In utero ventilation augments the left ventricular response to isoproterenol and volume loading in fetal sheep

In its normal circulatory environment, the fetal left ventricle can maximally increase output less than 2-fold, in contrast to the nearly 3-fold increase that occurs at birth. Several studies have attributed this finding to fetal myocardial "immaturity," and speculated that there is a rapid maturation of the myocardium in the perinatal period. We investigated the importance of the circulatory environment itself, rather than myocardial immaturity, by measuring left ventricular output (LVO) during in utero oxygen ventilation and isoproterenol infusion. We studied seven near-term fetal sheep greater than or equal to 2 d after placement of intravascular catheters, an endotracheal tube, and an electromagnetic flow transducer around the ascending aorta. We measured hemodynamic variables in the presence and absence of all combinations of oxygen ventilation, isoproterenol infusion, and volume infusion. Baseline LVO was normal (133 +/- 27 mL.kg-1.min-1). Individually, oxygen ventilation (136 +/- 11 mL.kg-1.min-1, p less than 0.001) and isoproterenol (48 +/- 11 mL.kg-1.min-1, p less than 0.05) increased LVO significantly; volume infusion did not. Their cumulative effect increased LVO nearly 3-fold (to 387 +/- 98 mL.kg-1.min-1), similar to levels seen in the newborn lamb. Mean left atrial pressure increased above right during oxygen ventilation (from 0.05 +/- 0.54 kPa to 0.82 +/- 0.39 kPa, p less than or equal to 0.0001). We conclude that the previously observed limitation in maximal LVO in the near-term fetus is primarily caused by its circulatory environment rather than relative myocardial immaturity, and speculate that a prominent Starling response is uncovered by decreases in left ventricular afterload and right ventricular constraint.     

Book reviews

Recent Advances in Avian Immunology Research. B. S. BHOGAL & G. KOCH (Eds), Progress in Clinical and Biological Research Volume 307, New York, Alan R. Liss, Inc., 1989. 238 pp. US$59–50. ISBN 0–8451–5157–6.

Mechanisms of Disease. A Textbook of Comparative General Pathology. D. O. SLAUSON & B. J. COOPER, Baltimore, Williams & Wilkins 2nd Ed., 1990. 541 pp., £43.50. ISBN 0–683–07743–0.

Poultry Diseases. F. T. W. JORDAN (Ed), London, Bailliere Tindall, 3rd Edition, 1990. 464 pp., £19.90. ISBN 0–7020–1339–0.     

POSSIBLE INVOLVEMENT OF INOSITOL-LIPID METABOLISM IN MALIGNANT HYPERTHERMIA

-Adrenoceptor stimulation may induce malignant hyperthermia(MH) in vivo. Consequently, we have investigated the effectsof the -adrenoceptor agonist phenylephrine and, for comparison,the effects of the ß-adrenoceptor agonist isoproterenolon inositol-lipid metabolism of malignant hyperthermia susceptible(MHS) and healthy control (MHN) swine. The experiments wereperformed on electrically stimulated (frequency 0.2 Hz) trabeculaeisolated from the right ventricles of the hearts of MHS andMHN animals. After labelling with [³H] inositol for 6 h, differentinositol phosphates were measured by high pressure liquid chromatography,including inositol 1 - phosphate, inositol 1,4-bisphosphate,inositol 1,3,4-trisphosphate, inositol 1,4,5-trisphosphate (1,4,5-IP₃)and inositol 1,3,4,5 - tetrakisphosphate. After stimulationwith isoproterenol, the inositol phosphate content did not increaseor vary between muscle from MHS and MHN animals. In contrast,all inositol phosphates increased after stimulation with phenylephrinein both muscle types, the effects being greater in MHS thanin MHN, especially as regards 1,4,5-IP₃ content. As 1,4,5-IP₃,a presumed second messenger, has been shown to mobilize intracellularcalcium, it is concluded that an enhanced -adrenergic responseis involved in the development of MH. ^*Address for correspondence: Abteilung für Anästhesiologie,Universitäts-Krankenhaus Eppendorf, Martinistrasse52, D-2000Hamburg 20, Germany. Presented in part at the 1989 Meeting of the European Academyof Anaesthesiology in Bonn.     

