Carotid artery elasticity decreases during pregnancy - the Cardiovascular Risk in Young Finns study.

BACKGROUND: The aims were to evaluate the effect of pregnancy on carotid artery elasticity and determine the associations between maternal lipids, endothelial function and arterial elasticity during pregnancy. METHODS: We examined 99 pregnant and 99 matched non-pregnant control women as part of a population-based prospective cohort study. Carotid artery elasticity indexes; carotid artery distensibility (CAD), Young's elastic modulus (YEM) and stiffness index (SI) as well as brachial artery flow-mediated dilation (FMD) were assessed using ultrasound; serum lipid levels were also determined. RESULTS: SI was 57% and YEM 75% higher and CAD 36% lower in the third trimester group than the corresponding values in the first trimester group. Serum cholesterol and triglyceride levels were significantly higher in women at the end of the pregnancy than at the beginning of pregnancy (P < 0.001) and in controls (P < 0.001). In multivariate analysis, gestational age was the only independent correlate of arterial elasticity in pregnant women. In controls, age (P ≤ 0.001) and common carotid diameter (P = 0.001-0.029) were associated with SI, YEM and CAD. CONCLUSIONS: The present study revealed that carotid artery elasticity declined towards the end of the pregnancy; this neither is straight correlating with maternal hyperlipidemia or the diameter of the carotid artery nor is it associated with changes in endothelial function.

Ambulatory arterial stiffness index and nocturnal blood pressure dipping in pregnancies complicated by hypertension.

BACKGROUND: The study sets out to examine differences in arterial stiffness and nocturnal blood pressure dipping as outcomes in women with gestational hypertension compared with healthy pregnant women during pregnancy and 3 months after delivery. METHODS AND RESULTS: We prospectively studied a cohort of 60 women during the third trimester of pregnancy; of them, 28 suffered pregnancy-induced hypertension or pre-eclampsia and 32 had uncomplicated singleton pregnancies. Subsequently, 42 of these were re-examined 3 months after delivery. In women with a hypertensive disorder, the nocturnal fall in blood pressure (dipping) was significantly smaller than in the normotensive group (systolic, P = 0·031; diastolic, P<0·001), but after pregnancy, this difference disappeared (systolic, P = 0·941; diastolic, P = 0·907). Ambulatory arterial stiffness index (AASI) assessed after pregnancy correlated inversely with fasting glucose level during pregnancy (r = -0·580, P = 0·018), both systolic (r = -0·651, P = 0·012) and diastolic (r = -0·687, P = 0·007) nocturnal dipping and total cholesterol concentration after pregnancy (r = -0·526, P = 0·036). CONCLUSIONS: A hypertensive disorder during pregnancy was associated with a flattened circadian blood pressure response, which was restored after delivery. Higher arterial stiffness predicted the signs of postpartum metabolic syndrome and correlated also with non-dipping, especially postpartum.

Need for insulin to control gestational diabetes is reflected in the ambulatory arterial stiffness index.

BACKGROUND: The aim was to evaluate the metabolic profile in conjunction with vascular function using the ambulatory arterial stiffness index (AASI) in women with uncomplicated pregnancies and in women with gestational diabetes mellitus (GDM). METHODS: Plasma glucose, lipids, HOMA -IR (homeostasis model assessment of insulin resistance) and AASI, as obtained from 24-hour ambulatory blood pressure monitoring in third trimester pregnancy and at three months postpartum, were measured in three groups of women: controls (N=32), women with GDM on diet (N=42) and women with GDM requiring insulin treatment (N=10). RESULTS: Women with GDM had poorer glycemic control and higher HOMA-IR during and after pregnancy and their total and LDL (low density lipoprotein) cholesterol levels were significantly higher after pregnancy than in the controls. After delivery, there was an improvement in AASI from 0.26±0.10 to 0.17±0.09 (P=0.002) in women with GDM on diet, but not in women with GDM receiving insulin whose AASI tended to worsen after delivery from 0.30±0.23 to 0.33±0.09 (NS), then being significantly higher than in the other groups (P=0.001-0.047). CONCLUSIONS: Women with GDM had more unfavorable lipid profile and higher blood glucose values at three months after delivery, the metabolic profile being worst in women requiring insulin. Interestingly, the metabolic disturbances at three months postpartum were accompanied by a tendency towards arterial stiffness to increase in women requiring insulin.

