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Biomedical subjects

G B Martin

Publications and source records attributed to G B Martin.

At least 19 recordsLinked to original sources

Microtiter plate binding assay for cholinergic compounds utilizing the nicotinic acetylcholine receptor.

A receptor-based binding assay for the determination of cholinergic compounds of the nicotinic acetylcholine receptor has been developed. By conducting the assay in a 96-well microtiter plate, the method is suitable for large-scale screening in drug development. Solid-phase extraction of the enzyme label significantly simplifies the assay protocol compared to earlier methods. The assay is based on immobilization of biotin-BSA on the microtiter which takes up avidin-labeled peroxidase due to avidin-biotin interaction. To perform the assay, a ligand (the analyte) and a biotin alpha-bungarotoxin conjugate (alpha Bgt-biotin) sequentially bind to a vesicle bound nicotinic acetylcholine receptor. This is done either in a test tube, assay I, or in a biotinylated microtiter well, assay II. Avidin-HRP is then added to this mixture; free alpha Bgt-biotin conjugate and immobilized biotin-BSA compete for the avidin sites. After the assay solution has been aspirated off, bound enzyme activity is determined which is directly related to the amount of alpha Bgt-biotin added. Dose-response curves of cholinergic compounds and Scatchard plots were generated to evaluate the apparent binding constants. Kinetic studies were conducted for the purpose of optimization. The final assay can be performed in under 4 h with a minimum of sample handling.

Animals

Construction of a yeast artificial chromosome library of tomato and identification of cloned segments linked to two disease resistance loci.

We have constructed a yeast artificial chromosome (YAC) library of tomato for chromosome walking that contains the equivalent of three haploid genomes (22,000 clones). The source of high molecular weight DNA was leaf protoplasts from the tomato cultivars VFNT cherry and Rio Grande-PtoR, which together contain loci encoding resistance to six pathogens of tomato. Approximately 11,000 YACs have been screened with RFLP markers that cosegregate with Tm-2a and Pto - loci conferring resistance to tobacco mosaic virus and Pseudomonas syringae pv. tomato, respectively. Five YACs were identified that hybridized to the markers and are therefore starting points for chromosome walks to these genes. A subset of the library was characterized for the presence of various repetitive sequences and YACs were identified that carried TGRI, a repeat clustered near the telomeres of most tomato chromosomes, TGRII, an interspersed repeat, and TGRIII, a repeat that occurs primarily at centromeric sites. Evaluation of the library for organellar sequences revealed that approximately 10% of the clones contain chloroplast sequences. Many of these YAC clones appear to contain the entire 155 kb tomato chloroplast genome. The tomato cultivars used in the library construction, in addition to carrying various disease resistance genes, also contain the wild-type alleles corresponding to most recessive mutations that have been mapped by classical linkage analysis. Thus, in addition to its utility for physical mapping and genome studies, this library should be useful for chromosome walking to genes corresponding to virtually any phenotype that can be scored in a segregating population.

Chloroplasts

Continuous central venous oximetry and shock index in the emergency department: use in the evaluation of clinical shock.

Initial therapy of shock in the emergency department (ED) emphasizes the normalization of physiologic variables such as heart rate (HR), mean arterial pressure (MAP), and central venous pressure (CVP) rather than restoration of adequate tissue oxygenation. After hemodynamic stabilization of MAP, CVP, and HR, the authors examined tissue oxygenation as indicated by continuous central venous oximetry (SCVO2), lactic acid concentration, and shock index (SI). Sixteen consecutive nonrandomized patients presenting to the ED of a large urban hospital in shock (MAP < 60 mm Hg, HR > 120 beats/min, and altered sensorium) were initially resuscitated with fluid, blood, inotropes, and/or vasoactive drug therapy to normalize MAP, CVP, and HR. In addition, SCVO2, arterial lactate concentration, and SI were measured after completion of resuscitation in the ED. Eight patients (group no. 1) had inadequate tissue oxygenation reflected by low SCVO2 (less than 65%). Four patients in group no. 1 had elevated arterial lactic acid concentration. All group no. 1 patients had an elevated SI (> 0.7) suggesting persistent impairment of left ventricular stroke work. Eight patients (group no. 2) had normal or elevated SCVO2 (> 65%). In group no. 2, arterial lactic acid concentration was elevated in six and SI in seven patients. Normalization of hemodynamic variables does not adequately reflect the optimal endpoint of initial therapy in shock in the ED. Most (94%) of these patients continue to have significant global ischemia and cardiac dysfunction as indicated by reduced SCVO2 and elevated lactic acid concentration and SI. Systemic tissue oxygenation should be monitored and optimized in the ED in these critically ill patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The clinical implications of continuous central venous oxygen saturation during human CPR.

