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Sven-Erik Ricksten

Publications and source records attributed to Sven-Erik Ricksten.

15 recordsLinked to original sources

Effects of thrombin inhibition with melagatran on renal hemodynamics and function and liver integrity during early endotoxemia.

Sepsis is associated with an activation of the coagulation system and multiorgan failure. The aim of the study was to examine the effects of selective thrombin inhibition with melagatran on renal hemodynamics and function, and liver integrity, during early endotoxemia. Endotoxemia was induced in thiobutabarbital-anesthetized rats by an intravenous bolus dose of lipopolysaccharide (LPS; 6 mg/kg). Sham-Saline, LPS-Saline, and LPS-Melagatran study groups received isotonic saline or melagatran immediately before (0.75 micromol/kg iv) and continuously during (0.75 micromol.kg(-1).h(-1) iv) 4.5 h of endotoxemia. Kidney function, renal blood flow (RBF), and intrarenal cortical and outer medullary perfusion (OMLDF) measured by laser-Doppler flowmetry were analyzed throughout. Markers of liver injury and tumor necrosis factor (TNF)-alpha were measured in plasma after 4.5 h of endotoxemia. In addition, liver histology and gene expression were examined. Melagatran treatment prevented the decline in OMLDF observed in the LPS-Saline group (P < 0.05, LPS-Melagatran vs. LPS-Saline). However, melagatran did not ameliorate reductions in mean arterial pressure, RBF, renal cortical perfusion, and glomerular filtration rate or attenuate tubular dysfunctions during endotoxemia. Melagatran reduced the elevated plasma concentrations of aspartate aminotransferase (-34 +/- 11%, P < 0.05), alanine aminotransferase (-21 +/- 7%, P < 0.05), bilirubin (-44 +/- 9%, P < 0.05), and TNF-alpha (-32 +/- 14%, P < 0.05) in endotoxemia. Melagatran did not diminish histological abnormalities in the liver or the elevated hepatic gene expression of TNF-alpha, intercellular adhesion molecule-1, and inducible nitric oxide synthase in endotoxemic rats. In summary, thrombin inhibition with melagatran preserved renal OMLDF, attenuated liver dysfunction, and reduced plasma TNF-alpha levels during early endotoxemia.

Animals↗

N-acetylcysteine attenuates kidney injury in rats subjected to renal ischaemia-reperfusion.

BACKGROUND: The aim of the present study is to examine the effects of N-acetylcysteine (NAC), a thiol-containing anti-oxidant, on renal function and morphology, and biomarkers of oxidative stress, in rats subjected to renal ischaemia-reperfusion (IR). METHODS: Sprague-Dawley rats underwent unilateral nephrectomy and either contralateral renal IR (40 min of renal arterial clamping), or sham manipulation. Treatment groups were: (1) IR-Saline, (2) IR-NAC, (3) Sham-Saline and (4) Sham-NAC. The N-acetylcysteine was administered in a dose of 200 mg/kg intraperitoneally at 24, 12 and 2 h before, and 24, 48 and 72 h after, renal IR. Plasma creatinine was measured on days 1, 3 and 7 after IR, and kidney histology was assessed on day 7. In separate groups of animals we measured renal levels of the anti-oxidant glutathione, markers of systemic oxidative stress (plasma ascorbyl radical, urinary 8-iso-prostaglandin F2alpha), and glomerular filtration rate (GFR) by 51Cr-EDTA clearance, on day 1 after renal IR. RESULTS: Treatment with NAC ameliorated the decline in GFR and reduced hyperkalaemia on day 1 (P<0.05), lowered plasma creatinine levels on days 1 and 3 (P<0.05), and decreased renal interstitial inflammation on day 7 (P<0.05), after renal IR. Kidney glutathione levels decreased significantly in group IR-Saline in response to IR (P<0.05), but were completely repleted in group IR-NAC. Groups with renal IR injury and acute renal failure showed increased plasma ascorbyl radical levels, and elevated urinary 8-iso-prostaglandin F2alpha excretion, compared with sham (P<0.05). N-acetylcysteine treatment reduced plasma ascorbyl concentrations 24 h after renal IR (P<0.05), but had no effect on the rate of urinary 8-iso-prostaglandin F2alpha excretion. CONCLUSIONS: N-acetylcysteine improves kidney function, and reduces renal interstitial inflammation, in rats subjected to renal IR. These effects were associated with increased renal glutathione levels, and decreased plasma ascorbyl concentrations, suggesting that NAC attenuates renal and systemic oxidative stress in this model.

