Effects of hydrocortisone on circulating and intramyocardial inflammatory mediators in severe septic rats with myocardial injury induced by Escherichia coli / 中华儿科杂志

<p><b>OBJECTIVE</b>Severe sepsis and septic shock remain the most common cause of death in intensive care units. The main causes of death in sepsis are the cardiac dysfunction and hypotension resistant to cateolamines. The prevalence of relative adrenal insufficiency in severe sepsis and septic shock was estimated at about 32%-51%. Several meta-analysis demonstrated that high-dose glucocorticoids decreased survival during sepsis, while stress doses of corticosteroids may benefit these patients. The exact reason for such widely divergent outcome produced by different doses of corticosteroid is still not understood. Therefore, the study was undertaken to observe the effects of different doses of hydrocortisone (HC) on circulating and intramyocardial inflammatory mediators in severe septic rats with myocardial injury induced by Escherichia coli (E. coli).</p><p><b>METHODS</b>The model was established by two injections of inactivated E. coli Forty male Wistar rats were randomly divided into five groups: high-dose of HC group (150 mg/kg), medium-dose group (20 mg/kg), low-dose group (6 mg/kg), model group (NS substituted for HC), and control group (NS for E. coli and HC). Each group had eight rats. After 2 hours of treatment, specimens were collected to measure serum cardiac troponin I (cTnI), tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), nitric oxide (NO) and total NO synthase (NOS). NO and total NOS in myocardial homogenate were also detected. The expression of inducible NOS (iNOS) of myocytes was investigated.</p><p><b>RESULTS</b>All the above-mentioned markers in model group significantly higher than those in control group. After HC injection, serum cTnI concentrations in low-dose group decreased to normal values compared to that of model group, while in another two HC groups, the concentrations were higher than those in model group. TNF-alpha level was not significantly influenced. But IL-1beta level declined to normal values, being prominent in low-dose HC group. Neither high-dose nor middle-dose HC could lower serum NO or total NOS, but low-dose HC could greatly inhibit both NO and NOS levels (P < 0.05). There was no significant difference in the level of NO and total NOS of myocardial homogenate between left and right ventricles. There was no iNOS expression by normal myocardium, while the expression in model group was significantly increased. After HC injection, the iNOS expressions by myocardium in three HC groups were weaker than those in model group. The intensity of iNOS signals became weak with the decrease in HC dose.</p><p><b>CONCLUSION</b>Different doses of HC might exert different effects on circulating and intramyocardial inflammatory mediators in severely septic rats with myocardial injury induced by E. coli. Low-dose HC could significantly inhibit such mediators as well as iNOS expression by cardiomyocytes. The results suggest that low dose HC exert protective effect on myocardial injury of severely septic rats.</p>

Effects of different doses of hydrocortisone on acute lung injury in rats with early septic shock induced by Escherichia coli / 中华儿科杂志

