evidence for increased intrathoracic fluid volume in man at high altitude.

To determine if subclinical pulmonary edema occurs commonly at high altitude, 25 soldiers participated in two consecutive 72-h field exercises, the first at low altitude (200-875 m) and the second at high altitude (3,000-4,300 m). Various aspects of ventilatory function and pulmonary mechanics were measured at 0, 36, and 72 h of each exercise. Based on physical examination and chest radiographs there was no evidence of pulmonary edema at high altitude. There was, however, an immediate and sustained decrease in vital capacity and transthoracic electrical impedance as well as a clockwise rotation of the transpulmonary pressure-volume curve. In contrast, closing capacity and residual volume did not change immediately upon arrival at high altitude but did increase later during the exposure. These observations are consistent with an abrupt increase in thoracic intravascular fluid volume upon arrival at high altitude followed by a more gradual increase in extravascular fluid volume in the peribronchial spaces of dependent lung regions.

Adolescent

Measurement of cardiac output by electrical impedance at rest and during exercise.

A comparison was made between cardiac output values determined by the dye dilution and electrical impedance methods in ten subjects at rest and during graded exercise on a bicycle ergometer. The cardiac output values determined by the two methods were linearly related and significantly (P less than 0.001) correlated (r = 0.90). Movement artifact associated with exercise at maximum or near-maximum work loads caused severe distortion of the dZ/dt wave form and prevented calculation of impedance cardiac output at these levels of work. Use of the lowest value of L (distance between mean value of L in the impedance stroke volume equation (SV = p(L2/ZO2) (dZ/dt)mt), resulted in nearly identical values for the least-squares line and equalvalue line of impedance and dye cardiac outputs. Although absolute values of cardiac output determined by the two methods were not identical in all subjects the changes in cardiac output were nearly identical during the different levels of exercise. The data support the validity of the impedance method as a noninvasive, atraumatic measure of cardiac output at rest and during graded exercise.

Adult

Sustained venoconstriction in man supplemented with CO2 at high altitude.

Venoconstriction occurs at high altitude. This study sought to determine whether hypoxia or hypocapnia is the cause of the venoconstriction. Five male subjects were exposed to 4,000-4,400 m (PB 440-465 mmHg) with supplemental 3.77 +/- 0.02% CO2 in a hypobaric chamber for 4 days. Similar alveolar O2 tensions were obtained in four control subjects exposed to 3,500-4,100 m (PB 455-492 mmHg) without CO2. A water-filled plethysmograph was used to determine forearm flow and venous compliance. Systemic blood pressure was measured with the cuff procedure. Catecholamines were measured in 24-h urine collections. Venous compliance fell at high altitude in both groups and was less (P less than 0.01) than control values. Forearm flow and resistance were unaltered at altitude in the group with CO2 supplementation while forearm flow decreased and resistance increased in the hypocapnic group at 72 h of exposure. Urinary catecholamines increased in the group with CO2 and remained unaltered in the hypocapnic group. It is concluded that hypoxia is responsible for decreasing venous compliance, and hypocapnia for increasing resistance and decreasing flow. Group differences observed in urinary catecholamines may be explained by differences in arterial pH.

Adolescent

Maintained stroke volume but impaired arterial oxygenation in man at high altitude with supplemental CO2.

Hypobaric hypoxia causes hypocapina and alkalosis, hemoconcentration and increased hematocrit, and a decreased cardiac stroke volume. To assess the role of the hypocapnic alkalosis in causing these other changes, five men were exposed to hypobaric hypoxia at a barometric pressure (PB) of 440 torr with an alveolar O2 tension of 55 torr for 5 days with 3.77% CO2 added to the atmosphere to prevent alkalosis. They did not lose weight, and arterial CO2 tension, pH, and cardiac stroke volume were unchanged. An unchanged hematocrit implied an unchanged plasma volume. During exercise to maximum, stroke volumes equaled sea level values but arterial hypoxemia was profound, the arterial O2 tension being 39 torr. By contrast, three men at high altitude without CO2 supplementation (PB=455 torr; alveolar PO2=56 torr) had weight loss, hypocapnia, alkalosis, and decreased stroke volume. Increased hematocrits suggested decreased plasma volumes. During exercise, arterial PO2 (48 torr) was higher than in the group receiving CO2. Maximum oxygen uptakes were decreased to a similar degree in the two groups. Catecholamine excretion doubled in the group with CO2 but in the group without CO2 catechoamine excretion was unchanged. A normal pH at high altitude apparently maintained plasma volume, which, with the increased catecholamine excretion, may have prevented a decrease in stroke volume. However, the subjects with CO2 added did not have enhanced oxygen transport, because their arterial oxygenation was impaired.

