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The aim of this manuscript was to establish a consensus for the management of acute and chronic venous obstruction among specialists in the UK. Specialist physicians representing vascular surgery, interventional radiology and hematology were invited to 3 meetings to discuss management of acute and chronic iliofemoral obstruction. The meetings outlined controversial areas, included a topic-by-topic review; and on completion reached a consensus when greater than 80% agreement was reached on each topic. Physicians from 19 UK hospitals agreed on treatment protocols and highlighted areas that need development. Potential standard treatment algorithms were created. It was decided to establish a national registry of venous patients led by representatives from the treating multidisciplinary teams. Technical improvements have facilitated invasive treatment of patients with acute and chronic venous obstruction; however, the evidence guiding treatment is weak. Treatment should be conducted in centers with multi-disciplinary input; robust, coordinated data collection; and regular outcome analysis to ensure safe and effective treatment and a basis for future evolvement.

Limb ischaemia is an important clinical problem due to the high prevalence of peripheral arterial disease (PAD) in the UK. The main risk factors are smoking and diabetes mellitus. In young patients, alternative diagnoses of embolus, thrombosis, arteritis, congenital anomaly, fibrosis and traumatic (including iatrogenic) arterial injury must be considered. Intermittent claudication, critical ischaemia and acute ischaemia are clinical diagnoses easily confirmed by ankle–brachial pressure index (ABPI) measurement. Non-invasive arterial assessment by duplex, magnetic resonance angiography and computed tomographic angiography are used to confirm the diagnosis and to plan intervention. Angiography is usually reserved for therapeutic intervention. Best medical therapy for PAD includes smoking cessation, aspirin, blood pressure control (angiotensin-converting enzyme inhibitors) and statin therapy. These interventions are proven to reduce heart attack and stroke. For claudicants, structured exercise classes improve maximum and pain-free walking distance; in addition, percutaneous angioplasty may be considered if they have a suitable lesion in the iliac, femoral or popliteal arteries. Patients with critical limb ischaemia require intervention to avoid limb loss; arterial reconstruction (angioplasty or bypass) is preferable to primary amputation, as preservation of mobility is an important determinant of quality of life. The acutely ‘threatened’ limb is a surgical emergency and requires immediate intervention, best performed in a specialized vascular unit.

Purpose To demonstrate the effectiveness of intramedullary fixation of severely displaced proximal humeral physeal fractures in skeletally immature children using the elastic stable intramedullary nail (ESIN). Methods Retrospective recruitment of 14 patients aged 10–15-years old with severely displaced proximal humeral physeal fractures between 1999 and 2004 in a single regional specialist paediatric orthopaedic hospital. The fractures were graded using the Neer classification; severe displacement constituted Neer II–IV or displacement >1 cm and angulation >45°. Patients were followed up and assessed using the Disabilities of the Arm, Shoulder and Hand score (DASH) and the Neer Shoulder score. Radiographs were assessed for deformity. Subjective satisfaction was assessed. Results Fourteen patients with mean follow-up of 30 months (12–66 m) from surgery. All fractures were radiologically united at a median time of eight weeks (7–10 weeks). At follow-up, Neer Shoulder mean score was 96.79 (range 83–100) and DASH mean score 2.26 (0–7.5). Subjectively 71% were very satisfied and 29% were satisfied. Conclusions We commend stabilisation using ESIN in the management of the displaced proximal humeral physeal fracture in older children, once reduction of the fracture has been achieved by either closed or open means. ESIN is safe and allows early return to pre-injury function.

The cervical internal carotid artery (ICA) is classically differentiated from the external carotid artery by an absence of branches. We present a rare case of an anomalous branch originating from the cervical ICA seen during carotid endarterectomy. This article describes the origin of this anatomical variation and its implication for clinicians.

BACKGROUND: The purpose of our study was to independently assess the reliability of the modified Herring lateral pillar classification. METHODS: Thirty-five standardized true anteroposterior radiographs of children in the fragmentation phase were independently assessed by 6 senior observers on 2 separate occasions (6 wk apart). The κ analysis was used to assess the interobserver and intraobserver agreement. RESULTS: Intraobserver analysis revealed at best only moderate agreement for 2 observers. Three observers showed fair consistency, whereas 1 remaining observer showed poor consistency between repeated observations (P < 0.01). The highest scores for interobserver agreement varying between moderate to good could only be established between 2 observers. For the remaining observers results were just fair (P < 0.01). CONCLUSIONS: This study highlights the lack of agreement between senior clinicians when applying the modified lateral pillar classification. The results from the Herring group were significantly better than ours, but utilized a weighted κ for analysis, which may have given artificially high scores. To our knowledge, this is the first time the modified lateral pillar classification has been independently tested for its reproducibility by a specialist pediatric orthopaedic unit.

