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Biomedical subjects

G B Martin

Publications and source records attributed to G B Martin.

At least 145 records · Page 8Linked to original sources

Roles of progesterone and oestradiol in determining the temporal sequence and quantitative expression of sexual receptivity and the preovulatory LH surge in the ewe.

In a series of experiments using a quantitative method for measuring receptivity and implants that allowed rapid and controlled changes in the blood concentrations of oestradiol-17 beta and progesterone, we have re-examined the roles of these steroids in the induction of sexual behaviour and the LH surge in ovariectomized ewes. Progesterone priming was found to increase the proportion of ewes showing oestrus, reduce the latency to the onset of oestrus, and increase the 'intensity' of the behaviour as measured by the receptivity index, but it did not affect the size of the LH surge. Progesterone was able to facilitate the expression of oestrus even when it was withdrawn 8 days before oestrogen treatment, suggesting that it exerts its effect by restoring the sensitivity of the oestrogen-refractory animal to oestrogen. When it was present at the time oestrogen was administered, progesterone inhibited the stimulatory effect of oestrogen, but this effect disappeared as soon as the progesterone was withdrawn. Thereafter, expression of both the behavioural and endocrine responses was delayed by 24-30 h. These data show that the timing of the preovulatory behavioural and endocrine events is determined primarily by the time of progesterone withdrawal. The amount of oestradiol and the timing of any rise in concentration serve only to modulate these effects.

Animals↗

Coronary perfusion pressure and the return of spontaneous circulation in human cardiopulmonary resuscitation.

Coronary perfusion pressure (CPP), the aortic-to-right atrial pressure gradient during the relaxation phase of cardiopulmonary resuscitation, was measured in 100 patients with cardiac arrest. Coronary perfusion pressure and other variables were compared in patients with and without return of spontaneous circulation (ROSC). Twenty-four patients had ROSC. Initial CPP (mean +/- SD) was 1.6 +/- 8.5 mm Hg in patients without ROSC and 13.4 +/- 8.5 mm Hg in those with ROSC. The maximal CPP measured was 8.4 +/- 10.0 mm Hg in those without ROSC and 25.6 +/- 7.7 mm Hg in those with ROSC. Differences were also found for the maximal aortic relaxation pressure, the compression-phase aortic-to-right atrial gradient, and the arterial PO2. No patient with an initial CPP less than 0 mm Hg had ROSC. Only patients with maximal CPPs of 15 mm Hg or more had ROSC, and the fraction of patients with ROSC increased as the maximal CPP increased. A CPP above 15 mm Hg did not guarantee ROSC, however, as 18 patients whose CPPs were 15 mm Hg or greater did not resuscitate. Of variables measured, maximal CPP was most predictive of ROSC, and all CPP measurements were more predictive than was aortic pressure alone. The study substantiates animal data that indicate the importance of CPP during cardiopulmonary resuscitation.

Aorta↗

Effect of epinephrine on end-tidal carbon dioxide monitoring during CPR.

End-tidal carbon dioxide (ETCO2) has been shown to correlate with coronary perfusion pressure (CPP) during CPR and has been proposed as a useful noninvasive monitor of CPR efficacy. The effects of therapeutic epinephrine dosing on ETCO2 and CPP in six dogs were examined. Ventricular fibrillation was induced and left untreated for five minutes before CPR was initiated. After five minutes of CPR, epinephrine 0.045 mg/kg IV was administered. CPP and ETCO2 were compared immediately before and two minutes after epinephrine administration. There was a significant increase in CPP from 12.2 +/- 9.6 to 26.8 +/- 7.1 mm Hg (P = .006) after epinephrine. This was accompanied by a significant decrease in ETCO2 from 8.2 +/- 2.9 to 3.8 +/- 2.0 mm Hg (P = .01). These data indicate that after epinephrine administration, caution must be exercised in using ETCO2 as an indicator of CPP.

Animals↗

Characterization of cerebral energetics and brain pH by 31P spectroscopy after graded canine cardiac arrest and bypass reperfusion.

