Biomedical subjects

B J Koos

Publications and source records attributed to B J Koos.

At least 37 records · Page 2Linked to original sources

PubMed1992

Anemia up-regulates pontine A1 adenosine receptors in fetal sheep.

A rise in central adenosine concentrations most likely triggers the inhibitory effects of acute hypoxia on fetal breathing movements. During prolonged O2 deficiency, the incidence of fetal breathing increases over time, an adaptation which may involve down-regulation of adenosine receptors. Therefore, isovolemic anemia was induced in chronically catheterized fetal sheep to determine the effects of acute O2 deprivation on the affinity of brainstem A1 adenosine receptors. Compared to control values, the mean hemoglobin concentration in 4 fetuses was lowered by 54% (to 3.7 +/- 0.4 g/dl) for 1 h and in 3 fetuses by 58% (to 3.8 +/- 0.6 g/dl) for 4 h. Mean preductal arterial pH during anemia was significantly reduced to values as low as 7.123 +/- 0.090, but mean paO2 and paCO2 were not significantly affected. The average incidence of fetal breathing movements was decreased by 80% during the first hour and by 50% during the fourth hour of anemia. In 3 fetuses with normal hemoglobin levels, about 32 +/- 6.0% of the A1 adenosine receptors in the brainstem were in the high affinity state. After 1 h of anemia, the percentage of high affinity receptors in the pons (but not medulla or midbrain) had significantly increased to 47 +/- 2.9%, but after 4 h of anemia all 3 brainstem regions had A1 receptor affinity within the range of control values. It is concluded that acute anemia induces a short-lived up-regulation of pontine A1 adenosine receptors, but anemia does not alter A1 receptor coupling in the midbrain where A1 receptors related to breathing inhibition may be located.

Anemia↗

PubMed1992

Fetal breathing, sleep state and cardiovascular adaptations to anaemia in sheep.

1. In unanaesthetized fetal sheep (greater than 0.8 term) prolonged anaemia initially reduced the incidences of low-voltage electrocortical activity, rapid eye movements and breathing activity; but the incidence of each returned to normal within 4-7 h. 2. Anaemia induced a persistent rise in fetal heart rate and plasma concentrations of adrenaline, noradrenaline and cortisol. 3. After 16 h the fetal haematocrit was returned to normal. Isocapnic hypoxia induced less than 1 h later also inhibited eye and breathing activity. 4. After 1 h fetal arterial PO2 (Pa,O2) was returned to normal. This rise in O2 tension was associated with an elevation in the incidence of low-voltage electrocortical activity, eye movements and breathing. Breathing movements also occurred during high-voltage electrocortical activity. 5. It is concluded that the brain PO2 set-point for hypoxic inhibition adapts rapidly to alterations in O2-carrying capacity and is probably due to changes in the concentration and/or receptor affinity of a central neuromodulator. Secondly, a rise in brain PO2 at birth may contribute to the onset of continuous breathing.

Adaptation, Physiological↗

PubMed1992

Adenosine stimulates breathing in fetal sheep with brain stem section.

Breathing responses to adenosine were determined in 12 chronically catheterized fetal sheep (greater than 0.8 term) in which hypoxic inhibition of breathing had been eliminated by brain stem section. The caudal extent of transection varied from the rostral midbrain to the pontomedullary junction. Isocapnic hypoxia [delta arterial PO2 (PaO2) of -12 Torr] doubled the incidence and depth of breathing activity and increased the incidence of eye movements. Intra-arterial infusion of adenosine (0.30 +/- 0.03 mg.min-1.kg fetal wt-1) increased the incidence and amplitude of breathing without affecting blood gases. Adenosine did not significantly alter the incidence of eye activity. Intra-arterial injection of oligomycin (120 +/- 26 micrograms/kg fetal wt), an inhibitor of mitochondrial oxidative phosphorylation, also stimulated breathing activity. In four fetuses with brain stem section, peripheral arterial chemodenervation blunted the stimulatory effects of hypoxia on breathing activity and abolished altogether the excitatory effects of adenosine. It is concluded that 1) hypoxia and adenosine likely inhibit breathing in normal fetuses by affecting similar areas of the brain stem and 2) in fetuses with brain section, hypoxic hyperpnea depends on peripheral and central mechanisms, whereas adenosine stimulates breathing via the peripheral arterial chemoreceptors.

Adenosine↗

PubMed1992

Adenosine in the treatment of maternal paroxysmal supraventricular tachycardia.