Flow-mediated vasodilation is not attenuated in hypertensive pregnancies despite biochemical signs of inflammation.

Background. Our objective was to evaluate endothelial function and markers of inflammation during and after pregnancy in normal pregnancies compared to pregnancies complicated with hypertension or preeclampsia (PE). Methods and Results. We measured endothelium-dependent brachial artery flow-mediated vasodilation (FMD) and high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α) in 32 women with normal pregnancy and in 28 women whose pregnancy was complicated with hypertensive disorder in the second half of pregnancy and minimum 3-month postpartum. Enhancement of endothelial function was greater in hypertensive than normal pregnancies, the mean FMD% being 11.0% versus 8.8% during pregnancy (P = 0.194) and 8.0% versus 7.9% postpartum (P = 0.978). Concentrations of markers of inflammation were markedly increased in pregnant hypertensive group compared to those after delivery (hsCRP 4.5 versus 0.80 mg/L, P = 0.023, IL-6 2.1 versus 1.2 pg/mL, P = 0.006; TNF-α 1.9 versus 1.5 pg/mL, P = 0.030). There were no statistically significant associations between the markers of inflammation and FMD. Conclusions. Brachial artery FMD was not attenuated in the third trimester hypertensive pregnancies compared to normal pregnancies, whereas circulating concentrations of hsCRP and IL-6 and TNF-α reacted to hypertensive complications.

Ambulatory arterial stiffness index is unchanged in uncomplicated third-trimester singleton and twin pregnancies.

OBJECTIVE: To document the ambulatory arterial stiffness index (AASI) during pregnancy compared to three months after delivery in singleton and twin pregnancies. DESIGN: Descriptive study with a follow-up design. SETTING: University hospital in Eastern Finland. POPULATION: 43 childbearing women; 32 with singleton and 11 with twin pregnancies. METHODS: Ambulatory blood pressure measurements were conducted using a digital ambulatory blood pressure system. AASI was calculated as 1 minus the regression slope of diastolic on systolic blood pressures obtained from 24-hour monitoring. MAIN OUTCOME MEASURES: Arterial stiffness measured by AASI. RESULTS: In normotensive pregnant women, the 95th percentiles of AASI were 0.40 in singleton and 0.46 in twin pregnancies, respectively, implying arterial normality and high elasticity. There were no differences in AASI values between singleton and twin pregnancies and no changes were observed postpartum. After delivery, but not during pregnancy, AASI correlated negatively with nocturnal systolic and diastolic blood pressure reduction (dipping) (r=-0.536, p=0.001; r=-0.674, p<0.001) and with maternal HDL (r=-0.363, p=0.038) and positively with maternal age (r=0.440, p=0.009), whereas maternal BMI had a significant impact on AASI both during and after pregnancy (r=0.366, p=0.016; r=0.377, p=0.028). CONCLUSIONS: Normal singleton or twin pregnancies had no detectable effects on AASI. However, pregnancy appeared to overcome the negative effects of low high-density lipoproteins, unfavorable dipping status and advanced maternal age on arterial stiffness, but not the effect caused by maternal body mass index.

Cardiovascular autonomic responses to head-up tilt in gestational hypertension and normal pregnancy.