STUDY OBJECTIVE: The purpose of this study was to observe, measure, and describe the changes in central venous oxygen saturation during CPR and immediately after return of spontaneous circulation. It also was to examine the clinical utility of continuous central venous oxygen saturation monitoring as a indicator of return of spontaneous circulation during CPR in human beings. DESIGN AND SETTING: Eight-month, prospective, non-outcome, observational, nonrandomized case series in the ED of a large urban hospital. TYPES OF PATIENTS: Adult normothermic, nontraumatic, out-of-hospital cardiopulmonary arrests. INTERVENTIONS: All patients were managed according to advanced cardiac life support guidelines. A proximal aortic and double-lumen central venous catheter was placed. Central venous oxygen saturation was measured continuously spectrophotometrically with a fiberoptic catheter in the central venous location. MEASUREMENTS: Aortic blood pressure and central venous oxygen saturation were simultaneously measured throughout each resuscitation. Return of spontaneous circulation was defined as a systolic blood pressure of more than 60 mm Hg for more than five minutes. RESULTS: One hundred patients who experienced 68 episodes of cardiac arrest were studied. Patients with return of spontaneous circulation had a higher initial and statistically higher mean and maximal central venous oxygen saturation than those without return of spontaneous circulation (P = .23, .0001, and .0001, respectively; P less than .05 is significant). No patient attained return of spontaneous circulation without reaching a central venous oxygen saturation of at least 30%. Only one of 68 episodes of return of spontaneous circulation was attained without reaching a central venous oxygen saturation of at least 40%. A central venous oxygen saturation of greater than 72% was 100% predictive of return of spontaneous circulation. CONCLUSION: Continuous central venous oxygen saturation monitoring can serve as a reliable indicator of return of spontaneous circulation during CPR in human beings.

Blood Circulation

High density molecular linkage maps of the tomato and potato genomes.

High density molecular linkage maps, comprised of more than 1000 markers with an average spacing between markers of approximately 1.2 cM (ca. 900 kb), have been constructed for the tomato and potato genomes. As the two maps are based on a common set of probes, it was possible to determine, with a high degree of precision, the breakpoints corresponding to 5 chromosomal inversions that differentiate the tomato and potato genomes. All of the inversions appear to have resulted from single breakpoints at or near the centromeres of the affected chromosomes, the result being the inversion of entire chromosome arms. While the crossing over rate among chromosomes appears to be uniformly distributed with respect to chromosome size, there is tremendous heterogeneity of crossing over within chromosomes. Regions of the map corresponding to centromeres and centromeric heterochromatin, and in some instances telomeres, experience up to 10-fold less recombination than other areas of the genome. Overall, 28% of the mapped loci reside in areas of putatively suppressed recombination. This includes loci corresponding to both random, single copy genomic clones and transcribed genes (detected with cDNA probes). The extreme heterogeneity of crossing over within chromosomes has both practical and evolutionary implications. Currently tomato and potato are among the most thoroughly mapped eukaryotic species and the availability of high density molecular linkage maps should facilitate chromosome walking, quantitative trait mapping, marker-assisted breeding and evolutionary studies in these two important and well studied crop species.

Centromere

Aortic pressure during human cardiac arrest. Identification of pseudo-electromechanical dissociation.

