Hydrocortisone how does it reduce cell damage

Transudate samples were collected over 2-min intervals at 0—2, 2—4, 4—6, 6—8, 12—14, and 18—20 min after start of reperfusion.

Therefore, during the first—decisive—8 min, all fluids coming from the heart were collected and quantified gravimetrically. Because the rate of transudate formation is pressure dependent, 12,17,20 we related it to the respective perfusion pressure established at the given flow rates in each heart.

The experimental groups are characterized in figure 1. Experimental protocols. Ischemia is defined as 20 min of no-flow warm ischemia, and re perfusion is defined as 20 min of constant-flow perfusion starting with a flow rate that had generated a perfusion pressure of 70 cm H 2 O under basal conditions equilibration. This served as a quantitative measure for formation of edema. In all groups, samples of effluent were used for assessing shedding of syndecan-1 CD , heparan sulfate, and hyaluronan as described in detail elsewhere.

This kit used a solid phase monoclonal B-B4 antibody and a biotinylated monoclonal B-D30 antibody raised against syndecan The detection steps rely on streptavidin—horseradish peroxidase and tetramethylbenzidine as chromogens. To measure heparan sulfate, samples were concentrated with kd-cutoff ultrafilters Millipore, Billerica, MA and aliquots used for an enzyme-linked immunosorbent assay Seikagaku Corporation, Tokyo, Japan based on two antibodies specific for heparan sulfate—related epitopes.

Hyaluronan measurements were performed using an enzyme-linked immunosorbent assay Echelon Biosciences Incorporated, Salt Lake City, UT based on an enzyme-linked antibody, after concentrating the samples with the aforementioned ultrafilters.

Lactate, purines, and uric acid were determined by high-performance liquid chromatography in samples of coronary effluent. Lactate is an indicator of the severity of ischemic challenge. Purine release is directly related to the rate of energy consumption and inversely related to the rate of energy production. Uric acid, the end product of enzymatic purine metabolism in the heart, is subject to further oxidative chemical degradation.

Therefore, hearts under oxidative stress typically release less urate relative to precursor purines than when oxidative stress is mitigated. Lactate was detected by its ultraviolet absorbance at nm.

Uric acid levels were determined according to Becker. Uric acid was detected by its ultraviolet absorbance at nm. In the case of purines, all were transformed first to uric acid and then determined as such.

This involved sequential enzymatic conversion of adenosine, inosine, hypoxanthine, and xanthine to urate. Electron microscopy was performed using a lanthanum fixation in modification of a method described by Vogel et al.

Data dealing with rates of flow, transport, or release are expressed per gram heart weight. Comparisons involving two groups were made using the Mann—Whitney U test for independent data or the Wilcoxon test for dependent data. For comparisons of more than two groups, analysis of variance on ranks analysis was performed.

Post hoc tests were performed using the Bonferroni method. The statistical software used to conduct the analyses was SigmaStat 3. Coronary flow rate was adjusted during the equilibration phase to achieve a constant perfusion pressure of 70 cm H 2 O. This individual baseline perfusion rate was then maintained during the entire, consecutive reperfusion phase. As shown in figure 2 , coronary perfusion pressure in group A increased already within the first 2 min of reperfusion This reflects an increase in coronary resistance.

In contrast, there was an initial pressure decrease in all groups treated with hydrocortisone group B: Decreases in perfusion pressure reflect coronary dilatation. Mean arterial coronary perfusion pressure MAP in relation to time during reperfusion.

Pretreatment with hydrocortisone was unable to prevent this group D. Adding hydroxyethyl starch to the Krebs-Henseleit buffer perfusate after hydrocortisone treatment group F minimized the pressure increase after the initial decrease, perfusion pressure merely returning to the basal level after 20 min of reperfusion Adding hydroxyethyl starch without hydrocortisone treatment produced no significant deviation versus the control group A during the entire reperfusion phase group E.