Paroxysmal supraventricular tachycardia is the most common sustained cardiac arrhythmia in pregnant women. Because nearly 50% of these supraventricular tachyarrhythmias fail to respond to vagal maneuvers, other therapies are used, including electrocardioversion and pharmacologic agents. Propranolol, verapamil, and adenosine have Food and Drug Administration-approved labeling for acute termination of supraventricular tachycardia. Verapamil has been the most commonly used agent in the general population but it has several shortcomings, such as its potential to cause or exacerbate systemic hypotension, congestive heart failure, bradyarrhythmias, and ventricular fibrillation. In addition, verapamil readily crosses the placenta and has been shown to cause fetal bradycardia, heart block, depression of contractility, and hypotension. Adenosine has several advantages over verapamil, including rapid onset, brevity of side effects, theoretical safety, and probable lack of placental transfer. Adenosine ultimately may prove to be the preferred agent for termination of paroxysmal supraventricular tachycardia in the gravid woman.

Adenosine↗

PubMed1991

Maturation of respiratory responses to graded hypoxia in rabbits.

The respiratory effects of graded hypoxia were determined in 8 rabbits on postnatal days 1, 6 and 21. Ventilation was measured in the unanesthetized state by plethysmography. Graded hypoxia was produced by reducing the fraction of inspired O2 to 0.15 (mild hypoxia) for 15 min and then lowering it further to 0.10 (moderate hypoxia) for another 15 min. Mild hypoxia initially stimulated breathing to the same extent in all 3 groups; however, with moderate hypoxia, the percent increase in ventilation was greater for older rabbits. The rise in ventilation was due to an increase in tidal volume and frequency in 1- and 21-day-old rabbits, and it was almost entirely the result of changes in frequency in 6-day-old rabbits. After 2-3 min of hypoxia (mild or moderate), a decline in ventilation was observed in all 3 groups. This reduction of respiration was greater in younger animals and with moderate hypoxia. Decreases in frequency and tidal volume contributed significantly to this fall in ventilation for 1- and 2-day-old rabbits. However, the fall in ventilation for 6-day-old pups occurred almost entirely by changes in tidal volume. It is concluded that the magnitude of phase 1 (increased ventilation) and phase 2 (decreased ventilation) responses to hypoxia depend upon the level of hypoxia and the age of the rabbit.

Aging↗

PubMed1991

Role of plasma adenosine in breathing responses to hypoxia in fetal sheep.

The importance of plasma adenosine in hypoxic inhibition of breathing movements was determined in chronically catheterized fetal sheep (greater than 0.8 term). Preductal arterial blood for adenosine measurements was withdrawn using a double lumen catheter to mix blood entering the catheter with a solution to stop adenosine metabolism. In 6 fetuses, isocapnic hypoxia (delta PaO2 congruent to -10 Torr) increased the average plasma adenosine concentration from 1.1 +/- 0.2 (SEM) to 2.0 to +/- 0.4 microM. During hypoxia, plasma levels of adenosine were inversely related to preductal arterial O2 content (CaO2) with values ranging between 1.6 and 4.0 microM when CaO2 was less than 3 ml/dl. Hypoxia also significantly reduced the incidence of fetal breathing and rapid eye movements. In other experiments, adenosine (0.36 +/- 0.03 mg/min/kg) was infused for one hour into the inferior vena cava of 5 fetuses. During this infusion, mean plasma concentration of adenosine was 2.8 +/- 0.3 microM, a value about 2.5 times the control average. Adenosine also significantly reduced the incidence of low voltage electrocortical activity, rapid eye movements and breathing activity. We conclude that hypoxic inhibition of fetal breathing most likely arises from an increase in central adenosine production, although during severe O2 deprivation (CaO2 less than 3 ml/dl) blood-borne adenosine could also contribute.

Adenosine↗

PubMed1990

Pregnancy and congenital heart disease.

Congenital heart disease as a complicating factor in pregnancy has assumed increasing clinical importance because improved techniques of surgical repair have resulted in a larger proportion of affected women living to the reproductive age. The most serious forms are those associated with pulmonary hypertension (such as the Eisenmenger syndrome), which carry a prohibitively high risk of maternal death. Complex forms of cyanotic heart disease, of which the commonest is the tetralogy of Fallot, are only slightly less dangerous. It has recently been recognized that children born to women with congenital heart disease are at increased risk of having cardiac defects; fetal echocardiography is therefore an important diagnostic test. Optimal care of the pregnant woman with congenital heart disease is best provided by a team consisting of internist-cardiologist, obstetrician-perinatologist, obstetric anesthesiologist, and ultrasonographer-echocardiographer.