AIMS: The aim of the present study was to evaluate the influence of gestational hypertension on hemodynamics and cardiovascular autonomic regulation at rest and their responses to head-up tilt (HUT). We prospectively studied 56 pregnant women (28 with gestational hypertension and 28 healthy pregnant women) during the third trimester of pregnancy and 3 months after pregnancy. MAJOR FINDINGS: In women with pregnancy-induced hypertension, compared with control women, there were significant differences in hemodynamics and in markers of cardiovascular regulation (p < 0.05 to p < 0.001). Postural change from the supine to the upright position was associated with significant changes in hemodynamic responses in both groups during pregnancy (from p < 0.05 to p < 0.001). Regulatory response to HUT in both groups was characterized with a decrease in HF power and increase in LF/HF ratio (from p < 0.01 to p < 0.001). Responses to HUT in total power and VLF power were attenuated in hypertensive pregnancies (p < 0.001 to p < 0.01, respectively, vs control group). CONCLUSIONS: Our results suggest that autonomic cardiovascular regulation may not play a major role in women with gestational hypertension . The lack of irreversible changes in autonomic nervous function in hypertensive women appeared to be a feature of gestational-induced hypertension.

Early initiation of enzyme replacement therapy improves metabolic correction in the brain tissue of aspartylglycosaminuria mice.

Aspartylglycosaminuria (AGU) is a lysosomal storage disease caused by deficient activity of glycosylasparaginase (AGA), and characterized by motor and mental retardation. Enzyme replacement therapy (ERT) in adult AGU mice with AGA removes the accumulating substance aspartylglucosamine from and reverses pathology in many somatic tissues, but has only limited efficacy in the brain tissue of the animals. In the current work, ERT of AGU mice was initiated at the age of 1 week with three different dosage schedules of recombinant glycosylasparaginase. The animals received either 3.4 U of AGA/kg every second day for 2 weeks (Group 1), 1.7 U/kg every second day for 9 days followed by an enzyme injection once a week for 4 weeks (Group 2) or 17 U/kg at the age of 7 and 9 days (Group 3). In the Group 1 and Group 3 mice, ERT reduced the amount of aspartylglucosamine by 34 and 41% in the brain tissue, respectively. No therapeutic effect was observed in the brain tissue of Group 2 mice. As in the case of adult AGU mice, the AGA therapy was much more effective in the somatic tissues than in the brain tissue of the newborn AGU mice. The combined evidence demonstrates that a high dose ERT with AGA in newborn AGU mice is up to twofold more effective in reducing the amount of the accumulated storage material from the brain tissue than ERT in adult AGU animals, indicating the importance of early detection and treatment of the disease.

Women with hypertensive pregnancies have difficulties in regaining pre-pregnancy weight and show metabolic disturbances.

The aim was to determine maternal weight gain and body composition during pregnancy and 3 months postpartum in women with uncomplicated singleton and twin pregnancies and in women with gestational diabetes (GDM) and gestational hypertension (GH). This prospective study includes four groups of subjects: those with an uncomplicated pregnancy (n = 32), those with a diagnosis of GH (n = 28), those with a diagnosis of GDM (n = 52), and those with twin pregnancy (n = 11). Their body compositions were estimated by a bioimpedance analysis and fasting lipids and glucose levels were determined during the pregnancy and 3 months after pregnancy. Women with GDM were 11.7 kg heavier than the reference group before pregnancy, whereas weight before pregnancy was not different in other investigated groups. Weight loss after delivery was attenuated in GH group. Percentage body fat remained elevated in women with GDM (34.1 +/- 7.0%) and hypertension (31.5 +/- 6.4%) at 3 months after pregnancy. Also their total cholesterol and low-density lipoprotein (LDL)-cholesterol levels as well as fasting glucose remained elevated in comparison to values of the reference group. In conclusion, women with hypertensive pregnancies, though not overweight before pregnancy, gain and retain excess gestational weight and this leads to metabolic abnormalities similar to those seen in women GDM. Thus, postpartum period appears to be critical for weight management and interventional programs are called for.

Gestational diabetic patients with adequate management have normal cardiovascular autonomic regulation during the third trimester of pregnancy and 3 months after delivery.

