Luis F. Carbonell

Oxidative stress in critically ill patients with systemic inflammatory response syndrome

ObjectiveTo evaluate whether critically ill patients with systemic inflammatory response syndrome, on admission to an intensive care unit, had more severe oxidative stress than those without this syndrome. DesignA prospective, cohort study. SettingA mixed medical and surgical adult intensive care unit with 12 beds. PatientsA total of 68 consecutive patients admitted to the intensive care unit. InterventionsVenous blood samples were routinely obtained within 24 hrs of admission. Measurements and Main ResultsPatients’ plasma total antioxidant capacity, the lipid peroxidation products malondialdehyde and 4-hydroxynonenal, reduced sulfhydryl groups, and nitrites/nitrates were measured by spectrophotometric technique at admission to the intensive care unit. Myeloperoxidase (enzyme-linked immunosorbent assay) and polymorphonuclear elastase (immuno-activation assay) were also measured on admission to the intensive care unit. The patients with criteria of systemic inflammatory response syndrome (n = 20) had higher Acute Physiology and Chronic health Evaluation III scores (determined by collecting the worst value within 24 hrs after admission to the intensive care unit) and plasma concentrations of lipid peroxidation products and nitrites/nitrates and lower plasma concentration of reduced sulfhydryl groups and plasma total antioxidant capacity than patients without the syndrome (n = 48). Moreover, the markers for leukocyte activation, myeloperoxidase and polymorphonuclear elastase, presented higher concentrations in the plasma of patients with systemic inflammatory response syndrome. ConclusionsPatients admitted to the intensive care unit with criteria of systemic inflammatory response syndrome had a more severe oxidative stress than patients without this syndrome.

Role of Nitric Oxide on Papillary Blood Flow and Pressure Natriuresis

This study examined whether nitric oxide synthesis blockade or potentiation (with N omega-nitro-L-arginine methyl ester [L-NAME] or N-acetylcysteine, respectively) can shift the relations between sodium excretion, papillary blood flow, and renal perfusion pressure. Papillary blood flow was measured by laser Doppler flowmetry. A low dose of L-NAME (3.7 nmol/kg per minute) reduced papillary blood flow only at high arterial pressure (140 mm Hg), but it had no effect on pressure natriuresis. Infusion of 37 nmol/kg per minute L-NAME reduced cortical blood flow by 9% at all perfusion pressures studied, lowered papillary blood flow by 8% and 19% at 120 and 140 mm Hg, respectively, and blunted the pressure-natriuresis response. The administration of 185 nmol/kg per minute L-NAME reduced cortical blood flow by 30% and decreased papillary blood flow by 25% in the range of 100 to 140 mm Hg of arterial pressure. Blockade of nitric oxide synthesis with L-NAME at all doses studied reduced papillary blood flow only at high renal perfusion pressures, but papillary blood flow remained essentially unchanged at low perfusion pressures, thus restoring papillary blood flow autoregulation. N-Acetyl-cysteine (1.8 mmol/kg) increased papillary blood flow by 9% and shifted the relations between papillary blood flow, sodium excretion, and renal perfusion pressure toward lower pressures. This effect of N-acetylcysteine on papillary blood flow was blocked by subsequent L-NAME administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma redox status relates to severity in critically ill patients

Objective To determine the relation between plasma redox status and severity of illness for patients admitted to an intensive care unit (ICU). Design A prospective cohort study. Setting A mixed medical and surgical adult ICU with 12 beds. Patients A total of 73 consecutive patients admitted to the ICU. Interventions Venous blood samples were routinely obtained within 24 hrs of admission. Measurements and Main Results Plasma total antioxidant capacity and lipoperoxides were measured by spectrophotometric technique at admission to the ICU. The plasma ratio total antioxidant capacity (mM)/lipoperoxides (&mgr;M) was used as an index of plasma redox status. Plasma concentration of the markers of leukocyte activation myeloperoxidase (enzyme-linked immunosorbent assay) and polymorphonuclear-elastase (immunoactivation assay) were also measured at admission to the ICU. Analysis of correlation between plasma ratio total antioxidant capacity/lipoperoxides and APACHE III score showed a negative association (p < .001, Spearman correlation test). Myeloperoxidase and polymorphonuclear-elastase correlated positively with Acute Physiology and Chronic Health Evaluation III scores (r2 = 0.58;p < .001; and r2 = 0.05;p = .035; respectively). Conclusions Plasma redox status relates to severity in critically ill patients. We propose that it would be reasonable to provide antioxidant therapy as part of routine management of patients admitted to a mixed ICU, regardless of the specific reason for ICU admission. Plasma redox status might become useful to evaluate the risk in critically ill patients.

