Biomedical subjects

G B Martin

Publications and source records attributed to G B Martin.

At least 109 records · Page 6Linked to original sources

PubMed1995

Dopaminergic control of LH secretion by the A15 nucleus in anoestrous ewes.

Annual variations in the secretion of LH are responsible for seasonal changes in ovulatory activity in ewes. This hormonal pattern reflects an increase in the intensity of the negative feedback exerted by oestradiol under long days. Neuropharmacological studies have shown that this inhibition of LH secretion involves activation of catecholaminergic systems from preoptic and mediobasal hypothalamus (MBH) by oestradiol during anoestrus, and that 5-hydroxytryptamine inputs may also play a role. Within the MBH, the most important structures appear to be the retrochiasmatic region of the hypothalamus, which contains the A15 dopaminergic nucleus, and the median eminence, which contains the axon terminals of the GnRH cells controlling the pulsatile release of LH. In ovariectomized ewes in which oestradiol tonically inhibits LH secretion during the anoestrous season, LH pulse frequency is increased when the cells of the A15 nucleus are destroyed. The median eminence and other mediobasal structures contain more catecholamines and their metabolites under long days than under short days. Microdialysis of the A15 nucleus in vivo during long days revealed increased catecholaminergic activity under oestradiol treatment due to stimulation of tyrosine hydroxylase, the rate-limiting enzyme in the pathway of catecholaminergic synthesis. Tyrosine hydroxylase activity within the median eminence is increased under the various photoperiodic regimens that inhibit LH secretion. Neurochemical changes in the A15 nucleus and median eminence, in response to photoperiodic or oestradiol treatments, suggest a functional relationship which acts at the level of the GnRH axon terminals.

Anestrus↗

PubMed1995

Nutritional influences on reproduction in mature male sheep and goats.

Changes in the nutrition of mature rams and goat bucks lead to profound responses in testicular size and therefore the rate of production of spermatozoa. These effects are largely due to changes in the size of the seminiferous tubules and in the efficiency of spermatogenesis. With the exception of severe undernutrition, the effects on spermatogenic function are not accompanied by similar changes in endocrine function of the testes, as measured by the production of testosterone or inhibin. In rams, moderate changes in nutrition affect gonadotrophin secretion for only a few weeks, whereas testicular growth is affected for several months. In mature male goats during the non-breeding season, nutrition-induced testicular growth does not seem to be associated with a gonadotrophin response. Such observations have led us to develop the hypothesis that nutrition-driven testicular growth is at least partly independent of changes in gonadotrophin secretion. The energetic components of the diet, rather than the protein content, seem to be responsible for affecting gonadotrophin secretion in rams. The volatile fatty acids, and not glucose, are the active factors, although intracerebral insulin may also play a role. Where these substrates act and whether they are also involved in the gonadotrophin-independent pathways requires testing. In conclusion, nutritional signals exert powerful effects on the reproductive system of mature male ruminants, and the responses are partly independent of changes in gonadotrophin secretion. In the gonads, the gametogenic tissue responds rapidly to changes in nutrition, but the endocrine compartments are less affected. Variations in the expression of the nutritional responses among sexes, breeds and species probably reflect variations in the role of this environmental factor as a modulator of reproductive function.

Animal Nutritional Physiological Phenomena↗

PubMed1994

Map-based cloning in crop plants: tomato as a model system II. Isolation and characterization of a set of overlapping yeast artificial chromosomes encompassing the jointless locus.