OBJECTIVE: The aim of the present study was to evaluate the influence of gestational diabetes mellitus (GDM) on hemodynamics and cardiovascular autonomic regulation at rest and their responses to head-up tilt (HUT). RESEARCH DESIGN AND METHODS: We prospectively studied 79 pregnant women (51 with GDM, 28 without GDM) during the third trimester of pregnancy and after parturition. The maternal electrocardiogram and arterial blood pressure were noninvasively measured. Heart rate and blood pressure were measured in the supine position and in the upright position. Stroke volume was assessed from noninvasive blood pressure signals, heart rate variability (HRV) was analyzed in frequency domain, and baroreflex sensitivity by the cross-spectral and sequence methods. RESULTS: Between the GDM group and control pregnant women there were no significant differences in hemodynamics and cardiovascular autonomic regulation throughout the protocol. Increased normalized low-frequency component and low-frequency to high-frequency ratio suggested a change in sympathovagal balance towards sympathetic predominance during pregnancy in both groups. The response to head-up tilt (HUT) was similar in both GDM and control pregnant women. The pregnancy modulated the response to HUT in systolic and diastolic blood pressure, stroke volume, cardiac index, peripheral resistance, total power of HRV, and its low- and high-frequency components. CONCLUSIONS: Our results suggest that pregnancy modulates cardiovascular autonomic regulation and hemodynamics equally in subjects with GDM and without GDM, suggesting that metabolic disorder during pregnancy does not result in cardiovascular dysfunction when GDM is in good balance.

ADMA concentration changes across the menstrual cycle and during oral contraceptive use: the Cardiovascular Risk in Young Finns Study.

OBJECTIVE: The aim of this study was to evaluate changes in the nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) levels during different menstrual cycle phases in young adult women with or without oral contraceptive (OC) use. DESIGN AND METHODS: The subjects (n=1079) originated from a large population-based, prospective cohort study conducted in Finland. Plasma ADMA, symmetric dimethylarginine (SDMA), L-arginine, C-reactive protein, creatinine, and brachial artery flow-mediated dilatation (FMD) were measured. The use of OCs and menstrual cycle phase were determined from a questionnaire. RESULTS: In non-OC users, ADMA (P=0.017), L-arginine (P=0.002), and ADMA/SDMA ratio (P<0.001) were significantly lower in the luteal phase than in the follicular phase of the menstrual cycle. Non-OC users also had significantly higher ADMA and SDMA concentrations (P<0.001) and lower L-arginine concentrations (P<0.001) compared to OC users of estrogen-containing pills. Progestin-only contraceptive pills (POPs) did not lower the ADMA level, but maintained it at the same level as in non-OC users. In OC users, there were no significant differences found in ADMA, FMD, or FMD% across menstrual cycle, whereas brachial artery diameter was significantly more decreased in the luteal phase (P=0.013) than in the follicular phase. CONCLUSION: We observed that the circulating ADMA concentration varies across the menstrual cycle in young women not using OCs, and women on OCs displayed significantly lower circulating ADMA concentrations than non-OC users, though this was not the case with POP contraception.

Flow mediated vasodilation and circulating concentrations of high sensitive C-reactive protein, interleukin-6 and tumor necrosis factor-alpha in normal pregnancy--The Cardiovascular Risk in Young Finns Study.