We measured aortic pressure during clinically apparent cardiac electromechanical dissociation (EMD). Patients with pulse pressures were designated as having pseudo-EMD; those without, as having true EMD. Of the 200 patients studied, 54 presented with EMD, and 40 others developed it during resuscitation. Of the 94 with EMD, 39 were found to have pseudo-EMD. We compared the two types of EMD for electrocardiographic duration, return of palpable pulses, and response to standard- and high-dose epinephrine. The mean resting aortic pressure was 18 +/- 11 mm Hg in patients with true EMD and 28 +/- 11 mm Hg in those with pseudo-EMD. The mean pulse pressure in patients with pseudo-EMD was 6.3 +/- 3.5 mm Hg. Patients with pseudo-EMD had a higher proportion of witnessed arrests, higher PaO2, and lower PaCO2 than patients with true EMD. Patients with pseudo-EMD had shorter QR and QRS durations than patients with true EMD. They had a better response to standard- and high-dose epinephrine than patients with true EMD. Many patients diagnosed clinically to be in EMD have mechanical cardiac activity; this should be considered when interpreting the results of cardiac arrest research.

Aged

Venous hyperoxia after cardiac arrest. Characterization of a defect in systemic oxygen utilization.

BACKGROUND: Supranormal mixed venous oxygen saturation (mixed venous hyperoxia), although reported, has never been characterized in humans resuscitated from cardiac arrest (postarrest cardiogenic shock). By contrast, cardiogenic shock without cardiopulmonary arrest (primary cardiogenic shock) is accompanied by mixed venous hypoxia under similar conditions of low oxygen delivery (DO2). The appearance of mixed venous hyperoxia indicates an excessive supply relative to demand in perfused tissue or cellular impairment of oxygen utilization, ie, low systemic oxygen consumption (VO2). Failure to improve VO2 has been associated with a poor outcome in other shock states. STUDY OBJECTIVE: This study evaluates the clinical significance of mixed venous hyperoxia and its implications for impaired systemic oxygen utilization. The oxygen transport patterns in surviving and nonsurviving cardiac arrest patients are compared for their prognostic and therapeutic implications. STUDY DESIGN: Consecutive, nonrandomized series. SETTING: Large urban emergency department (ED). PARTICIPANTS: Adult normothermic, nontraumatic out-of-hospital cardiac arrest patients presenting to the ED who develop a return of spontaneous circulation (ROSC). INTERVENTIONS: On arrival to the ED, a fiberoptic catheter was placed in the central venous position for continuous central venous oxygen saturation monitoring (ScvO2). A proximal aortic catheter was placed via the femoral artery for blood pressure monitoring. Upon ROSC, the fiberoptic catheter was advanced to the pulmonary artery. Mean arterial pressure (MAP), cardiac index (CI), VO2, DO2, systemic oxygen extraction ratio (OER), and systemic vascular resistance index (SVRI-dynes.s/cm5.m2) were measured immediately and every 30 min. The duration of cardiac arrest (DCA) in minutes and amount of epinephrine (milligrams) administered during ACLS was recorded. MEASUREMENTS AND RESULTS: Twenty-three patients were entered into the study. Survivors (living more than 24 h) and nonsurvivors (living less than 24 h) were compared. CONCLUSIONS: These findings indicate an impairment of systemic oxygen utilization in postarrest cardiogenic shock patients. In spite of a lower DO2 than survivors, the OER in nonsurvivors remained lower than expected. Venous hyperoxia is a clinical manifestation of this derangement. Epinephrine dose may have a causal relationship. The inability to attain a VO2 of greater than 90 ml/min.m2 after the first 6 h of aggressive therapy was associated with a 100 percent mortality in 24 h.

Aged

Concentrations of plasma melatonin and luteinizing hormone in domestic gilts reared under artificial long or short days.