A map-based cloning technique for crop plants is being developed using tomato as a model system. The target gene jointless is a recessive mutation that completely suppresses the formation of flower and fruit pedicel abscission zones. Previously, the jointless locus was mapped to a 3 cM interval between the two molecular markers TG523 and RPD158. Physical mapping of the jointless region by pulsed-field gel electrophoresis demonstrated that TG523 and RPD158 reside on a 600 kb SmaI fragment. In this study, TG523 was used as a probe to screen a tomato yeast artificial chromosome (YAC) library. Six tomato YAC (TY) clones were isolated, ranging from 220 to 380 kb in size. Genetic mapping of YAC ends demonstrated that this set of overlapping YACs encompasses the jointless locus. Two YAC ends, TY159L (L indicates left end) and TY143R (R indicates right end), cosegregate with the jointless locus. Only one of the six YACs (TY142) contained single-copy DNA sequences at both ends that could be mapped. The two ends of TY142 were mapped to either side of the jointless locus, indicating that TY142 contains a contiguous 285 kb tomato DNA fragment that probably includes the jointless locus. Physical mapping of the TY142 clone revealed that TY159L and TY143R reside on a 55 kb SalI fragment. Southern blot hybridization analysis of the DNAs of tomato lines nearly isogenic for the jointless mutation has allowed localization of the target locus to a region of less than 50 kb within the TY142 clone.

Base Sequence↗

PubMed1994

Chromosome 2-specific DNA clones from flow-sorted chromosomes of tomato.

We obtained DNA clones specific to tomato chromosome 2 from a small number of chromosomes collected by flow sorting. Suspensions of metaphase chromosomes were prepared from 3-month-old tomato cell cultures of Lycopersicon pennellii. Isolated chromosomes stained with chromomycin A3 and Hoechst 33258 were analyzed on an EPICS 753 flow cytometer using a UV laser to excite Hoechst fluorescence and a 458 nm laser to excite chromomycin A3 fluorescence. Chromosomes from well-resolved peaks on a bivariate flow karyotype were sorted directly onto membrane filters for spot-blot analysis. The filters were processed and hybridized with chromosome-specific repetitive DNA probes. In this way tomato chromosome 1 and chromosome 2 were assigned to peaks in the bivariate flow karyotypes. One thousand copies of the putative chromosome 2 were flow-sorted directly into microfuge tubes. DNA specific to chromosome 2 was amplified by a polymerase chain reaction (PCR) technique using universal 22mer degenerate oligonucleotide primers (DOP) sequences. DOP-PCR yields a smear of fragments of various sizes from 250 to 1600 bp. Amplified products were cloned into the Bluescript plasmid vector. Approximately 11% of the clones contained sequences with highly repetitive elements, and 85% contained only low-copy-number sequences. Eleven clones containing low-copy-number sequences that detect restriction fragment length polymorphisms were placed on the molecular linkage map of tomato. All showed linkage to chromosome 2.

Amino Acid Sequence↗

PubMed1994

The effect of zinc deficiency on wool growth and skin and wool follicle histology of male Merino lambs.

The aims of this work were to quantify the requirements of Zn for wool growth in growing male Merino lambs, and to describe the histological lesions of Zn deficiency in skin and wool follicles. Four groups of male Merino lambs (n 4) weighing 22 kg were fed ad lib. for 96 d on diets that contained 4 (basal diet), 10, 17 or 27 mg Zn/kg. Sheep in a fifth group were fed on the diet containing 27 mg Zn/kg, but were pair-fed to sheep on the 4 mg Zn/kg diet. Zn was added to the basal diet as ZnSO4 to give the respective treatment concentrations. Sheep fed on the diet containing 4 mg Zn/kg showed clinical signs of Zn deficiency and lower feed intakes and wool growth than sheep in the other groups. Their wool fibres were improperly keratinized and the wool follicles contained a higher proportion of apoptotic bodies than other groups. There was no evidence of parakeratosis and the rate of bulb-cell production was not affected. Sheep from other groups showed no clinical signs of Zn deficiency, and mean feed intakes and growth rates did not differ significantly between sheep fed on diets containing 10, 17 or 27 mg Zn/kg. However, wool growth was reduced in sheep fed on the diet containing 10 mg Zn/kg compared with those fed on diets containing 17 or 27 mg/kg. The mean concentration of Zn in the plasma at which wool growth was 90% of maximum was 0.5 mg/l. The equivalent value for the diet was 12 mg/kg, with 95% confidence intervals of 8 to 16 mg/kg. The results suggest that Zn deficiency reduces wool growth through a specific mechanism, perhaps involving impaired protein synthesis.

