The effects of COVID-19 on placental morphology.

The impact of the COVID-19 infection, caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), during the pandemic has been considerably more severe in pregnant women than non-pregnant women. Therefore, a review detailing the morphological alterations and physiological changes associated with COVID-19 during pregnancy and the effect that these changes have on the feto-placental unit is of high priority. This knowledge is crucial for these mothers, their babies and clinicians to ensure a healthy life post-pandemic. Hence, we review the placental morphological changes due to COVID-19 to enhance the general understanding of how pregnant mothers, their placentas and unborn children may have been affected by this pandemic. Based on current literature, we deduced that COVID-19 pregnancies were oxygen deficient, which could further result in other pregnancy-related complications like preeclampsia and IUGR. Therefore, we present an up-to-date review of the COVID-19 pathophysiological implications on the placenta, covering the function of the placenta in COVID-19, the effects of this virus on the placenta, its functions and its link to other gestational complications. Furthermore, we highlight the possible effects of COVID-19 therapeutic interventions on pregnant mothers and their unborn children. Based on the literature, we strongly suggest that consistent surveillance for the mothers and infants from COVID-19 pregnancies be prioritised in the future. Though the pandemic is now in the past, its effects are long-term, necessitating the monitoring of clinical manifestations in the near future.

Aminopeptidase A (ENPEP) gene polymorphisms and preeclampsia: Descriptive analysis.

OBJECTIVE: The etiology of preeclampsia (PE) remains elusive. Recent genome-wide association studies have identified a number of genetic variants associated with blood pressure variations in east Asians. One of the genetic variants is the aminopeptidase A (ENPEP) gene, which converts angiotensin II to angiotensin III. The C allele of rs6825911 is a risk for hypertension. The current study investigated whether genetic variants of ENPEP play a role in the pathogenesis of preeclampsia. STUDY DESIGN: The study was a descriptive analysis of gene polymorphisms of ENPEP; 602 pregnant women of African ancestry [normotensive (n = 245) and PE (n = 357)] were recruited. The two groups were divided according to their HIV status. The PE group consisted of early- and late-onset sub-categories. A single nucleotide polymorphism of rs6825911 was analyzed using the TaqMan® Probe mix and by means of real time polymerase chain reaction. RESULTS: The risk of C allele for PE was 1.07 (95 % CI 0.83-1.38, P = 0.589) for allele comparison and the risk for preeclampsia CC to CT/TT was 1.33 (95 % CI 0.96-1.85, P = 0.086). The sub analysis for the PE group without HIV infection the risk of C allele was 1.25 (95 % CI 0.838-1.78, P = 0.199) and the risk of PE of CC to CT/TT was 1.51 (95 %CI: 0.96-2.35, P = 0.071). CONCLUSION: This is the first study in a homogenous South African population of African ancestry to show that the variant of ENPEP gene does not play a role in pathogenesis of preeclampsia.

Association of gene polymorphisms of four components of renin-angiotensin-aldosterone system and preeclampsia in South African black women.

OBJECTIVE: To investigate the association of the gene polymorphisms of: angiotensinogen (AGT), renin (REN), angiotensin II receptor 1 (AT1R) and angiotensin II receptor 2 (AT2R), in the pathogenesis of PE in South African Black women. METHODOLOGY (STUDY DESIGN): 603 pregnant women; 246 normotensive and 357 with PE (early-onset=187, late-onset=170), were recruited. Each study group was subdivided into HIV infected and uninfected groups. The distribution and frequencies of gene polymorphisms of AGT (M235T), REN (C-5312T), AT1R (A1166C) and AT2R (C3123A) were determined in purified DNA by Real Time Polymerase Chain Reaction. RESULTS: The distribution of T allele and TT genotype of AGT in PE were significantly higher than the normotensive group (95% vs 91%, OR 1.9, 95%CI 1.2-3.1, p=0.0051; 90% vs 83%, OR 1.84, 95%CI 1.11-3.05, p=0.01) respectively. The distributions of genotypes of REN, AT1R and AT2R were similar in PE and normotensive groups. CONCLUSION: The T allele of AGT may play a role in the pathogenesis of PE. The genotypes of REN, AT1R and AT2R were not associated with the development of PE.