<p><b>OBJECTIVE</b>To observe the effects of different doses of hydrocortisone (HC) on acute lung injury (ALI) and inflammatory response in rats at early stage of septic shock induced by Escherichia coli and to investigate the possible mechanisms for such differences.</p><p><b>METHODS</b>ALI model of early septic shock was induced in rats by two injections of Escherichia coli at 5 hours interval, with the first intraperitoneal injection of 6.50 x 10(10) cfu/kg and followed by an external jugular vein injection of 2.00 x 10(11) cfu/kg. Forty Wistar rats were randomly divided into the following five groups: normal control, ALI without HC treatment, high-dose HC (150 mg/kg), medium-dose HC (20 mg/kg) and low-dose HC (6 mg/kg). Two hours after the treatment, the specimens were collected for histopathological examination and the biological indexes of lung injury were measured. The expressions of intercellular adhesion molecule-1 (ICAM-1) and glucocorticoid receptor (GR) in lung tissues were also investigated by immunohistochemical assays.</p><p><b>RESULTS</b>The biological indexes of lung injury [wet/dry weight ratio (g/g), total protein concentration in bronchoalveolar lavage fluid (mg/L) and lung permeability index (10(-3))] in ALI group (4.76 +/- 0.10, 278.96 +/- 60.45, 4.73 +/- 0.60) were significantly increased as compared to those in normal control group (4.10 +/- 0.07, 67.46 +/- 13.27, 1.12 +/- 0.15) (P < 0.05). The grades of ALI pathologic changes in ALI group (11.13 +/- 1.13) was significantly higher than that in the normal control group (0.50 +/- 0.53, P < 0.05). The ratio of expression area of ICAM-1 in ALI group (0.149 +/- 0.037) was significantly increased as compared to that in the normal control group (0.051 +/- 0.018) (P < 0.05). The ratio of expression area of GR all group (0.043 +/- 0.037) was significantly decreased as compared to that in the normal Control group (0.124 +/- 9.040) (P < 0.05) After administration of HC, all the lung injury indexes, pathological grades and the ratios of expression area of ICAM-1 and GR were significantly improved, with the most remarkable effects observed in the low-dose HC group. The expressions of ICAM-1 and GR showed a significantly negative linear correlation (r = 0.55, P < 0.0001).</p><p><b>CONCLUSION</b>These results indicated that the low-dose HC treatment had the most remarkable effects of improving the biological indexes of lung injury, inflammatory mediators and pathological changes. These HC dose dependent therapeutic effects might be associated with the level of GR expression.</p>

Effects of aminoguanidine in different dosages on renal function in endotoxin induced rabbits shock model / 中华儿科杂志

<p><b>OBJECTIVES</b>To explore the effects of aminoguanidine (AG) in different dosages on renal function in endotoxin induced rabbits shock model in the early stage and to approve the effects of dose-depended and time-depended of AG.</p><p><b>METHODS</b>Fourty New Zealand rabbits under anaesthesia were randomly divided into 5 groups: sham group, LPS group, the first group of AG, the second group of AG, the third group of AG. Each rabbits from the four groups received Escherichia Coli O55B5 LPS 400 micro g/kg to induce endotoxic shock except sham group. Edotoxic shock was diagnosed when the mean arterial pressure (MAP) decreased to 30%. Each rabbits in sham group and LPS group received 5ml NS, in the other three groups were infused with AG 30 mg/kg (the first group of AG), 50 mg/kg (the second group of AG), 100 mg/kg (the third group of AG) in 5ml NS, respectively. Urine output was recorded at the following time points, before injecting IPS (T(0)), shock (T), 1 h (T(1)), 2 h (T(2)), 3 h (T(3)), 4 h (T(4)), 5 h (T(5)) and 6 h (T(6)) after shock. Plasma nitrate and nitrite (NO(3)(-)/NO(2)(-), stable products of NO), BUN, Scr, RBP were determined at the time points of T, T(2), T(4) and T(6).</p><p><b>RESULTS</b>LPS increased NO(3)(-)/NO(2)(-), BUN, Scr, RBP [from (47 +/- 5) micro mol/L, (5.8 +/- 1.5) mmol/L, (41 +/- 10) micro mol/L, (240 +/- 61) ng/L (T(0)) to (160 +/- 18) micro mol/L, (15.5 +/- 1.8) mmol/L, (166 +/- 23) micro mol/L, (1580 +/- 180) ng/L (T(6)), respectively, P < 0.01]; Urine output decreased significantly [from (17.6 +/- 2.8) ml (T(0)) to (1.3 +/- 0.6) ml (T(6)), P < 0.01]. AG attenuates the increasing of NO(3)(-)/NO(2)(-), BUN, Scr and RBP, and decreasing of urine output. NO(3)(-)/NO(2)(-) of the first, second and third group of AG at T(6) were (58 +/- 8), (50 +/- 14) and (46 +/- 9) micro mol/L, respectively. Compared to LPS group, there was a significant difference (P < 0.01). BUN was (8.2 +/- 2.9), (7.5 +/- 1.9) and (5.5 +/- 1.8) mmol/L, respectively at T(6). Compared to LPS group, there was a significant deference (P < 0.01). RBP was (350 +/- 60), (272 +/- 72) and (248 +/- 103) ng/L, respectively at T(6) (compared to LPS group, there was a significant deference. P < 0.05, < 0.05, < 0.01). Urine output was (11. 1 +/- 2.4), (12. 1 +/- 1. 3) and (17.1 +/- 2. 4) ml, respectively on T(6) (compared to LPS group, there was a significant deference, P < 0.01). AG of 100 mg/kg showed the best effect among three AG groups.</p><p><b>CONCLUSION</b>AG inhibited NO formation in dose-depended and time depended way. AG attenuated the changes of renal function induced by NO.</p>