Recovery of cerebral energy metabolism is used to indicate CNS viability after ischemia. This study utilized 31P nuclear magnetic resonance (NMR) spectroscopy to measure cerebral energy state and intracellular pH in dogs subjected to 8, 12, or 16 min of cardiac arrest and reperfusion using cardiopulmonary bypass. Spectra were obtained throughout ischemia and initial reperfusion and repeated at 30 and 144 h post ischemia. Neurologic deficit scoring was performed at 12 and 24 h post insult and then daily. High-energy phosphates were depleted by the end of all ischemic intervals. Recovery occurred within 60 min of reperfusion and persisted with no differences in the rate of return between groups (p greater than 0.05). Brain pH (pHb) decreased by the end of ischemia in all groups (p less than 0.0001). Neither the pHb nadir nor its recovery differed between groups (p greater than 0.05). Although longterm neurologic outcome differed between groups, the spectra were similar. Assessment of cerebral energy state using 31P NMR spectroscopy does not appear to be a sensitive indicator of neurologic outcome after global ischemia in dogs. Return of high-energy phosphates may be a necessary but not sufficient condition for cerebral recovery after ischemia. The return of high-energy phosphates after a 16-min cardiac arrest, however, indicates a potential for neurological recovery.

Acid-Base Equilibrium↗

Plasma epinephrine levels in resuscitation with cardiopulmonary bypass.

Since the highest plasma epinephrine levels have been recorded during resuscitation, we evaluated the isolated effect of cardiac arrest upon adrenomedullary secretion. We determined plasma epinephrine in dogs resuscitated with cardiopulmonary bypass (CPB) after cardiac arrest periods of 12 (CPB-12; n = 4) or 16 min (CPB-16; n = 5). Through 2 h of CPB and the following 6 h of critical care, there was no difference between CPB-12 and CPB-16 regarding most cardiopulmonary functional variables. Plasma epinephrine was markedly elevated immediately after initiation of CPB (p less than .01 at 1 min CPB vs. basal) and returned rapidly to basal concentrations. Comparison of plasma epinephrine levels between CPB and standard CPR groups showed that responses to cardiac arrest were similar (p greater than .05 at 1 min CPB vs. 11.5 min CPR). We conclude that cardiac arrest is the main or sole determinant of the plasma epinephrine elevation of resuscitation.

Animals↗

The effect of cardiopulmonary bypass resuscitation on cardiac arrest induced lactic acidosis in dogs.

The adequacy of end organ blood flow following a cardiac arrest varies depending on the artificial reperfusion technique utilized and may critically affect patient outcome. Both oxygen consumption (VO2) and arterial lactate values have previously been used to assess tissue perfusion. Cardiopulmonary bypass resuscitation (CPB) is a reperfusion technique capable of providing near normal end organ blood flow. The purpose of this investigation was to study the effect of femoro-femoral veno-arterial CPB resuscitation compared to standard CPR on VO2 and arterial lactic acid values after a prolonged cardiac arrest. Ten mongrel dogs were electrically fibrillated and left in cardiopulmonary arrest without therapy for 12 min. Resuscitation was attempted according to a standardized protocol utilizing either CPB (n = 5) or standard external CPR (n = 5). Oxygen consumption values and arterial lactic acid samples were obtained at baseline, at timed intervals throughout resuscitation and after return of spontaneous circulation in successfully resuscitated dogs. Baseline hemodynamic and biochemical measurements were similar in both treatment groups (P greater than 0.05). Oxygen consumption (440 +/- 50 ml/min/M2) and mean arterial lactic acid values (7.44 +/- 2.25 mmol/l) were significantly higher at 1 min of resuscitation in CPB-treated dogs compared to dogs treated with CPR (60 +/- 10 ml/min/M2) (3.16 +/- 0.69 mmol/l) respectively (P less than 0.05). Mean arterial lactic acid values rose significantly at each sampling interval during CPR (P less than 0.05) but began to decrease after 5 min of resuscitation in the CPB animals and were not significantly different than baseline after 60 min of bypass (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis, Lactic↗

The effect of CO2 and non-CO2-generating buffers on cerebral acidosis after cardiac arrest: A 31P NMR study.