The impact of a modified World Health Organization surgical safety checklist on maternal outcomes in a South African setting: A stratified cluster-randomised controlled trial.

BACKGROUND: In South Africa (SA), the Saving Mothers Reports have shown an alarming increase in deaths during or after caesarean delivery. OBJECTIVE: To improve maternal surgical safety in KwaZulu-Natal Province, SA, by implementing the modified World Health Organization surgical safety checklist for maternity care (MSSCL) in maternity operating theatres. METHODS: The study was a stratified cluster-randomised controlled trial conducted from March to November 2013. Study sites were 18 hospitals offering maternal surgical services in the public health sector. Patients requiring maternal surgical intervention at the study sites were included. Pre-intervention surgical outcomes were assessed. Training of healthcare personnel took place over 1 month, after which the MSSCL was implemented. Post-intervention surgical outcomes were assessed and compared with the pre-intervention findings and the control arm. The main outcome measure was the mean incidence rate ratios (IRRs) of adverse incidents associated with surgery. RESULTS: Significant improvements in the adverse incident rate per 1 000 procedures occurred with combined outcomes (IRR 0.805, 95% confidence interval (CI) 0.706 - 0.917), postoperative sepsis (IRR 0.619, 95% CI 0.451 - 0.849), referral to higher levels of care (IRR 1.409, 95% CI 1.066 - 1.862) and unscheduled return to the operating theatre (IRR 0.719, 95% CI 0.574 - 0.899) in the intervention arm. Subgroup analysis based on the quality of implementation demonstrated greater reductions in maternal mortality in hospitals that were good implementers of the MSSCL. CONCLUSIONS: Incorporation of the MSSCL into routine surgical practice has now been recommended for all public sector hospitals in SA, and emphasis should be placed on improving the quality of implementation.

Pre-eclampsia: its pathogenesis and pathophysiolgy.

Pre-eclampsia is a pregnancy-specific disorder that has a worldwide prevalence of 5-8%. It is one of the main causes of maternal and perinatal morbidity and mortality globally and accounts for 50 000-60 00 deaths annually, with a predominance in the low- and middle-income countries. It is a multi-systemic disorder however its aetiology, pathogenesis and pathophysiology are poorly understood. Recently it has been postulated that it is a two-stage disease with an imbalance between angiogenic and anti-antigenic factors. This review covers the latest thoughts on the pathogenesis and pathology of pre-eclampsia. The central hypothesis is that pre-eclampsia results from defective spiral artery remodelling, leading to cellular ischaemia in the placenta, which in turn results in an imbalance between anti-angiogenic and pro-angiogenic factors. This imbalance in favour of anti-angiogenic factors leads to widespread endothelial dysfunction, affecting all the maternal organ systems. In addition, there is foetal growth restriction (FGR). The exact aetiology remains elusive.

Soluble fms-like tyrosine kinase-1 in HIV infected pre-eclamptic South African Black women.

INTRODUCTION: Hypertensive disorders of pregnancy are the commonest direct cause of maternal deaths in South Africa, 83% being attributed to pre-eclampsia. Elevated placental sFlt-1 levels are linked with angiogenic disruption and subsequent pre-eclampsia development. The impact of HIV infection on pre-eclampsia is controversial. Its effect on angiogenic imbalance in both normotensive and pre-eclamptic pregnancies remains unknown. METHODS: We examined the immunolocalisation of both membrane bound and soluble forms of Flt-1, within placentae of HIV negative and positive normotensive and pre-eclamptic pregnancies at term using immunohistochemistry and immuno-electron microscopy. RESULTS: Strong Flt-1 and sFlt-1 immunoreactivity was observed within endothelial, syncytio and cytotrophoblast cells. Subcellularly, gold particles were localised predominantly within the endoplasmic reticulum and mitochondria and occurring free within the cytoplasm. There was no significant effect of HIV on Flt-1 and sFlt-1 immunoexpression in both exchange and stem villi. A significant effect of type of pregnancy (normotensive vs pre-eclamptic) on Flt-1 and sFlt-1 immunoexpression (p = 0.003) within exchange rather than stem villi, indicated that the pre-eclamptic had elevated Flt-1 and sFlt-1 expressions compared to the normotensive pregnant women. There was no interaction between HIV and pregnancy type (normotensive vs pre-eclampsia) for Flt-1 and sFlt-1 expressions in both exchange and stem villi. A weak correlation of Flt-1 and sFlt-1 intensity between the exchange and stem villi was noted. DISCUSSION: Elevated immunoexpression of Flt-1 and sFlt-1 within trophoblasts suggests an autocrine mode of action on trophoblast invasion and differentiation thereby contributing to abnormal placentation with consequential endothelial dysfunction in pre-eclampsia. CONCLUSION: Irrespective of the HIV status, placental Flt-1 and sFlt-1 expressions remain elevated in pre-eclampsia compared to normotensive pregnancies.