However, time control measurements without ischemia also showed a slight increase in perfusion pressure with no difference between the control and hydrocortisone-treated groups min 20; groups G and H: Figure 3 presents transudate flow normalized to the individually pertaining perfusion pressure. The resulting baseline values measured during the equilibration phase showed no differences among the groups.

Transudate formation in relation to sampling period during reperfusion. Transudate flow was normalized to perfusion pressure. Pretreatment with hydrocortisone completely prevented the increase in coronary leak that developed during reperfusion group B.

Leak was also attenuated in the presence of colloid hydroxyethyl starch, group E. Interestingly, the effects of hydrocortisone and colloid were additive, group F having the lowest transudate values of all postischemic hearts fig.

Treatment with heparinase alone induced no significant increase in transudate formation. Hydrocortisone showed little effect after treatment with heparinase.

If anything, transudate tended to be higher, with significant differences to both other hydrocortisone-treated groups group D vs. Metabolic parameters of hearts subjected to ischemia—reperfusion are listed in table 1. Lactate release was identical in groups A and B during equilibration. Basal purine release was identical in groups A and B. Uric acid was released in comparable concentrations in group A and B hearts during equilibration. After the peak, rates of release declined significantly to similar values after 10 min table 1.

The ratio of urate release to release of precursor purines gives an indication of the degree of oxidative stress. For groups A and B, the basal release of urate was approximately equal to that of nonconverted precursor purines ratio In early reperfusion minutes 0—5 , purine release increased overproportionally, and attention should be drawn to a difference between group A ratio and group B ratio , i.

This indicates a relative reduction in oxidative stress in hearts reperfused after hydrocortisone treatment. Such an effect was still evident at 20 min of reperfusion ratio Net colloid extravasation of hydroxyethyl starch was calculated as the product of transudate formation per gram heart weight and hydroxyethyl starch concentration in the transudate. As shown in figure 4A , ischemia—reperfusion enhanced shedding of syndecan-1 to fold.

Application of hydrocortisone significantly decreased shedding at all times group A vs. Measurements of constitutional parts of the glycocalyx in coronary venous effluent. A Syndecan-1 release in relation to sampling period during reperfusion. B Heparan sulfate release in relation to sampling period during reperfusion. Heparan sulfate was also detected in the effluent of all hearts basal value 3.

Ischemia—reperfusion induced strong shedding of heparan sulfate from the glycocalyx fig. Application of hydrocortisone led to a significantly lower rate of release of heparan sulfate throughout reperfusion group A vs.

Electron microscopic photographs illustrating the state of the endothelial glycocalyx of coronary vessels are depicted in figure 5. No glycocalyx could be visualized in groups A, D, or E, but severe tissue edema was observed figs.

On the other hand, a mostly intact glycocalyx was seen in hydrocortisone-treated groups B and F with slight formation of edema figs. The time control groups, G and H, that did not undergo ischemia or heparinase application also showed an intact glycocalyx figs.

Electron microscopic views of the hearts stained to reveal the glycocalyx. A and B Control experiment after 20 min of warm ischemia and reperfusion.

The endothelial glycocalyx is nearly completely degraded, and a significant formation of edema is visualized. A is an overview, and B is a close-up view of the degraded glycocalyx.

C and D After treatment with hydrocortisone and 20 min of warm ischemia and reperfusion. Endothelial glycocalyx is mostly intact, and less edema formation can be seen. C is an overview, and D is a close-up view of the intact glycocalyx. E and F Heart perfused for 35 min without ischemia. E is an overview, and F is a close-up view of the intact glycocalyx. Mean wet—to—dry weight ratios of isolated hearts were 7. The ratios were higher in all groups with a significant degradation of the glycocalyx, i.

Inform your health care professional if you are pregnant or may be pregnant prior to starting this treatment. Pregnancy category C use in pregnancy only when benefit to the mother outweighs risk to the fetus. For both men and women: Do not conceive a child get pregnant while taking Hydrocortisone. Barrier methods of contraception, such as condoms, are recommended. Discuss with your doctor when you may safely become pregnant or conceive a child after therapy.