Plasma melatonin concentrations were measured every 1-2 h over 24 h and plasma luteinizing hormone (LH) concentrations every 15 min over 12 h in domestic gilts reared under artificial light regimens that had previously been used to demonstrate photoperiodic effects on puberty. In Expt 1, the light regimens both commenced at 12 h light: 12 h dark (12L:12D) and either increased (long-day) or decreased (short-day) by 15 min/week until the long-day gilts were receiving 16L:8D and the short-day gilts 8L:16D at sampling. In Expt 2, both light regimens commenced at 12L:12D and either increased (long-day) or decreased (short-day) by 10 or 15 min/week to a maximum of 14.5L:9.5D or a minimum of 9.5L:14.5D before being reversed. Sampling took place when daylength had returned to 14L:10D (long-day) or 10L:14D (short-day). In immature gilts housed at 12L:12D (Expt 1) and in postpubertal (Expt 1) and prepubertal (Expt 2) gilts reared under long-day or short-day light regimens, mean plasma melatonin concentrations were basal (3.6 pg/ml) when the lights were on and increased to peak concentrations greater than 15 pg/ml within 1-2 h after dark, before declining gradually to basal concentrations at or near the end of the dark phase. In prepubertal gilts bearing subcutaneous melatonin implants and reared under long-days (Expt 2), mean plasma melatonin concentration in the 6 h before dark was 91.9 +/- 5.26 pg/ml and 125.0 +/- 6.66 pg/ml 1 h after dark, but this increase was not statistically significant. In Expt 2, the short-day gilts had fewer LH pulses (2.6 +/- 0.25 vs. 4.6 +/- 0.24; P less than 0.01) in the 12-h sampling period than the long-day gilts, but the amplitude of the pulses (2.28 +/- 0.23 vs. 1.26 +/- 0.16 ng/ml; P less than 0.01) and the area under the LH curve (78.8 +/- 5.60 vs. 47.3 +/- 6.16; P less than 0.01) was greater in the short-day gilts. In the short-day, but not in the long-day, gilts LH pulses were more frequent (2.0 +/- 0.0 vs. 0.6 +/- 0.25; P less than 0.01), but had a smaller area (61.9 +/- 7.2 vs. 120.2 +/- 23.6; P less than 0.05) in the 6 h of dark than in the 6 h of light, which together made up the 12-h sampling period.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Effects of dietary zinc deficiency on gonadotrophin secretion and testicular growth in young male sheep.

The hypothesis that the secretion of gonadotrophins would be reduced by zinc deficiency was tested in five groups of four young Merino rams (initial liveweight 22 kg). Four groups were fed ad libitum with diets containing 4, 10, 17 or 27 micrograms Zn g-1. The effects of loss of appetite on the deficient diet was controlled by feeding a fifth group (pair-fed control) at a rate of 27 micrograms Zn g-1, but the amount of feed offered was restricted to that eaten voluntarily by the deficient (4 micrograms Zn g-1) group. Blood was sampled every 20 min for 32 h on two occasions before the treatments were imposed and 96 days later, at the end of the experiment. The rams were injected with gonadotrophin-releasing hormone (GnRH; 10 ng kg-1 i.v.) after each serial sampling, and with naloxone (1 mg kg-1 i.v.) 24 h after the end of the final GnRH test. In the group that were fed the diet with the lowest zinc content, the concentration of zinc in blood plasma was reduced to 18% of that in the pair-fed controls (P < 0.05) and was within the deficient range. The appetite of the deficient rams was half that of the controls fed 27 micrograms Zn g-1 ad libitum and there was no increase in liveweight or testicular diameter during pubertal development. Similar, but smaller, effects were observed in the pair-fed controls. There were no significant differences between pair-fed and deficient groups in the frequency of the luteinizing hormone (LH) pulses or in the concentration of follicle-stimulating hormone (FSH), but the secretion of gonadotrophins was markedly lower in both groups than in the control rams fed ad libitum. The response to GnRH was not affected by treatment, but the increase in LH pulse frequency evoked by naloxone was lower in the deficient animals than in other groups. The animals fed zinc at intermediate rates (10-17 micrograms g-1) showed similar responses to the controls fed ad libitum. It is concluded that the specific effects of zinc deficiency on testicular function were small. Most of the reduction in testicular growth in rams fed a deficient diet was not specifically related to the trace element, but was due to the fall in energy and protein intake caused by the loss of appetite. This leads to a reduction in the frequency of GnRH pulses secreted by the hypothalamus, and to low rates of gonadotrophin secretion by the pituitary gland.