There is controversy regarding the use of alkalinizing agents during reperfusion after cardiac arrest. The potential deleterious effects of sodium bicarbonate (bicarb) administration, including paradoxic cerebral acidosis, have led to the search for alternative agents. Tromethamine (tris) is a non-CO2-generating buffer that has been proposed for use during cardiopulmonary resuscitation. The purpose of this experiment was to compare the ability of tris with bicarb to correct brain pH (pH B) during reperfusion after a 12-minute cardiac arrest. Adult mongrel dogs were instrumented and placed in the bore of a Bruker Biospec 1.89 tesla superconducting magnet system. Ventricular fibrillation was induced; after 12 minutes, cardiopulmonary bypass was initiated and maintained for two hours with minimum flows of 80 mL/kg/min. Bicarb (n = 5) or tris (n = 5) were administered to correct arterial pH as rapidly as possible. 31P NMR spectra were obtained at baseline and throughout ischemia and reperfusion. The pH B was determined with the inorganic phosphate relative to the phosphocreatine resonance signal shift. Profile analysis indicates a difference between groups (P less than .02) related to an initial delay in pH B correction in the tris group. By 48 minutes of reperfusion, pH B did not differ between the groups. Moreover, there was no evidence of paradoxic cerebral acidosis in the bicarb group. Although tris corrects blood pH as quickly as bicarb, it is less effective in correcting pH B. Absence of paradoxic acidosis may be caused by efficient elimination of CO2 by cardiopulmonary bypass.

Acidosis↗

CPR-dependent consciousness: evidence for cardiac compression causing forward flow.

We present the case of a patient with cardiac arrest and resuscitation in whom, consistent with direct cardiac compression, large aortic-to-right atrial systolic pressure gradients occurred. Forward blood flow during CPR was sufficient for the patient to maintain consciousness. Although aortic-to-right atrial diastolic gradients adequate to maintain coronary perfusion in experimental models were generated, in our patient, cardiac function could not be restored and the resuscitation was ultimately unsuccessful.

Blood Circulation↗

Bradyrhizobium japonicum glnB, a putative nitrogen-regulatory gene, is regulated by NtrC at tandem promoters.

The glnB gene from Bradyrhizobium japonicum, the endosymbiont of soybeans (Glycine max), was isolated and sequenced, and its expression was examined under various culture conditions and in soybean nodules. The B. japonicum glnB gene encodes a 12,237-dalton polypeptide that is highly homologous to the glnB gene products from Klebsiella pneumoniae and Escherichia coli. The gene is located directly upstream from glnA (encoding glutamine synthetase), a linkage not observed in enteric bacteria. The glnB gene from B. japonicum is expressed from tandem promoters, which are differentially regulated in response to the nitrogen status of the medium. Expression from the downstream promoter involves the B. japonicum ntrC gene product (NtrC) in both free-living and symbiotic cells. Thus, glnB, a putative nitrogen-regulatory gene in B. japonicum, is itself Ntr regulated, and NtrC is active in B. japonicum cells in their symbiotic state.

Amino Acid Sequence↗

Role of hypothalamic catecholamines in the regulation of luteinizing hormone and prolactin secretion in the ewe during seasonal anestrus.

Separate studies with ewes have shown that catecholamines play an inhibitory role in the control of LH secretion during anestrus, and that there are structures in the lateral retrochiasmatic area (L-RCh), which could be involved in the regulation of gonadotrophin secretion. These observations have led to the hypothesis that the catecholaminergic structures in the L-RCh mediate the inhibition of pulsatile LH secretion by estradiol in the anestrous ewe. We tested this hypothesis by injecting 6-hydroxydopamine (6OH-DA) into the L-RCh of ovariectomized ewes during the anestrous season, and comparing the secretion of LH and prolactin in these animals with that in sham (injected with vehicle) and control (no injection) animals, in the presence and absence of exogenous estradiol. Finally, the effectiveness of the toxin was assessed by immunocytochemical techniques. When the ewes were treated with estradiol, LH pulse frequency was significantly lower in the controls (mean 1.1 pulses/4 h) and shams (0 pulses/4 h) than in the ewes treated with 6OH-DA (3.1 pulses/4 h). When the estradiol implants were removed, the frequencies increased to 5.1 pulses/4 h for the controls and 5.7 pulses/4 h in the ewes treated with 6OH-DA. These were not significantly different. Plasma prolactin levels were significantly reduced by 6OH-DA treatment. The 6OH-DA ewes recovered their response to estradiol by 14 weeks after the injection. The anatomical study at the end of the experiment revealed a difference between treated and control ewes of only 15% in the numbers of dopaminergic cells in the L-RCh.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Simultaneous aortic, jugular bulb, and right atrial pressures during cardiopulmonary resuscitation in humans. Insights into mechanisms.