Delivery, Obstetric↗

PubMed1990

Fetal breathing, sleep state, and cardiovascular responses to adenosine in sheep.

The possibility that adenosine mediates hypoxic inhibition of fetal breathing and eye movements was tested in nine chronically catheterized fetal sheep (0.8 term). Intracarotid infusion of adenosine (0.25 +/- 0.03 mg.min-1.kg-1) for 1 h to the fetus increased heart rate and hemoglobin concentration but did not significantly affect mean arterial pressure or blood gases. As with hypoxia, adenosine decreased the incidence of rapid eye movements by 55% and the incidence of breathing by 77% without significantly affecting the incidence of low-voltage electrocortical activity. However, with longer (9 h) administration, the incidence of breathing and eye movements returned to normal during the adenosine infusion. Intravenous infusion of theophylline, an adenosine receptor antagonist, prevented most of the reduction in the incidence of breathing and eye movements normally seen during severe hypoxia (delta arterial PO2 = -10 Torr). It is concluded that 1) adenosine likely depresses fetal breathing and eye movements during hypoxia and 2) downregulation of adenosine receptors may contribute to the adaptation of breathing and eye movements during prolonged hypoxia.

Adenosine↗

PubMed1990

Fetal breathing and cardiovascular responses to graded methemoglobinemia in sheep.

Graded methemoglobinemia (MetHb) was produced in unanesthetized fetal sheep to determine the effects on brain oxygenation. MetHb was induced by infusing methemoglobin-containing erythrocytes in exchange for fetal blood. During the hour after MetHb was established, fetal methemoglobin concentrations averaged 1.23 +/- 0.12 (mild MetHb), 1.71 +/- 0.13 (moderate MetHb), and 2.27 +/- 0.17 g/dl (severe MetHb). MetHb reduced mean arterial O2 content by approximately 19 (mild MetHb), 29 (moderate MetHb), and 39% (severe MetHb). The average preductal arterial PO2 fell by 1.6 (-7%), 2.8 (-11%), and 4.0 Torr (-16%) for mild, moderate, and severe MetHb, respectively. Fetal heart rate increased significantly during mild and moderate MetHb, and mean arterial pressure fell slightly during moderate and severe MetHb. The incidences of fetal breathing and eye movements were reduced in a dose-dependent manner when the calculated brain end-capillary PO2 was less than 14 Torr. We conclude that: 1) the effective capillary PO2 in the fetal brain can be significantly reduced by increasing the distance between non-methemoglobin-laden erythrocytes in capillaries and 2) hypoxic inhibition of fetal breathing probably arises from discrete areas of the brain having a PO2 less than 3 Torr.

Animals↗

PubMed1989

Effects of regular and decaffeinated coffee on fetal breathing and heart rate.

The effects of maternal consumption of regular or decaffeinated coffee on the fetus were determined in eight pregnant women at 32 to 36 weeks of gestation. This was a single-blind crossover study in which two cups of caffeinated or decaffeinated coffee were consumed after an overnight fast. The total maternal caffeine ingested was 454 +/- 4 mg for regular coffee and 12 +/- 0.4 mg for decaffeinated coffee. Maternal consumption of regular coffee was associated with a twofold increase in the incidence of fetal breathing activity and a significant fall in baseline fetal heart rate. Decaffeinated coffee also increased the incidence of fetal breathing activity and produced a slight reduction in fetal heart rate. These results indicate that maternal consumption of regular and decaffeinated coffee can stimulate fetal breathing. Moreover, these results suggest that caffeinated coffee can produce baseline shifts in fetal heart rate.

Blood Glucose↗

PubMed1989

A microcomputer program for real-time data acquisition in the perinatal physiology laboratory.

This report describes a real-time data acquisition system using the IBM PC-AT microcomputer, and software specifically engineered for the perinatal physiology laboratory. The system samples up to sixteen analog signals at a rate ranging from 1 to 1024 Hz. Calibrated digital values are displayed on the computer monitor and stored on disk. The system can perform algebraic computations and estimate derivatives. Pattern recognition algorithms are included for the detection and characterization of uterine contractions and fetal breathing movements. Two different noise-rejection filters are implemented. Output of signals via a digital-to-analog converter is supported. The system has been used to record a broad variety of physiologic variables in a number of different studies.