Tuberculosis in medical doctors - a study of personal experiences and attitudes.

BACKGROUND: The concurrent TB and HIV epidemics in sub-Saharan Africa place all health care workers (HCWs) at increased risk of exposure to Mycobacterium tuberculosis. AIM: This study explores personal experiences, attitudes and perceptions of medical doctors following treatment for TB within the healthcare system. METHOD: Sixty-two medical doctors who were diagnosed and treated for TB during 2007 - 2009 agreed to participate and complete a semi-structured questionnaire. RESULTS: The response rate was 64.5% (N=40). Mean age ±SD of participants was 33.7±10.6 years. A correct diagnosis of TB was made within 7 days of clinical presentation in 20% of participants, and was delayed beyond 3 weeks in 52.5%. Non-routine special investigations and procedures were performed in 26 participants. Complications following invasive procedures were reported by 8 participants. Multi-drug resistant TB (MDR-TB) was diagnosed in 4 participants. Nineteen considered defaulting on their treatment because of drug side-effects. The majority (n=36) expressed concerns regarding lack of infection control at the workplace, delays in TB diagnosis and negative attitudes of senior medical colleagues and administrators. Ninety per cent of participants indicated that their personal illness experiences had positively changed their professional approach to patients in their current practice. CONCLUSION: The inappropriate delays in diagnosis in a large number of participants, coupled with a number of negative personal perceptions towards their treatment, are cause for concern. The results further amplify the need for improved educational and awareness programmes among all healthcare personnel (including hospital administrators), adherence to national health guidelines, effective infection control measures, pre- and post-employment screening in all HCWs, and changes in attitudes on the part of senior medical colleagues and administrators.

The effect of Kraussianone-2 (Kr2), a natural pyrano-isoflavone from Eriosema kraussianum, in an L-NAME- induced pre-eclamptic rat model.

This study aimed to investigate the effects of Kraussianone-2 (Kr2), a pyrano-isoflavone isolated from the roots of Eriosema kraussianum N. E. Br. (Fabaceae) on various fetal and physiological parameters in pregnant, L-NAME treated Sprague-Dawley rats. Twenty-four pregnant Sprague-Dawley dams were divided into three groups (n = 8), i.e. the control group (CON), the experimental control group (PRE), where the pre-eclampsia-like symptoms were induced using L-NAME, and the experimental group (EK2), where the pre-eclampsia-like symptoms were once again induced using L-NAME, however, these animals were treated with Kr2. On gestation day 20 the animals were sacrificed, at which time a laparotomy was performed and the number of live pups were counted and their corresponding birth and placental weights were recorded. Blood was also collected in heparin-coated tubes and the plasma samples were then analysed for specific variables using commercially available kits for rats. Kraussianone-2 administration decreased fetal mortality and demonstrated a trend toward increasing birth and placental weights in this model. Furthermore, Kr2 administration also reduced blood pressure amplification and decreased the plasma concentrations of two antiangiogenic factors, soluble fms-like tyrosine kinase1 (sFlt-1) and soluble endoglin (sEng). We speculate that Kr2, by improving uterine artery blood flow, results in improved fetal outcomes and decreased antiangiogenic factors in pregnant, L-NAME treated, Sprague-Dawley rats.