Animals↗

PubMed1994

High atrial natriuretic peptide concentrations blunt the pressor response during cardiopulmonary resuscitation in humans.

OBJECTIVE: To determine the relationship of circulating atrial natriuretic peptide concentrations to the pressor response to high-dose epinephrine in patients undergoing cardiopulmonary resuscitation (CPR) for cardiac arrest. DESIGN: Prospective study. PATIENTS: Fourteen normothermic, adult, prehospital and emergency department patients suffering unexpected cardiac arrest. INTERVENTION: Patients received high-dose epinephrine (0.2 mg/kg) i.v. when standard advanced cardiac life support (including multiple 1-mg dosages of epinephrine) failed to result in return of spontaneous circulation. MEASUREMENTS AND MAIN RESULTS: Cardiac arrest patients were separated into those patients with and without detectable serum atrial natriuretic peptide concentrations, and were termed the "low atrial natriuretic peptide" and "high atrial natriuretic peptide" groups, respectively. Their aortic pressure response to high-dose (0.02 mg/kg) epinephrine was compared. The proportion with positive assays was compared with a group of healthy control subjects. Fourteen patients were studied. Eight patients had low serum atrial natriuretic peptide concentrations and six patients had high circulating atrial natriuretic peptide concentrations. The mean concentration in the high atrial natriuretic peptide group was 151 +/- 82 pg/mL. The proportion with positive assays (six of 14 patients) was greater than in the group in spontaneous circulation (three of 29 patients) (p = .002). The maximal increase in the aortic relaxation-phase pressures after high-dose epinephrine was 9 +/- 7 torr (1.2 +/- 0.9 kPa) in the low atrial natriuretic peptide group and 0 +/- 5 torr (0 +/- 0.7 kPa) in the high atrial natriuretic peptide group (p = .03). The maximal increase in the aortic compression pressures after high-dose epinephrine was 17 +/- 13 torr (2.3 +/- 1.7 kPa) in the low atrial natriuretic peptide group and 2 +/- 10 torr (0.3 +/- 1.3 kPa) in the high atrial natriuretic peptide group (p = .03). Thus, pressor responses after high-dose epinephrine administration were observed in patients in the low atrial natriuretic peptide group, but this response was absent in patients in the high atrial natriuretic peptide group. CONCLUSIONS: Cardiac arrest patients receiving CPR have higher circulating atrial natriuretic peptide concentrations than healthy subjects. High serum atrial natriuretic peptide concentrations may antagonize the vasopressor response to epinephrine. Blocking this effect of atrial natriuretic peptide may improve outcomes in patients suffering cardiac arrest.

Adult↗

PubMed1994

A member of the tomato Pto gene family confers sensitivity to fenthion resulting in rapid cell death.

Leaves of tomato cultivars that contain the Pto bacterial resistance locus develop small necrotic lesions within 24 hr after exposure to fenthion, an organophosphorous insecticide. Recently, the Pto gene was isolated and shown to be a putative serine/threonine protein kinase. Pto is one member of a multigene family that is clustered within a 400-kb region on chromosome 5. Here, we report that another member of this gene family, termed Fen, is responsible for the sensitivity to fenthion. Fen was isolated by map-based cloning using closely linked DNA markers to identify a yeast artificial chromosome clone that spanned the Pto region. After transformation with the Fen gene under control of the cauliflower mosaic virus (CaMV) 35S promoter, tomato plants that are normally insensitive to fenthion rapidly developed extensive necrotic lesions upon exposure to fenthion. Two related insecticides, fensulfothion and fenitrothion, also elicited necrotic lesions specifically on Fen-transformed plants. Transgenic tomato plants harboring integrated copies of the Pto gene under control of the CaMV 35S promoter displayed sensitivity to fenthion but to a lesser extent than did wild-type fenthion-sensitive plants. The Fen protein shares 80% identity (87% similarity) with Pto but does not confer resistance to Pseudomonas syringae pv tomato. These results suggest that Pto and Fen participate in the same signal transduction pathway.