Pressure gradients across and between the head and chest were studied during mechanical cardiopulmonary resuscitation (CPR) in 22 humans. Patients in medical cardiac arrest, managed by ACLS guidelines, underwent placement of aortic arch (Ao), jugular venous bulb (JVB), and right atrial (RA) catheters. Simultaneous pressures were measured, and intercatheter gradients were calculated. The JVB to RA pressure difference is the gradient between the cervical and central venous circulations. It was negative when averaged throughout the CPR cycle and was more negative during compression than relaxation, -19 +/- 12 and -2 +/- 6 mm Hg, respectively. This indicates that the intrathoracic pressure rise was not transmitted to the jugular venous system, supporting the concept of a competent jugular valve mechanism during CPR. It is consistent with the thoracic pump model of cerebral perfusion. JVB to RA was positive only during early relaxation, allowing blood return from the head. The Ao to JVB gradient, although not equal to cerebral perfusion pressure, is the maximum potential pressure gradient for blood flow across the cerebral vasculature. It was positive throughout CPR, 25 +/- 17 during compression, and 9 +/- 10 mm Hg during relaxation. The Ao to RA gradient during the relaxation phase is CPR coronary perfusion pressure. In most patients, it was minimally positive in both phases of the CPR cycle: 7 +/- 14 in compression and 7 +/- 9 mm Hg during relaxation. This appears to be inadequate in providing sufficient blood flow to meet the metabolic needs of the myocardium. Four patients had larger gradients during compression suggestive of cardiac compression.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

LH, FSH and ovulation rate in ewes treated with exogenous oestradiol.

In two experiments, mature Merino ewes were fitted with subcutaneous implants containing oestradiol-17 beta or empty implants (control). Peripheral concentrations of LH and FSH were measured during luteal and follicular phases, which were synchronized by means of intravaginal progestagen-impregnated sponges. The ovulation rates of the ewes were determined by laparoscopy, 1 week after luteolysis. In Exp. 1, small implants (3 mm) decreased the LH pulse frequency before luteolysis. In the ewes with oestradiol implants, the amplitude of the preovulatory surge of LH was reduced and the onsets of the LH and FSH surges were delayed. There was no effect of oestradiol on LH baseline, LH pulse amplitude or in the concentration of FSH during the luteal or follicular phases. In Exp. 2, larger implants (10 mm) were inserted for the luteal, follicular, or luteal + follicular phases. The control ewes had empty implants. In the ewes with oestradiol implants, LH pulse frequencies were decreased during the luteal phase. This decrease persisted throughout the follicular phase, even though the oestradiol implants had been removed. There were no differences in the other measures of LH or FSH in the luteal or follicular phases. Ovulation rates were not affected by oestradiol treatment in either experiment, indicating that the regulation of LH pulse frequency is not a critical factor in the determination of ovulation rate in ewes. This was supported by retrospective analysis of the gonadotrophin profiles of single and twin-ovulating ewes, in which all measures of LH were similar between the two groups. However, twin-bearing ewes had slightly higher circulating concentrations of FSH during the luteal phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of level of food intake of ewes on the secretion of LH and FSH and on the pituitary response to gonadotrophin-releasing hormone in ovariectomized ewes.