BACKGROUND: Traditional risk factors such as hyperlipidemia induce a state of inflammation that impairs vascular function. Despite marked maternal hyperlipidemia, endothelial function improves during pregnancy. In non-pregnant state increased circulating levels of pro-inflammatory cytokines and high sensitive C-reactive protein (hsCRP) lead to attenuated flow mediated vasodilation. Relation between endothelial function and pro-inflammatory cytokines has not been studied thoroughly in pregnancy. The aim of this study was to evaluate the effect of pregnancy on hsCRP and pro-inflammatory cytokines and their associations with vascular endothelial function. METHODS: As part of population-based, prospective cohort Cardiovascular Risk in Young Finns study conducted in Finland we measured brachial artery flow mediated dilation (FMD) and serum concentrations of hsCRP, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in 57 pregnant Finnish women throughout gestation and 62 control women matched for age and smoking. RESULTS: HsCRP-concentration was greater in pregnancy compared to non-pregnant controls (median hsCRP 2.52 mg l(-1) versus 1.21 mg l(-1), P<0.001). IL-6-concentration was slightly increased in pregnancy compared with the non-pregnant controls (median 1.66 versus 1.32 mg l(-1), non-significant [NS]) and TNF-alpha-concentration was slightly decreased in pregnant group (2.11 versus 2.38 pg ml(-1), NS). FMD increased during pregnancy and IL-6 had a positive correlation to the FMD in pregnancy (R = 0.288, P = 0.031). CONCLUSIONS: Improvement of FMD in normal pregnancy was not affected by increase in hsCRP concentration. We found an association with IL-6 and FMD but we believe that improvement in endothelial function during normal pregnancy is not caused by variation in hsCRP, IL-6 or TNF-alpha.

Maternal serum ADMA is not associated with proinflammatory cytokines or C-reactive protein during normal pregnancy.

Normal pregnancy is associated with changes in the immune system. We studied whether asymmetrical dimethylarginine (ADMA) is associated with this immune system change by assaying high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). The cytokine and dimethylarginine serum concentrations were determined from women with normal pregnancy (n=77) and healthy non-pregnant controls (n=61) matched for age and smoking status as a part of a large population-based, prospective cohort study conducted in Finland. The hsCRP levels were significantly elevated in the second (P=0.016) and third trimesters (P=0.001) of pregnancy compared to the levels of non-pregnant women. IL-6 levels were significantly higher in the third trimester (P=0.029) of pregnancy than in non-pregnant state. TNF-alpha concentrations did not change significantly during pregnancy. ADMA and SDMA concentrations were significantly lower during pregnancy compared to the levels of non-pregnant women (P<0.001). There was no significant association between ADMA and inflammation markers regardless of the elevated serum concentrations of hsCRP and IL-6 in the third trimester of normal pregnancy. These results suggest that maternal systemic ADMA and SDMA concentrations are more likely to become decreased due to the hemodilution and increased renal clearance than being directly influenced by the change of cytokines during pregnancy.

Serum L-homoarginine concentration is elevated during normal pregnancy and is related to flow-mediated vasodilatation.

BACKGROUND: Normal pregnancy is associated with enhanced vasodilatation because of the increased nitric oxide (NO) production. Because L-homoarginine can act as a substrate for NO production, concentrations of L-homoarginine in normal pregnancy were assessed in the present study to test whether L-homoarginine is associated with endothelial function. METHODS AND RESULTS: Healthy non-pregnant (n=61) and pregnant women (n=58) were studied in a cross-sectional study. L-homoarginine, L-arginine, asymmetric dimethylarginine and symmetric dimethylarginine concentrations were determined simultaneously by high-performance liquid chromatography. Endothelium-dependent brachial artery flow-mediated dilation (FMD) was measured by ultrasound. The serum L-homoarginine concentration was significantly higher during the second and the third trimesters compared with the levels in the non-pregnant women (4.8+/-1.7 and 5.3+/-1.5 vs 2.7+/-1.0 micromol/L, p<0.001, respectively). In line with this, FMD increased in response to pregnancy (p<0.05). Three months after delivery, the L-homoarginine concentrations and FMD were comparable to those recorded in the non-pregnant females. The concentration of L-homoarginine correlated significantly with gestational age (r=0.426, p=0.001) and brachial artery diameter and FMD (r=0.362, p=0.006 and r=0.306, p=0.022, respectively) in pregnancy. CONCLUSIONS: L-homoarginine appears to be increased during the second and third trimesters of pregnancy and may contribute to the enhanced endothelial function in normal pregnancies.

