Mesna protects intestinal mucosa from ischemia/reperfusion injury

BACKGROUND: Mesna is a thiol used for the prevention of oxazaphosphorine-induced hemorrhagic cystitis. However, its antioxidant properties on renal and hepatorenal oxidative damage, as well as its mucoprotective effect on the intestinal epithelium have also been shown. The aim of this study was to investigate the potential beneficial effect of mesna on ischemia/reperfusion (I/R)-induced oxidant damage of the intestinal mucosa. MATERIALS AND METHODS: Wistar rats were subjected to intestinal I/R for 30 min, induced by occlusion of the superior mesenteric artery, followed by 60 min reperfusion. Mesna was administered at 3 time points relative to ischemia; 60 min before ischemia, at the onset of ischemia or at the onset of reperfusion. At the end of the study period, jejunal segments were excised and assessed for histopathologic score, apoptotic index using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling (TUNEL) assay and glutathione/glutathione disulfide (GSH/GSSG) ratio, as a marker of oxidative stress. RESULTS: I/R caused deterioration of histological characteristics and induction of apoptosis and oxidative stress in the intestinal mucosa. Changes regarding histology and apoptosis were prevented when mesna was administered 60 min before ischemia, but were attenuated when mesna was administered at the onset of ischemia or reperfusion. In all mesna groups, oxidative stress was reduced. CONCLUSIONS: Mesna can ameliorate or even prevent intestinal I/R injury by reducing oxidative stress.     

Antibody-induced modulation of the leukocyte CD11b integrin prevents mild but not major renal ischaemic injury.

BACKGROUND: CD11/CD18 beta(2) integrins are involved in leukocyte adhesion to the activated endothelium, and therefore represent a possible therapeutic target in the prevention of ischaemic acute renal failure (ARF). METHODS: To assess the effect of an anti-CD11b monoclonal antibody (mAb) in ischaemic ARF, uninephrectomized Fischer rats were subjected to 45 or 60 min of warm renal ischaemia, then received 1 mg of anti-CD11b mAb 5 min before reperfusion. RESULTS: After 45 min of ischaemia, renal function tests at 24 and 48 h were less altered in mAb-treated than in control rats, but after 60 min of ischaemia the same level of renal insufficiency was observed in the two groups. In parallel, milder tubular necrosis and less leukocyte infiltration were observed in the treated group after 45 min of ischaemia, but no difference was seen after 60 min compared to the control group. The mAb was detected on blood neutrophils up to 48 h after infusion and a marked down-regulation of CD11b expression on neutrophil surfaces was documented by flow cytometry. CONCLUSION: These results indicate that anti-CD11b mAb administered prior to reperfusion decreases moderate ischaemic ARF but fails to prevent renal injury secondary to prolonged ischaemia in this model.     

Early renal post-ischaemic tissue damage and dysfunction with contribution of A1-adenosine receptor activation in rat

Aim:   This study investigated the effect of a selective A₁-adenosine receptor (A₁-AR) antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), on the renal dysfunction and histological damage induced by ischaemia/reperfusion at an early stage.
Methods:   Pentobarbital anaesthetised rats were prepared for measuring renal functional variables. Ischaemia was induced by bilateral renal artery clamping for 30 min followed by a 4 h reperfusion period. In DPCPX-treated rats, it was infused (i.v.) at 10 µg/kg per min before and after renal ischaemia. Both kidneys were examined using light and electron microscopy.
Results:   The renal ischaemic challenge resulted in major histological and ultrastructural damages, which were associated with decreased creatinine clearance, absolute potassium-excretion and effective free-water reabsorption, but increased fractional sodium-excretion and urine flow during reperfusion period. In DPCPX-treated rats, the histological and ultrastructural damage to the kidneys was improved along with the decrease in creatinine clearance and increase in fractional sodium-excretion being smaller, but the increase in urine flow being larger than those of the non-treated rats, while absolute potassium-excretion and effective free-water reabsorption were equal to those of the sham-operated rats.
Conclusion:   These findings suggest that endogenous activation of A₁-AR contributes to the early development of renal ischaemia/reperfusion injury.     

Improved GFR and renal plasma perfusion following remote ischaemic conditioning in a porcine kidney transplantation model

Delayed graft function (DGF) complicates approximately 25% of kidney allografts donated after brain death (DBD). Remote ischaemic conditioning (rIC) involves brief, repetitive, ischaemia in a distant tissue in connection with ischaemia/reperfusion in the target organ. rIC has been shown to induce systemic protection against ischaemic injuries. Using a porcine kidney transplantation model with donor (63 kg) recipient (15 kg) size mismatch, we investigated the effects of recipient rIC on early renal plasma perfusion and GFR. Brain death was induced in donor pigs (n = 8) and kidneys were removed and kept in cold storage until transplantation. Nephrectomized recipient pigs were randomized to rIC (n = 8) or non‐rIC (n = 8) with one kidney from the same donor in each group. rIC consisted of 4 × 5 min clamping of the abdominal aorta. GFR was significantly higher in the rIC group compared with non‐rIC (7.2 ml/min vs. 3.4 ml/min; ΔGFR = 3.7 ml/min, 95%‐CI: 0.3–7.2 ml/min, P = 0.038). Renal plasma perfusion in both cortex and medulla measured by dynamic contrast‐enhanced magnetic resonance imaging (MRI) was significantly higher over time in the rIC group compared with non‐rIC. This experimental study demonstrated a positive effect of rIC on early graft perfusion and function in a large animal transplantation model.     

