Background Because protamine is administered to reverse heparin, a drug that might itself affect the pharmacologic properties of protamine, this study was designed to assess the properties of protamine alone and in the presence of heparin in conscious dogs. Methods Twelve dogs were instrumented to continuously record cardiac and regional hemodynamics. On separate occasions, a dose of protamine (0.5, 1, 3, 5, and 8 mg/kg) was randomly administered either alone or in the presence of heparin (ratio 100 IU/mg). Heparin (300 IU/kg) and protamine (3 mg/kg) were administered in the presence of N-methyl-L-arginine, a specific nitric oxide synthase inhibitor. Identical experiments were performed with protamine (8 mg/kg) in the absence of heparin on a separate occasion. Results Protamine alone produced limited cardiac and regional changes. In the presence of heparin, protamine produced hypotension at 3, 5, and 8 mg/kg, vasodilatation at 3 and 5 mg/kg, and a more pronounced dose-dependent increase in pulmonary pressure at 3, 5, and 8 mg/kg. Simultaneously, transient carotid vasodilatation at 3 and 5 mg/kg, coronary and hepatic vasodilatation at 3, 5, and 8 mg/kg, as well as a decrease in vertebral vascular resistance were recorded at 1, 3, and 8 mg/kg. Protamine produced an immediate increase followed by a secondary decrease in renal vascular resistance. Protamine-induced secondary pulmonary pressor effects were attenuated. In the presence of heparin, nitric oxide synthase blockade selectively attenuated protamine-induced immediate hypotension, systemic vasodilatation, and coronary, mesenteric, and hepatic vasodilations as well as the decrease in portal blood flow and accentuated the renal vasoconstriction. Conclusions The presence of heparin accentuated the decrease in cardiac function induced by protamine as well as its effects on regional circulation. The data provide evidence that the nitric oxide pathway is involved in the systemic and selective regional heparin-protamine-mediated vasodilatation in conscious dogs.
Mechanisms by which hemorrhagic shock leads to hemodynamic disturbances are not fully understood. Nuclear factor kB (NF‐kB) is a nuclear transcription factor that regulates expression of genes critical for the regulation of diseases. We hypothesize that NF‐kB is responsible for the hemodynamic changes associated with hemorrhagic shock in conscious rats. Under isoflurane, catheters were implanted into the aorta to record mean blood pressure (MAP) and heart rate (HR) and in the femoral vein for drug administrations. Cardiac output (CO) was recorded through Doppler flow probe. A blood volume of 2.0 ml/100 g of body weight was withdrawn over a 5‐min to induce moderate hemorrhage. Group 1 (n=6) was subjected to moderate hemorrhage only. Group 2 (n=5) was hemorrhaged in the presence of TPCK, an inhibitor of NF‐kB at 10 mg/kg sc. Our data show that hemorrhagic shock induced decreases in MAP by 30%, HR by 40% whereas CO remained unchanged. Moderate hemorrhage induced significant systemic vasoconstriction. As compared to hemorrhaged animals, TPCK restored MAP to baseline. Furthermore, moderate hemorrhage‐induced systemic vasoconstriction was significantly reduced in the presence of TPCK. Our data suggest that NF‐kB plays a major role in the hemodynamic changes induced by moderate hemorrhage. Development of NF‐kB inhibitors that will be tissue‐specific and/or isoform‐specific as therapeutic agents need to be pursued.
Background In vitro, halothane appears to affect the role played by nitric oxide in the regulation of vascular tone and cardiac function. In vivo, the results of the interactions between halothane and the nitric oxide pathway remain controversial. The authors investigated the effects of halothane on the cardiac and regional hemodynamic properties of N-methyl-L-arginine (NMA), a specific nitric oxide synthase inhibitor, in dogs. Methods Twenty-five dogs were chronically instrumented. Aortic pressure, the first derivative of left ventricular pressure, cardiac output, heart rate, and carotid, coronary, mesenteric, hepatic, portal and renal blood flows were continuously recorded. N-methyl-L-arginine was infused intravenously at 20 mg/kg over 1 min in awake dogs (n = 11) and in 1.2% halothane-anesthetized dogs (n = 10). As a control group, the remaining four dogs were studied awake and during 1.2% halothane for 2 h in the absence of NMA. Results In awake dogs, NMA produced a sustained pressor response (34%) and systemic vasoconstriction (40%) associated with a decrease in cardiac output (16%). Regional circulation changes included an immediate and transient increase in carotid (43%) and coronary (237%) blood flows and a subsequent decrease in carotid blood flow (25%). Hepatic and mesenteric blood flows also decreased, by 43% and 16%, respectively. Except for the coronary circulation, regional vascular resistance increased significantly. Halothane did not affect the pressor response to NMA but did blunt the cardiac output changes. Consequently, the systemic vasoconstriction after nitric oxide synthase inhibition was of shorter duration and of lesser magnitude during halothane anesthesia. Halothane also blunted the carotid, mesenteric, and renal vasoconstriction induced by NMA. Finally, in 1.2% halothane-anesthetized dogs, NMA induced a coronary vasoconstriction. Conclusions Halothane minimally interferes with the systemic and regional hemodynamic consequences of nitric oxide synthase blockade. The nature and magnitude of the interaction depend on the territory in which they occur.