Do not breast feed while taking Hydrocortisone. Self-Care Tips: If you are on Hydrocortisone for a long period of time, you may be more susceptible to infection. Wash your hands well, and report any symptoms of infection to your healthcare provider if noted. If you are given eye drops or eye ointment: You may be more sensitive to the light.

Wearing sunglasses may help. It is normal to notice a little blurriness for a short time after the drops or ointments are placed in your eyes. Notify your healthcare provider with any changes in vision, blurriness, or eye pain. If you are given eye drops or eye ointment: Ask your healthcare provider if you may wear contact lenses. Contact lenses may absorb Hydrocortisone. Wash your hands well before putting eye drops, to decrease the chance of a bacterial infection in your eyes.

If you are Hydrocortisone as a lotion topical to treat skin disorders: Do not apply to open areas of skin, or if you have open or weeping sores. Topical Hydrocortisone should not be used for a long time. Discuss this with your healthcare provider. Certain brands of Hydrocortisone can be applied to the rectal area to treat hemorrhoids, or local inflammation, either by a suppository of ointment. Make sure that the preparation that you are using was made specifically for the rectal area.

In a pill form: Take Hydrocortisone with food to lessen an upset stomach. Also take Hydrocortisone early on in the day before noon, if possible , so you will be able to sleep better at night.

If you have diabetes, Hydrocortisone may increase your blood sugar levels. Notify your healthcare provider that you are diabetic. You may need close monitoring. Drink 2 to 3 quarts of fluid every 24 hours, unless you were told to restrict your fluid intake, and maintain good nutrition.

To reduce nausea, take anti-nausea medications as prescribed by your doctor, and eat small, frequent meals. In general, drinking alcoholic beverages should be avoided. You should also limit caffeine intake colas, tea, coffee and chocolate, especially. These beverages may irritate your stomach.

If you experience symptoms or side effects, especially if severe, be sure to discuss them with your health care team. Monitoring and Testing: You will be checked regularly by your health care professional while you are taking Hydrocortisone, to monitor side effects and check your response to therapy. How Hydrocortisone Works: Corticosteroids are naturally produced by the adrenal gland in the body.

Note: We strongly encourage you to talk with your health care professional about your specific medical condition and treatments. Corticosteroids have long been used as an adjuvant in severe sepsis [ 19 , 20 ] due to their anti-inflammatory properties. Nevertheless, the effects of corticosteroids on septic patients are still controversial [ 21 , 22 ]. Some previous studies showed that short-time administration of high doses of corticosteroids had no significant effects on the outcome of septic patients [ 22 , 23 ].

On the contrary, other studies have shown that prolonged administration of low-dose hydrocortisone improved shock reversal [ 24 , 25 ]. More importantly, there have been no relevant studies in the Chinese population. Thus, more well-designed studies focusing on the effects of hydrocortisone treatment in septic patients are still greatly needed.

In the present study, we measured serum inflammatory cytokines during treatments to explore the potential mechanisms by which hydrocortisone benefits severe sepsis patients. Interestingly, we found obviously attenuated pro-inflammatory cytokines in the hydrocortisone-treated patients vs.

These pro-inflammatory cytokines have been shown to activate neutrophils and stimulate the coagulation system, thus acting synergistically in inducing shock [ 26 ].

At baseline, the hydrocortisone-treated patients had an elevated level of pro-inflammatory cytokine expression. After they received hydrocortisone treatment, these serum concentrations of cytokines clearly fell. However, the levels of cytokines in non-hydrocortisone-treated patients remained relatively stable or decreased gradually during treatment.

Therefore, our results suggest that hydrocortisone reduces the pro-inflammatory condition in severe sepsis patients, thus potentially improving outcome. Our results also indicated that increased MAP, CVP, SVR, and ScvO 2 were associated with hydrocortisone treatment, evidenced by the synchronous increase of hemodynamic parameters with hydrocortisone treatment.