Early in incubation the nuclei of the chick chorioallantoic capillaries are randomly distributed around the capillary lumen; later most of them are located on the portion of the capillary surface opposite the inner shell membrane. This is one of the complex of processes that results in progressive thinning of the diffusion pathway for gases between the external environment and the blood of the embryo. The present study quantified this nuclear “relocation”. Our data show a progressive relocation of the endothelial nuclei from the tenth through the sixteenth day at an average rate of 6% per day.

A 70-year-old male presented with groin pain and swelling 11 days following a pulmonary vein isolation procedure via an unguided femoral venous puncture for atrial fibrillation. On the fourth visit, his haemoglobin level had dropped from 14.2 gl−1 to 10.7g l−1. Repeat duplex imaging revealed a large haematoma with deep flow. A CT angiogram revealed a pseudoaneurysm of a right common femoral branch artery. A subsequent angiogram revealed active bleeding, and the feeding artery was coiled. Pseudoaneurysms are recognized complications of vascular intervention, but more commonly occur anteriorly in major vessels. This elusive presentation reminds us of several important points. First, with the increasing use of interventional techniques across all medical specialties, the use of image guidance to aid vessel access is paramount for safety; not all specialties currently practise this routinely. Furthermore, we should consider arterial injury in all patients, including those who have had venous puncture. Injuries may not necessarily occur at the anterior vessel wall, and may well be deeper. Finally, there should be a low threshold for alternative imaging if symptoms are out of context with clinical findings.

Intimal hyperplasia and atherosclerosis are the Achilles' heels of vascular interventions. Many cytokines and growth factors have been shown to mediate these pathological processes. There are conflicting data concerning the expression of transforming growth factor-β1 (TGFβ1) antigen in human intimal hyperplasia and atherosclerotic lesions and conflicting views about whether TGFβ1 is pro- or anti-atherogenic. The presence of TGFβ1 is not sufficient to infer activation of its signaling pathway because TGFβ1 may be present in inactive complexes.A sensitive immuno-fluorescence assay (cyanine-3 tyramide signal amplification system) was used on human coronary artery and aorta sections with early or advanced stage lesions to detect TGFβ1, activin, Smad2-P, a marker of the activated TGFβ1/activin pathway and components of latent TGFβ complexes.All antigens were readily detected in the media and neointima of early stage lesions. The levels were either reduced or undetectable in the media of advanced lesions but were increased in the neointima in areas of high cell density. In marked contrast to activin, TGFβ1 and LAP1 expression levels were closely correlated with Smad2-P throughout the artery wall.Discrepancies in previous data for TGFβ1 expression are probably due to assay sensitivity. TGFβ1, but not activin, expression is consistently correlated with Smad pathway activation in the artery wall. The pattern of Smad2 activation supports a model in which TGFβ/activin signaling is anti-atherogenic in the media of normal artery walls but is equally compatible with an anti-atherogenic or pro-atherogenic response to TGFβ/activin in the neointima of lesions.

Objective Determination of skeletal age is essential for predicting eventual leg length discrepancies and predicting the accurate timing for surgical intervention in order to correct any discrepancy. To our knowledge, there has not been an interdisciplinary comparison of the degree of agreement in determining skeletal bone age. Materials and methods We evaluated 30 left hand/wrist radiographs (children aged 16 months to 10 years 6 months) on two separate occasions between musculoskeletal paediatric radiologists, paediatric orthopaedic surgeons and a senior radiographer after appropriate training. Results All clinicians were able to reliably age patients with good intra- and interobserver agreement. Conclusion We suggest that following tuition, orthopaedic surgeons are able to reliably age patients from X-rays.

