Local blood flow velocities in the carotid body of fetal sheep and newborn lambs

Summary Elastically-suspended microelectrodes were used in the vascularly isolated blood-perfused carotid body of fetal and newborn lambs as well as of 6–7-day-old lambs to measure local blood flow velocities by means of hydrogen clearance. Fetal sheep (n=9) carotid bodies elicited mean local blood velocity values between 0.008 and 0.11 cm·s^–1, whereas newborn lamb carotid bodies (n=7) showed values between 0.008 and 0.067 cm·s^–1 at a perfusion pressure range between 30 and 150 mmHg. The 6–7-day-old lamb carotid bodies (n=5) were characterized by values of 0.003 and 0.049 cm·s^–1 over the same perfusion pressure range. Fetal carotid body values were statistically significantly higher than the values of the 6–7-day-old lamb carotid bodies, whereas the newborn carotid body values showed no significant difference to both other groups. The flow velocity/perfusion pressure relationship peaked at perfusion pressure values between 100 and 150 mmHg in all groups with a reduced steepness in the lamb carotid body. It is concluded that local blood flow velocities in the carotid body are similar to that in other organs, and that after birth local blood flow velocities in the carotid body decrease during the first week of life, probably induced by vasoconstriction, changed blood gas values, and/or increasing shunt flow.Abbreviations significance level - D diffusion coefficient - i.v. intravenous - n number of experiments - PCO ₂ carbon dioxide partial pressure - pH negative logarithm of hydrogen ion concentration - PH ₂ hydrogen partial pressure - Po PH₂ with perfusion - P PH₂ without perfusion - PO ₂ oxygen partial pressure - PP perfusion pressure - r radius     

Quantitative studies of rat carotid body type I cells

The general structure and results of quantitative studies of rat carotid body type I cells are described. In contrast to previous reports, there was no change in mitochondrial V/v% on stimulating the carotid body with 10% oxygen. The volume of cytoplasm occupied by electron-dense cored vesicles was significantly increased, whilst their density per square micrometre of cytoplasm was decreased during hypoxia. Thus, the size of vesicles is increased by hypoxic stimulation. On the basis of vesicle diameter and density we were unable to find evidence of more than one variety of type I cell.     

Quantitative studies of rat carotid body type I cell nerve endings

The results of a stereological and morphometric analysis of rat carotid body type I cell nerve endings are described. 66.9% of endings possessed symmetrical junctions. Of the remaining endings, 3.6% were presynaptic and 26% were postsynaptic to type I cells; 3.6% of endings had a reciprocal configuration. Apart from membrane specialisations, no other ultrastructural criteria were found to distinguish the different types of endings. Ventilation with 100% and 10% oxygen showed that the hypoxic mixture reduced synaptic vesicle concentration in the nerve endings; this effect was independent of the innervation to the carotid body.     

Quantitative studies of the cat carotid body. III. The type I cells

The work reported here examines the quantitative ultrastructure of cat carotid body type I cells, and the effects of hypoxia on the cells. On the basis of size and density of electron-dense cored vesicle (EDCV) we were unable to identify more than one major population of type I cells. Prior ventilation of the animals with 10% O2 resulted in an increase in the volume percentage (Vv%) of mitochondria and a decrease in the Vv% of EDCV as compared to the values after ventilation with 100% O2. The lack of effect of prior denervation of the carotid body on the hypoxic changes suggests that the effects are not mediated via an efferent pathway.     

Origin and development of the catecholamine-storing cells of the human fetal carotid body

Summary The carotid bifurcation areas of 25 human fetuses aged from 8 to 22 weeks were studied using the formaldehyde-induced fluorescence method. A long process from the sympathetic trunk reached the area at the age of 8 weeks contacting with the carotid body primordium. Brightly fluorescent cells can be seen both in the carotid body and in the ganglionic process. Migration of these cells from the sympathetic trunk to the carotid body is suggested. The connection from the sympathetic trunk to the carotid body totally disappeared after the tenth week, leaving no fluorescent elements between these two. Control electron microscopy and light microscopy were performed to identify the fluorescent and nonfluorescent components of the human fetal carotid body.     