The hemodynamic reversal is critical for preventing septic shock and the survival of severe sepsis patients [ 32 , 33 ]. Our results were consistent with a previous study by Keh et al.

Innate immune response is the major anti-pathogen mechanisms in most septic infections. Monocytes and granulocytes eliminate bacterial pathogens via phagocytic effects. In the present study, we also explored the effect of hydrocortisone on phagocytosis of monocytes and granulocytes. Importantly, there was no significant difference in monocyte phagocytosis and granulocyte phagocytosis before vs. These data indicate that the hydrocortisone treatment does not impair the anti-bacterial function of innate immune cells and is in line with results of previous studies [ 34 , 35 ].

Treatment of severe sepsis can be very complicated, and outcome can be influenced by many factors, such as the time of finding the source of infection and administration of effective antibiotics [ 8 ].

Our observational study included a moderate number of patients, which might not have been sufficient to control all the confounding factors between the hydrocortisone-treated patients and non-hydrocortisone-treated patients. Thus, large-scale observational studies and clinical trials are still needed to validate the value of using hydrocortisone treatment in certain severe sepsis patients. In conclusion, our prospective cohort study indicates that hydrocortisone treatment has potential anti-inflammatory and hemodynamic reversal and stability effects in severe sepsis patients.

These key ameliorations may benefit the patients by preventing septic shock. Conflict of interest. National Center for Biotechnology Information , U. Journal List Med Sci Monit v. Med Sci Monit. Published online May Author information Article notes Copyright and License information Disclaimer.

Corresponding author. Corresponding Author: Cong Ding, e-mail: moc. Received Jul 13; Accepted Aug This article has been cited by other articles in PMC.

Results We treated 43 Conclusions Based on these results, we believe that hydrocortisone treatment has potential anti-inflammatory, hemodynamic reversal, and stability effects on severe sepsis patients.

Material and Methods Study population We performed a prospective cohort study to evaluate the effect of hydrocortisone treatment on preventing the development of septic shock from severe sepsis. Measurements Baseline characteristics of each patient were measured and recorded within 6 h after their admission to the Emergency Department.

Monocyte and granulocyte isolation Heparinized anti-coagulated peripheral blood was collected from the severe sepsis patients. Phagocytosis assay Phagocytosis assay was performed by following the method previously described [ 14 ]. Result Characteristics of enrolled patients As shown in Figure 1 , this prospective cohort study enrolled a total number of severe sepsis patients from the Emergency Department. Open in a separate window.

Figure 1. Flowchart of patient selection. The numbers of selected patients were plotted. Table 1 Characteristics of the patients at inclusion and their treatments. Hydrocortisone treatment reduced pro-inflammatory cytokines We measured the serum levels of multiple inflammation regulatory cytokines at time of admission and analyzed their changes during the treatment.

Figure 2. Hydrocortisone treatment promoted hemodynamic stability As shown in Figure 3 , hemodynamic parameters were plotted at different time points after admission to the Emergency Department. Figure 3.

Hydrocortisone treatment did not affect the phagocytosis of immune cells Since the innate immune cells are the major cell type that eliminates pathogens in sepsis, we evaluated the influence of hydrocortisone administration on phagocytosis of innate immune cells.

Figure 4. Discussion Although the mortality rates of infectious diseases have been significantly decreased by antibiotics and supportive care, they are still threats to health, especially in immune-compromised patients [ 15 — 17 ]. Conclusions In conclusion, our prospective cohort study indicates that hydrocortisone treatment has potential anti-inflammatory and hemodynamic reversal and stability effects in severe sepsis patients.

Footnotes Conflict of interest None. References 1. Epidemiology of severe sepsis. Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care. Crit Care Med. Martin GS. Sepsis, severe sepsis and septic shock: Changes in incidence, pathogens and outcomes.

Expert Rev Anti Infect Ther. Epidemiology of sepsis syndrome in 8 academic medical centers. The epidemiology of sepsis in the United States from through N Engl J Med. Sepsis: A new hypothesis for pathogenesis of the disease process.