Algorithms↗

PubMed1988

Prenatal diagnosis of inv(X)(q12q28) in a male fetus.

Amniocentesis and prenatal chromosome analysis were performed for advanced maternal age. The fetus was male with a paracentric inversion in the long arm of the X chromosome. The mother and a brother also carried the inversion. The pregnancy continued to term and the infant is developing normally at one year of age.

Adult↗

PubMed1988

Fetal breathing and sleep state responses to graded carboxyhemoglobinemia in sheep.

To investigate CO effects on brain oxygenation, graded carboxyhemoglobinemia (HbCO) was produced in nine unanesthetized fetal sheep by infusing CO-laden erythrocytes in exchange for fetal blood. For the 1st h after this procedure, the mean fetal carboxyhemoglobin levels were 16.5 +/- 0.4% [control (C) = 1.4 +/- 0.4%] for mild HbCO, 22.7 +/- 0.6% (C = 1.8 +/- 0.4%) for moderate HbCO, and 27.8 +/- 0.5% (C = 2.1 +/- 0.7%) for severe HbCO. This induction of HbCO significantly reduced mean preductal arterial PO2 values to 4.3 Torr below control for mild HbCO, 4.6 Torr below control for moderate HbCO, and 5.5 Torr below control for severe HbCO. The respective arterial O2 contents were decreased by 17, 21, and 29%. Mean arterial pH was lowered only during severe HbCO, and arterial PCO2 values were unchanged. HbCO produced a fetal tachycardia. Mean arterial blood pressure was only increased during severe HbCO. The incidences of rapid eye movements and breathing activity were decreased by HbCO in a dose-dependent manner. When related to calculated brain tissue PO2, these decreases were similar to those measured during hypoxic hypoxia and anemia, suggesting that carboxyhemoglobin effects result solely from diminished oxygenation. It is concluded that 1) the peripheral arterial chemoreceptors in the fetus apparently have little effect on hypoxic inhibition of breathing and 2) the carboxyhemoglobin concentrations required to inhibit fetal breathing are greater than those likely to be encountered clinically.

Animals↗

PubMed1988

Fetal breathing adaptation to prolonged hypoxaemia in sheep.

Prolonged (6 days) fetal hypoxaemia was produced by placing pregnant ewes in an environmental chamber. A constant flow of N2 into the chamber reduced the fraction of inspired oxygen (Fi02) to 0.139 +/- 0.001, simulating an altitude of 4270 m. This reduced maternal PaO2 by about 39 mmHg and PaCO2 by nearly 5 mmHg, which produced a hypocapnic (delta PaCO2 = -5 mmHg) hypoxaemia (delta PaO2 = -8 mmHg) in the fetus. An analysis of the first 4 h of breathing recorded each day (1800-2200 h; start of hypoxaemia: 1200 h) showed that the incidence (12 +/- 2.0 min/day) during the first day of hypoxaemia was significantly less (P less than 0.05) than that (24 +/- 3.1 min/h) during the same time of the control day. By the second day, breathing had returned to normal. Further analysis indicated that a normal incidence of breathing may have occurred as early as 14 h after starting hypoxaemia. These results suggest that fetal breathing movements adapt rather quickly to this degree of hypocapnic hypoxaemia.

Acclimatization↗

PubMed1988

Effects of hypoxaemia and hypercapnia on breathing movements and sleep state in sinoaortic-denervated fetal sheep.

The role of the systemic arterial chemoreceptors in regulating breathing movements was determined in 7 chronically catheterized fetal sheep with carotid denervation and vagal section. Fetal hypoxaemia (delta PaO2 = -11.4 +/- 0.6 mmHg) decreased significantly the incidence of rapid-eye-movements (control = 26 +/- 1.5 min/h; hypoxia = 12 +/- 2.6 min/h, P less than 0.001) and breathing activity (control = 18 +/- 1.0 min/h; hypoxia = 8 +/- 1.1 min/h, P less than 0.001). However, the lag in onset of inhibition (approximately 8 min) was significantly greater (P less than 0.05) than for normal fetuses. The incidence of low voltage electrocortical activity was not affected. Hypercapnia (delta PaCO2 = 9.5 +/- 1.1 mmHg) increased significantly the incidence of rapid-eye-movements and breathing activity. Hypercapnia also increased the mean amplitude of breathing activity and reduced the average breath interval. Rapid-eye-movements and breathing activity were depressed significantly by hypoxaemic hypercapnia. These observations suggest that hypoxic inhibition does not require afferent activity from the aortic or carotid bodies nor from other chemoreflexes mediated by the vagus. However, such peripheral input may be responsible for a more rapid onset of inhibition in normal fetuses.