Analysis of Variance

Rapid identification of markers linked to a Pseudomonas resistance gene in tomato by using random primers and near-isogenic lines.

An approach to isolating DNA sequences that are linked to important plant genes is described. The strategy is based upon a recent modification of the polymerase chain reaction in which synthetic primers are used to amplify random sequences from genomic DNA. This technique, used in conjunction with near-isogenic lines (which differ only by the presence or absence of the target gene and a small region of surrounding DNA), leads to the rapid identification of sequences linked to the gene of interest. The feasibility of this method has been demonstrated by analyzing a pair of tomato near-isogenic lines that differ for a region on chromosome 5 that contains a gene (Pto) conferring resistance to Pseudomonas syringae pv. tomato. One hundred forty-four random primers were screened on these lines, and seven amplified products were identified that were present in one but not the other line. Of four products that were further investigated, three were confirmed by segregation analysis to be tightly linked to the Pto gene. Linked sequences identified by this method are useful for detecting the presence of the target gene in plant populations (e.g., in plant breeding) and, if very tightly linked, as starting points for a chromosome walk to isolate the gene. Since near-isogenic lines are a typical product of plant breeding and classical genetic studies, this method is applicable to a wide variety of species.

Base Sequence

The effect of standard- and high-dose epinephrine on coronary perfusion pressure during prolonged cardiopulmonary resuscitation.

We studied the effect of standard and high doses of epinephrine on coronary perfusion pressure during cardiopulmonary resuscitation in 32 patients whose cardiac arrest was refractory to advanced cardiac life support. Simultaneous aortic and right atrial pressures were measured and plasma epinephrine levels were sampled. Patients remaining in cardiac arrest after multiple 1-mg doses of epinephrine received a high dose of 0.2 mg/kg. The increase in the coronary perfusion pressures was 3.7 +/- 5.0 mm Hg following a standard dose, not a statistically significant change. The increase after a high dose was 11.3 +/- 10.0 mm Hg; this was both statistically different than before administration and larger than after a standard dose. High-dose epinephrine was more likely to raise the coronary perfusion pressure above the previously demonstrated critical value of 15 mm Hg. The highest arterial plasma epinephrine level after a standard dose was 152 +/- 162 ng/mL, and after a high dose, 393 +/- 289 ng/mL. Because coronary perfusion pressure is a good predictor of outcome in cardiac arrest, the increase after high-dose epinephrine may improve rates of return of spontaneous circulation.

Aorta

Hormonal control of proceptive and receptive sexual behavior and the preovulatory LH surge in the ewe: reassessment of the respective roles of estradiol, testosterone, and progesterone.

When estrous behavior is induced in ovariectomized ewes by subjecting them to progestagen priming followed by a dose of estrogen large enough to guarantee estrus in all animals, an abnormally long period of estrus in induced, suggesting that the regime of steroid replacement needs modification. Using quantitative tests for proceptivity and receptivity, we studied the patterns of sexual behavior of intact ewes and then attempted to reproduce them in the same animals after they had been ovariectomized. We used various combinations of exogenous estrogen, androgen, and progestagen and compared the behavioral responses with an endocrine response, the preovulatory surge of luteinizing hormone (LH). In intact ewes, sexual behavior and the LH surge were closely synchronized and their characteristics differed slightly between the middle and the end of the breeding season. Proceptive behavior was not greatly affected by the frequency of tests, but the duration of receptivity was significantly reduced by frequent testing. In ovariectomized ewes, we found that: (a) progesterone priming is essential for normal patterns of receptive and proceptive behavior, and for synchronizing the behavioral and endocrine responses to estrogen; (b) androgens do not play a major role in the control of either receptive or proceptive behavior; and (c) the inclusion of a low dose of estrogen with the progestagen in the 'priming' regime improves the responses to estradiol-17 beta. Under these conditions, the timing, intensity and duration of the behavior are very close to those observed in the same ewes when they were intact and cycling spontaneously.

Animals

Effects of arterial and venous volume infusion on coronary perfusion pressures during canine CPR.

