Biomedical subjects
Publications and source records attributed to T Clutton-Brock.
This is the second of two extracts from Why Mothers Die 2000-2002, issued on 12 November 2004 by the Confidential enquiry into Maternal and Child Health (CEMACH), reproduced with permission. The full report can be accessed via their web site: http://www.cemach.org.uk/
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OBJECTIVES: Although retrograde cerebral perfusion has become a popular adjunctive technique and may improve cerebral ischemic tolerance during hypothermic circulatory arrest, direct cerebral metabolic benefit has yet to be demonstrated in human subjects. We investigated the post-arrest metabolic phenomena with and without retrograde cerebral perfusion in patients. METHODS: In a prospective randomized trial, 42 patients undergoing aortic surgery requiring hypothermic circulatory arrest were allocated to receive hypothermic circulatory arrest alone (n = 21) or hypothermic circulatory arrest with additional retrograde cerebral perfusion (n = 21). Circulatory arrest was commenced at 15 degrees C, and retrograde perfusion was instituted through the superior vena cava at a maximum jugular bulb pressure of 25 mm Hg. Transcranial, paired, repeated samples of the arterial and jugular bulb blood were analyzed for oxygen and glucose. Velocity in the right middle cerebral artery was also measured simultaneously. RESULTS: There were 3 (7.1%) deaths and 3 (7.1%) episodes of neurologic deficit. Mean bypass and circulatory arrest duration (in minutes) were similar between groups (P =.4 and.14). The mean retrograde perfusion duration was 23 minutes. Post-arrest nasopharyngeal temperature was similar (15.3 degrees C vs. 15.3 degrees C). Retrograde perfusion did not affect post-arrest oxygen extraction, glucose extraction, or jugular bulb Po(2). There was no immediate lactate release immediately after hypothermic circulatory arrest. CONCLUSIONS: Retrograde cerebral perfusion did not influence immediate post-arrest nasopharyngeal temperature or cerebral metabolic recovery. The low jugular bulb Po(2) suggests equivalent ischemia. These findings cast doubt on the effectiveness of retrograde cerebral perfusion as a metabolic adjunct to hypothermic circulatory arrest.
Pulmonary hypertension is found in about 10% of patients with systemic lupus erythematosis (SLE). Pulmonary hypertension may be present at the time of diagnosis or may develop after the diagnosis of SLE or anti-phospholipid syndrome (APS). It often presents in the reproductive years and has a significant impact on pregnancy outcome, being a significant cause of indirect maternal deaths. In our observational case series of three patients there were two deaths (66%). In cases 1 and 2 the pulmonary hypertension developed during pregnancy and deteriorated rapidly with markedly abnormal mean pulmonary artery pressures of 80 and 70 mmHg respectively prior to death. Both patients died within 48 hours of delivery. In case 3 the pulmonary hypertension was milder and was diagnosed very early in pregnancy. The patient received multidisciplinary care from the first trimester and the management of the pregnancy, delivery and the early puerperium was planned. Careful epidural anaesthesia was used and the patient had invasive monitoring on the intensive therapy unit (ITU) for 72 hours. Women with pulmonary hypertension need to be aware of the high risk of maternal mortality associated with pregnancy but we believe that an improvement in outcome can be achieved by careful assessment and the use of a multidisciplinary approach from early in pregnancy.
1. Studies of the effect of vagus nerve stimulation on ventricular myocardial function in mammals are limited, particularly in the human. 2. The present study was designed to determine the effect of direct electrical stimulation of the left vagus nerve on left ventricular contractile state in hearts paced at 10 % above the natural rate, in anaesthetised pigs and anaesthetised human subjects undergoing open chest surgery for coronary artery bypass grafting. 3. Contractility of the left ventricle was determined from a series of pressure-volume loops obtained from a combined pressure and conductance (volume) catheter placed in the left ventricle. From the measurements a regression slope of the end-systolic pressure-volume relationship was determined to give end-systolic elastance (Ees), a load-independent measure of contractility. 4. In six anaesthetised open chest pigs, stimulation of the peripheral cut end of the left cervical vagus nerve induced a significant decrease in Ees of 26 +/- 14 %. 5. In nine patients electrical stimulation of the left thoracic vagus nerve close to its cardiac branch resulted in a significant drop in Ees of 38 +/- 16 %. 6. The effects of vagal stimulation were blocked by the muscarinic antagonist glycopyrronium (5 mg kg(-1)). 7. Administration of the beta-adrenoreceptor antagonist esmolol (1 mg kg(-1)) also attenuated the effect of vagal stimulation, indicating a degree of interaction of vagal and sympathetic influences on contractility. 8. These studies show that in the human and pig heart the left vagus nerve can profoundly decrease the inotropic state of the left ventricular myocardium independent of its bradycardic effect.