Prophylactic pinning of an asymptomatic hip in Slipped Capital Femoral Epiphysis (SCFE) is controversial. Bone age has been used as a predictor of future contralateral slip risk and also in the decision making for prophylactic intervention. The efficacy of bone age at predicting a contralateral slip was tested in this study. Eighteen Caucasian children prospectively had bone age assessment using wrist and hand radiographs when presenting with a unilateral SCFE. After in situ fixation of the affected side prospective monitoring was performed at regular intervals in the outpatient department. Surgical intervention was undertaken if the contralateral hip was symptomatic. Three children (2 boys and 1 girl) went on to develop a contralateral slip at a mean of 20 months from initial presentation. Six children were deemed at risk of contralateral slip due to a bone age ofor = 12.5 years for boys andor = 10.5 years for girls. Only one from this group developed a contralateral slip. The relative risk of proceeding to a contralateral slip when the bone age is below the designated values was 1 (95% confidence interval of 0.1118 to 8.95). The sensitivity and specificity were 33% and 66% respectively. The positive predictive value was 15% and the diagnostic efficiency was 61%. Although this is a small study, it would appear that delayed bone age by itself is not a good predictor of future contralateral slip. Routine prophylactic pinning is not justified based on bone age alone, with the risks of surgical fixation it carries. A prospective long term longitudinal study is required.

The purpose of preoperative evaluation is to identify and, if necessary, implement measures to prepare higher risk patients for surgery. Preoperative evaluation can decrease the length of hospital stay as well as minimize postponed or cancelled surgeries [4]. With the high likelihood of un- derlying coronary artery disease and the high degree of haemodynamic cardiac stress with profound alteration in heart rate, blood pressure, vascular volume, bleeding and clotting tendencies, vascular surgery represents an inter- mediate (1–5%)to high (>5%)mortality risk.

1. 1. The respiratory properties and 2,3-DPG concentration were studied in blood of rats from birth to 83 days of age and compared with adult values. 2. 2. Newborn rat blood had a Hb concentration of 9.3 ± 1.1 g% significantly lower (P < 0.01) than 14.2 ± 1.4 g% for adults. 3. 3. The lowest value for Hb concentration occurred at day 5, then it rose to reach adult levels by 83 days of age. 4. 4. The Bohr factor for rat blood was −0.603 ± 0.066 Δ log pO2/ΔpH (N = 18). 5. 5. The P50 of newborn rats was significantly lower (P < 0.01) than adult values (24.6 ± 1.0 vs 38.7 ± 1.8mm Hg), but rose to the adult level by day 23 of life. 6. 6. The concentration of 2,3-DPG in newborn rat blood was 2.53 ± 1.78 μmol/g Hb, significantly lower (P < 0.01) than 13.93 ± 1.66 μmol/g Hb for adults. 7. 7. The concentration of 2,3-DPG rose steadily in the postnatal period and reached adult levels by day 18, close to the time when P50 values also reached the adult range. 8. 8. The pH difference across the red cell membrane decreased with age and therefore does not explain the rise in P50. Neither P50 nor 2,3-DPG concentration values in the neonate overshot adult values. 9. 9. The data collected in this study and information available for other species suggest that the time of disappearance of postnatal anemia depends upon the growth rate of the species.

The oxygen consumption (Vo2) of 12 normal women was measured at monthly intervals during pregnancy and 2, 6 and 12 weeks and 6 months postpartum. At each study session measurements were made sitting at rest, during standard steady-state exercise on a bicycle ergometer, and for 10 minutes of recovery. A significant increase in exercise Vo2 was observed in late pregnancy when compared to paired postpartum values. The oxygen debt incurred by standard exercise was also greater in late pregnancy than 12-14 weeks postpartum.

Minute ventilation, end-tidal PCO2, O2 and CO2 concentrations in expired air, pulse rate and arterial blood pressure were measured in the last half of pregnancy in eight women taking methadone daily. Measurements were made with the subjects seated at rest, during the steady state of 50-watt bicycle exercise, and during recovery. Calculations of O2 consumption. CO2 production, alveolar ventilation and oxygen debt were made. Studies were repeated in five subjects postpartum. Methadone diminishes the normal hyperventilation of pregnancy and its effect persists for more than 24 h. When comparisons are made of pregnant and postpartum values, some respiratory stimulation during pregnancy is apparent. Maternal oxygen debt following standard exercise during pregnancy is diminished after the daily dose of methadone and the maternal heart rate response to exercise is diminished concurrently. The maternal hypoventilation induced by methadone and maintained during exercise may be relevant to the low birth weights and high incidence of sudden infant death syndrome observed by others in the offspring of methadone-dependent women.