Intraarterial (IA) volume infusion has been reported to be more effective than intravenous (IV) infusion in treating cardiac arrest due to exsanguination. A rapid IA infusion was felt to raise intraaortic pressure and improve coronary perfusion pressure (CPP). The purpose of this study was to determine if IA or IV volume infusion could augment the effect of epinephrine on CPP during CPR in the canine model. Nineteen mongrel dogs with a mean weight of 26.3 +/- 4.2 kg were anesthetized and mechanically ventilated. Thoracic aortic (Ao), right atrial (RA) and pulmonary artery catheters were placed for hemodynamic monitoring. Additional Ao and central venous catheters were placed for volume infusion. Ventricular fibrillation was induced and Thumper CPR was begun after 5 min (t = 5). At t = 10, all dogs received 45 micrograms/kg IV epinephrine. Six animals received epinephrine alone (EPI). Five dogs received EPI plus a 500 cc bolus of normal saline over 3 min intravenously (EPI/IV). Another group (n = 8) received EPI plus the same fluid bolus through the aortic catheter (EPI/IA). Resuscitation was attempted at t = 18 using a standard protocol. There was a significant increase in CPP over baseline in all groups. The changes in CPP from baseline induced by EPI, EPI/IV and EPI/IA were 20.6 +/- 3.7, 22.8 +/- 4.2 and 22.2 +/- 2.4 mmHg, respectively. Volume loading did not augment the effect of therapeutic EPI dosing. By increasing both preload and afterload, volume administration may in fact be detrimental during CPR.

Animals

Cerebral lactate uptake during cardiopulmonary resuscitation in humans.

Animal studies have shown cerebral lactate uptake under conditions of anoxia and ischemia. Cerebral lactate uptake in humans during cardiopulmonary resuscitation (CPR) has not been previously reported in the literature. Forty-five patients receiving CPR underwent simultaneous sampling through jugular venous bulb, right atrial, and central aortic catheterization. The mean net cerebral lactate uptake (central aortic minus jugular venous bulb) was 0.76 +/- 1.86 and 0.80 +/- 2.03 mM on initial measurement and 10 min later, respectively. Both measurements were statistically significant (p = 0.01) compared to normal controls who have net cerebral output of lactate of -0.18 +/- 0.1 mM. Seventy-one percent of all patients had a cerebral uptake on initial sampling and this gradient persisted upon sampling 10 min later in 68% of the remaining 40 patients who did not have a return of spontaneous circulation. Among multiple variables measured, patients who exhibited a cerebral lactate uptake were 13.2 years younger (p = 0.004), received an additional 7.6 min of CPR (p = 0.05), and had a mean arterial lactate concentration of 4.8 mM higher (p = 0.005) than the nonuptake group. The pathophysiologic explanation of cerebral lactate uptake during CPR is multifactorial and includes utilization and/or diffusion.

Aged

Neurophysiological control of the secretion of gonadotrophin-releasing hormone and luteinizing hormone in the sheep--a review.

The anterior pituitary gland secretes pulses of luteinizing hormone (LH) in response to pulses of gonadotrophin-releasing hormone (GnRH) released into the hypophysial portal blood by the hypothalamus. The pulsatile nature of the secretions is very important because the frequency of the pulses is directly related to the activity of the GnRH neurons. We can therefore take advantage of this phenomenon to develop mechanistic interpretations of responses to experimental treatments designed to unravel the neural pathways that influence what is, arguably, the most important individual signal controlling the activity of the reproductive system. We might also resolve the disagreements in the literature covering the neuropharmacology of gonadotrophin secretion. In this review, we describe work towards this end in the sheep. Most (95%) of the 2500 GnRH cell bodies in the sheep brain are located in a region covering the anterior hypothalamus, the medial preoptic area, the diagonal band of Broca, and the septum. The axons of up to 50% of these cells terminate in the organum vasculosum of the lamina terminalis. The remainder terminate in the median eminence and form the final common pathway for the many factors that affect gonadotrophin secretion. Among the factors known to affect the frequency of the pulses (or the activity of the GnRH neurons) are nutrition, pheromones, photoperiod and gonadal steroids (negative and positive feedback). Factors that affect GnRH pulse amplitude are more difficult to determine because variations in pituitary responsiveness prevent the use of LH patterns as a 'bioassay'. Techniques developed recently have allowed the direct measurement of GnRH pulse amplitude and revealed inhibitory effects of oestradiol, but we do not know whether this effect is due to a reduction in the amount of GnRH released by each neurone or a reduction in the number of neurones releasing a pulse. It is unlikely that the factors that alter pulse frequency do so by directly affecting the GnRH cells. For example, it is obvious that other cells, with specific receptors for pheromonal or nutritional stimuli, formulate a signal that is transferred to the GnRH cells via interneurones. Similarly, it is likely that a hypothalamic clock intervenes between photoperiodic inputs and GnRH output. Opioidergic neurons have been proposed as a link in this system, but the complexity of their action makes it unlikely that they directly affect the GnRH neurons. The responses to steroids are simple and rapid, but steroid receptors have not been found in GnRH cells, so at least one other set of interneurones is involved.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Aortic-carotid artery pressure differences and cephalic perfusion pressure during cardiopulmonary resuscitation in humans.