DL-ethionine Treatment of Adult Pancreatic Donors: Amelioration of Diabetes in Multiple Recipients with Tissue From a Single Donor

Transplantation of adult rat pancreatic islet tissue as a free graft requires the separation of islet from exocrine tissue to avoid host injury or graft destruction by digestive enzymes. The poor yield from islet isolation techniques currently necessitates the use of multiple donors to ameliorate diabetes in a single recipient. DL-ethionine (DLE) is an agent selectively toxic to the exocrine pancreas. We examined the effect of DLE administration on pancreatic digestive enzyme content and islet mass in adult Lewis rats and the ability of such pancreatic tissue dispersed by collagenase digestion without specific islet isolation to ameliorate diabetes when transplanted to the portal vein of syngeneic rats with streptozotocin induced diabetes. Rats fed normal chow supplemented with 0.5% DLE for 14-20 days showed a logarithmic loss of pancreatic mass. Total pancreatic amylase content declined to 0.3 + 0.1 mg, less than 3% of control values (14.3 +/- 1.0 mg). Total insulin content in DLE treated rats was 87 +/- 8 microg, not significantly different from control rats (101 +/- 7 microg). Histological examination confirmed the selective atrophy of exocrine tissue in DLE treated rats. Fresh pancreatic tissue prepared from a single DLE treated donor ameliorated diabetes 75% of the time when transplanted to one or two recipients and 65% of the time when divided between three of four recipients. Tissue prepared from a single DLE treated donor and stored for 24-48 hours ameliorated diabetes 91% of the time when divided between one or two recipients. Only four of 31 diabetic rats transplanted with fresh pancreatic tissue from untreated adult donors became normoglycemic. Pretreatment of adult rats with DLE induces selective exocrine atrophy, permits dispersed pancreatic tissue from a single donor to ameliorate experimental diabetes in up to four recipients, and allows tissue to be preserved by culture for up to 48 hours without specific islet isolation.     

The efficacy of protein supplementation in overcoming urea toxicity in sheep.

1. In the first experiment sheep taken from pasture were given a low-protein diet for six weeks in individual pens. Then, for 1 week, groups were given a supplement of lucerne chaff, safflower meal or lucerne chaff plus safflower meal. In the second experiment eighteen sheep maintained on lucerne chaff rather than pasture were then depleted of protein to a greater extent by feeding on a restricted low-protein diet. Six of the sheep received a supplement of molasses throughout the period of protein depletion while six of the sheep on the basal ration received a supplement of safflower meal after 6 weeks on the low-protein diet. 2. The urea tolerance of the sheep, is indicated by blood ammonia levels after oral dosing with aqueous solutions of urea, was determined after the period of supplementation. "Arginine synthetase" activity (combined activities of argininosuccinate synthetase (EC 6.3.4.5) and argininosuccinate lyase (EC 4.3.2.1) was determined in liver samples obtained by biopsy at various intervals during the experiment. 3. Supplementation for 7 d with 73 g crude protein (nitrogen X 6-25)/d increased the tolerance to urea as indicated by reduced blood NH3 levels, and also increased "arginine synthetase" activity. 4. Giving supplements of molasses delayed the onset of urea toxicity but not the extent of toxicity. 5. It is suggested that short-term feeding of protein concentrates to sheep before giving urea supplements can increase their tolerance to urea.     

Increased incidence of cardiac complications in kidney transplant recipients with cytomegalovirus disease

BACKGROUND: The transplant literature has not shown cytomegalovirus (CMV) disease to be a significant risk factor for posttransplant cardiac complications. A large number of nontransplant studies have, however, reported an association between coronary heart disease (CHD) and CMV disease. Pathology studies have demonstrated a high incidence of CMV in atheromatous plaques from the coronary circulation. METHODS: We performed multivariate analysis to determine if posttransplant CMV disease was a significant risk factor for cardiac complications in kidney transplant recipients. We also performed univariate analysis to determine which cardiac complications were more common in the recipients with CMV disease. RESULTS: Between January 1, 1984 and June 30, 1997, 1859 adults underwent kidney transplants at our institution. Of these, 377 developed one of the following cardiac complications posttransplant: myocardial infarction, angina, arrhythmia, congestive heart failure, and angiographic vessel occlusion. By multivariate analysis, significant risk factors for one of the above cardiac complications were recipient age >50 years [odds ratio (OR)=2.5, P=0.0001], diabetes (OR=1.99, P=0.0001), a history of cardiac disease pretransplant (OR= 1.34, P=0.04), and CMV disease (OR=1.5, P=0.01). Univariate analysis demonstrated that recipients with CMV disease had a higher overall incidence of cardiac complications. Arrhythmias, congestive heart failure, and vessel occlusion were more common in those with CMV disease. The incidence of myocardial infarction, angina, and cardiac arrest did not differ between the two groups (recipients with versus without CMV disease). CONCLUSIONS: CMV disease is associated with an increased risk of cardiac complications in kidney transplant recipients. In our series, angiographic vessel occlusion was more common in recipients with CMV disease. This interesting finding may support the theory that CMV plays some role in the pathogenesis of CHD.     

