Biomedical subjects

A M Perks

Publications and source records attributed to A M Perks.

At least 37 records · Page 2Linked to original sources

PubMed1991

Lung liquid production by in vitro lungs from fetal guinea pigs: studies with metabolic inhibitors.

Lungs from fetal guinea pigs (62 +/- 2 days of gestation) were supported in vitro for 3 h, and lung liquid production was measured by dye dilution. Eighteen untreated preparations produced fluid at 1.76 +/- 0.30 mL.kg-1 body weight.h-1 during the first hour, with no significant changes in later hours. When inhibitors of respiratory processes were placed in the outer saline during the middle hour, production changed significantly, as follows: (a) sodium iodoacetate at 10(-3) M stopped production (87.2 +/- 10.3 and 100% reductions, successive hours; n = 6), at 10(-4) M it reduced production (60.0 +/- 10.3 and 63.4 +/- 9.3% reduction, successive hours; n = 12); (b) sodium fluoride, 10(-3) M, almost stopped production (93.2 +/- 12.1 and 89.5 +/- 9.3% reductions, successive hours; n = 6); (c) sodium cyanide at high concentration (10(-3) M) reduced production slowly (35.5 +/- 12.3 and 73.1 +/- 22.4%; successive hours; n = 6); (d) sodium azide, 10(-3) M, also reduced production (67.6 +/- 14.2 and 59.7 +/- 14.0%, successive hours; n = 6); total lactate lost rose 1.8 +/- 0.5 fold; (e) dinitrophenol produced strong reabsorptions; at 10(-3) M, production fell 115.4 +/- 15.9 and 113.1 +/- 47.3%, successive hours (n = 4), and at 2 x 10(-4) M it fell 143.8 +/- 33.8 and 153.4 +/- 26.7%, successive hours (n = 6); total lactate lost rose 2- to 3-fold. Control preparations showed no significant changes. The results suggest that lung liquid production requires glycolysis and aerobic metabolism. However, reabsorption appears to continue on glycolysis alone, a particularly useful situation for neonates suffering respiratory distress.

Animals↗

PubMed1990

Fluid production by in vitro lungs from fetal guinea pigs.

Lungs from fetal guinea pigs (54-67 days of gestation) were supported in vitro, and lung liquid secretion rates were measured by a dye-dilution technique. The average secretion rate in the first hour was 2.14 +/- 0.08 (SE) mL x kg-1 body weight.h-1 (0.21 +/- 0.01 mL/h) (n = 450); this was comparable to intact preparations. In an independent study of 30 lungs, secretion continued unchanged for 3 h, with no significant change in fluid composition. Between 54 days and term, production appeared to fall in terms of millilitres per kilogram per hour. The following agents were placed in the supporting saline during the middle hour of incubation. (i) Sodium iodoacetate: at 10(-4) M this produced a fall in secretion (fall, succeeding hours; 55.4 +/- 23.0 and 64.9 +/- 17.5%; n = 6); at 10(-3) M it stopped secretion (fall, succeeding hours; 87.2 +/- 10.3 and 100%, n = 6). (ii) Ouabain: at 10(-5) M there was no change in production (n = 6); at 10(-4) M, four preparations were unaffected, two reduced production. (iii) Epinephrine (10(-7) M) produced a significant fall in production in all cases (n = 6); in four preparations secretion reduced (average fall, 64.4 +/- 10.8%); in two preparations there was reabsorption (average rate, -1.03 mL.kg-1.h-1). This extends the effect of epinephrine to the guinea pig, and suggests that the in vitro preparation is a useful model for studies of the fetal lung.

Animals↗

PubMed1990

The effects of furosemide and bumetanide on lung liquid production by in vitro lungs from fetal guinea pigs.