Blood pressure and heart rate variability analysis of orthostatic challenge in normal human pregnancies.

The aim of the present study was to evaluate pregnancy-related changes in autonomic regulatory functions in healthy subjects. We studied cardiovascular autonomic responses to head-up tilt (HUT) in 28 pregnant women during the third trimester of pregnancy and 3 months after parturition. The maternal ECG and non-invasive beat-to-beat blood pressure were recorded in the horizontal position (left-lateral position) and during HUT in the upright position. Stroke volume was assessed from blood pressure signal by using the arterial pulse contour method. Heart rate variability (HRV) was analysed in frequency domain, and baroreflex sensitivity by the cross-spectral and the sequence methods. In the horizontal position, all frequency components of HRV were lower during pregnancy than 3 months after parturition (P < 0.01 to <0.001), while pregnancy had no influence on normalized low frequency and high frequency powers. During pregnancy haemodynamics was well balanced with only minor changes in response to postural change while haemodynamic responses to HUT were more remarkable after parturition. In pregnant women HRV and especially its very low frequency component increased in response to HUT, whereas at 3 months after parturition the direction of these changes was opposite. Parasympathetic deactivation towards term is likely to contribute to increased heart rate and cardiac output at rest, whereas restored sympathetic modulation with modest responses may contribute stable peripheral resistance and sufficient placental blood supply under stimulated conditions. It is important to understand cardiovascular autonomic nervous system and haemodynamic control in normal pregnancy before being able to judge whether they are dysregulated in complicated pregnancies.

Subtle changes in ADMA and l-arginine concentrations in normal pregnancies are unlikely to account for pregnancy-related increased flow-mediated dilatation.

BACKGROUND: Our objective was to investigate whether serum concentrations of asymmetric dimethylarginine (ADMA) or l-arginine correlate to hyperlipidemia or endothelial function in normal pregnancy compared with the non-pregnant subjects. METHODS AND RESULTS: As a part of population-based, prospective cohort Cardiovascular Risk in Young Finns study conducted in Finland we examined 57 pregnant Finnish women throughout gestation and 62 control women matched for age and smoking. Serum glucose, triglycerides (TG), total cholesterol (TC), low-density cholesterol (LDL-C), high-density cholesterol (HDL-C) and ADMA, symmetric dimethylarginine (SDMA) and l-arginine were determined concomitantly with endothelium-dependent brachial artery flow-mediated dilation (FMD), measured by ultrasound. All serum lipid concentrations were significantly higher in pregnant women than in non-pregnant women (P < 0.001 for each). The mean serum ADMA concentration in pregnant women was significantly lower compared with the non-pregnant controls (0.513 micromol l(-1) +/- 0.0593 versus 0.577 micromol l(-1) +/- 0.0710, P < 0.001). Lowered ADMA concentrations did not correlate statistically to FMD in these healthy pregnant women but FMD was enhanced towards the end of pregnancy. CONCLUSIONS: ADMA and l-arginine concentrations fall in normal pregnancy despite marked hypercholesterolemia. Endothelium-dependent vasodilation is enhanced in normal pregnancy but is not statistically correlated to maternal serum ADMA or l-arginine concentrations.

Asymmetric dimethylarginine is not elevated in exfoliation syndrome but symmetric dimethylarginine is related to exfoliative glaucoma.