Acetylcysteine↗

Thoracic epidural versus intravenous patient-controlled analgesia after cardiac surgery: a randomized controlled trial on length of hospital stay and patient-perceived quality of recovery.

BACKGROUND: Perioperative thoracic epidural analgesia reduces stress response and pain scores and may improve outcome after cardiac surgery. This prospective, randomized trial was designed to compare the effectiveness of patient-controlled thoracic epidural analgesia with patient-controlled analgesia with intravenous morphine on postoperative hospital length of stay and patients' perception of their quality of recovery after cardiac surgery. METHODS: One hundred thirteen patients undergoing elective cardiac surgery were randomly assigned to receive either combined thoracic epidural analgesia and general anesthesia followed by patient-controlled thoracic epidural analgesia or general anesthesia followed by to patient-controlled analgesia with intravenous morphine. Postoperative length of stay, time to eligibility for hospital discharge, pain and sedation scores, degree of ambulation, lung volumes, and organ morbidities were evaluated. A validated quality of recovery score was used to measure postoperative health status. RESULTS: Length of stay and time to eligibility for hospital discharge were similar between the groups. Study groups differed neither in postoperative global quality of recovery score nor in five dimensions of quality of recovery score. Time to extubation was shorter (P < 0.001) and consumption of anesthetics was lower in the patient-controlled thoracic epidural analgesia group. Pain relief, degree of sedation, ambulation, and lung volumes were similar between the study groups. There was a trend for lower incidences of pneumonia (P = 0.085) and confusion (P = 0.10) in the patient-controlled thoracic epidural analgesia group, whereas cardiac, renal, and neurologic outcomes were similar between the groups. CONCLUSIONS: In elective cardiac surgery, thoracic epidural analgesia combined with general anesthesia followed by patient-controlled thoracic epidural analgesia offers no major advantage with respect to hospital length of stay, quality of recovery, or morbidity when compared with general anesthesia alone followed by to patient-controlled analgesia with intravenous morphine.

Aged↗

Vasopressors and intestinal mucosal perfusion after cardiac surgery: Norepinephrine vs. phenylephrine.