Respiratory characteristics of blood from two adult killer and two adult beluga whales were studied. Both of these are dolphins; killer whales attain weights up to 7000 kg and belugas up to 700 kg. Oxygen dissociation curves of the blood were constructed at 37 °C and corrected to a plasma pH of 7.40. Beluga whale blood had a significantly higher (P O .01) oxygen capacity than killer whale blood (25.8 ± O .6 vs 21.8 ± O .5 vol%). The mean P 50 values were 25.2 ± O .5 and 24.4 ± O .1 mm Hg, respectively, for killer and beluga whale blood and these are significantly different (P O .05). The Bohr factor for killer whale blood (− O .602 ± O .148 Δ log P O 2 / Δ pH) was not significantly different than that for beluga whale blood (− O .782 ± O .073), but the Haldane effect for killer whale blood (7.0 vol%) was smaller than for beluga whale blood (9.4 vol%). The concentration of 2,3-diphosphoglycerate in killer whale blood was significantly higher (P O .01) than in beluga whale blood(15.12 μ mol/g Hb vs 11.49 ± O .63 μ mol/g Hb). Starch gel electrophoresis showed that killer whale hemoglibin has two major components and beluga whale hemoglobin has only one major component. The fast-moving component of killer whale hemoglobin and the single major component of beluga whale hemoglobin migrate at the same rate as human A hemoglobin. A relationship between body weight and blood oxygen affinity, which is seen in land mammals, is not apparent in the published data for aquatic mammals.

Respiratory characteristics of blood from sixteen adult male galagos were studied (8 brown and 8 black). The average body weight of the black galagos was significantly higher than that of the brown(1.512 +/- 0.162 vs. 0.988 +/- 0.099 kg, respectively). The blood oxygen capacities for black and brown galagos were 20.6 +/- 1.9 and 21.5 +/- 1.8 vol percent, respectively. The Bohr factor for blood from the black galago was -0550 +/- 0.039 (n = 9) and for brown galago blood was -0.523 +/- 0.050 (n = 6). There was no significant (P greater than 0.05) difference in P50 values of blood from the two subspecies of galagos, 36.7 +/- 1.1 vs. 37.7 +/- 0.9 mm Hg for the black and brown, respectively. The Haldane effect for black galago blood was higher than that for brown (7.5 vs. 65 vol percent, respectively). The concentrations of 2.3-DPG were similar in black and brown galago blood, 16.16 +/- 1.52 vs. 16.37 +/- 0.76 mumol/g Hb, respectively. Starch gel electrophoresis showed three major components of hemoglobin from both subspecies. There is a trend toward decreasing blood oxygen affinity as one ascends the primate evolutionary scale, which may be secondary to the trend toward a greater adult body weight.

We have previously demonstrated that continuous incubation in elevated concentrations of ambient oxygen leads to accelerated growth of the chick embryo. We now report that a similar growth response is elicited by acute (72 h) exposure beginning on the 16th day of incubation. White Leghorn eggs were paired by initial weight and incubated in air for 15 days in forced-draft incubators. Embryos were sampled on days 11, 13 and 15 (experiments 1, 2, 3) or 13, 14 and 15 (experiment 4), freed of all extra-embryonic membranes and weighed. On day 16 the experimental group was switched to 60% O2. The control group was maintained in air. A portion of the remaining eggs from each group was opened on days 16, 17 and 18 (experiment 4), or alternatively all the remaining eggs were opened at the end of the 18th day of incubation (experiments 1, 2, 3). Linear regression analysis of growth curves obtained by plotting log wet embryo weight (g) vs log incubation age (d) showed a significantly greater rate of growth (slope) for days 15-18 in embryos exposed to 60% O2. These results support the hypothesis that growth of the chick embryo is normally limited by the availability of oxygen.

Heart ventricles from chick embryos incubated in 60% O2 (hyperoxia) on the 16th through the 18th days of incubation were 21% heavier than those from control embryos maintained in 21% O2 (normoxia). Heart ventricles from embryos incubated in 15% O2 (hypoxia) were 8% lighter than controls. Changes in ventricular weight were accompanied by proportional changes in protein content (21% more in hyperoxic ventricles; 8% less in hypoxic ventricles). Ventricular tissue DNA content showed a significant increase in hyperoxia. Tissue protein/DNA ratios were significantly higher in hyperoxia and lower in hypoxia. These data suggest that increased O2 availability led to hypertrophy of chick embryo ventricular cells and an increase in the level of DNA synthesis. Cytochrome oxidase activity per mg DNA was 15–25% higher in hyperoxic ventricles than in hypoxic ventricles. This result is consistent with our previous findings that alterations in O2 availability affect the O2 consumption rate of the chick embryo in ovo, and it provides direct evidence that a phenomenon repeatedly observed in vitro is of importance in vivo. In contrast to the heart, O2 availability did not affect the wet weight, protein or DNA contents, or cytochrome oxidase activity of the chick embryo brain.