Lungs from fetal guinea pigs of 61 +/- 3 days of gestation were supported in vitro for 3 h, and lung liquid secretion rates were measured by a dye dilution technique based on Blue Dextran 2000. Ten preparations that had received no treatment showed an average secretion rate of 1.12 +/- 0.28 mL.kg-1 body weight.h-1 during the first hour, and there were no significant changes over the following 2 h. In studies of 54 fetal lungs, furosemide, bumetanide, control ethanol carrier, or saline alone were placed in the supporting medium during the middle hour of the 3-h incubations (ABA design). Furosemide at 10(-3) M reduced secretion 83.4 +/- 16.8%; at 10(-4) and 10(-5) M it produced smaller reductions. Bumetanide at 10(-3) M usually produced reabsorption (129.9 +/- 23.0% reduction), at 10(-4) M it reduced secretion 30.9 +/- 11.8%, but at 10(-5) M it was ineffective. Control carrier and saline were without effect. The ability of the loop diuretics to produce reabsorption of fluid in some preparations suggests the unmasking of an active reabsorptive process. The results also suggest that lung liquid secretion in the fetal guinea pig, as in the sheep, is dependent on a Na+ and Cl- cotransport system.

Animals↗

PubMed1990

The effects of temperature change on lung liquid production by in vitro lungs from fetal guinea pigs.

Lungs from fetal guinea pigs of 58-65 days of gestation were supported in vitro for 3 h, and lung liquid production rates were measured by a dye dilution technique. In 36 control preparations, incubated continuously at 37 degrees C, the average production rate in the first hour was 1.46 +/- 0.23 ml/h per kg body weight; there was no significant change over the following two h. In 36 further preparations the temperature was changed during the middle hour (ABA), with the following % reductions in production rates: at -1 degrees C (relative to 37 degrees C), 68.2 +/- 17.1%; -2 degrees C, 125.5 +/- 30.1% (reabsorption); -3 degrees C, 103.8 +/- 32.8% (reabsorption); -5 degrees C, 82.7 +/- 16.6%, -8 degrees C, 94.7 +/- 1.8 %; +2 degrees C, 100.7 +/- 12.6% (all significant, P less than 0.025-0.005). Slow recoveries followed a return to starting conditions, except after the increase in temperature, 10(-6) M amiloride abolished reabsorption, but not depression, during the maximal effects of temperature reduction (at -2 degrees C, n = 6); amiloride had no effect on control preparations (n = 6). These results suggest that: (a) reductions of 2-3 degrees C, as seen in the delivery room, abolish secretion, but not reabsorption of lung fluid; larger reductions stop both processes; (b) the reabsorptions seen after a fall in temperature depend on Na(+)-transport mechanisms; (c) lung liquid production was sensitive to a rise in temperature, so that fevers might adversely affect lung development, and (d) the fall in temperature at birth may be an important factor in the early reabsorption of lung liquid.

Absorption↗

PubMed1989

The effects of arginine vasopressin and epinephrine on lung liquid production in fetal goats.

The effects of arginine vasopressin (AVP) and epinephrine on lung liquid secretion were investigated in 67 acute fetal goats (116 days of gestation to term) with intact umbilical cords after caesarean section. Secretion was measured by an impermeant tracer technique. AVP was infused intravenously (1.6-39.2 mU/(kg.min); 2 h) into 26 fetuses. All fetuses below 130 days of gestation, except one, showed no response. All above 133 days reduced secretion, or turned to reabsorption, except at the lowest infusion rate. The effect persisted, and usually increased postinfusion. Expansion of the lungs with saline did not change the response. The percentage reductions were linearly related to the logarithm of the infusion rate (threshold, 1.42 mU/(kg.min]. The absolute reductions were linearly related to fetal weight. Epinephrine was infused intravenously (0.30-6.72 micrograms/(kg.min); 1-2 h) into 12 fetuses. All fetuses (118 days to term) reduced secretion or reabsorbed by the second hour. At the highest infusion rate, reabsorption was immediate; at the lowest, secretion increased slightly, then fell significantly in the second hour. Epinephrine acted at levels considered physiological at delivery in the sheep. AVP appears to act at plasma levels found in most vaginal deliveries; it may augment epinephrine-induced reabsorption during stress, and help long-term removal of lung fluid.

Animals↗

PubMed1986

The effects of bumetanide and furosemide on lung liquid secretion in fetal sheep.