OBJECTIVES: To evaluate the potential differential effects of norepinephrine, an alpha1-, beta1-, and beta2-receptor agonist, to the alpha1-agonist phenylephrine on jejunal mucosal perfusion, gastric-arterial PCO2 gradient, and the global splanchnic oxygen demand-supply relationship after cardiac surgery. DESIGN: A randomized, prospective, interventional crossover study. SETTING: A university cardiothoracic intensive care unit. PATIENTS: Ten patients were studied during propofol sedation and mechanical ventilation after uncomplicated coronary artery bypass surgery. INTERVENTIONS: Each patient received randomly and sequentially norepinephrine (0.052+/-0.009 microg/kg/min) and phenylephrine (0.50+/-0.22 microg/kg/min) to increase mean arterial blood pressure by 30%. MEASUREMENTS AND MAIN RESULTS: Data on jejunal mucosal perfusion, jejunal mucosal hematocrit, and red blood cell velocity (laser Doppler flowmetry) as well as gastric-arterial Pco2 gradient (tonometry) and splanchnic oxygen extraction were obtained before (control) and during a 30-min drug infusion period after the target mean arterial blood pressure was reached. The procedure was sequentially repeated for the second vasopressor. Both drugs induced a 40-46% increase in systemic vascular resistance with no change in cardiac index. Neither jejunal mucosal perfusion, jejunal mucosal hematocrit, red blood cell velocity, nor gastric-arterial Pco2 gradient was affected by any of the vasopressors. Splanchnic oxygen extraction increased from 38.2% to 43.1% (p<.001) with norepinephrine and from 39.3% to 47.5% (p<.001) with phenylephrine. This increase was significantly more pronounced with phenylephrine compared with norepinephrine (p<.05). Mixed venous-hepatic vein oxygen saturation gradient increased with both drugs (p<.01), and the increase was more pronounced with phenylephrine (p<.05). Splanchnic lactate extraction was not significantly affected by any of the vasopressors. CONCLUSIONS: Phenylephrine induced a more pronounced global alpha1-mediated splanchnic vasoconstriction compared with norepinephrine. Neither of the vasoconstrictors impaired perfusion of the gastrointestinal mucosa in postcardiac surgery patients. The lack of norepinephrine-induced, alpha1-mediated impairment of gastrointestinal perfusion is not explained by a beta2-mediated counteractive vasodilation but instead by possible mucosal autoregulatory escape.

Aged↗

Autoregulation of human jejunal mucosal perfusion during cardiopulmonary bypass.

Animal studies have suggested that autoregulation of intestinal blood flow is severely impaired during cardiopulmonary bypass (CPB). We investigated the jejunal mucosal capacity to autoregulate perfusion during nonpulsatile CPB (34 degrees C) in 10 patients undergoing elective cardiac surgery. Changes in mean arterial blood pressure (MAP) were induced by altering the CPB flow rate randomly for periods of 3 min from 2.4 L/min/m2 to either 1.8 or 3.0 L/min/m2. Jejunal mucosal perfusion (JMP) was continuously recorded by laser Doppler flowmetry. A typical pattern of flow motion (vasomotion) was recorded in all patients during CPB. Variations in CPB flow rates caused no significant changes in mean JMP, jejunal mucosal hematocrit, or red blood cell velocity within a range of MAP from 50 +/- 15 to 74 +/- 16 mm Hg. The vasomotion frequency and amplitude was positively correlated with CPB flow rate. IV injections of prostacyclin (10 microg, Flolan) blunted vasomotion and increased JMP from 192 +/- 53 to 277 +/- 70 (P < 0.05) perfusion units despite a reduction in MAP from 59 +/- 12 to 45 +/- 10 mm Hg (P < 0.05). Prostacyclin-induced vasodilation resulted in loss of mucosal autoregulation (pressure-dependent perfusion). We conclude that autoregulation of intestinal mucosal perfusion is maintained during CPB in humans.

Aged↗

Differential effects of human atrial natriuretic peptide and furosemide on glomerular filtration rate and renal oxygen consumption in humans.

OBJECTIVE: Imbalance in the renal medullary oxygen supply/demand relationship can cause hypoxic medullary damage and ischemic acute renal failure. Human atrial natriuretic peptide (h-ANP) increases glomerular filtration rate in clinical acute renal failure. This would increase renal oxygen consumption due to increased tubular load of sodium. Loop diuretics are commonly used in acute renal failure. Data on the effects of loop diuretics on glomerular filtration rate and renal oxygen consumption in humans are, however, controversial. We evaluated the effects of h-ANP and furosemide on renal oxygen consumption, glomerular filtration rate, and renal hemodynamics in humans. DESIGN AND SETTING: Prospective two-agent interventional study in a university hospital cardiothoracic ICU. PATIENTS: Nineteen uncomplicated, mechanically ventilated postcardiac surgery patients with normal renal function. INTERVENTIONS: h-ANP (25 and 50 ng/kg per minute, n=10) or furosemide (0.5 mg/kg per hour, n=9). MEASUREMENTS AND RESULTS: Renal plasma flow and glomerular filtration rate were measured using the infusion clearance technique for (51)Cr-labeled EDTA and paraaminohippurate, corrected for by renal extraction of PAH. h-ANP increased glomerular filtration rate, renal filtration fraction, fractional excretion of sodium, and urine flow. This was accompanied by an increase in tubular sodium reabsorption (9%) and renal oxygen consumption (26%). Furosemide infusion caused a 10- and 15-fold increase in urine flow and fractional excretion of sodium, respectively, accompanied by a decrease in tubular sodium reabsorption (-28%), renal oxygen consumption (-23%), glomerular filtration rate and filtration fraction (-12% and -7%, respectively). CONCLUSIONS: The filtered load of sodium is an important determinant of renal oxygen consumption. h-ANP improves glomerular filtration rate but does not have energy-conserving tubular effects. In contrast, furosemide decreases tubular sodium reabsorption and renal oxygen consumption and thus has the potential to improve the oxygen supply/demand relationship in clinical ischemic acute renal failure.