1. 1. Eleven hemodynamic and respiratory studies were carried out using five adult, unanesthetized American opossum (Didelphis virginiana). Nine of these eleven studies were considered basal. The mean and standard deviation of various parameters are reported for those nine studies. 2. 2. The average body weight was 3·29 kg and the mean rectal temperature was 35·2°C. 3. 3. Cardiac output averaged 439 ml/min (134 ml/kg per min). 4. 4. Related hemodynamic parameters were: heart rate, 175 beats/min; mean carotid and pulmonary artery blood pressures, 119 and 15 mm Hg, respectively; stroke volume, 2·6 ml/stroke; peripheral vascular resistance, 22,190 dyne sec cm−5 and hemoglobin flow, 13·5 g/kg per min. 5. 5. The concentration of O2 in arterial blood was 10·9 ml/100 ml; arterial blood was 86 per cent saturated with O2 and had an O2 tension(pO2) of 83 mm Hg. 6. 6. The mixed venous blood had an O2 concentration of 5·3 ml/100 ml, was 42 per cent saturated and had a pO2 of 38 mm Hg. 7. 7. Mean oxygen consumption by the Fick method was 7·6 ml/kg per min (N = 7) compared to 7·1 ml/kg per min (N = 8) by the chamber method with an overall mean of 7·3 ml/kg per min (N = 15).

1. 1. Oxygen dissociation curves were constructed on whole blood (N = 23), incubated whole blood (N = 6), dialyzed blood (n = 3) and dialyzed blood with added 2,3-diphosphoglycerate (2,3-DPG) (N= 2), 2. 2. Hemoglobin concn averaged 12.0 ± 2.2 g%. 3. 3. The mean plasma pH after tonometry of whole blood averaged 7.375 ± 0.059 with a mean intraerythrocytic pH of 7.080 ± 0.020 which resulted in a pH gradient (ΔpH) across the red cell membrane of 0.295 ± 0.045. 4. 4. The O2 tension required to half saturate opossum hemoglobin (P50) in whole blood was 42.3 ± 2.5 mm Hg. 5. 5. The Bohr factor (Δ log Po2/ΔpH) calculated in this study was −0.526 ± 0.05. 6. 6. The electrophoretic pattern of opossum hemoglobin exhibits one major band which migrates slightly faster than human A hemoglobin. 7. 7. The mean 2,3-DPG concn in fresh, whole opossum blood was 14.74 ± 1.25μm/g Hb. 8. 8. Incubation of whole blood for 24 hr at 37°C reduced the concn of red cell 2,3-DPG to 1.39 μm/g Hb and increased the O2 affinity, shifting the P50 10 mm Hg to the left (25.7 vs 36.0 mm Hg). 9. 9. Dialysis effectively decreased 2,3-DPG concn (2.09 vs 14.66 μm/g Hb). 10. 10. The addition of 2,3-DPG (30 μm/g Hb) to the dialysate decreased the O2 affinity, shifting the mean P50 10.8 mm Hg to the right (43.8 vs 33.0 mm Hg).

The diffusion equilibrium method was used to measure uterine blood flow (Qut) and oxygen consumption (VutO 2 ) of 7 Pygmy goats in the last third of pregnancy. VutO 2 was 9.3 ± 1.3 (mean ± SEM) ml · min −1 · kg −1 weight of the uterus and its contents: the placenta, fetus and fetal membranes. This O 2 requirement was provided by a high blood flow (349 ± 48 ml · min −1 · kg −1 ) and a narrow arteriovenous difference (2.4 ± 0.1 vol %) across the uterus. Maternal arterial O 2 content (Ca O 2 ) was varied by incurring chronic anemia in 3 animals. Ca O 2 over the range 6.5–12.8 vol % did not affect uterine blood flow or the arteriovenous oxygen content difference across the uterus. Weight specific (ml · min −1 · kg −1 ) Vut O 2 did not differ in animals whose total uterine weights varied over a wide range and uterine vein oxygen tension and content did not fall prior to delivery. We conclude that the absolute uterine blood flow varies over a wide range to meet the requirements of the uterine contents.