BACKGROUND: Hyperhomocysteinemia (HH), oxidative stress and endothelial dysfunction are all implicated as possible pathogenetic factors in exfoliation syndrome (XFS) and exfoliative glaucoma (XFG). Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide and plasma level of ADMA is often elevated in HH. Thus the present study was undertaken to study plasma levels of ADMA with concomitant measurement of symmetric dimethylarginine (SDMA) and L-arginine (L-Arg) in XFS and XFG. METHODS: This cross-sectional, prospective study involved 36 XFS patients, 11 of them having XFG, and 36 age- and gender-matched controls. Fasting plasma ADMA, SDMA and L-Arg levels of participants were determined. A special view was created how plasma L-Arg, ADMA and SDMA correlate to plasma homocysteine (P-Hcy). In addition, the influence of P-Hey values derived from our previous study on the above mentioned parameters were evaluated by cut-off values of P-Hcy, 12 micromol/l for women and 14.5 micromol/l for men. RESULTS The mean plasma ADMA, SDMA and L-Arg levels were 0.41, 0.49 and 62.9 micromol/l in the XFS/XFG group, and 0.41, 0.44 and 69.7 micromol/l in the control group, respectively. As all parameters within the XFS and control group were compared, no statistical significance was stated. On the other hand, a positive correlation was observed between plasma SDMA and P-Hcy in XFGs (P = 0.002), and additionally, also a statistically significant difference was in plasma SDMA between the two groups sorted by cut-off levels of P-Hcy 0.49 +/- 0.15 vs. 0.36 +/- 0.04 micromol/l, above and below cut-off levels, respectively (P = 0.001), but not between ADMA in a respective assay. The mean values of L-Arg were 64.6 +/- 17.2 vs. 74.8 +/- 13.3 microg/l, respectively (P = 0.031). In the XFS subgroup, on the contrary, there was no positive correlation between P-Hcy and plasma SDMA. CONCLUSIONS: A positive correlation of plasma SDMA in respect to P-Hcy in XFGs and increase of SDMA in mild or intermediate hyperhomocysteinemia may indicate SDMA as a marker of developing XFG in hyperhomocysteinemic

Tissue substance P levels in acute experimental burns.

PURPOSE OF STUDY: To determine the tissue concentrations of substance P (SP) in burns of different depths and to see whether the concentrations of SP relate to the previously reported late increase in tissue histamine concentrations. MATERIALS AND METHODS: Experimental animal study with pigs. Superficial, partial thickness and full thickness burns were created and the microdialysis method used to collect samples for substance P analysis from burned and non-burned control tissue during a 24-h follow-up. RESULTS: Substance P concentrations increase after 4h in the partial and full thickness burns reaching the peak at 18 and 12h, respectively. The increase was later and more modest in the superficial and control sites. At 24h the SP median concentrations in the superficial, partial and full thickness burns were 28%, 85% and 140% higher than in the control site, respectively. There was a peak in the SP concentration in serum at 4h followed by a decrease and stabilization at a level about 15 pg/ml. CONCLUSIONS: The release of substance P in tissue is a possible cause of the late increase in tissue histamine in burns. Medical inhibition of SP is of clinical interest in preventing late histamine liberation in burns.

Comparison of HPLC method and commercial ELISA assay for asymmetric dimethylarginine (ADMA) determination in human serum.

The performance of a new ELISA assay kit (DLD Diagnostika GmbH, Hamburg, Germany) for the determination of asymmetric dimethylarginine (ADMA) was evaluated against a reversed phase HPLC method. ADMA concentrations of 55 serum samples were measured with both methods. The intra-assay CV for ADMA-ELISA was 19% (n=10). Inter-assay CVs for ADMA-ELISA were 9% for kit control 1 (0.410+/-0.037 microM) and 14% for kit control 2 (1.174+/-0.165 microM). The intra- and inter-assay CVs for HPLC assay for ADMA were 2.5% (0.586+/-0.015 microM) and 4.2% (0.664+/-0.028 microM), respectively. There was no correlation between these two methods (R(2)=0.0972). The effect of storage conditions of the samples on ADMA concentrations was investigated by HPLC. ADMA concentration was stable after four freezing and thawing cycles. Overall, the HPLC method offered better sensitivity, selectivity and, very importantly, simultaneous determination of ADMA, SDMA, l-homoarginine and l-arginine.