Animals Breathed Room Air Research Articles

The influence of heart rate on pulmonary arterial-left ventricular pressure relationships at end-diastole.

Increased resistance to blood flow stemming from structural and functional abnormalities of the lungs may cause pressure in the pulmonary artery to exceed that in the left ventricle at the end of ventricular diastole. This study explores the possible contribution of heart rate to the diastolic pressure gradient observed in the presence of acutely induced hypoxia. Pulmonary hemodynamics were examined in mongrel dogs with chronic atrioventricular dissociation with and without hypoxia at two different heart rates and during sequential increments in heart rate while the animals breathed room air. Studies during sequential pacing indicate that heart rate was of greater importance than blood flow in determining the magnitude of the gradient. Heart rate has to be considered when the causes of pulmonary hypertension and the effects of drugs or other agents on the pulmonary circulation are being investigated.

Failure of carbon monoxide to induce myocardial infarction in cholesterol-fed cynomolgus monkeys (Macaca fascicularis)

Twenty-six adult female cynomolgus monkeys (Macaca fascicularis) were randomly assigned to four groups which were fed on a standard laboratory diet or a semipurified diet containing cholesterol. In two of the groups, the monkeys were exposed intermittently to CO throughout the day for 14 months; the control animals breathed room air. No myocardial infarctions were observed, and the ECG showed a transitory injury current in only one animal. No differences in plasma cholesterol levels or in aortic and coronary atherosclerosis could be attributed to CO exposure.

Respiratory responses to ACTH and dexamethasone in unanesthetized goats

The effect of dexamethasone and adrenocorticotropin (ACTH) treatment (12 and 36 hr) on hypercapnic respiratory drive was studied in three unanesthetized goats with carotid loops. Minute ventilation, respiratory frequency, fractions of expired 0; and CO;, and arterial pH, CO 2 tension and bicarbonate concentration were measured while each animal breathed room air, 2.5% CO 2 and 5% CO 2 in air. Oxygen consumption, respiratory dead space and alveolar ventilation were calculated. With maintenance of unchanged metabolic acid-base status, the hormone treatments uniformly increased respiratory excitability without altering respiratory sensitivity. No changes in oxygen consumption were associated with the observed increase in respiratory responsiveness. The similarity of respiratory response changes occurring during ACTH and dexamethasone treatment suggests that glucocorticoids are the operative agents and that the induced effect occurs within the first twelve hours after treatment initiation.

Uneven distribution of maternal and fetal placental blood flow, as demonstrated using macroaggregates, and its response to hypoxia.

A technique is described for studying the distribution of blood flow to the maternal and fetal placental vessels in sheep and dogs with radioactive labeled macroaggregates of albumin. When the maternal animal breathed room air the distribution of maternal placental blood flow was uneven among the cotyledons as well as within a given cotyledon. Fetal blood flow was also distributed nonuniformly among and within the cotyledons. The relation of maternal to fetal placental blood flow was also markedly uneven (coefficient of correlation, tau = 0.066). After the animal was made hypoxic by breathing 10-12% O(2) the distribution of maternal, fetal, and maternal/fetal placental flows became more uniform. The coefficient of correlation of maternal to fetal flow was high (tau = 0.53, P < 0.01). While the maternal animal breathed room air, after ligation of a major branch of the umbilical artery the distribution of maternal, fetal, and maternal/fetal flows in the remaining two-thirds to three-fourths of the placenta became more uniform. The correlation coefficient for maternal to fetal flow was high (tau = 0.35, P < 0.01).It appears that under normal circumstances with uneven distribution of blood flows there is a considerable portion of the placenta that does not receive blood flow in optimum quantities to promote efficient O(2) exchange. Failure to consider the influence of nonuniform maternal flow/fetal flow will result in overestimation of mean maternal-fetal oxygen tension gradients, and thus underestimation of the placental diffusing capacity for oxygen. In response to maternal hypoxia or compromise of the fetal placental circulation the distribution of maternal, fetal, and maternal/fetal flows becomes more uniform, thereby increasing the efficiency of placental O(2) exchange.

The graded response to stimulation of medullary respiratory neurons

The discharge activity of medullary respiratory neurons was measured concurrently with pulmonary ventilation in decerebrated and anesthetized cats. Resting values in animals breathing room air were compared with responses evoked by hypercapnia, hypoxia and hyperoxia. During CO 2 stimulation, changes in total spike output of both inspiratory and expiratory neurons directly correlated with changes in minute ventilation and the impulse frequency of the spike discharge correlated with tidal volume. Recruitment was a minor component of graded medullary respiratory activity, and the number of active respiratory units remained nearly constant over wide ranges of ventilation from near apnea to substantial hyperpnea. In individual neurons, the frequency response to different levels of stimulation was graded but often nonlinear and its magnitude differed from cell to cell. Some neurons discharged with maximal frequency at relatively low levels of ventilation whereas others augmented their frequency only as much larger tidal volumes were produced. Hypoxia induced less consistent neuronal responses than did either hypercapnia or hyperoxia, and depressed expiratory units. The vagus influenced equally the number of impulses discharged by both inspiratory an expiratory neurons and modified the graded response chiefly by limiting the duration of each burst of impulses and the number of impulses in the burst. It appears that the medullary respiratory neuron population regulates the magnitude of ventilation primarily by changes in the impulse frequency and total number of discharges of already active cells rather than by increasing or decreasing the number of cells actively discharging during each breath.

Ventilatory responses to intravenous and inspired carbon dioxide in anesthetized cats

Conflicting evidence exists concerning the importance of neural influences on ventilatory control during continuing states of muscular exercise in mammals. Neural factors appear to be required in certain dog preparations, but to be unnecessary in rats where intravenous CO 2 has been found to be handled differently from inspired CO 2. This relationship between intravenous and inspired CO 2 was studied in six cats anesthetized with hexobarbital and urethane. In order to produce venous loading of carbon dioxide in animals breathing room air, approximately one-third of the resting cardiac output was continuously removed from the peripheral end of the severed vena cava, pumped through a homologous lung and continuously returned to the central vena cava. When the homologous lung was ventilated with 100% CO 2, carbon dioxide production at four times the resting level was observed in the expired air of the experimental animal. The relationships between Pa co 2 and e observed during intravenous CO 2 loads were indistinguishable from those seen during exposure to CO 2 in the inspired air. These observations provide further evidence against theories ( Yamamoto and Edwards, 1960) which require differing ventilatory responses to differing routes of CO 2 administration.

Relation of respiratory alkalosis to hypokalemia in anesthetized dogs during altitude stress

Results of this investigation confirm the hypothesis that respiratory alkalosis is directly related to hypokalemia in dogs during their exposure to moderate altitude stress. Anesthetized animals were placed in a decompression chamber and subjected to a simulated altitude of 30,000 ft for 30 min. Arterial blood samples were obtained prior to and during the decompression period. In one series of 14 experiments in which animals breathed room air, the mean plasma K+ concentration declined from 3.9 to 3.4 mEq/ liter after 30 min. Respiratory alkalosis was demonstrated by a marked rise in blood pH (from 7.37 to 7.56) and fall in pCO2 (from 40 to 23 mm Hg) which appeared after 5 min. In a second series of 15 experiments in which dogs breathed a gas mixture containing 20% CO2 (partial pressure = 45 mm Hg at 30,000 ft), 21% O2, and 59% N2, respiratory alkalosis was effectively prevented and the characteristic hypokalemia failed to occur. It appears that potassium ions leave the plasma and enter the tissues as a secondary response to alkalosis. Submitted on March 14, 1961