Classical discrimination conditioning of heart rate (HR) and respiratory-motor (RM) activity was examined in 16 newborn (average age = 1 day) and 8 neonatal (average age = 2 weeks) pygmy goats over 4 days of conditioning involving an electric shock US and auditory CSs. On the 4th day, one-half of the animals in each group received a low to moderate dose of ethanol to test the resistance of the CRs to drug effects. Discriminated conditioning of RM activity but not HR occurred in the newborn group, indicating an absence of close coupling between skeletal-motor activity and HR at this early age. While the newborn group failed to show recognizable HR reactions to the CSs during the 4 days of testing, it did show a long-latency brady-cardia UR beginning at 2 days of age that may have been secondary to baroreceptor reflex actions. The neonatal group displayed conditioning of both HR and RM activity. The similar latencies of the two types of CRs during the CS suggested that they may have been related to each other. However, the fact that the RM CR developed a day before the HR CR, combined with the observation that ethanol modified the HR CR but not the RM CR, supports the view that there was considerable independence between the two types of CRs.

Incubation of eggs in 60% oxygen has been shown to enhance growth of the chick embryo. To determine whether oxygen accelerates growth over a range of concentrations, eggs were incubated in 40% or 70% O2. Control eggs, pair-matched by initial weight, were simultaneously incubated in room air (21% O2). Embryo and organ weights from matched pairs of eggs were compared on incubation days 14, 16 and 18 (40% O2) or 10, 12, 14, 16 and 18 (70% O2). Embryos incubated in 40% O2 displayed a pattern of growth enhancement similar to that previously reported for 60% O2. Accelerated embryonic growth was maintained through day 18. The heart showed the greatest percentage increase in weight over control, exceeding that of the whole embryo on days 16 and 18. The brain displayed significant enhancement only on day 16. Weight of the liver was unaffected by hyperoxia. Embryos in 70% O2 exhibited accelerated growth in all of the tissues examined early in incubation. Growth rate of the hyperoxic embryos then declined, so that embryo weight on day 18 did not differ from control. The brain, heart, eye, and proventriculus plus gizzard from 70% O2 embryos weighed significantly less than controls on day 18. Growth inhibition was most striking in the heart; heart/body weight ratio of 70% O2 embryos was significantly less than control throughout the observation period. The results confirm the growth accelerative effect of oxygen and suggest that the degree of growth enhancement is proportional to the ambient oxygen concentration. Accelerated growth cannot be maintained, however, in 70% O2.

The respiratory properties and concentrations of 2,3-diphosphoglycerate (2,3-DPG) in kitten blood were studied during fetal life and from birth to 100 days of age and compared with adult values. Fetal blood had a hemoglobin concentration (Hb) of 10.4 g%, within the normal adult range. Newborn kittens in the first 24 hr of life had Hb values averaging 13.4 g%. Hb then fell gradually, reaching a low value at about 35 days of age and subsequently rising. At 100 days of age Hb values were again similar to those of adult cats. The pH difference across the red cell membrane was significantly higher during fetal life than after birth. The P50 value for fetal blood was similar to adult blood (34.1 ± 0.6 vs. 35.2±0.8 mm Hg, respectively) but P50 values within the first 24 hr of life were significantly lower (P

Five children with D-transposition of the great arteries continued to have an elevated blood 2,3-DPG concentration and a lowered blood oxygen affinity for at least 10 days following corrective surgery. Five of ten children in whom arterial oxygen saturation was elevated at least 6 months following surgery, continued to have saturations of less than 90%. Thus, some postoperative patients appear to have a continuing need for facilitated tissue oxygen availability following the Mustard operation (interatrial baffle procedure).

Reducing blood oxygen affinity may enhance myocardial oxygen delivery during ischemia. We evaluated this hypothesis in awake, previously instrumented dogs that received a 20 ml/kg infusion of a solution of dihydroxyacetone, phosphate, and pyruvate after acute occlusion of either the left anterior descending or circumflex coronary artery. This infusion reduced blood oxygen affinity (BOA) after 2 hours; the P50 increased from 29.9 +/- 0.7 torr (mean +/- SD) to 32.1 +/- 0.6 torr; P less than 0.01 (BOA group). Four dogs received 20 ml/kg of phosphate and pyruvate solution to assess volume effects (V group), and five dogs were controls (C group). The 2-hour P50 values in V and C were unchanged. Regional flow (15-mum spheres) reduction 2 hours postocclusion was compared to the percent tissue infarcted determined by histology 7-9 days after occlusion for multiple samples from the endocardial layer of the left ventricle. When flow was less than 40% of normal, V and C had 55% infarction while BOA had 37% (P less than 0.05); at flow less than 20% of normal, V and C had 79% infarction while BOA had 38% (P less than 0.001); and at less than 10% of normal, V and C 87% and 94% infarction, respectively, while BOA had 56% (P less than 0.001). Reducing blood oxygen affinity after coronary artery occlusion significantly decreased the extent of myocardial necrosis for the same degree of ischemia. Reducing BOA may increase oxygen delivery to ischemic myocardium when flow is restricted.