OBJECTIVE: Animal studies have shown an aortic-carotid artery pressure difference during cardiopulmonary resuscitation (CPR), which compromises cerebral perfusion. This pressure difference is most marked with prolonged CPR and can be abolished with administration of high doses of epinephrine. To better understand the mechanism of cerebral blood flow during CPR in humans, we determined the aortic-carotid artery pressure difference, the cephalic perfusion pressure (the carotid artery-jugular vein pressure difference), and thoracic inlet venous "valving" (the central venous-jugular vein pressure difference), while administering standard doses of epinephrine. DESIGN: Prospective study with randomization as to which side the carotid artery was catheterized. SETTING: The resuscitation room of a large urban hospital's emergency department. PATIENTS: Fifteen adults in normothermic, nontraumatic prehospital cardiac arrest treated according to Advanced Cardiac Life Support guidelines, including administration of 1 mg epinephrine iv every 5 mins. INTERVENTIONS: The descending aorta, cervical common carotid artery, internal jugular vein, and central venous system were catheterized. Pressures were recorded during standard CPR for 5 mins after administration of 1 mg epinephrine iv. MEASUREMENTS AND MAIN RESULTS: Most patients received CPR for greater than 20 mins before the first epinephrine dose and for greater than 45 mins before pressure recording as described above. There was no significant difference between aortic and carotid artery compression and relaxation phase pressures. The mean +/- SD compression central venous-jugular vein pressure difference was 22.1 +/- 15.0 mm Hg, and the mean cephalic perfusion pressure was 20.8 +/- 19.5 mm Hg. CONCLUSIONS: There is no clinically important aortic-carotid artery pressure difference during human CPR using the standard dose of epinephrine, even with prolonged CPR. Despite carotid artery patency and thoracic inlet venous valving, the cephalic perfusion pressure is low during CPR in humans.

Aged

Nuclear magnetic resonance spectroscopy study of human brain after cardiac resuscitation.

We used 31P nuclear magnetic resonance spectroscopy to study the cerebral metabolic function of eight patients with severe postischemic anoxic encephalopathy secondary to cardiac arrest. Spectroscopy was performed at 18 +/- 13 and 64 +/- 20 hours after resuscitation. Glasgow Coma Scale scores at the time of initial and repeat spectroscopy were 3.6 +/- 1.2 and 3.5 +/- 1.2, respectively. In those patients whose spectra were of adequate quality to monitor pH, all demonstrated tissue alkalosis in at least one brain region. The mean brain pH at initial spectroscopy was 7.14 +/- 0.09 and was significantly alkalotic when compared with age- and sex-matched normal controls (pH = 6.98 +/- 0.04, p less than 0.0001). Five of the eight patients showed at least one region of persistent alkalosis at repeat spectroscopy, whereas one patient demonstrated severe acidosis with a pH of 6.42. Spectra demonstrated marked metabolic heterogeneity, ranging from normal in appearance to complete obliteration of all high-energy phosphates with only inorganic phosphate remaining.

Aged

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