Acute Kidney Injury↗

Bedside estimation of absolute renal blood flow and glomerular filtration rate in the intensive care unit. A validation of two independent methods.

OBJECTIVE: To evaluate various treatment strategies in critically ill patients with ischaemic acute renal failure, there is a need for reliable bedside measurements of total renal blood flow (RBF), glomerular filtration rate (GFR) and renal oxygen consumption without the need for urine collection. DESIGN: The continuous renal vein thermodilution method and the infusion clearance techniques were validated against the gold standard technique, the urinary clearance of paraaminohippurate (PAH) and chromium ethylenediaminetetraacetic acid, respectively. SETTING: University hospital cardiothoracic ICU. PATIENTS: Seventeen uncomplicated mechanically ventilated post-cardiac surgical patients. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Renal blood flow, GFR and the renal filtration fraction (FF) were measured for two consecutive 30-min periods by urinary clearance and compared with simultaneous measurements made by the thermodilution and infusion clearance techniques. Urinary clearance for PAH was corrected for by renal extraction of PAH. The within-group error, repeatability coefficient and the coefficient of variation were highest for the thermodilution technique and lowest for the infusion clearance technique with regard to RBF, GFR and FF. The infusion clearance technique had a higher agreement with the urinary clearance method than the thermodilution method. For estimations of RBF and GFR, the between-group errors were 33% and 43% comparing infusion clearance with urinary clearance and 65% and 67% comparing thermodilution with urinary clearance. CONCLUSIONS: The infusion clearance method had the highest reproducibility and the highest agreement with the urinary clearance reference method. The renal vein thermodilution technique is less reliable in the ICU setting due to poor repeatability and poor agreement with the reference method.

Aged↗

Recombinant human atrial natriuretic peptide in ischemic acute renal failure: a randomized placebo-controlled trial.

OBJECTIVE: Acute renal failure is associated with significant morbidity and mortality rates. Need for dialysis is an independent risk factor for early mortality after complicated cardiac surgery. Human atrial natriuretic peptide (h-ANP) is a potent endogenous natriuretic and diuretic substance. Exogenous administration of h-ANP increases glomerular filtration rate and renal blood flow in clinical acute renal failure. We have studied the effects of h-ANP on renal outcome in ischemic acute renal failure. DESIGN: A prospective, double-blind, randomized, placebo-controlled study. SETTING: Cardiothoracic intensive care units of two tertiary care centers. PATIENTS: Sixty-one patients with normal preoperative renal function suffering from postcardiac surgical heart failure requiring significant inotropic and vasoactive support. INTERVENTIONS: The patients were randomized to receive a continuous infusion of either recombinant h-ANP (50 ng.kg(-1).min(-1)) or placebo when serum creatinine increased by >50% from baseline. The treatment with h-ANP/placebo continued until serum creatinine decreased below the trigger value for inclusion or the patients fulfilled predefined criteria for dialysis. MEASUREMENTS AND MAIN RESULTS: The primary outcome variable was dialysis on or before day 21 after the start of treatment. Secondary renal outcome variables were dialysis-free survival at day 21 and creatinine clearance. Twenty-nine patients were assigned h-ANP and 30 placebo. Six (21%) patients in the h-ANP group compared with 14 (47%) in the placebo group needed dialysis before or at day 21 (hazard ratio, 0.28; 95% confidence interval, 0.10-0.73; p =.009). Eight (28%) patients in the h-ANP group compared with 17 (57%) in the placebo group suffered from the combined end point dialysis or death before or at day 21 (hazard ratio, 0.35; 95% confidence interval, 0.14-0.82; p =.017). h-ANP improved creatinine clearance in contrast to placebo (p =.040). CONCLUSIONS: Infusion of h-ANP at a rate of 50 ng.kg(-1).min(-1) enhances renal excretory function, decreases the probability of dialysis, and improves dialysis-free survival in early, ischemic acute renal dysfunction after complicated cardiac surgery.