This study was purposed to set up real-time quantitative RT-PCR technique and to measure leukemia fusion gene transcripts in patients with chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL) and acute promyelocytic leukemia (APL). All plasmids containing the target gene sequences were constructed to establish the standard curves. A TaqMan based real-time quantitative RT-PCR was performed to measure aberrant fusion gene transcripts in 130 samples of peripheral blood (PB) or bone marrow (BM) from 49 patients with leukemia. The results showd that the BCR-ABL(P210) transcripts were detected in 28 (82.4%) out of 34 CML patients (the ratios of BCR-ABL(P210)/ABL varied from 0.01 to 3.19) and also in 2 (33.3%) out of 6 ALL patients. The BCR-ABL(P190) transcripts were detected in 2 (33.3%) out of 6 ALL patients. The BCR-ABL(P210) and BCR-ABL(P190) transcripts were both detected in 1 (2.9%) CML patients. The PML/RARalpha transcripts were detected in 7 (77.8%) out of 9 APL patients (the ratio of PML-RARa/ABL varied from 0.0014 to 3.199). The relative frequency of both bcr1 and bcr3 was 42.9%, while that of bcr2 was 14.3%. The transcript level of aberrant fusion gene varied from the clinical situation of patient. It is concluded that real-time quantitative PCR is a reliable, innovative and promising technology with high sensitivity and specialty. It has potential clinical value for defining diagnosis, typing tumor, selecting treatment, measuring the tumor load, monitoring fusion gene expression level and evaluating therapeutic strategies, which is worthy to be popularized.
Objective: To investigate the effects and mechanism of sodium hydrosulfide on rat epidermal cells intervened with serum from burned rat (hereinafter referred to as burn serum). Methods: The experimental research method was used. Ten male Sprague-Dawley (SD) rats aged eight months were taken to prepare normal rat serum (hereinafter referred to as normal serum), 30 male SD rats aged eight months were taken to prepare burn serum after full-thickness burn, and epidermal cells (the third passage)isolated from 10 SD rats born one day were used for the experiments. The cells were divided into normal serum group treated with normal serum and burn serum group treated with burn serum. Cell counting kit 8 method was used to detect cell survival rate after 1, 2, 4, 6, and 8 h of culture, respectively, to screen the subsequent intervention time of burn serum. The cells were divided into burn serum control group treated only with burn serum and 50, 100, 150, 200, 250 μmol/L sodium hydrosulfide groups treated with burn serum+ sodium hydrosulfide at corresponding final molarity. After 30 min of culture following the burn serum intervention, the cell survival rate was detected as above to screen the subsequent intervention concentration of sodium hydrosulfide. The cells were divided into burn serum control group treated with burn serum only and sodium hydrosulfide only group, glibenclamide only group, and sodium hydrosulfide+ glibenclamide group treated with burn serum+ corresponding reagents. After 5, 10, 15 min of culture following the burn serum intervention, the cell survival rate was detected as above to screen the subsequent intervention time of glibenclamide. The cells were divided into burn serum control group treated with burn serum and sodium hydrosulfide only group, glibenclamide only group, and sodium hydrosulfide+ glibenclamide group treated with burn serum+ corresponding reagents. After completing corresponding culture time of each reagent, the mitochondria were extracted to detect cytochrome c oxidase (CCO) activity using a spectrophotometer, and the protein expression level of adenosine triphosphate (ATP)-sensitive potassium channel was detected by Western blotting. Except for the number of samples for ATP-sensitive potassium channel protein detection, which was 3, the number of samples for the other indicators was 10. Data were statistically analyzed with analysis of variance for factorial design, one-way analysis of variance, least significant difference (LSD)-t test, LSD test, and Bonferroni correction. Results: Compared with that of normal serum group, the cell survival rate was significantly decreased in burn serum group after only 4 and 6 h of culture (t=4.02, 6.42, P<0.05). An overall comparison showed statistically significant differences in cell survival rate among the time points within normal serum group and burn serum group (F=19.74, 4.48, P<0.05 or P<0.01). Four hours of culture was selected as the subsequent intervention time of burn serum. After 30 min of culture following the burn serum intervention, compared with that of burn serum control group, only 150, 200, 250 μmol/L sodium hydrosulfide groups had a significantly higher cell survival rate (P<0.01), thus 150 μmol/L was selected as the subsequent intervention concentration of sodium hydrosulfide. Compared with that of burn serum control group, the cell survival rate decreased