Comparison of cerebrovascular effects of intravenous cocaine injection in fetal, newborn, and adult sheep

Cocaine may cause stroke, intracranial hemorrhage, seizures, and neurobehavioral abnormalities in fetuses, newborns, and adults, and there could be developmental and/or species differences in mechanisms for these cocaine-induced cerebrovascular effects. To evaluate developmental differences in responses to cocaine, we compared the cerebrovascular and metabolic responses to a 2 mg/kg iv cocaine dose in unanesthetized fetal (n = 8, previously reported, direct fetal injection), newborn (n = 6), and adult (n = 12) sheep. We measured cerebral blood flow, mean arterial blood pressure, and arterial and venous O(2) content, and we calculated cerebral O(2) consumption and cerebral vascular resistance at baseline and at 30 s and at 5, 15, and 60 min after cocaine injection. Cerebral blood flow increased 5 min after injection in the fetus and newborn, but not until 15 min in the adult. In the fetus, cocaine caused a transient cerebral vasoconstriction at 30 s; in all three groups, cocaine caused cerebral vasodilation, which was delayed in the adult. Cerebral metabolic O(2) consumption increased 5 min after injection in the fetus and newborn, but not until 15 min after injection in the adult. Arterial O(2) content decreased 5 min after injection in the fetus and 15 min after injection in the adult. We speculate that clinical differences in response to cocaine injection may be explained, in part, by these developmental differences in the cerebrovascular and metabolic responses to cocaine.     

Nutrient and waste product concentration differences in upper and lower body arteries of fetal sheep

Well oxygenated blood returning from the placenta is preferentially shunted into the left side of the fetal heart and the ascending aorta. This results in higher oxygen saturation in arterial blood supplying the fetal upper body than in blood supplying the lower body. Since the placenta is also the site of nutrient and waste exchange, we evaluated differences in arterial concentrations of nutrients and waste products in fetal upper and lower body. Studies were carried out on ten, chronically catheterized, third trimester, fetal sheep. Blood samples, drawn simultaneously from the carotid and femoral arteries, were analyzed for glucose, oxygen saturation, oxygen content, total amino acids, lactate, urea nitrogen, and hydrogen ion concentration. Carotid arterial blood had higher levels of glucose (1.4 +/- 0.1 mg/dl (SEM); P less than 0.001), of alpha-amino nitrogen (0.4 +/- 0.1 mg/dl, equivalent to amino acid concentration difference of 2.5 mg/dl, P less than 0.025), of oxygen saturation (9.9 +/- 0.5%, P less than 0.001), and of oxygen content (1.0 +/- 0.1 ml/dl; P less than 0.001). Carotid values exceeded femoral by an average of 10% for glucose, 4% for amino nitrogen, 29% for oxygen saturation and 23% for oxygen content. Carotid arterial blood had lower urea nitrogen, (-0.5 +/- 0.2 mg/dl; P less than 0.05) and hydrogen ion (-1.1 +/- 0.1 nM/L; P less than 0.001) concentrations, but these differences averaged only 2% between vessels. Lactate concentration in the carotid and femoral arteries was the same. Fetal glucose and oxygen levels were closely related.(ABSTRACT TRUNCATED AT 250 WORDS)     

Muscarinic influences on growth hormone secretion in the fetal and neonatal sheep: pharmacological studies and in vitro binding studies