Acute Kidney Injury↗

Effects of norepinephrine alone and norepinephrine plus dopamine on human intestinal mucosal perfusion.

OBJECTIVES: To evaluate the effect of norepinephrine alone and norepinephrine combined with dopamine on jejunal mucosal perfusion, gastric-arterial pCO(2) gradient, and global splanchnic oxygen demand-supply relationship after cardiac surgery. DESIGN: A prospective interventional study. SETTING: A university cardiothoracic intensive care unit. PATIENTS: Eighteen patients were studied during propofol sedation and mechanical ventilation after uncomplicated coronary artery bypass surgery. INTERVENTIONS: After control measurements, each patient received norepinephrine (50+/-26 ng.kg.min) to increase mean arterial blood pressure by 30% followed by addition of low-dose dopamine (2.6+/-0.3 microg x kg x min). Postdrug control measurements were performed 120 min after discontinuation of the catecholamines. MEASUREMENTS AND RESULTS: Norepinephrine induced a 32% increase in systemic vascular resistance with no change in cardiac index. Neither jejunal mucosal perfusion, assessed by laser Doppler flowmetry, nor gastric-arterial pCO(2) gradient (tonometry) was affected by norepinephrine. Splanchnic O(2)-extraction increased ( P<0.05) and this increase was positively correlated to the individual dose of norepinephrine ( r = 0.78, P<0.0001). Splanchnic lactate extraction was increased by norepinephrine ( P<0.05). None of the patients had splanchnic lactate production during norepinephrine infusion. The addition of dopamine increased cardiac index by 27% ( P<0.001) and decreased splanchnic O(2 )extraction. Dopamine increased jejunal mucosal perfusion by 32% ( P<0.001) while the gastric-arterial pCO(2) gradient remained unchanged. CONCLUSIONS: Vasopressor therapy with norepinephrine after cardiac surgery did not jeopardize intestinal mucosal perfusion in spite of a dose-dependent increase of the global splanchnic oxygen demand-supply relationship. The addition of dopamine increased intestinal mucosal perfusion.

Aged↗

Tumor necrosis factor gene polymorphism is associated with enhanced systemic inflammatory response and increased cardiopulmonary morbidity after cardiac surgery.