significantly in glibenclamide only group after 5 and 15 min of culture following burn serum intervention (P<0.05) and increased significantly in glibenclamide only group after 10 min of culture following the burn serum intervention and sodium hydrosulfide only group at each time point (P<0.05 or P<0.01). The cell survival rate in sodium hydrosulfide+ glibenclamide group was significantly lower than that of sodium hydrosulfide only group at each time point (P<0.05). The difference in cell survival rate was statistically significant among the time points within glibenclamide only group (F=11.81, P<0.01). Five minutes of culture was selected as the subsequent intervention time of glibenclamide. After 35 min of culture following the burn serum intervention, compared with (1.62±0.08) nmol·min(-1)·mg(-1) and 0.682±0.063 in burn serum control group, the CCO activity of cells and the protein expression level of ATP-sensitive potassium channel were significantly increased in sodium hydrosulfide only group ((1.99±0.09) nmol·min(-1)·mg(-1) and 0.932±0.014, P<0.01) and significantly decreased in glibenclamide only group ((1.44±0.09) nmol·min(-1)·mg(-1) and 0.600±0.012, P<0.01); the CCO activity of cells and the protein expression level of ATP-sensitive potassium channel in sodium hydrosulfide+ glibenclamide group ((1.79±0.06) nmol·min(-1)·mg(-1) and 0.744±0.071) was significantly lower than those of sodium hydrosulfide only group (P<0.05 or P<0.01). Conclusions: Sodium hydrosulfide can improve the survival rate of rat epidermal cells after burn serum intervention, by a mechanism which is related to the alleviation of epidermal cell mitochondrial damage and mediated by ATP-sensitive potassium channel.
Objective
To evaluate the relationship between the lung volume (LV) in inspiration and expiration,pulmonary function tests (PFT),and other CT measurements of emphysema index (EI) and mean lung density (MLD) in patients with chronic obstructive pulmonary disease (COPD).
Methods
Seventy-six patients with COPD were included.Three-dimension analysis was performed to obtain the following CT parameters on the inspiratory and expiratory phases: EI,MLD,LV.The ratios and differences of MLD and LV between the two phases were calculated (ΔMLD,ΔLV,MLDex/in,LVex/in).Not only the linear correlations between the lung volume parameters and PFT but also the correlations of lung volume parameters with the other CT parameters were tested by the Spearman rank correlation test and multivariant step wise regression.
Results
LVex/inhad negative correlations with forced expiratory volume in 1 second% predicted[FEV1%,(54.32±7.11) ]and the ratio of forced expiratory volume in 1 second to forced vital capacity[FEV1/FVC,(49.12±8.01) %] (r=-0.69,-0.56,P<0.01),but it had the positive correlation with the ratio of residual volume to total lung capacity[RV/TLC,(58.03±8.55) %,Spearman coefficients 0.66,P<0.01].LVex/in (0.67±0.12) was positively correlated with MLDex/in (0.89±0.04,r=0.88,P<0.01).The further multivariate step wise regression demonstrated that EI,LV and MLD could introduce a regression equation withR2=0.77 and 0.73,respectively (P<0.01).
Conclusions
There is an association between LVex/in and the parameters of routine PFT,which can reflect the collapsibility of lung.Moreover,LVex/incan be considered to be equivalent to MLDex/in.Taking into account the impact of scanning parameters on MLDex/in,LVex/inmay play a complementary role in the assessment of pulmonary function.
Key words:
Pulmonary disease,chronic obstructive; Respiratory function tests;
Objective This retrospective multicentre observational study was performed to assess the predictors of acute kidney injury (AKI) in patients with acute decompensated heart failure (ADHF) in emergency departments in China. Methods In total, 1743 consecutive patients with ADHF were recruited from August 2017 to January 2018. Clinical characteristics and outcomes were compared between patients with and without AKI. Predictors of AKI occurrence and underdiagnosis were assessed in multivariate regression analyses. Results Of the 1743 patients, 593 (34.0%) had AKI. AKI was partly associated with short-term all-cause mortality and cost. Cardiovascular comorbidities such as coronary heart disease, diabetes mellitus, and hypertension remained significant predictors of AKI in the univariate analysis. AKI was significantly more likely to occur in patients with a lower arterial pH, lower albumin concentration, higher creatinine concentration, and higher N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration. Patients treated with inotropic agents were significantly more likely to develop AKI during their hospital stay. Conclusion This study suggests that cardiovascular comorbidities, arterial pH, the albumin concentration, the creatinine concentration, the NT-proBNP concentration, and use of inotropic agents are predictors of AKI in patients with ADHF.
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