Thirty-four experiments were carried out on the effects of loop diuretics on lung liquid secretion in 20 fetal sheep (128-145 days gestation) with indwelling catheters. Bumetanide placed in the lung liquid at 2.19 +/- 0.52 X 10(-4) M produced immediate reabsorption of fluid, and effects lasted 3 hr (n = 6). Bumetanide at 1.1 +/- 0.17 X 10(-5) M reduced secretion significantly for 2 hr (n = 4), but at 1.07 +/- 0.06 X 10(-6) M there was no clear effect (n = 6). Controls showed no significant change (n = 6). Furosemide was less effective. At 3.1 +/- 0.07 X 10(-3) M it produced an immediate reabsorption, which lasted 3 hr, but at 1.0 +/- 0.04 X 10(-4) M it increased secretion slightly (n = 4); controls showed no significant change (n = 6). The results are consistent with the presence of a chloride transport system, perhaps with sodium cotransport, as the major factor in fetal lung liquid secretion.

Animals↗

PubMed1985

The rate of production of lung liquid in fetal goats, and the effect of expansion of the lungs.

Fetal goats (95-155 days of gestation), delivered by Caesarian section, under chloralose (50 mg/kg), with intact umbilical cords, were monitored for lung fluid production by an impermeant tracer method. The average rate of production was 13.4 +/- 2.3 ml/h, or 6.0 +/- 0.9 ml/h per kg. Production rose exponentially towards birth, by both parameters, significant P less than 0.0001 (ml/h), or P less than 0.0005 (ml/h per kg). This indicated an increase in lung liquid production due to both growth and increased activity of the tissues. However, considerable individual variability, even between twins, suggested that this general pattern was modulated by physiological requirements. In 14 fetuses (plus 12 controls), expansion of the lungs with volumes of saline similar to those of the first inspirations (saline, 15-40 ml, matched to the optical density of the lung fluid; inspiration by spirometer, 20-25 ml), caused reduction of secretion or reabsorption of fluid. Secretion changed to reabsorption at about 50% expansion, and the probable physiological limit was estimated at 62-68% expansion. The logarithm of the % fall in production was linearly related to the % expansion (r = 0.88; P less than 0.0001); therefore, small expansions (equivalent to intrauterine breathing) would have little effect, but larger changes such as first breaths, would produce rapidly escalating effects. Controls showed no similar activity. Changes in Na+ and Cl- ions are in parallel to those of water. However, K+ ions moved into the lungs after expansion, in the opposite direction to Na+ ions, and against their concentration gradient. It is suggested that expansion of the lungs activates a Na+/K+ ATP-ase pump to aid reabsorption of salt and water at birth.

Animals↗

PubMed1984

The effects of bradykinin on the contractile activity of the isolated rat ovary.

Studies of ovarian contractility were carried out on 43 rat ovaries maintained in vitro. Eighteen ovaries showed spontaneous motility. In 65 of 155 tests (42%), synthetic bradykinin (3.75-25.0 ng/ml saline) produced sustained increases in ovarian tone, or stimulated phasic contractions. Failure to respond was related to the stage of the oestrous cycle. Sensitivity was highest around ovulation (00.00-04.00 h oestrus), when there were 25 responses in 26 tests, and the linear relationship between the response and the logarithm of the concentration suggested a threshold of 2.9 ng/ml saline. Sensitivity fell later in oestrus, and reached its lowest point in metoestrus (1 response in 20 tests). Since the plasma kinin system is activated before ovulation, and the threshold to bradykinin was within reported plasma kinin levels, it seems possible that plasma kinins are involved in contractile processes associated with ovulation.

Animals↗

PubMed1983

The kinin system and ovulation: changes in plasma kininogens, and in kinin-forming enzymes in the ovaries and blood of rats with 4-day estrous cycles.

Rats with 4-day estrous cycles showed a 51% fall in plasma kininogen in early proestrus (1200-1500). Levels remained depressed throughout ovulation, and then recovered steadily. The initial fall corresponded well with the LH surge. Initial attempts were made to detect enzymes which might be responsible for the change. Kinin-forming enzymes, in either precursor or active forms, were absent from the ovaries in diestrus, but appeared at the onset of the fall in kininogen (kinin-forming activity, 2.87 +/- 0.83 ng bradykinin (BK) equiv. X g wet tissue-1 X min-1). They rose 10-fold just before ovulation, and then declined rapidly. This major peak, and a corresponding one in plasma, may have reflected the presence of follicular proteases. Plasma kinin-forming enzymes showed no apparent change when the kininogen first declined. They then disappeared, suggesting a more delayed activation and destruction. It seems possible that LH induces kinin-forming enzymes in the ovaries, and induces a later activation of plasma enzymes, to produce kinins which may be involved in vascular and permeability changes important in ovulation, and perhaps concerned in the mechanisms of positive feed-back with the pituitary.