Amino Acid Sequence↗

PubMed1994

Effects of dietary zinc deficiency on the reproductive system of young male sheep: testicular growth and the secretion of inhibin and testosterone.

The effects of dietary zinc deficiency on testicular development in young Merino rams (initial live mass, 22 kg) were tested. Four groups of five rams were fed ad libitum with diets containing 4, 10, 17 or 27 micrograms Zn g-1. To control the effects of loss of appetite caused by zinc deficiency, a fifth group (pair-fed control) was fed the diet containing 27 micrograms Zn g-1, but the amount of feed offered was restricted to that eaten voluntarily by the zinc deficient (4 micrograms Zn g-1) rams they were paired with. After 96 days on the diets, epididymal and testicular masses did not differ significantly between the animals fed 10, 17 or 27 micrograms Zn g-1 ad libitum, but were significantly lower in pair-fed controls, and lowest in the zinc-deficient animals. Testicular responsiveness to LH, as measured by testosterone production, increased substantially in most rams as the experiment progressed, the only exception being the zinc-deficient group, in which the response to LH was lower than in any of the other groups. Testicular concentrations of zinc and testosterone were lower in the zinc-deficient animals than in all the other groups. Plasma inhibin concentrations fell as the experiment progressed in rams fed 17 and 27 micrograms Zn g-1 ad libitum, but not in the other groups. The pair-fed control rams had smaller seminiferous tubules and less lumen development than did the controls fed ad libitum (27 micrograms Zn g-1), which were similar to the animals fed 10 or 17 micrograms Zn g-1. In zinc-deficient rams, the tubule development was further retarded and the interstitial regions were more extensive than in the other groups. We conclude that the overall effect of zinc deficiency on testicular development is due to a combination of a non-specific effect (low gonadotrophin concentrations caused by the low feed intake) and a specific effect due to the lack of zinc. The zinc-specific effect is localized within the testis where it reduces the development of the capacity to produce testosterone, leading to low intratesticular concentrations of testosterone, a critical factor for the growth, development and function of the seminiferous tubules.

Animals↗

PubMed1994

Effects of nutrition on testicular size and the concentrations of gonadotrophins, testosterone and inhibin in plasma of mature male sheep.

The effects of nutrition on the hypothalamo-pituitary-gonadal axis were studied in three groups of six mature Merino rams that were fed for 56 days with a ration that maintained their initial live mass (intermediate diet: 675 g chaff plus 175 g lupins), the same ration with a lupin supplement (high diet: 675 g chaff plus 825 g lupins), or about half of the intermediate ration (low diet: 475 g chaff plus 125 g lupins). Lupin seed provides a highly (95%) digestible source of energy and protein. Plasma concentrations of LH, FSH, testosterone and inhibin were measured in blood samples collected over 24 h on the day before dietary treatments began (day-1), then on days 0, 1, 5, 14, 28 and 56. Compared with the intermediate diet, the high diet significantly increased live mass within 14 days and testicular size within 28 days, and these differences increased steadily throughout the experiment. Plasma FSH concentrations and LH pulse frequency increased within 5 days, but these effects were maintained for only 14 days. Decreasing the nutritional status reduced live mass and testicular size within 7 days, led to a low LH pulse frequency that persisted throughout the experiment, but did not affect FSH concentrations. Significantly less testosterone was secreted over 24 h in the low dietary group than in the intermediate or high group until day 28. The high group tended to secrete more than the intermediate group, but only at the beginning of the experiment when LH pulse frequencies differed between these groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Nutritional Physiological Phenomena↗

PubMed1994

Testicular morphology and androgen profiles following testicular ischaemia in rams.