The effect of level of food intake on LH and FSH profiles and pituitary sensitivity to gonadotrophin-releasing hormone (GnRH) was investigated in two groups of 12 ovariectomized ewes. Ewes with a high intake (group H) had a mean daily intake (+/- S.E.M.) of 1.99 +/- 0.075 kg dry matter (DM)/head per day while ewes with a moderate intake (group M) consumed a mean of 1.02 +/- 0.021 kg DM/head per day. Ovaries were surgically removed from six ewes of each group on day 11 of the luteal phase and from the remainder 30 h after an injection of 100 micrograms prostaglandin analogue given on day 11 to induce luteolysis. During both the luteal phase and the follicular phase, mean LH and FSH concentrations and LH pulse frequencies and amplitudes were unaffected by the level of intake but mean plasma prolactin concentrations were higher (P less than 0.05) in group H than in group M ewes in the follicular phase. Mean LH and FSH concentrations at day 2 after ovariectomy were unaffected by treatment while mean prolactin concentrations were higher (P less than 0.05) in group H than in group M ewes. At day 7 after ovariectomy, mean LH and FSH concentrations were lower (P less than 0.05) in group H than in group M ewes although mean LH pulse frequencies and pulse amplitudes were not significantly affected by the level of intake at either time.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Diminished role of LHRH in the control of gonadotroph morphology and function in the long-term castrated male rat.

It was found in previous studies that the neurotransmitter control of the secretion of LHRH and LH differs between long-term castrated and ovariectomized rats. One interpretation of these data was that there was a reduced 'positive drive' in the male, and the question was raised 'how do the gonadotrophs of long-term castrated rats maintain a high level of LH secretion?'. In the present series of experiments, evidence for a reduced dependence of the gonadotrophs upon LHRH stimulation is provided. Although sensitivity to native LHRH was not completely lost in long-term castrated rats, two potent LHRH antagonists (D-pyroglu1,D-Phe2,D-Trp3,6)-LHRH and (N-acetyl-3,4-dehydro-Pro,p-fluoro-D-Phe2,D-Trp3,6)-LHRH, were found to inhibit LH secretion in short-term castrated and long-term ovariectomized rats, but not in long-term castrated rats. Neither blockade of axonal transport with colchicine nor immunoneutralization of LHRH with an antiserum against LHRH (both administered 48 h before blood sampling) produced reductions in serum concentrations of LH in long-term castrated rats, although these treatments significantly suppressed LH levels in short-term castrated animals. Chronic (6-day) infusions of the second LHRH antagonist (up to 450 micrograms/day) neither reduced LH secretion nor altered the morphology of the 'castration cells' in the pituitaries of long-term castrated rats. Chronic treatment with testosterone (15 days), however, reversed these parameters to some extent, and when the testosterone treatment was coupled with chronic infusions of the LHRH antagonist, significantly lower serum levels of LH and reductions in the size of the castration cells were observed. These data thus indicate that castration cells may function autonomously, without the need for LHRH, and that testosterone in some way restores the dependency on LHRH and/or the responsiveness to LHRH of these cells.

Animals↗

Biphasic response in the secretion of gonadotrophin-releasing hormone in ovariectomized ewes injected with oestradiol.

In ovariectomized ewes, an injection of oestrogen initially inhibits the tonic secretion of LH, and then induces a large release of LH similar to the preovulatory surge in intact ewes. The pattern of hypothalamic secretion of gonadotrophin-releasing hormone (GnRH) into the pituitary portal blood during this biphasic response to oestrogen was investigated in conscious, unrestrained, ovariectomized adult Ile-de-France ewes during the breeding season. The ewes were ovariectomized and implanted with cannulae for portal blood collection on the same day. Seven days later, portal and peripheral blood samples were collected simultaneously every 5 min for 25 h. The ewes were injected with oestradiol-17 beta (25 micrograms i.v. and 25 micrograms i.m.) 6.25 h after the start of sampling. GnRH and LH were measured by radioimmunoassay in portal and jugular plasma samples respectively. A clear pulsatile pattern of LH secretion was observed before the oestradiol injection in all the ewes, followed by the typical biphasic decrease (negative feedback) and increase (positive feedback) in mean concentrations. The sampling period was divided, for analysis, into pretreatment, negative feedback and positive feedback phases. Before injection with oestradiol, the GnRH pulses were clearly defined in portal blood and were always synchronized with LH pulses in the peripheral circulation. The frequency was 5.9 +/- 0.6 pulses/6 h (mean +/- S.E.M.), and the amplitude was 31.6 +/- 7.6 pmol/l. During negative feedback, both the frequency (4.2 +/- 0.5 pulses/6 h, P less than 0.01) and amplitude (15.2 +/- 4.6 pmol/l, P less than 0.05) of the GnRH pulses decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Secretion of LH, FSH and oestradiol-17 beta during the follicular phase of the oestrous cycle in the ewe.