Animals↗

PubMed1983

Changes in plasma kininogen levels in rats before ovulation, and after treatment with luteinizing hormone and oestradiol-17 beta.

The pre-ovulatory fall in plasma kininogens in rats with 4 day oestrous cycles started between 12.00 and 15.00 h pro-oestrus, reached a maximum decline of 51% by 18.00 h pro-oestrus, and started to recover before ovulation. Because these changes appeared to correspond with the LH-surge, and to follow the peak in plasma oestradiol-17 beta levels, both of these hormones were tested for possible effects on plasma kininogens. Intracardiac injections of 110 IU of equine LH into dioestrous rats were followed by a decline of 30.8 +/- 6.7% in plasma kininogens, 6 h after injection (significant, P less than 0.01). Values were still depressed, but recovering, 12 h after treatment; the reduction was 21.3 +/- 5.8% (significant, P less than 0.01). Controls showed no decline. Injections of oestradiol-17 beta (1.0 micrograms/100 g body weight) produced no significant effects. It is suggested that the LH surge may be responsible, at least in part, for the decline in plasma kininogens seen before ovulation.

Animals↗

PubMed1982

Melanocyte-stimulating activity in fetal, newborn and adult guinea-pigs: studies of the pituitary, blood plasma and amniotic fluid.

Melanocyte-stimulating activity in the pituitary and plasma of fetal, newborn and adult guinea-pigs, and in amniotic fluid, was bioassayed on isolated Anolis skin. In the fetuses, levels in the posterior, anterior and whole pituitary increased exponentially between 39 and 70 days of gestation; in all cases, the increases were close to 35-fold in terms of ng/lobe, and 6-fold in ng/mg of lyophilized tissue. The increases were due to growth, and to an increased accumulation within the tissues. Ratios of activity in the posterior pituitary: anterior pituitary: hypothalamus approximated 200:30:1 (ng/mg of dry tissue). Fetal plasma levels showed some scatter; however, there were no trends with age, and the average value (10.0 +/- 1.6 ng/ml) was close to that of the mothers (10.6 +/- 2.6 ng/ml). Plasma activity appeared to fall markedly around birth; newborn pups, 2-6 hours after birth, showed levels 65% below those of the fetuses, and also below those of the adults (significant; P less than 0.05). At the same time the pituitary levels increased; this suggested a shut-down in release. The possible implications of this in the birth processes are discussed. Amniotic fluid showed only low, inconsistent activity, below 1% of plasma levels.

Amniotic Fluid↗

PubMed1982

Studies of factors which stimulate lung fluid secretion in fetal goats.

Twenty near-term fetal goats, delivered by Caesarian section, under chloralose (50 mg/kg), with intact umbilical cords, were monitored for lung fluid production by a dye dilution method. Controls, and fetuses given slow infusions of saline (0.9% (w/v) NaCl at 0.028 - 0.042 ml/kg per min, intravenous, for 2 h), showed no significant increases in lung fluid production, Na+ secretion, or Na+ concentration in lung fluid. Intermediate rates of infusion (0.053 ml/kg per min for 2 h) did not increase fluid production, but significantly increased Na+ secretion and Na+ concentration in lung fluid. Fast infusions (0.084 - 0.24 ml/kg per min for 2-3 h) increased significantly fluid secretion (up to 40-fold), Na+ secretion (up to 9.3-fold), and Na+ concentration in lung fluid (increases up to 5.2 mequivalents/l); in one case, spontaneous reabsorption was reversed to secretion. Prolactin, placed directly in the lungs (10 micrograms/ml fluid), by the third hour; controls showed no changed. In all cases Cl- behaved similarly to Na+; K+ moved partly independently. Synthetic pentagastrin (infused at 0.12-2.5 micrograms/kg per min, intravenous) did not stimulate secretion. The results suggest that the fetal lungs may influence salt-water balance, and this may be under prolactin control.

Animals↗

PubMed1979