UNLABELLED: Cardiopulmonary bypass induces a systemic inflammatory response characterized by alterations in cardiopulmonary function. Mediators for this morbidity are the cytokines tumor necrosis factor (TNF)-alpha and interleukins. A genomic polymorphism within the TNF locus is associated with increased TNF-alpha levels and high mortality in severe trauma and sepsis. We assessed the relationship of biallelic polymorphisms of the TNF locus in patients undergoing elective cardiac surgery to release of proinflammatory cytokines and cardiopulmonary morbidity. TNF genotypes, plasma concentrations of TNF-alpha, interleukin-6, and cardiopulmonary morbidity were studied in 95 unselected, consecutive patients undergoing routine cardiac surgery. TNF genotypes were determined by the solid-phase minisequencing method. Patients homozygous for the TNFB2 allele (n = 42) displayed larger peak concentrations of TNF-alpha (11.3 +/- 1.3 versus 7.8 +/- 0.7 pg/mL; P = 0.013) and interleukin-6 (153 +/- 27 versus 87 +/- 7 pg/mL; P = 0.010) when compared with patients homozygous or heterozygous for TNFB1 (n = 53). The TNFB2 homozygotes had a higher incidence of left ventricular dysfunction (31% versus 9%; P = 0.029; odds ratio 3.84 [95% confidence interval, 1.40-24.3]), postoperative pulmonary dysfunction (24% versus 6%; P = 0.016; odds ratio 5.21 [95% confidence interval, 1.49-18.3]), and a lower pulmonary oxygenation index (29 +/- 1.9 versus 36.1 +/- 1.8; P = 0.013). Patients homozygous for the TNFB2 allele may develop an enhanced systemic inflammatory response with an increased risk of cardiopulmonary morbidity after cardiac surgery. IMPLICATIONS: The associations between tumor necrosis factor (TNF) gene polymorphism, plasma cytokines, and cardiopulmonary function after elective cardiac surgery were evaluated. Patients homozygous for the TNFB2 allele displayed larger concentrations of TNF-alpha and interleukin-6 and had an increased risk of developing left ventricular and pulmonary dysfunction compared with TNFB1 homo- or heterozygotes.

Adult↗

The effects of isoflurane-induced electroencephalographic burst suppression on cerebral blood flow velocity and cerebral oxygen extraction during cardiopulmonary bypass.

UNLABELLED: We investigated the effects of isoflurane-induced burst suppression, monitored with electroencephalography (EEG), on cerebral blood flow velocity (CBFV), cerebral oxygen extraction (COE), and autoregulation in 16 patients undergoing cardiac surgery. The experimental procedure was performed during nonpulsatile cardiopulmonary bypass (CPB) with mild hypothermia (32 degrees C) in fentanyl-anesthestized patients. Middle cerebral artery transcranial Doppler flow velocity, right jugular vein bulb oxygen saturation, and jugular venous pressure (JVP) were continuously measured. Autoregulation was tested during changes in mean arterial blood pressure (MAP) within a range of 40-80 mm Hg, induced by sodium nitroprusside and phenylephrine before (control) and during additional isoflurane administration to an EEG burst-suppression level of 6-9/min. Isoflurane induced a 27% decrease in CBFV (P < 0.05) and a 13% decrease in COE (P < 0.05) compared with control. The slope of the positive relationship between CBFV and cerebral perfusion pressure (CPP = MAP - JVP) was steeper with isoflurane (P < 0.05) compared with control, as was the slope of the negative relationship between CPP and COE (P < 0.05). We conclude that burst-suppression doses of isoflurane decrease CBFV and impair autoregulation of cerebral blood flow during mildly hypothermic CPB. Furthermore, during isoflurane administration, blood flow was in excess relative to oxygen demand, indicating a loss of metabolic autoregulation of flow. IMPLICATIONS: The effects of isoflurane on cerebral blood flow velocity (CBFV) and oxygen extraction (COE) as a function of perfusion pressure were studied. When added to fentanyl anesthesia, isoflurane induced a 27% and 13% decrease in CBFV and COE, respectively. CBFV became more pressure-dependent with isoflurane indicating an impaired autoregulation.

Aged↗

Effects of lung volume reduction surgery on left ventricular diastolic filling and dimensions in patients with severe emphysema.