Animals↗

PubMed1987

Fetal breathing, sleep state, and cardiovascular responses to graded hypoxia in sheep.

Graded isocapnic hypoxemia was produced in unanesthetized fetal sheep by varying the inspired O2 concentration (21, 12, 10.5, and 9%) of the ewe. This produced corresponding mean preductal arterial O2 tension (PaO2) values of 25.2 +/- 1.1 (control), 20.1 +/- 1.0 (mild hypoxia), 17.8 +/- 0.9 (moderate hypoxia), and 16.8 +/- 1.4 Torr (severe hypoxia). These were associated with mean arterial O2 contents (CaO2) of 7.18 +/- 0.44, 5.19 +/- 0.34, 4.24 +/- 0.33, and 3.27 +/- 0.20 ml/dl, respectively. The most severe hypoxia was associated with metabolic acidosis and fetal bradycardia. Hypoxia did not reduce significantly the incidence of low-voltage electrocortical activity. The incidence of breathing and rapid eye movements was not affected by mild hypoxia; however, the incidence of both was significantly reduced during moderate and severe hypoxia. It is concluded that 1) acute reductions in the mean PaO2 of 5.9 +/- 0.6 Torr and CaO2 of 2.00 +/- 0.23 ml/dl are critical in that greater reductions inhibit fetal eye and breathing activity and 2) hypoxia probably inhibits eye and breathing movements by altering sleep state.

Animals↗

PubMed1987

Fetal breathing, sleep state, and cardiovascular responses to graded anemia in sheep.

Graded anemia was produced for 2 h in 10 unanesthetized fetal sheep by infusing plasma in exchange for fetal blood. This reduced the mean fetal hematocrits during the 1st h of anemia to 19.7 +/- 0.5% [control (C) = 28.2 +/- 1.1%] for mild anemia, 17.4 +/- 0.9% (C = 30.0 +/- 1.1%) for moderate anemia, and 15.1 +/- 1.0% (C = 29.2 +/- 1.3%) for severe anemia. The respective mean arterial O2 contents (CaO2) were 4.46 +/- 0.20, 3.89 +/- 0.24, and 3.22 +/- 0.19 ml/dl. Mean arterial PO2 was reduced significantly (by 2 Torr) only during moderate anemia, and mean arterial pH was decreased only during severe anemia. No significant changes occurred in arterial PCO2. Fetal tachycardia occurred during anemia. Mean arterial pressure was reduced by 2-3 mmHg during mild anemia; however, no significant blood pressure changes were observed for moderate or severe anemia. The incidence of rapid-eye movements and breathing activity was not affected by mild anemia, but the incidence of both was reduced significantly during moderate and severe anemia. It is concluded that 1) a reduction in CaO2 of greater than 2.48 +/- 0.22 ml/dl by hemodilution inhibits rapid-eye movements and breathing activity, and 2) the PO2 signal for inhibition does not come from arterial blood but from lower PO2 in tissue.

Anemia↗

PubMed1987

Predict fetal brain PO2 during hypoxaemia and anemia in sheep.

The mean brain PO2 of fetal sheep was calculated using equations based on the Krogh cylinder model of O2 diffusion. This analysis took into account the effect of red cell spacing on capillary PO2. Uncompensated changes in arterial O2 tension, the radius of the Krogh cylinder, and metabolic rate of brain tissue were predicted to affect mean brain PO2 more than uncompensated changes in brain blood flow or haemoglobin concentration. Under normal conditions (CaO2 = 7.42 ml/dl), the mean PO2 of the fetal brain was calculated to be about 12 mmHg. Hypoxaemia decreased the predicted mean O2 tension to 7.6 mmHg (CaO2 = 5.19 ml/dl), 5.0 mmHg (CaO2 = 4.11 ml/dl), and 4.3 ml/dl (CaO2 = 3.50 ml/dl). Isovolaemic anaemia reduced mean brain PO2 to 8.7 mmHg (CaO2 = 4.40 ml/dl), 8.3 mmHg (CaO2 = 3.94 ml/dl), and 7.3 mmHg (CaO2 = 3.19 ml/dl). During anaemia the increased distance between red cells was calculated to contribute significantly to brain hypoxaemia. A summary equation is presented which enables the investigator to estimate easily the mean PO2 of the fetal brain when several factors are changed from standard values.

Anemia↗