Effect of dexamethasone, aminoguanidin, amrinone on oxygen utilization in endotoxin shock rabbits / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the effect of three kinds of drug with different mechanism, dexamethasone (Dex), aminoguanidin (AG) and amrinone (Amr) on oxygen utilization in endotoxic shock rabbits.</p><p><b>METHODS</b>Thirty-five rabbits were randomly allocated into five groups: operation, lipopolysaccharide (LPS), Dex, Amr and AG. The endotoxin shock was induced by intravenously injecting LPS (400 micro g/kg). The arterial blood gas, mixed venous blood gas and cardiac output were recorded at 30 min after the operation (T(0)), shock status (T), 1 - 6 h after the treatment (T(1)-T(6)). The oxygen delivery (DO(2)), oxygen consumption (VO(2)) and extraction ratio of oxygen (ERO(2)) were calculated.</p><p><b>RESULTS</b>All the parameters in five groups showed no significant differences (P > 0.05) at T(0). Six hours after treatment, rabbits in Dex group presented with significantly improved DO(2) (12.4 +/- 3.1) ml/(kg.min), P < 0.01 and VO(2) (5.1 +/- 1.6) ml/(kg.min), P < 0.05 compared with DO(2) (8.1 +/- 2.4) ml/(kg.min) and VO(2) (2.7 +/- 1.0) ml/(kg.min) in LPS group. Rabbits in AG group showed significantly increased DO(2) (17.0 +/- 2.8) ml/(kg.min) (P < 0.01), (17.2 +/- 2.5) ml/(kg.min) (P < 0.05), compared with (12.2 +/- 2.6), (14.1 +/- 3.8) ml/(kg.min) in LPS group at T(1) and T(2), respectively, but there was no significant difference (11.2 +/- 1.7) ml/(kg.min) (P > 0.05) at T(6). The VO(2) increased significantly, (5.0 +/- 1.0) ml/(kg.min) (P < 0.01) compared with LPS group at T(6). The VO(2) of Amr group was significantly higher than LPS group at T(3) and T(4). At T(6), the DO(2) and VO(2) were (9.5 +/- 1.3) and (4.1 +/- 1.5) ml/(kg.min), respectively, but there was no significant difference compared with LPS group. There was no significant difference in ERO(2) among groups (P > 0.05).</p><p><b>CONCLUSION</b>The dexamethasone, aminoguanidin, amrinone can improve oxygen utilization in endotoxic shock rabbits, especially for dexamethasone and aminoguanidin.</p>

Clinical application of simplified pediatric critical illness scoring system / 中华儿科杂志