The relative influences of density-dependent and -independent processes on vital rates and population dynamics have been debated in ecology for over half a century, yet it is only recently that both processes have been shown to operate within the same population. However, generalizations on the role of each process across species are rare. Using a process-orientated generalized linear modelling approach we show that variations in fecundity rates in populations of three species of ungulates with contrasting life histories are associated with density and winter weather in a remarkably similar manner. However, there are differences and we speculate that they are a result of differences in size between the species. Much previous research exploring the association between vital rates, population dynamics and density-dependent and -independent processes has used pattern-orientated approaches to decompose time-series into contributions from density-dependent and -independent processes. Results from these analyses are sometimes used to infer associations between vital rates, density and climatic variables. We compare results from pattern-orientated analyses of time-series with process-orientated analyses and report that the two approaches give different results. The approach of analysing relationships between vital rates, density and climatic variables may detect important processes influencing population dynamics that time-series methodologies may overlook.
The Allee effect describes a scenario in which populations at low numbers are affected by a positive relationship between population growth rate and density, which increases their likelihood of extinction. The importance of this dynamic process in ecology has been under-appreciated and recent evidence now suggests that it might have an impact on the population dynamics of many plant and animal species. Studies of the causal mechanisms generating Allee effects in small populations could provide a key to understanding their dynamics.
Tissue hypoxia may be defined as abnormal oxygen utilization such that cells are experiencing anaerobic metabolism. Tissue hypoxia can be defined biochemically by low levels of ATP, high levels of NADH, or decreased oxidized cytochrome aa3. It is possible to measure these biochemical markers in the laboratory setting with, for example, nuclear magnetic resonance spectroscopy. However, this is not as yet a clinical option. There is no 'gold standard' for the diagnosis of clinical hypoxia. We can detect the gross consequences of tissue hypoxia, such as organ dysfunction and metabolic markers of anaerobic metabolism (e.g. lactic acidosis). We have also become familiar with the measurement of both global and regional oxygen dispatch and consumption. However, organ dysfunction and metabolic acidosis consistent with established tissue hypoxia commonly exists in the presence of normal and even supra normal global measures of oxygen dispatch and consumption. Therefore, we should ideally make measurements at the end of the oxygen trail, i.e. cellular oxygen delivery and effective utilization.
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OBJECTIVE: Elevated pulmonary vascular resistance and transpulmonary gradient are predictors of increased perioperative mortality in patients undergoing orthotopic heart transplantation. Sodium nitroprusside and prostacyclin PGI2 are routinely used to assess the reversibility of pulmonary vascular resistance and transpulmonary gradient in heart transplant candidates, but their use is limited by their systemic vasodilatory effect. The aim of this study was to evaluate the systemic and pulmonary haemodynamic effects of low concentration (10 and 20 parts per million) inhaled nitric oxide in patients with severe heart failure with elevated transpulmonary gradient and pulmonary vascular resistance undergoing assessment for cardiac transplantation, and to compare the haemodynamic effects of inhaled nitric oxide with those of sodium nitroprusside and prostacyclin PGI2. METHOD: In 10 consecutive patients with elevated transpulmonary gradient (16+/-2 mm Hg) and pulmonary vascular resistance (3.6 +/-0.3 Wood units (WU)) nitric oxide (10 and 20 parts per million in 23% inspired oxygen (O2) via a tight fitting facemask) and increasing doses of intravenous sodium nitroprusside and prostacyclin were administered in a random, single-blinded fashion. RESULTS: Inhalation of nitric oxide (10 ppm) reduced the transpulmonary gradient (-7+/-2 mm Hg; P<0.01) and pulmonary vascular resistance (-1.8+/-0.4 WU; P<0.001) but did not affect the systemic vascular resistance (-0.3+/-1 WU) or mean systemic arterial pressure (-1.3 5 mm Hg). Sodium nitroprusside and prostacyclin reduced the transpulmonary gradient (-4.5+/-2 mm Hg; P<0.01 and -3.6+/-2 mm Hg; P<0.05), pulmonary vascular resistance (-1.5+/-0.4 WU; P<0.001 and -1.3+/-0.4 WU; P<0.01), systemic vascular resistance (-7+/-2 WU; P<0.01 and -7.2+/-2 WU; P<0.01) and mean systemic arterial pressure (-15+/-5 mm Hg; P<0.01 and -18+/-4 mm Hg; P<0.01). CONCLUSION: Low-concentration inhaled nitric oxide is as effective as sodium nitroprusside and prostacyclin in reducing transpulmonary gradient and pulmonary vascular resistance, and is highly pulmonary vasoselective.