Arteriosclerotic changes were induced in the internal spermatic artery of rams to determine whether there is a link between this condition and some pathological conditions of the testes, similar to those that cause infertility in men. Eight weeks after the induction of testicular ischaemia, blood plasma was collected simultaneously from the jugular and spermatic veins after an LH injection (10 micrograms) and assayed for testosterone. The rams were then castrated and sections of the testis, ductuli efferentes and spermatic cord were examined quantitatively and qualitatively. Vascular disturbance decreased the percentage of normal spermatogenic epithelium (P < 0.01) and the diameter of the seminiferous tubules (P < 0.001). These effects were accompanied by an increase in the percentage of the interstitial region within the testis (P < 0.05). Macrophages, lymphocytes and other inflammatory cells became numerous in the interstitium as damage to the seminiferous epithelium progressed. The most striking feature of the ischaemic testis was the focal damage of the spermatogenic epithelium, that is, sections of the same testis exhibited both normal and germ cell-depleted seminiferous tubules. Concentrations of testosterone in peripheral plasma were not significantly altered by either unilateral or bilateral testicular ischaemia; however, the concentration of testosterone was higher in the experimental spermatic vein than in the contralateral spermatic vein (P < 0.05) as was the ratio of LH:testosterone (P < 0.05). Unilateral vascular disturbance of the testis did not cause damage in the contralateral testis. The ductuli efferentes of these rams also showed structural changes as a result of vascular disturbance.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗

PubMed1994

Effect of nutrition on seasonal patterns of LH, FSH and testosterone concentration, testicular mass, sebaceous gland volume and odour in Australian Cashmere goats.

The effects of season and diet on LH, FSH and testosterone concentrations, testicular mass, sebaceous gland volume and male odour were examined in mature Australian cashmere goat bucks fed ad libitum with diets of low or high quality for 16 months under natural photoperiod at 29 degrees S, 153 degrees E (n = 6 per treatment). Each week plasma was sampled, the bucks were weighed, scored for male odour and assessed for testicular mass based on scrotal circumference. Each month a skin sample was taken from the occipital region for histological assessment of sebaceous gland volume. For each variable there was a clear circannual cycle that was significantly influenced by dietary treatment. In bucks fed the low-quality diet, the timing of seasonal changes in LH and testosterone concentration, sebaceous gland volume and odour score was similar, with a mid-autumn peak. In each case the high-quality diet advanced, extended the duration and increased the magnitude of the seasonal increase. FSH concentrations peaked in late spring (in bucks on the high-quality diet) or summer (in bucks on the low-quality diet), reaching a nadir in early winter. The high-quality diet significantly increased concentrations only in the last 2 months of the experiment (spring). There was no overall association between these variables and change in testicular mass; instead, it was strongly correlated with voluntary feed intake and change in body mass, themselves subject to seasonal variation with a winter or spring peak. The high-quality diet induced large increases in body mass and testicular mass during the first months of the experiment without influencing the seasonally low concentrations of FSH, LH and testosterone present at the time. These results demonstrate that the male, like the female, Australian cashmere goat, exhibits marked reproductive seasonality, and that nutrition is a powerful modulator of the seasonal cycle. They suggest that testosterone concentration, sebaceous gland volume and odour score are ultimately dependent upon LH secretion, which appears to be under strong seasonal (photoperiodic) control, with the effects of enhanced nutrition limited to periods when photoperiodic inhibition is waning. However, seasonal regulation of testicular mass, and therefore sperm production, appears to be primarily dependent on changes in voluntary feed intake and growth, with the seasonal cycle of testicular mass more a consequence of the seasonal appetite or growth cycle than of changing gonadotrophin concentrations.

Animal Nutritional Physiological Phenomena↗

PubMed1993

Map-based cloning of a protein kinase gene conferring disease resistance in tomato.