<p><b>OBJECTIVE</b>To simplify the Pediatric Critical Illness Scoring (PCIS), to evaluate the simplified PCIS and to make the simplified scoring system applicable in the grassroots hospitals.</p><p><b>METHODS</b>Totally 1,036 patients were scored by PCIS on 1, 3, 7 and the last (discharged or dead) hospital days. The PCIS has 10 items. The full score is 100. The scores of approximately 100, approximately 80, and approximately 70 represent non-serious, serious, and extremely serious patients' condition. The PaO(2) and pH (2 items), BUN or creatinine (3 items), plasma sodium and potassium (5 items) were deleted from PCIS's 10 items in turn. The remaining 8, 7, and 5 items were applied as new scoring system after the original scores were multiplied by 0.8, 0.7, and 0.5. The simplified PCIS was evaluated by comparing the patients' condition that was assessed by PCIS. The consistency rate of patients' condition that was obtained by using PCIS and simplified PCIS should be over 80%. The mortality of non-serious, serious, and extremely serious groups that were defined by using PCIS and simplified PCIS was observed and compared.</p><p><b>RESULTS</b>When 2, 3 and 5 items were deleted from the PCIS on d1 scoring the consistency rates of the patients' condition were 82.6%, 80.7%, and 69.9%. While 5 items remained on d1 scoring the consistency rate was lower than 80%. When the same 2, 3 and 5 items were deleted from PCIS on d3, d7 and last scoring, the consistency rates of the patients' condition were 81.5% approximately 97.1%. The PCIS and simplified PCIS had a close correlation (r = 0.629-0.948, P < 0.001). In PCIS the mortality rates of non-serious, serious and extremely serious patients were significantly different. When simplified PCIS was used, the mortality rates of the three groups also had significant differences (chi(2) = 86.13-740.33, P < 0.001). Within a group of patients with the same condition, the mortality rates were not significantly different for PCIS and simplified PCIS. For instance, on d1 and last scoring, the mortality rates of extremely serious patients were 29.8%, 67.3% for PCIS and 30.0%-27.9%, 66.3%-64.4% for simplified PCIS.</p><p><b>CONCLUSION</b>When 2 items (PaO(2) and pH) were deleted from d1 PCIS scoring and 5 items (PaO(2) and pH, BUN or creatinine, plasma sodium and potassium) were deleted from d3, d7, and last PCIS scoring, the results of assessment of patients' condition were basically the same as those of PCIS. The consistency rates of PCIS and simplified PCIS were > 80%. When simplified PCIS was applied, mortality rates of non-serious, serious, and extremely serious patients were significantly different that were the same as those of PCIS. In patients with the same condition, the mortality rates were not significantly different between the simplified PCIS and PCIS.</p>

Significance of Change of Gastric Mucosal Partial Pressure of Carbon Dioxide in Rabbit Model with Septic Shock / 实用儿科临床杂志

Objective To observe the change of gastric mucosal-arterial partial pressure of carbon dioxide gap [p(g-a)(CO2)] in septic shock rabbit.Methods Sixteen anesthetized and mechanically ventilated rabbit were randomly assigned to 2 groups:shock group(n=8) and control group(n=8).The rabbit in shock group were challenged with intravenous injection of 2 mg/kg Lipopolysaccharides from Escherichia coli.The rabbit in control group were intravenous injection of normal saline solution.Mean arterial pressure(MAP) and heart rate were continuously recorded by multichannel physiologic recorder.Cardiac index(CI) and superior mesenteric blood flow index(SMBFI) were continuously monitored by doppler flowmeter.Gastric mucosal partial pressure of carbon dioxide [pg(CO2)] was evaluated by gas tonometry every 10 min.Arterial and venous blood gas analysis,hemoglobin,and lactate levels were measured every 1 hour.Results The parameters remained stable in control group,but the parameters changed significantly in shock group.Compared with baseline levels,2 hours after Lipopolysaccharides infusion in shock group,MAP decreased from(78?5) mmHg to(50?2) mmHg(1 mmHg=0.133 kPa)(F=145.3 P

Effect of Low-Dose Hydrocortisone on Expression of Hippocampus Nuclear Factor-Kappa B,Inhibitory Kappa Bin Lipopolysaccharide-Induced Septic Rats / 实用儿科临床杂志

Objective To investigate the effect of low-dose hydrocortisone(HC)on hippocampus nuclear factor kappa B((NF-?B)),I?B expression in lipopolysaccharide(LPS)induced septic rats and the role of NF-?B signal transcription pathway in pathogenesis.Methods Fifty-four rats were randomly divided into 3 groups: control group(A group,n=6),model group(B group,n=24),low-dose HC treatment group(C group,n=24).The septic rat model was established by intraperitoneal injection LPS(1 mg/kg),as the intervention by caudal vein injection low-dose HC(6 mg/kg),each of B and C group was subdivied into 2,8,16,24 hours respectively after LPS injection(n=6).At serial time points,the animals in each group were sacrificed,brain tissue samples were harvested to determine NF-?B,I?B expression by immunhistochemistry in hippocampus.Results In B group: NF-?B expression was up regulated compared with A group(P