Adult

Increased 2,3-diphosphoglycerate during normocapnic hypobaric hypoxia.

The effect of 96 h of exposure to hypobaric hypoxia with and without 3.8% CO2 supplementation was studied in two groups of subjects. Five subjects (CO2) were exposed to 440-465 mm Hg barometric pressure (4000-4400 m), and 4 subjects (no-CO2) were exposed to 455-492 mm Hg (3500-1400 m) in order to produce similar levels of resting end-tidal PO2. After 24 h, 2,3-DPG levels of both groups significantly increased and remained elevated. The CO2 group had higher levels than the non-CO2 group after 48 and 72 h. Concurrent measurements of P50 showed similar changes over the same time course. Mean corpuscular hemoglobin concentrations remained normal for 48 h and then decreased in both groups, the CO2 group showing the larger decrease. We conclude that altitude exposure may produce an increase in 2,3-DPG without the presence of respiratory alkalosis previously thought necessary.

Adolescent

Measurement of pleural effusion by electrical impedance.

Changes in the electrical impedance of the thorax were recorded from various electrode arrays on the thorax during the infusion and withdrawal of saline, plasma, or blood from the right, left, or both hemithoraxes. Impedance changes correlated linearly with the volume of infused fluid. The resistivity of the infused fluid significantly affected the sensitivity (omega/ml) of the impedance method in detecting specific fluid accumulations. The use of hemithoracic electrode arrays permitted the localization of fluid accumulations to a specific hemithorax. Various factors that can alter the magnitude and interpretation of impedance changes are discussed, as they would affect the clinical interpretation of impedance changes, particularly in postoperative patients.

Animals

Evaluation of a microcrystalline bovine collagen hemostatic agent in canine solid viscera injury using abdominal impedance plethysmography.

Bioelectric impedance as a sensitive noninvasive technique for detecting and monitoring changes in compartmental body fluid volume was used to compare the efficacy of two hemostatic agents in controlling postoperative abdominal bleeding following surgically induced solid viscera injury. Gelatin foam-oxidized cellulose sponge and bovine MCHH were both effective topical hemostatic agents. It appears that MCCH has certain advantages over conventional agents.

Abdominal Injuries

Acute mountain sickness: increased severity in eucapnic hypoxia.

This study examined the hypothesis that prevention of hypocapnia and alkalosis would ameliorate the symptoms of acute mountain sickness (AMS). Five subjects were exposed to simulated high altitude for 4 d with 3.8% CO2 added to the chamber to maintain normocapnia. Four other subjects were exposed for 4 d to hypobaric hypoxia without CO2 supplementation, and became hypocapnic. Barometric pressure was lower in the group with added CO2 so that alveolar oxygen tensions (55-60 mm Hg) would not be different. The severity of symptoms was clearly greater in normocapnic than in hypocapnic subjects. Thus, prevention of hypocapnia did not alleviate AMS symptoms. The efficacy of CO2 addition in reducing symptoms, as reported by earlier workers, was probably the result of induced hyperventilation and partial relief of hypoxia. Indeed, in the present study with two comparably hypoxic groups, CO2 addition augmented the sysptoms, possibly by causing increased cerebral vasodiladation and spinal fluid pressure.

Acute Disease

Altered immune function in hypercholesterolemic monkeys.

Humoral and cellular immune responses to several antigens were compared in control and hypercholesterolemic groups of monkeys. Chronic hypercholesterolemia, with concomitant hyperphospholipidemia and hypotriglyceridemia, was produced experimentally by feeding monkeys a high-fat, high-cholesterol diet. When studied prior to infection, hypercholesterolemic monkeys exhibited impaired development of precipitating antibodies against ovalbumin, enhanced sensitivity to tuberculin antigen (stimulated apparently by mycobacterial components in complete Freund adjuvant), and an increased rate of clearance of colloidal carbon from blood. During pneumococcal infection the ability of neutrophiles from hypercholesterolemic monkeys to reduce nitroblue tetrazolium dye showed an increase greater than that of control monkeys; both groups exhibited increased but comparable final clearance rates of colloidal carbon, although the increment of increase was smaller in hypercholesterolemic monkeys.

Animals