In several lek-breeding populations of birds and mammals, females arriving on leks tend to join males that already have females in their territories. This might occur either because females have an evolved preference for mating with males that are attractive to other females, or because they join groups of other females to obtain greater safety from predation or dangerous harassment by males. We have previously used controlled experiments to show that oestrous fallow deer females join males with established harems because they are attracted to female groups rather than to the males themselves. Here we demonstrate that the preference for males with females over males without females is specific to oestrous females and weak or absent in anoestrous ones, and that it is not associated with a preference for mating with males that have previously been seen to mate with other females. Furthermore, oestrous females given the choice between males that do not already have females with them show no significant preference for antlered over deantlered males or for older males over younger ones. We conclude that female attraction to other females on the lek is likely to be an adaptation to avoiding harassment in mixed-sex herds. In this situation, a male's ability to maintain the cohesion of his harem may be the principal cause of variation in mating success between males.
OBJECTIVE: To quantify the precision and bias for two standard blood gas analyzers when measuring PCO2 in five different test solutions (blood, normal saline, human albumin solution, succinylated gelatin 4%, and Hartmann's solution). DESIGN: A comparative laboratory study of two blood gas analyzers measuring known PCO2 in test solutions prepared with a thin film tonometer. MEASUREMENTS: The PCO2 was determined simultaneously in both blood gas analyzers. The precision and bias for both machines were calculated from the measured PCO2. RESULTS: Analyzer 1 showed a negative bias of between 66.4% and 39.2% when measuring PCO2 in saline. Under the same conditions, analyzer 2 showed a negative bias of between 17.7% and 17.9% for PCO2 in the mid- and high ranges of PCO2, but a positive bias in the low range. Both machines measured PCO2 with satisfactory bias and precision in blood. The use of succinylated gelatin 4% as a test solution improved the bias and precision of both machines. CONCLUSIONS: Because of the large bias and precision, neither of these machines is suitable for measuring PCO2 in saline solution. The use of succinylated gelatin 4% as a test solution improves the bias and precision of both machines and we favor this solution for nasogastric tonometry. Even with succinylated gelatin 4%, there is a large negative bias with analyzer 1 and our preference is to use analyzer 2. We recommend that other workers review critically the performance of blood gas electrode systems when measuring PCO2 in saline solution. Because of varying performance of "standard" machines, we also recommend that each institution determine its own reference range for intramucosal pH.
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A comparison was made of arterial pressures measured invasively from a radial arterial cannula and non-invasively from the middle finger using the 2300 Finapres (Ohmeda) during induction and maintenance of anaesthesia. Digital outputs of both pressures were captured directly onto computer hard disk; data recorded during flushing of the arterial line were excluded from analysis. We studied 53 patients undergoing cardiac, major vascular and neurosurgical procedures; 17705 comparisons of systolic, diastolic and mean pressure were analysed. Overall correlations between Finapres and invasive pressures were poor (r = 0.82, 0.68 and 0.78 for systolic, diastolic and mean pressures, respectively). The Finapres exhibited a high level of accuracy and precision in some recordings. However, patient data sets showed marked variability in average pressure differences (invasive minus Finapres) when examined individually or grouped by operation type. Unexplained variations in pressure difference with time and absolute pressure were observed also. Whilst providing useful beat-to-beat information on arterial pressure trends, the Finapres cannot be recommended as a universal substitute for invasive arterial pressure monitoring.
The Inspiron Nebuliser 002305 with air entrainment was assessed as a gas delivery device in a continuous positive airway pressure system. Inspired oxygen concentrations, total gas flows and pressures within the system were measured over a range of settings, with and without positive and expiratory pressure. Inspired oxygen concentrations and total flows were completely disrupted when a positive and expiratory pressure valve was applied, and the system failed to generate continuous positive airway pressure. We would not therefore recommend the Inspiron nebuliser as a gas delivery system for continuous positive airway pressure.