Randomised controlled trial of zinc supplementation in malnourished Bangladeshi children with acute diarrhoea

OBJECTIVE: To evaluate the impact of zinc supplementation on the clinical course, stool weight, duration of diarrhoea, changes in serum zinc, and body weight gain of children with acute diarrhoea. DESIGN: Randomised double blind controlled trial. Children were assigned to receive zinc (20 mg elemental zinc per day) containing multivitamins or control group (zinc-free multivitamins) daily in three divided doses for two weeks. SETTING: A diarrhoeal disease hospital in Dhaka, Bangladesh. PATIENTS: 111 children, 3 to 24 months old, below 76% median weight for age of the National Center for Health Statistics standard with acute diarrhoea. Children with severe infection and/or oedema were excluded. MAIN OUTCOME MEASURES: Total diarrhoeal stool output, duration of diarrhoea, rate of weight gain, and changes in serum zinc levels after supplementation. RESULTS: Stool output was 28% less and duration 14% shorter in the zinc supplemented group than placebo (p = 0.06). There were reductions in median total diarrhoeal stool output among zinc supplemented subjects who were shorter (less than 95% height for age), 239 v 326 g/kg (p < 0.04), and who had a lower initial serum zinc (< 14 mmol/l), 279 v 329 g/kg (p < 0.05); a shortening of mean time to recovery occurred (4.7 v 6.2 days, p < 0.04) in those with lower serum zinc. There was an increase in mean serum zinc in the zinc supplemented group (+2.4 v -0.3 mumol/l, p < 0.001) during two weeks of supplementation, and better mean weight gain (120 v 30 g, p < 0.03) at the time of discharge from hospital. CONCLUSIONS: Zinc supplementation is a simple, acceptable, and affordable strategy which should be considered in the management of acute diarrhoea and in prevention of growth faltering in children specially those who are malnourished.     

Growth of Pakistani children in relation to the 1990 growth standards

This study was designed to compare the growth of Pakistani schoolchildren in the UK with the 1990 UK growth standards. Measurements of height, weight, and sitting height were performed on 785 Pakistani schoolchildren aged 5-14 years with the mean values for each age and sex being plotted on the UK growth standards. The results were expressed as SD scores relative to the 1990 reference data. The mean height for the boys was only 0.2 SD scores below the mean for the new growth standards with the mean height for the girls being 0.4 SD scores below the mean. The mean values for weight and body mass index were 0.3 and 0.5 SD scores less than the mean for boys and girls respectively. This study demonstrates that the growth of Pakistani schoolchildren in the UK is comparable to the 1990 UK growth standards with only minor differences. It is not safe to assume that short stature or low body weight in a Pakistani child is due to his or her ethnic background.     

Adaptive response of human melanoma cells to methylglyoxal injury

The effects of methylglyoxal on the growth of a line of human melanoma cells are investigated. Methylglyoxal inhibits cell growth in a dose- dependent manner and causes an increase in glyceraldehyde 3-phosphate dehydrogenase, and glyoxalase 1 and glyoxalase 2 specific activities. The cellular response to increasing concentrations of methylglyoxal in the culture medium is also studied by measuring L-lactate production, reduced-oxidized glutathione levels and apoptotic cell death. Methylglyoxal seems to promote a change of cell population phenotypic repertoire toward a more monomorphic phenotype. In conclusion, methylglyoxal seems to induce an enzymatic cellular response that lowers methylglyoxal levels and selects the most resistant cells.