Sildenafil citrate decreases sFlt-1 and sEng in pregnant l-NAME treated Sprague-Dawley rats.

OBJECTIVES: We have previously shown that sildenafil citrate improves various fetal outcomes in pregnant, L-NAME treated, Sprague-Dawley rats. We therefore aimed to identify which component/s of this diverse pathophysiologic cascade is/are improved by this drug. STUDY DESIGN: This study is a sub-analysis of plasma samples obtained in a previous study in which 24 pregnant Sprague-Dawley dams were divided into three groups (n=8) i.e. the control group (CON), the experimental control group (PRE) where the pre-eclampsia-like symptoms were induced using l-NAME, and the experimental group (SCT) where the pre-eclampsia-like symptoms were once again induced using L-NAME but these animals were treated with sildenafil citrate. On gestation day 20 blood samples were collected in heparin-coated tubes and plasma samples were then analysed for specific variables using commercially available kits for rats. RESULTS: There was a significant increase in the plasma levels of soluble fms-like tyrosine kinase1 (sFlt-1) in the PRE group (1228.80±116.29 pg/ml) when compared to the CON (774.91±26.81 pg/ml) and SCT (698.98±20.78 pg/ml) groups, respectively (p<0.001). The plasma levels of soluble endoglin (sEng) were significantly decreased in the SCT group (149.47±3.72 ng/ml) when compared to the CON (178.52±5.33 ng/ml) and PRE (183.44±8.294 ng/ml) groups, respectively (p<0.01). Plasma nitric oxide and l-arginine levels showed a decreasing trend in the PRE groups when compared to the control (CON) and treated (SCT) groups, respectively. CONCLUSION: Sildenafil citrate reduces the plasma levels of anti-angiogenic factors, sFlt-1 and sEng, in pre-eclamptic (L-NAME induced) Sprague-Dawley rats and may therefore be responsible for the reduction in blood pressure and proteinuria as well as the improved fetal outcomes noted in an earlier study.

Sildenafil citrate improves fetal outcomes in pregnant, L-NAME treated, Sprague-Dawley rats.

OBJECTIVES: This study aimed to investigate the effects of sildenafil citrate on various fetal and physiological parameters, including fetal mortality, number of pups, placental weights and micro-albuminuria in pregnant, L-NAME treated Sprague-Dawley rats. STUDY DESIGN: Twenty-four pregnant female Sprague-Dawley rats were divided into 3 groups (n=8). In the L-NAME treated group (PRE), l-NAME (0.3 g/l, drinking water) was used to induce pre-eclampsia-like symptoms on day 1 of the experiment. The experimental group (SCT) also received L-NAME (0.3 g/l, drinking water) on day 1 of the experiment. However, sildenafil citrate (10 mg/kg, s.c., daily) was administered as the test compound from day 7 until day 19. The experimental control (CON) did not receive either L-NAME or sildenafil citrate. L-NAME administration was discontinued in both the PRE and the SCT groups on day 19 of the experiment and the animals were given access to normal drinking water ad libitum. All the animals were sacrificed on day 20, at which time a laparotomy was performed and the various fetal parameters measured. On day 0 and day 20, blood pressure measurements were recorded non-invasively and protein estimations in 24h urine samples were conducted. RESULTS: Sildenafil citrate decreased fetal mortality and protein excretion and further demonstrated a trend toward increasing birth and placental weights in pregnant, L-NAME treated, Sprague-Dawley rats. In addition, sildenafil citrate administration ameliorated the amplification of the L-NAME induced hypertension in the SCT group. CONCLUSION: We speculate that sildenafil citrate by potentiating the effects of nitric oxide in vivo improves uterine artery blood flow resulting in improved fetal outcomes in pregnant, L-NAME treated, Sprague-Dawley rats.

The in vivo effects of Tulbhagia violacea on blood pressure in a salt-sensitive rat model.