To investigate the ontogenesis of potential cholinergic influences on growth hormone secretion we administered the cholinesterase inhibitor neostigimine, (120 micrograms/kg) to fetal sheep (n = 16) between 77 and 143 days of gestation and to infant lambs (n = 5). Neostigmine administration was associated with a marked rise in fetal growth hormone concentrations. The integrated release of growth hormone in the hour following fetal neostigmine administration was 2880 +/- 425 ng.min/ml compared to -618 +/- 206 ng . min/ml (P less than 0.001) following saline administration (n = 19). There was no relationship between gestational age and the response to neostigmine. In the infant lamb, neostigmine was associated with a lesser (P less than 0.001) but significant (P less than 0.02) growth hormone response. The integrated release was 704 +/- 410 ng . min/ml (n = 5) compared to -44 +/- 40 ng . min/ml following saline (n = 11). The fetal response to neostigmine was abolished by the administration of atropine (200 micrograms/kg bolus followed by 400 micrograms/kg per h infusion) 5 min prior to neostigmine (n = 4). This demonstrates that the effect of neostigmine was mediated by muscarinic receptors. Atropine itself had no effect on fetal growth hormone release (n = 6). In vitro binding studies with the muscarinic ligand, 1-quinuclidinyl [phenyl-4 (n) -3H] benzilate) were performed on homogenates of fetal (n = 3) and adult (n = 3) pituitaries. Scatchard analysis demonstrated both a high affinity and low affinity binding site. The concentration per mg. of original tissue of each of these binding sites was higher (P less than 0.05) in fetal than adult homogenates.(ABSTRACT TRUNCATED AT 250 WORDS)     

Carbonic anhydrase in the carotid body and the carotid sinus nerve

It is well known that carbonic anhydrase plays an important role in the physiological responses of carotid-body chemoreceptors to hypercapnia. Nevertheless the precise location of the enzyme within the carotid body has been a matter of controversy for many years. Using the Hansson method we found histochemical evidence that this enzyme is localized in type I cells. Type II cells and nerve terminals did not show enzymatic activity. These results allow us to define the carotid body as a secondary receptor in the context of the "acidic hypothesis" of transduction in the carotid body.     

Carbonic anhydrase in the carotid body and the carotid sinus nerve

Summary It is well known that carbonic anhydrase plays an important role in the physiological responses of carotidbody chemoreceptors to hypercapnia. Nevertheless the precise location of the enzyme within the carotid body has been a matter of controversy for many years. Using the Hansson method we found histochemical evidence that this enzyme is localized in type I cells. Type II cells and nerve terminals did not show enzymatic activity. These results allow us to define the carotid body as a secondary receptor in the context of the acidic hypothesis of transduction in the carotid body.     

Ventilatory and carotid body chemoreceptor responses to purinergic P2X receptor antagonists in newborn rats

Adenosine triphosphate, acting through purinergic P2X receptors, has been shown to stimulate ventilation and increase carotid body chemoreceptor activity in adult rats. However, its role during postnatal development of the ventilatory response to hypoxia is yet unknown. Using whole body plethysmography, we measured ventilation in normoxia and in moderate hypoxia (12% fraction of inspired O?, 20 min) before and after intraperitoneal injection of suramin (P2X? and P2X? receptor antagonist, 40 mg/kg) in 4-, 7-, 12-, and 21-day-old rats. Suramin reduced baseline breathing (～20%) and the response to hypoxia (～30%) in all rats, with a relatively constant effect across ages. We then tested the effect of the specific P2X? antagonist, A-317491 (150 mg/kg), in rats aged 4, 7, and 21 days. As with suramin, A-317491 reduced baseline ventilation (～55%) and the hypoxic response (～40%) at all ages studied. Single-unit carotid body chemoreceptor activity was recorded in vitro in 4-, 7-, and 21-day-old rats. Suramin (100 μM) and A-317491 (10 μM) significantly depressed the sinus nerve chemosensory discharge rate (～80%) in normoxia (Po? ～150 Torr) and hypoxia (Po? ～60 Torr), and this decrease was constant across ages. We conclude that, in newborn rats, P2X purinergic receptors are involved in the regulation of breathing under basal and hypoxic condition, and P2X?-containing receptors play a major role in carotid body function. However, these effects are not age dependent within the age range studied.