The oxygen affinities of blood from eight Basenji dogs homozygous for classical erythrocyte pyruvate kinase deficiency and four dogs heterozygous for the defect were compared with blood from 14 Labrador retrievers and two normal Basenji dogs. The homozygous dogs showed significant anemia compared to heterozygous and normal dogs (P is less than 0.01). The average blood P50 value (at 38C and plasma pH of 7.40) for both homozygous and heterozygous dogs was significantly higher (P is less than 0.01) than for normal dogs (33.6+/-0.4 and 31.8+/-0.7 vs 30.8+/-0.6 mm Hg). The concentrations of 2,3-DPG in the blood of both heterozygous and homozygous dogs were significantly higher than normal values. Four months after splenectomy P50 values declined to normal in four homozygous Basenji dogs without any change in the degree of anemia or blood 2,3-DPG concentrations. Iron kinetic studies showed a shorter plasma clearance time in a homozygous than in a normal dog with the heterozygote falling midway between. The red cell life span in the normal and heterozygous dogs was approximately 120 days. The 59Fe studies on the homozygous dog indicate markedly different survival characteristics which can be attributed to the existence of three populations of red cells differing in their life spans.

Heart rate and stroke volume were measured serially in subjects at rest in the sitting position and at the onset and end of a 6-minute period of upright bicycle exercise. Twenty-three subjects, with normal pregnancy were studied in late gestation and again post partum. Rest and exercise cardiac outputs in late gestation were not different from those in the postpartum period. Heart rate was higher at rest and stroke volume lower during exercise in late gestation than post partum. At the end of exercise, stroke volume fell dramatically in late gestation but not post partum. Ten women prospectively identified as physically fit had responses that were not different from those of the nonfit cohort in late gestation. Post partum, the physically fit women had exercise responses typical of-trained persons and different from those of the nonfit cohort. In late gestation, rest and exercise hemodynamics in subjects in the sitting position appeared to be dominated by factors influencing venous return, independent of physical fitness.

Pregnant Pygmy goats were trained to walk on a treadmill up a 10 degree grade at a rate of 1.5 mile/hr for 10 min. Hemodynamic measurements were made in duplicate during late pregnancy and postpartum, at rest and after 3 min of exercise. All kids were weighed within 12 hr of delivery to assess the effect of exercise on fetal growth. Pulse rate, cardiac output and oxygen consumption were higher during pregnancy than postpartum, at rest and also during exercise. Stroke volume increased significantly with exercise. Peripheral vascular resistance (pvr) at rest was lower during pregnancy than postpartum, and decreased significantly during exercise, especially in pregnancy. Exercise was associated with a fall in arterial P(CO2) during pregnancy and postpartum. In goats, as in humans, the increased oxygen demands of pregnancy, during exercise and at rest, are met by an increased cardiac output rather than by increased peripheral oxygen extraction. The individual birth weights of twins, triplets and quadruplets from Pygmy goats who were exercised during late pregnancy were smaller than birth weights of matched newborns from control animals.

We studied the rates of change of expired ventilation (V E , BTPS), O 2 , STPD) and CO 2 production (V CO 2 , STPD) at the start and stop of 6 min of 50-W bicycle exercise, comparing 20 healthy young women at 38 weeks of pregnancy (G) and 3 months postpartum (NG). V O 2 , V CO 2 and VE were significantly greater at rest for G than for NG. The absolute increases of V O 2 and V CO 2 from steady-state rest (SSR) to steady-state exercise (SSE) were the same for G and NG. The absolute increase of V E from SSR to SSE was significantly greater for G than NG. V CO 2 and V E increased more rapidly in G than NG, but only during the first 90 sec of exercise. Recovery rates after exercise were equal for G and NG. We believe that lower extremity muscles of G contract on more distended veins at the onset of exercise, forcing increased volumes of venous blood through the lungs, increasing V O 2 and V CO 2 . V E follows V CO 2 closely.