AIM OF THE STUDY: The in vivo effects of Tulbhagia violacea on systemic arterial blood pressure and on the renin-angiotensin system in a Dahl salt-sensitive rat model were investigated. MATERIALS AND METHODS: Animals were treated for 14 days intraperitoneally as follows: Tulbhagia violacea (Tvl) (50mg/kg b.w.), captopril (Cap) (10mg/kg b.w.) or DMSO (Con). Baseline blood pressures were recorded prior to the commencement of the study and biweekly during the experimental period. Urine volume and sodium concentration were measured during the experimental period. On day 15, animals were anaesthetized (sodium thiopentane, 50mg/kg, i.p.), blood samples for aldosterone levels were taken and the kidneys removed for determining AT1a mRNA expression. RESULTS: Cap and Tvl groups showed significantly reduced AT1a mRNA expressions by 3.11- and 5.03-fold, respectively, when compared to the Con group (p<0.05). When compared to baseline blood pressures (day 0); Cap and Tvl showed reductions in systolic blood pressure (SBP) of 7.76+/-0.41% and 9.12+/-0.31%, respectively (mean% decrease from day 0 to day 14). In contrast, in the Con group the systolic blood pressure increased from day 0 to day 14 by 4.66+/-0.56%. Blood pressure changes in all treated groups differed from Con significantly. Systolic blood pressure decreased with the decrease in AT1a mRNA expressions in these groups. When comparing day 0 to day 14, urine output increased in the Cap and Tvl groups. In the Con group, urinary volume was reduced by day 14 as compared to day 0. Urinary sodium excretion was increased in the treated groups by day 14. CONCLUSION: It can be concluded that Tulbhagia violacea reduces systemic arterial blood pressure in the Dahl rat by decreasing renal AT1 receptor gene expression and hence modulating sodium and water homeostasis.

Immunolocalisation and endothelin-1 values In pre-eclampsia: an immunocytochemical study.

Maternal plasma ET-1 levels and the immunolocalisation of ET1 in the fetal membranes of pre-eclamptic primigravidae at >/=28 weeks, gestation were studied. The levels of maternal plasma ET1 and immunoreactive ET-1 were increased in pre-eclampsia. Immunoreactive ET-1 was localised in the amnion, chorion and decidua of normal pregnant women as well as those with preeclampsia-eclampsia. Intense labelling was observed in moderate pre-eclampsia (BP 140/90 - 170/110 mmHg) with very intense labelling in severe pre-eclampsia (BP >170/110 mmHg), especially in the amniotic epithelium, chorionic villi, maternal blood vessels, cytotrophoblasts and giant cells of the decidua. The increased ET-1 levels demonstrated in fetal membranes of pre-eclamptic women are probably produced in a paracrine and/or autocrine manner, contributing to the hypertension, vasospasm and fetal growth restriction characteristic of the syndrome. A larger study would be required to show significant change in endothelin production in pre-eclampsia.

Endothelin-1 and endothelin receptor status in kidney transplants undergoing acute rejection.

Endothelin-1 (ET-1) is a potent vasoconstrictor with vasopressor and mitogenic effects. Blood samples were collected from 21 renal transplant patients undergoing acute rejection at the time of diagnostic kidney biopsy: there were 20 men and one woman, mean age 35.6 years. All patients were on triple immunosuppressive therapy with cyclosporine A, azathioprine and methylprednisolone. Twenty living kidney donors pre-uninephrectomy (11 men and nine women, mean age 34 years) served as controls. Control kidney was obtained from fresh autopsy material and normal kidney tissue from nephrectomies for malignancy. Mean plasma ET-1 was significantly increased at 1.56 +/- 0.2 pg ml(-1) during acute rejection compared to 0.74 +/- 0.06 pg ml(-1) in donors (p = 0.0009 unpaired t-test). ET(A) receptor immunolabelling was visualised in distal tubules and collecting ducts with minimal labelling in the glomeruli and blood vessels of control kidney tissue ET(A) receptor labelling was similar in kidney biopsies with acute rejection. ET(B) receptor immunolabelling was significantly increased in glomeruli (p = 0.002) and decreased in distal tubules (p = 0.004) in kidneys with acute rejection compared to control kidney tissue. While these findings may account for the oedema and hypertension observed during acute rejection, the exact significance needs to be studied further.

Zinc status in vitamin B6 deficiency.