STUDY OBJECTIVES: Data on the influence of lung volume reduction surgery (LVRS) on cardiac function and hemodynamics are scarce and controversial. Previous studies have focused mainly on right ventricular function and pulmonary hemodynamics. Here, we evaluated the effects of LVRS on left ventricular (LV) end-diastolic filling pattern, dimensions, stiffness, and performance, as well as pulmonary and systemic hemodynamics. DESIGN: A prospective, open, controlled study. PATIENTS: Patients with severe emphysema undergoing LVRS (10 patients). Patients scheduled for pulmonary lobectomy due to carcinoma (ie, the lobectomy group) served as control subjects (10 patients). MEASUREMENTS: LV dimensions and mitral flow velocities were measured by transesophageal, two-dimensional, Doppler echocardiography, and central hemodynamics were measured by a pulmonary artery thermodilution catheter. Measurements were performed during anesthesia in the supine position, before and after surgery, without and with passive leg elevation. RESULTS: Baseline cardiac index (CI) [- 21%], stroke volume index (SVI) [- 31%], stroke work index (SWI) [- 26%], and LV end-diastolic area index (EDAI) [- 15%] were significantly (p < 0.001) lower, whereas LV end-diastolic stiffness (LVEDS) did not differ in the LVRS group compared to the lobectomy group. The time from peak early diastolic filling to zero flow (E-dec time) [58%] and the deceleration slope of early diastolic filling (E-dec slope) [45%] were significantly higher (p < 0.01), whereas peak early diastolic filling velocity (E-max) [- 31%; p < 0.01] and the proportion of E-max vs peak late diastolic filling velocity (A-max) [ie, the E/A ratio] (- 27%; p < 0.001) were significantly lower compared to the lobectomy group. LVRS significantly increased CI (40%; p < 0.001), SVI (34%; p < 0.001), SWI (58%; p < 0.001), LV EDAI (18%; p < 0.001), E-max (44%; p < 0.01), A-max (15%; p < 0.05) and E/A ratio (28%; p < 0.01), decreased E-dec time (- 31%; p < 0.05) and E-dec slope (- 98%; p < 0.01), and had no effect on LVEDS. In the lobectomy group, surgery affected none of these variables. CONCLUSIONS: LV function is impaired in patients with severe emphysema due to small end-diastolic dimensions. LVRS increases LV end-diastolic dimensions and filling, and improves LV function.

Aged↗

Effects of N-acetyl-L-cysteine on renal haemodynamics and function in early ischaemia-reperfusion injury in rats.

1. Renal ischaemia-reperfusion (IR) severely compromises kidney function and has been shown to cause persistent abnormalities in intrarenal blood flow. The aim of the present study was to examine whether N-acetyl-L-cysteine (NAC), a thiol-containing anti-oxidant, improves renal haemodynamics and function during early reperfusion in rats subjected to renal IR. 2. Male Sprague-Dawley rats were divided into groups receiving either isotonic saline (IR-Saline; n = 8) or NAC (IR-NAC; n = 8) prior to (200 mg/kg, i.p., 24 and 12 h before acute experimentation) and during acute renal clearance experiments (bolus 150 mg/kg followed by a continuous infusion of 43 mg/kg per h, i.v.). During acute experimentation, thiobutabarbital-anaesthetized rats were subjected to a right-sided nephrectomy, followed by left kidney IR (40 min renal artery occlusion). Left kidney function and blood flow and intrarenal cortical and outer medullary perfusion measured by laser-Doppler flowmetry was analysed at baseline, during ischaemia and for 80 min of reperfusion. 3. Renal IR produced an approximate 85% reduction in glomerular filtration rate (GFR) and a pronounced increase in fractional urinary sodium excretion, throughout reperfusion, with no statistically significant differences between groups. 4. During reperfusion, total renal blood flow and cortical and outer medullary perfusion rapidly returned to levels not significantly different from baseline in both groups. The relative increase in renal vascular resistance in response to IR was more pronounced in NAC-treated rats compared with saline-treated animals (P < 0.05). 5. In conclusion, treatment with NAC did not improve kidney function during the first 80 min after renal IR. In addition, the marked reduction in GFR following reperfusion was not associated with any detectable abnormalities in intrarenal perfusion.

Acetylcysteine↗