The Pto gene in tomato confers resistance to races of Pseudomonas syringae pv. tomato that carry the avirulence gene avrPto. A yeast artificial chromosome clone that spans the Pto region was identified and used to probe a leaf complementary DNA (cDNA) library. A cDNA clone was isolated that represents a gene family, at least six members of which genetically cosegregate with Pto. When susceptible tomato plants were transformed with a cDNA from this family, they were resistant to the pathogen. Analysis of the amino acid sequence revealed similarity to serine-threonine protein kinases, suggesting a role for Pto in a signal transduction pathway.

Amino Acid Sequence↗

PubMed1993

Analysis of the hormonal control of female sexual behavior and the preovulatory LH surge in the ewe: roles of quantity of estradiol and duration of its presence.

Dose-response relationships have been suggested for the role of estradiol (E2) in the induction of both the LH surge and estrous behavior in the ewe. However, it is not always clear whether it is the amount of E2 or the length of time that E2 is present that is important. Furthermore, in previous studies, the intensity of sexual behavior has rarely been studied quantitatively. Our aims in this work were to analyze in more detail the effects of two injected doses of estradiol benzoate (25 or 50 micrograms) for the induction of both the LH surge and estrous behavior (experiment I) and to dissociate the roles of quantity and duration of presence of E2 as administered by implants (experiment II). Increasing the dose of E2 in both experiment I and experiment II decreased the latency to onset of both the LH surge and the receptivity. The duration of E2 presence marginally affected the latency of both responses and the duration of the LH surge. By contrast, the duration of receptivity depended largely on the duration of E2 presence (experiment II: r = 0.569, P < 0.01). This result explains the dose-duration effect mentioned previously in the literature and found in experiment I. The maximum response increased with dose in both experiment I and experiment II for receptivity and only in experiment I for the LH surge. We conclude that, at estrus, E2 acts in a similar fashion to induce receptive behavior and the LH surge but controls the maximum levels and the duration of these endocrine and behavioral responses differently.

Animals↗

PubMed1993

Immunological approaches to fertility regulation in domestic livestock.

Antibodies to hormones have been used extensively to study endocrine regulation of reproduction and in recent times they have been commercially exploited as therapeutic agents to manipulate reproduction. Despite the release of two commercial products, little is known about the mechanism of action of immunoneutralization. The presence of hormone-binding antibodies in the circulation and the detection of hormone antibody complexes in blood has led investigators to suggest a vascular site of action for immunoneutralization. However, a vascular site of action is difficult to reconcile with some of the known effects of immunoneutralization to the boar taint steroid (5 alpha-androst-16-en-3-one) to androstenedione and to gonadotrophin-releasing hormone. In this paper we review some of our recent research into the mechanism of action of androstenedione immunoneutralization. We suggest that hormonal immunoneutralization of androstenedione may take place in the extracellular compartment or within the plasma membrane where antibodies to androstenedione may bind to a specific steroid-binding protein in the plasma membrane of granulosa cells.

Androstenedione↗

PubMed1993

A model for follicle selection and the determination of ovulation rate in the ewe.

A model for folliculogenesis is proposed that is based as far as possible on a knowledge of physiological, rather than anatomical, changes taking place during follicle development. The model is therefore functional, rather than descriptive, and consists of five classes of follicles that have been defined by their dependency and sensitivity to gonadotrophins. These classes are: primordial, committed, gonadotrophin-responsive, gonadotrophin-dependent and ovulatory. The model is an attempt to encourage discussion and to promote the integration of morphological models of folliculogenesis with recent advances in the molecular endocrinology of the ovarian follicle. Two hypotheses for the mechanisms that determine ovulation rate are developed in light of the model. In the first, multiple ovulation results when the viability of gonadotropin-dependent follicles is enhanced. In the second, multiple ovulation is caused by increasing the number of gonadotrophin-responsive follicles available for further development; this results from the increasing rate of folliculogenesis and the throughput of follicles. The final section of this paper examines how these two hypothetical mechanisms, which are not mutually exclusive, appear to account for most of the known genetical and environmental effects on ovulation rate of sheep. In particular, the effects of nutrition, genotype, exogenous gonadotrophins, immunity to both oestrogens and androgens, and immunity to inhibin are discussed.