Three groups of young male Wistar rats were maintained on diets consisting of 7 mg pyridoxine hydrochloride/kg diet (control and pair-fed groups) and 0 mg pyridoxine hydrochloride/ kg diet (deficient group) for six weeks. The zinc status of all rats was assessed by measuring their erythrocyte zinc-metallothionein-1 (Zn-Mt-1) and plasma zinc levels. A significant difference (p < 0.001) in plasma zinc levels was observed between the deficient group and the control and pair-fed groups (1.35 micrograms/ml +/- 0.08, 1.99 micrograms/ml +/- 0.06 and 2.03 micrograms/ml +/- 0.07 respectively). Erythrocyte Zn-Mt-1 levels were significantly lower in vitamin B6 deficient rats when compared to control animals. No significant difference in Zn-Mt-1 levels existed between vitamin B6 deficient and pair-fed groups suggesting that the reduced Zn-Mt-1 levels in vitamin B6 deficient rats may be due entirely to their decreased food intake (8.9 g/day compared to 15 g/day of control rats).

11 beta-Hydroxysteroid dehydrogenase activity in mesenteric arteries of spontaneously hypertensive rats.

1. 11 beta-Hydroxysteroid dehydrogenase (11-HSD) activity in mesenteric arteries of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats was determined and expressed as the percentage conversion of [3H]-corticosterone to [3H]-11-dehydrocorticosterone. 2. 11-HSD activity was significantly decreased in mesenteric arteries of both 4 and 9 week old SHR (8.4 +/- 0.8%, 5.0 +/- 1.5%, respectively) compared with WKY rats (12.4 +/- 0.6%, 15.8 +/- 0.7%, respectively; P < 0.05). 3. Total RNA from rat vascular smooth muscle cells (VSMC) and endothelial cells (EC) were prepared with selective precipitation in 3 mol/L LiCl/6 mol/L urea. The expression of 11-HSD mRNA was confirmed in the rat VSMC but its mRNA expression was not detected in EC, using northern blot analysis. 4. The results in this study indicate that 11-HSD in the vascular wall may play a role in the pathogenesis of hypertension in SHR.

Changes in lipopolysaccharide concentrations in hepatic portal and systemic arterial plasma during intestinal ischemia in monkeys.

The time course of changes in the level of plasma lipopolysaccharides (LPS) in both the hepatic portal and the systemic arterial circulations, together with changes in cardiovascular parameters, was ascertained during a 1 hr occlusion of the superior mesenteric artery (SMA) in six primates. The LPS concentrations before occlusion of the SMA in the hepatic portal and systemic arterial circulation were 0.051 +/- 0.009 and 0.065 +/- 0.011 ng/ml, respectively (NS). At the end of the occlusion period, there was no significant increase in either the hepatic portal or systemic arterial plasma LPS concentrations. Immediately on removal of the occlusion, however, the LPS concentration in the portal plasma increased and peaked at 0.431 +/- 0.124 ng/ml (P less than 0.01) within 17.5 +/- 1.71 min, whereas in the systemic arterial circulation the LPS concentration began to rise but only after a delay of approximately 10 min to peak at 0.287 +/- 0.126 ng/ml (P less than 0.05) within 32.5 +/- 4.23 min of reperfusion. The mean arterial pressure (MAP) declined during the reperfusion period from 98.6 +/- 6.89 to 65.0 +/- 9.5 mm Hg (P less than 0.05). The heart rate showed a small but not significant increase (P greater than 0.2) after about 80 min of reperfusion. These data indicate that the gut is the source of the increased plasma LPS concentration following occlusion of the SMA.

Oral administered nonabsorbable antibiotics prevent endotoxemia in primates following intestinal ischemia.