The hypothesis that oxygen availability limits growth of the normal chick embryo late in development predicts that an increase in oxygen availability would accelerate the rate of growth and, therefore, metabolism. We tested the prediction concerning metabolism by comparing the oxygen consumption (V O 2 ) and carbon dioxide production (V CO2 ) of 14–18 day embryos acutely exposed to either 60% or 100% O 2 with those of normoxic (21% O 2 ) controls. Two hours of hyperoxia produced increases in both V O 2 and V CO 2 ; however, repeated measurements over time in normoxia also demonstrated a significant increase in gas exchange, presumably due to normal growth of the embryos. After correcting for the increase in V O 2 due to growth, there was no effect of 60% O 2 on day 14. Thereafter the stimulatory effect of 60% O 2 increased gradually, reaching 6.1% on day 18. V CO 2 was 4 to 6% higher in embryos acutely exposed to 60% O 2 than in normoxic controls throughout the observation period, although the difference was significant only to day 18. The V O 2 of embryos acutely exposed to 100% O 2 was not significantly different from that observed in 60% O 2 , and was still significantly elevated 3 h after the eggs were returned to 21% O 2 . We conclude that acute hyperoxia late in incubation elicits an increased in embryonic V O 2 and V CO 2 , with little or no effect on the respiratory exchange ratio, and that the stimulation of gas exchange by 100% O 2 persists after the embryo is returned to normoxic conditions. These findings support the hypothesis that oxygen availability limits growth and metabolism of the normoxic chick embryo late in development.

The diffusing capacity of the hen's egg for carbon monoxide (D τ CO ) increases during incubation, reflecting the development of the chrioallantoic circulation. Previous work showed that the increase in D τ CO could be diminished by incubating eggs in a 60% oxygen environment. The present work explored the effects of impeding gas exchange on the development of D τ CO . Half the shell area was covered during incubation by a removable neoprene membrane which limited D τ CO by approximately 20%. No difference could be detected between the D τ CO values (measured with the membrane removed) of these eggs and control eggs in incubated in the same 21% oxygen environment without a neoprene membrane. We conclude that the development of the chorioallantoic circulation is at its maximum under normal conditions of incubation and cannot be accelerated by restricting gas exchange.

Discussion of the major cardiovascular changes accompanying pregnancy, labor, and delivery serves as a background for understanding the pathophysiologic changes presented by specific cardiac lesions endangering women during pregnancy.

Respiratory characteristics of whole blood from four antelope (Antilocapra americana) were studied. The blood- oxygen capacity averaged 22.5 vol%. Oxygen dissociation curves were constructed at 38 °C and corrected to a plasma pH of 7.40. The mean blood P50 value was 28.3±0.7 mm Hg. The Bohr factor (Δ log Po2/Δ pH) was −0.473±0.040. The concentration of 2,3-diphosphoglycerate averaged 1.01±0.08 μ mole/g Hb. Starch gel electrophoresis showed that antelope hemoglobin has only one major component which migrates at a slower rate than human hemoglobin A. The pH difference across the red cell membrane was 0.251±0.040, and it remained unchanged over a wide range of plasma and intraerythrocytic pH values. Antelope erythrocytes do not sickle under high oxygen tension and high pH environments as has been observed in many species of deer.

Blood samples from a yak, llama, camel, deer, and African elephant were analyzed for oxygen capacity, "standard bicarbonate" content, oxygen dissociation curve, and the magnitude of the Bohr and Haldane effects. These parameters of the respiratory function of the blood have been related to the morphology of the red cells, to the weights of the animals, and to the most important electrolytes in the erythrocytes and in the plasma. The high affinity for oxygen described previously for llama blood is shared by its relative, the camel. Both these animals have a high concentration of hemoglobin within their erythrocytes. Blood from the African elephant showed the greatest affinity for oxygen among the subjects studied.

1. Three instances of congenital pelvic fistulas complicating pregnancy with pertinent medical studies and obstetrical and surgical procedures are reviewed. 2. The limited number of observations of this condition recorded in the literature make all conclusions tentative. Nevertheless, it appears that a congenital pelvic arteriovenous fistula is a nonhereditary nonfamilial lesion, not as rare as the few reports suggest. 3. The size and symptomatology may increase with age and repeated advanced pregnancies. It may be the cause of antepartum bleeding, postpartum hemorrhage, and premature labor but not fetal anomalies. 4. Arteriovenous aneurysm is a justification for contraception or even sterilization in multiparas, and, in the presence of pregnancy, a possible indication for therapeutic abortion or delivery by cesarean section. 5. The condition is often best palliated until serious symptomatology threatens; whereupon radical surgical correction under the best auspices should be arranged. It is generally not amenable to operation during pregnancy, although interruption of the lymphogastric vasculature may prevent excessive blood loss.