Animal Nutritional Physiological Phenomena↗

PubMed1993

Functional responses to extremely high plasma epinephrine concentrations in cardiac arrest.

OBJECTIVE: To evaluate the action of high-dose epinephrine by measuring simultaneously its vasopressor and norepinephrine releasing effects in humans during cardiac arrest. DESIGN: A prospective study on consecutive patients admitted with cardiac arrest. SETTING: Emergency Department in a large, urban hospital. PATIENTS: Eighteen patients with out-of-hospital cardiac arrest undergoing cardiopulmonary resuscitation (CPR). INTERVENTIONS: Catheterization of both the aorta and right atrium for the recording of pressure and collection of blood samples. Throughout the study period (12.5 mins), 18 patients received epinephrine at both the standard dose (1 mg, approximately 0.015 mg/kg) and high dose (0.2 mg/kg). Blood samples were drawn five times, every 2.5 mins. MEASUREMENTS AND MAIN RESULTS: Plasma epinephrine and norepinephrine concentrations; aorta, right atrial, and coronary perfusion pressures. Epinephrine concentrations (normal at rest = 160 +/- 10 [SEM] pmol/L) were increased at the time of the first sample (2.5 mins) by approximately 3,000-fold (to approximately 0.5 mumol/L), and, increased further to 12,000-fold (approximately 2.0 mumol/L) during the study. Aortic pressure increased from 20 +/- 3 to 28 +/- 3 mm Hg (p < .001), and coronary perfusion pressure increased from 4 +/- 3 to 10 +/- 3 mm Hg (p < .001). Simultaneous plasma norepinephrine concentrations were 30-fold higher than the normal resting value of 1.30 +/- 0.04 nmol/L, and increased by 90-fold during the study (p < .001). The spectral distributions of the individual correlations between plasma epinephrine and norepinephrine concentrations were segregated into high correlations (r > .83) in 12 of 18 patients and low r values (r = .29 to .79) in the remaining six patients. The distribution of the correlations was nonuniform by the Kolmogorov-Smirnov goodness-of-fit test with p < .001; this profile suggests that norepinephrine responsiveness to epinephrine can separate two populations, one of which (r > .83) would have preserved viability of the corresponding epinephrine receptors. The correlations between plasma epinephrine concentrations and coronary perfusion pressures were distributed more evenly, also in a nonuniform pattern (p < .02 by Kolmogorov-Smirnov goodness-of-fit test) and the relationship between the two sets of correlations was not significant. CONCLUSIONS: Despite the very high prevailing plasma epinephrine concentrations during cardiac arrest, further epinephrine increases still elicit biological responses. The present work provides physiologic support for the use of large doses of epinephrine during the course of CPR.

Adult↗

PubMed1993

Simultaneous radial, femoral, and aortic arterial pressures during human cardiopulmonary resuscitation.