Plasma lipopolysaccharide (LPS) concentrations have been found to increase during a temporary occlusion of the superior mesenteric artery (SMA). We have attempted to show, by a prophylactic oral administration of a nonabsorbable antibiotic to monkeys subjected to an SMA occlusion shock, that the increased LPS is intestinal in origin. A total of eight monkeys were subjected to a temporary occlusion of the SMA. Four monkeys received prophylactic oral administration of a nonabsorbable antibiotic, while the rest acted as controls. The plasma LPS concentrations before occlusion in the control and the kanamycin group were 0.069 +/- 0.006 and 0.092 +/- 0.005 ng/ml, respectively. At the end of the 1-hr occlusion period the plasma LPS concentration in the controls increased to 0.09 +/- 0.009 ng/ml (P less than 0.1) and peaked to 0.378 +/- 0.103 ng/ml (P less than .001) within 20 min of reperfusion. Thereafter, the plasma LPS concentration returned slowly to baseline. In the kanamycin group the plasma LPS concentration remained at baseline throughout both the occlusion and reperfusion periods. These data suggest that the origin of the increased plasma LPS concentration seen following temporary occlusion of the SMA is from the gut, and is information of possible importance in patients about to undergo intestinal surgery.

Portal and systemic plasma lipopolysaccharide concentrations in heat-stressed primates.

Lipopolysaccharide (LPS) concentrations in hepatic portal and systemic arterial plasma were determined in five anesthetised monkeys heat-stressed by an environmental temperature of 41.0 +/- 0.3 degrees C and 100% relative humidity. As the rectal temperature (Tr) rose, the LPS concentrations in both the portal and systemic arterial plasma remained at the pre-heat-stress levels of 0.088 +/- 0.017 and 0.078 +/- 0.021 ng/ml (N.S.), respectively, until a Tr of 42.5-43.0 degrees C, when the LPS concentration increased slowly, first in the portal plasma and then in the systemic plasma. On the other hand, the concentration of plasma anti-LPS IgG antibodies began to decline at temperatures as low as 40 degrees C from 20.66 +/- 7.35 micrograms/ml (portal) and 22.14 +/- 7.43 micrograms/ml (arterial) to 5.51 +/- 1.28 micrograms/ml (portal) (P less than .05) and 4.6 +/- 1.69 micrograms/ml (arterial) (P less than .05) just prior to death. Above a Tr of 43 degrees C, the LPS concentration increased rapidly to a maximum of 0.244 +/- 0.05 ng/ml (portal) (P less than .01) and 0.224 +/- 0.06 ng/ml (arterial) (P less than .01). The mean arterial pressure remained more or less constant at 112 +/- 17.03 mm Hg until a Tr of 41.5 degrees C and then rapidly declined as Tr rose (P less than .01). The heart rate rose gradually from 154 +/- 14 min-1 as Tr increased and then rapidly after a Tr of 41.5 degrees C to a maximum of 307 +/- 13 min-1 at 43.0 degrees C. Thereafter it declined rapidly until death.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma endotoxin concentration in healthy primates and during E. coli-induced shock.

The normal range for circulating plasma endotoxin concentration was determined in 62 healthy primates (vervet monkeys, Cerecopithecus aethiops) by the chromogenic substrate modification of the Limulus amoebocyte lysate test, and found to have a mean of 0.076 +/- 0.004 ng/ml (range 0.000 to 0.0127). Four anesthetized primates received an LD100 iv infusion of Escherichia coli over one hour. Plasma concentrations of endotoxin (lipopolysaccharide, LPS) and anti-LPS IgG, and viable E. coli colonies in circulating whole blood samples were determined at specified intervals. Plasma antiendotoxin IgG concentration was determined by an enzyme-linked immuno-absorbent assay, and viable bacterial counts were assayed by standard plate count techniques. LPS concentration increased during E. coli infusion to a mean of 1.13 +/- 0.068 ng/ml (p less than .001) with a concomitant decrease in the concentration of anti-LPS IgG to 59 +/- 5% of control values (p less than .005). Viable circulating E. coli colonies increased during the infusion to a maximum of 425 X 10(6) cfu/ml 10 min after the completion of the infusion, but fell precipitously 20 min later to 10.1 X 10(6) cfu/ml. When each animal succumbed, their respective plasma LPS concentrations were still raised, whereas no viable circulating E. coli colonies were present at a dilution of 10(2). Elevated plasma LPS could prove to be a significant circulating pathogen during Gram-negative bacterial shock and supports the possible association between plasma LPS and morbidity, and mortality in septic shock.