Hormone replacement therapy for oxidative stress in postmenopausal women with hot flushes

Objective To assess the association of hot flushes during postmenopause with oxidative stress and to determine whether hormone replacement therapy (HRT) affects the plasma redox status of postmenopausal women. Methods We conducted a prospective clinical study of 49 postmenopausal women who have (n = 29) or do not have (n = 20) hot flushes. Twelve of the postmenopausal women with hot flushes and six without were treated with HRT (estradiol patches and medroxyprogesterone acetate) for 4 months. Plasma level of estradiol, total antioxidant status, reduced sulfhydryl groups, lipoperoxides, total cholesterol, and triglycerides were measured at 4-month intervals in both groups, before and after treatment. Results Postmenopausal women who have hot flushes, had lower total basal antioxidant status in plasma (.9 ± .01 compared with 1.14 ± .01 mmol/L), lower concentration of reduced sulfhydryl groups (145 ± 4 compared with 200 ± 3 μmol/L), and higher concentration of lipoperoxides (2.88 ± .04 compared with 2.61 ± .04 μmol/L) than women without hot flushes. After HRT, total antioxidant status and reduced sulfhydryl groups increased, and lipoperoxides decreased similarly in both groups. Hormone replacement therapy decreased the frequency of hot flushes per day from 11.2 ± 0.8 to 1.4 ± 0.3. Conclusion Hot flushes in postmenopausal women were associated with the oxidative process. Hormone replacement therapy decreases oxidative stress and the number of episodes of hot flushes. Because oxidative stress is associated with a high risk for cardiovascular diseases, HRT might protect women with hot flushes.

Depletion of liver glutathione potentiates the oxidative stress and decreases nitric oxide synthesis in a rat endotoxin shock model.

Objective To verify the effects of liver glutathione depletion on redox status and nitric oxide system in a rat endotoxic shock model. Design Prospective, randomized, controlled study on rats. Setting A cardiocirculatory research laboratory. Subjects A total of 28 Sprague-Dawley male rats (200–250 g body weight) were divided into four experimental groups. Interventions Arterial blood, liver, and lung samples were taken from each animal under sodium pentobarbital (40 mg/kg ip) anesthesia 4 hrs after lipopolysaccharide (LPS group: 5 mg/kg ip; n = 7) or vehicle (control group: isotonic NaCl sterile solution ip; n = 7) treatments,. Phorone (250 mg/kg ip) was injected to deplete glutathione in another two experimental groups of rats 30 mins before LPS (phorone+LPS group; n = 7) or vehicle (phorone group; n = 7) treatments, and 4 hrs later the same samples as in LPS and control groups were taken under anesthesia. Measurements and Main Results Compared with the control group, the LPS group presented higher plasma concentration of end products of nitric oxide metabolism nitrites/nitrates, higher lung activity of inducible nitric oxide synthase, and oxidative stress defined by increased plasma concentration of the lipid peroxides malonaldehyde and 4-hydroxynonenal, and decreased plasma total antioxidant capacity. Treatment with phorone depleted liver glutathione (80% to 90%). In the liver glutathione-depleted animals, the oxidative stress induced by LPS was potentiated and blunted the increases in inducible nitric oxide synthase and plasma nitrites/nitrates. Conclusion These results show that depletion of the liver glutathione increases the oxidative stress and decreases nitric oxide synthesis of LPS-induced shock in rats.

Hemodynamic effects of hypertonic saline in the conscious rat.

The present study examines the role of vasopressin and the sympathetic nervous system on the hemodynamic effects of an infusion of hypertonic saline (NaCl 1.5 M) in conscious rats. The cardiovascular response to hypertonic saline was similar in both untreated and hexamethonium-pretreated rats. Mean arterial pressure increased by 15 mmHg as a consequence of the elevation of total peripheral resistance, while cardiac index was decreased. The administration of an antagonist to the pressor activity of vasopressin in rats with intact reflexes, partially decreased mean arterial pressure and total peripheral resistance and increased cardiac index toward basal values. In contrast, the hemodynamic response to hypertonic saline was totally reverted when the vasopressin antagonist was injected in the hexamethonium-pretreated rats. The results of the present study indicate that the hypertensive response induced by hypertonic saline in conscious rats is due to the vasoconstrictor effects of both vasopressin and the sympathetic nervous system.

Cardiocirculatory responses to AII and AVP in conscious rats.

Cardiac and peripheral circulatory responses to changes in afterload with angiotensin II (AII) and vasopressin (AVP) were investigated in ganglion-blocked (hexamethonium) conscious rats. Cardiac output (CO) was measured by thermodilution. Both hormones were infused at a dose adjusted to increase mean arterial pressure 70% above baseline. AVP (11.4

Effect of estrogen and angiotensin-converting enzyme inhibitor on vascular remodeling in ovariectomized spontaneously hypertensive rats.

2.2 ng/kg/min. n = 6) decreased CO from 43.4