OBJECTIVE: To examine the validity of interchanging arterial sites and their responses to graded doses of epinephrine during human cardiopulmonary resuscitation (CPR). DESIGN: Consecutive case series. SETTING: Large, urban Emergency Department. PATIENTS: Adult, normothermic, nonhemorrhagic cardiac arrest patients. INTERVENTIONS: While receiving advanced cardiac life support, patients received right atrial (n = 40), aortic (n = 40), radial (n = 40), and femoral (n = 17) artery catheters. Pressures were measured simultaneously at baseline, after 0.01 mg/kg and 0.2 mg/kg of epinephrine. MEASUREMENTS AND MAIN RESULTS: The mean aortic compression-phase pressure was 9.3 +/- 10 (SD), 8.1 +/- 11, and 4.4 +/- 9.5 mm Hg higher than radial artery pressure at baseline, after 0.01 mg/kg, and 0.2 mg/kg of epinephrine, respectively (all statistically significant). When compared with the femoral artery at the same time points, the mean aortic compression-phase pressure was also 3.0 +/- 6.8, 1.9 +/- 8, and 0.6 +/- 7.7 mm Hg higher, respectively (none statistically significant). The aortic relaxation-phase pressure was 1.3 +/- 3.6, 1.1 +/- 3.8, and 1.6 +/- 2.5 mm Hg lower than the radial artery at baseline, after 0.01 mg/kg and 0.2 mg/kg of epinephrine, respectively (all statistically significant). When compared with the femoral artery at the same time points, the aortic relaxation-phase pressure was 0.6 +/- 2.0, 0.3 +/- 3.3, and 0.3 +/- 2.4 mm Hg lower, respectively (none statistically significant). CONCLUSIONS: Radial artery relaxation-phase pressure, although statistically higher, correlated with aortic relaxation-phase pressure. Femoral artery relaxation-phase pressure was not statistically different from aortic relaxation-phase pressure. Aortic pressure was statistically higher and had a lower correlation with radial artery pressures during compression phase. The aortic to radial artery and aortic to femoral artery compression-phase gradients abated with increasing doses of epinephrine therapy. Caution must be used when substituting compression-phase pressure obtained at radial or femoral artery sites for aortic pressure during human CPR. Coronary artery perfusion pressures obtained with radial and femoral arteries correlate with aortic pressure when measuring the response to vasopressor therapy during CPR when an interpretable waveform exists.

Aged↗

PubMed1993

A characterization of hypothalamic-pituitary-adrenal axis function during and after human cardiac arrest.

OBJECTIVE: This study characterizes hypothalamic-pituitary-adrenal axis function during cardiopulmonary arrest and after return of spontaneous circulation. DESIGN: Prospective case series. SETTING: A large urban emergency department and intensive care unit over an 8-month period. PATIENTS: Two hundred five adult patients presenting in cardiopulmonary arrest to an urban emergency department. Three patients known to be taking corticosteroids were excluded from the study. MEASUREMENTS AND MAIN RESULTS: Cortisol concentrations were measured before and after advanced cardiac life support and for five consecutive hours after return of spontaneous circulation. Adrenocorticotropic hormone (ACTH) concentrations were measured before advanced cardiac life support and when the cosyntropin stimulation tests were performed 6 and 24 hrs after the return of spontaneous circulation. The mean initial serum cortisol concentration was 32.0 +/- 33.1 micrograms/dL (882.9 +/- 913.2 nmol/L). Fifty-three percent of patients had cortisol concentrations of < 20 micrograms/dL (< 552 nmol/L) at the end of cardiac arrest. Among 44 patients who achieved return of spontaneous circulation, 98% had initial cortisol concentrations of > 10 micrograms/dL (> 276 nmol/L) and 73% of patients had initial cortisol concentrations of > 20 micrograms/dL (> 552 nmol/L). Mean serum cortisol concentrations increased significantly (p = .0001) from 1 to 6 hrs after return of spontaneous circulation and decreased significantly (p = .03) from 6 to 24 hrs. A serum cortisol concentration of < 30 micrograms/dL (< 828 nmol/L) was associated with a 96% and 100% mortality rate at 6 and 24 hrs, respectively. Mean ACTH concentrations were increased without a significant difference between the initial and 6-hr concentrations. Mean ACTH concentrations decreased between 6 and 24 hrs (p = .06). There were no significant responses to the cosyntropin stimulation at 6 and 24 hrs. CONCLUSIONS: Cortisol concentrations after out-of-hospital cardiac arrest are lower than those concentrations reported in other stress states. There is an association between cortisol concentrations and short-term survival after cardiac arrest. Survivors have a significantly greater increase in serum cortisol concentrations than nonsurvivors during the first 24 hrs. Lower than expected cortisol concentrations for the extreme stress of cardiac arrest may have pathologic significance in the hemodynamic instability seen after return of spontaneous circulation. The etiology of the low cortisol concentrations may be primary adrenal dysfunction.

Adrenocorticotropic Hormone↗