Plasma concentrations of LH, FSH and oestradiol-17 beta were measured in blood samples taken at 15 min intervals for 48 h during the follicular phase of four Merino ewes. The amplitude of pulses of LH and the mean concentration of LH were higher at the beginning of the follicular phase, 36-24 h before the preovulatory surge of LH (amplitude 2.4 ng ml-1, mean concentration 3.9 ng ml-1), than at the end, 24-0 h before the preovulatory surge (amplitude 1.2 +/- 0.1 ng ml-1; mean concentration 1.4 +/- 0.1 ng ml-1). There was no change in the inter-pulse interval during this time (mean 74 +/- 5 min). Over the same period, oestradiol levels increased from 7-8 pg ml-1 to a peak of 10-15 pg ml-1. Mean FSH concentrations declined (36-24 h: 3.6 ng ml-1 vs 24-0 h: 1.8 +/- 0.3 ng ml-1) before rising at the time of the preovulatory surge of LH and again 24 h later. It was concluded that the biphasic response of LH to oestrogen that is seen in ovariectomized ewes may also operate during the follicular phase of the oestrous cycle in entire ewes.

Animals↗

Role of the Bradyrhizobium japonicum ntrC gene product in differential regulation of the glutamine synthetase II gene (glnII).

We isolated the ntrC gene from Bradyrhizobium japonicum, the endosymbiont of soybean (Glycine max), and examined its role in regulating nitrogen assimilation. Two independent ntrC mutants were constructed by gene replacement techniques. One mutant was unable to produce NtrC protein, while the other constitutively produced a stable, truncated NtrC protein. Both ntrC mutants were unable to utilize potassium nitrate as a sole nitrogen source. In contrast to wild-type B. japonicum, the NtrC null mutant lacked glnII transcripts in aerobic, nitrogen-starved cultures. However, the truncated-NtrC mutant expressed glnII in both nitrogen-starved and nitrogen-excess cultures. Both mutants expressed glnII under oxygen-limited culture conditions and in symbiotic cells. These results suggest that nitrogen assimilation in B. japonicum is regulated in response to both nitrogen limitation and oxygen limitation and that separate regulatory networks exist in free-living and symbiotic cells.

Genes↗

Interactions between inhibin, oestradiol and progesterone in the control of gonadotrophin secretion in the ewe.

Experiments were carried out to test the hypothesis that inhibin and oestradiol act synergistically to inhibit the secretion of FSH, to test for effects of progesterone, and to compare the FSH and LH responses to ovarian feedback. In Exp. 1, with 11 ovariectomized and 12 intact Romanov ewes during the anoestrous season, doses of oestradiol (administered by means of subcutaneous implants) that restored normal LH pulse frequencies were insufficient to restore normal concentrations of FSH. In Exp. 2, with 48 ovariectomized Welsh Mountain ewes during the breeding season, a factorial design with 4 ewes per cell was used to assess the responses in LH and FSH to 3 doses of oestradiol (s.c. implants) and 4 doses of bovine follicular fluid ('inhibin', 0.2-1.6 ml s.c. every 8 h). This was done initially in the absence of progesterone and then after 7 days of treatment with progesterone (s.c. implants). Analysis of variance revealed a significant synergistic interaction between oestradiol and inhibin on the plasma concentrations of FSH. Progesterone had little effect. In contrast, there was a significant synergistic interaction between oestradiol and progesterone on the concentrations of LH. 'Inhibin' also inhibited LH secretion but this effect was independent of the two steroids. We conclude that there are basic differences in the way that ovarian feedback acts to control the secretion of LH and FSH in the ewe. FSH secretion appears to be primarily controlled by the synergistic action of oestradiol and inhibin on the anterior pituitary gland, while the secretion of LH is inhibited during the follicular phase by an effect of oestrogen at pituitary level and during the luteal phase by the synergistic action of oestradiol and progesterone at the hypothalamic level. Inhibin, or another non-steroidal factor in follicular fluid, may also play a minor role in the control of LH secretion.

Animals↗