Prevention of cold ischaemia-reperfusion injury by an endothelin receptor antagonist in experimental renal transplantation.

BACKGROUND: Endothelin (ET) is known to play a role in the pathogenesis of warm ischaemic renal damage, however, little is known about its involvement in renal cold ischaemia. This study was designed to investigate the response of ET after kidney cold ischaemia, and to assess the potential protective effect of bosentan, a dual, non-selective ET(A)/ET(B) receptor antagonist, against cold ischaemia reperfusion injury in a rat model of syngeneic renal transplantation. METHODS: Kidneys from Lewis rats were transplanted, either immediately or after 5 h of cold preservation. After 48 h, contralateral nephrectomy was performed. Rats were organized into three groups: Tr-NoISC, no cold ischaemia; Tr-ISC, 5 h cold ischaemia; and Tr-BOS, 5 h cold ischaemia plus bosentan (100 mg/kg/day, from the day before transplantation until the seventh day post-transplantation). On day 7, plasma and tissue immunoreactive ET (irET), as well as ET mRNA tissue expression, were evaluated. Renal function was measured by means of serum creatinine on days 3, 4, 5 and 7, and by creatinine clearance on day 7. Conventional histology was performed. RESULTS: The ischaemic group had significantly higher plasma irET levels than the non-ischaemic group and significantly lower levels than the bosentan group. Tissue irET levels and ET mRNA expression were similar in the ischaemic and bosentan groups and were higher than in the non-ischaemic group. Throughout the follow-up, serum creatinine was significantly higher in the ischaemic group than in the bosentan group. Moreover, creatinine decreased rapidly in the bosentan group after nephrectomy, whereas it continued to increase for 48 h in the ischaemic group. Kidneys from the ischaemic group showed a higher degree of tubular-cell necrosis and epithelial-cell detachment than kidneys from the bosentan group. CONCLUSIONS: We conclude that cold ischaemia and preservation damage induces an increase in renal ET mRNA and irET expression in the reperfusion phase, contributing both to the deterioration of renal function and to tubular necrosis. Bosentan is effective in protecting kidneys from this cold ischaemia reperfusion damage. Non-selective ET(A)/ET(B) receptor antagonists might be potentially useful in clinical renal transplantation.     

Remote ischaemic pre‐conditioning for the prevention of acute kidney injury

Acute kidney injury (AKI) is a common complication associated with high morbidity and mortality in hospitalized patients. One potential mechanism underlying renal injury is ischaemia/reperfusion injury (IRI), which attributed the organ damage to the inflammatory and oxidative stress responses induced by a period of renal ischaemia and subsequent reperfusion. Therapeutic strategies that aim at minimizing the effect of IRI on the kidneys may prevent AKI and improve clinical outcomes significantly. In this review, we examine the technique of remote ischaemic preconditioning (rIPC), which has been shown by several trials to confer organ protection by applying transient, brief episodes of ischaemia at a distant site before a larger ischaemic insult. We provide an overview of the current clinical evidence regarding the renoprotective effect of rIPC in the key clinical settings of cardiac or vascular surgery, contrast‐induced AKI, pre‐existing chronic kidney disease (CKD) and renal transplantation, and discuss key areas for future research.     

L-Arginine given after ischaemic preconditioning can enhance cardioprotection in isolated rat hearts.

OBJECTIVE: Ischaemic or pharmacological preconditioning with L-arginine has been reported to be insufficient for optimal cardioprotection. The ability of nitric oxide (NO) to enhance ischaemic preconditioning was assessed, and the role of L-arginine-induced ischaemic preconditioning in myocardial protection was determined. METHODS: Isolated rat hearts were prepared and divided into six groups: control hearts (control, n=6) were perfused without global ischaemia at 37 degrees C for 160 min; global ischaemia hearts (GI, n=6) were subjected to ischaemia for 20 min and reperfusion for 120 min; ischaemic preconditioned hearts (IP, n=6) received 2 min of zero-flow global ischaemia followed by 5 min reperfusion, before 20 min of global ischaemia; L-arginine hearts (ARG, n=6) received 1 mmol/l L-arginine for 5 min, before 20 min of global ischaemia; ischaemic preconditioning plus nitro-L-arginine methyl ester hearts (IP+L-NAME, n=6) received 2 min of ischaemic preconditioning and 5 min reperfusion with 3 mmol/l L-NAME in Krebs-Henseleit buffer, before 20 min of global ischaemia; and ischaemic preconditioning plus L-arginine hearts (IP+ARG, n=6) received 2 min of ischaemic preconditioning and 5 min reperfusion with 1 mmol/l L-arginine in Krebs-Henseleit buffer. Haemodynamic parameters and coronary flow were recorded continuously. Nitrites and nitrates (NOx) were measured 5 and 60 min after reperfusion, and infarct size was also determined. RESULTS: In the IP+ARG group, significant amelioration and preservation of left ventricular peak developed pressure and coronary flow was observed compared with the GI, IP, ARG and IP+L-NAME groups. Infarct size in the IP+ARG group was reduced significantly compared with that in the GI, IP, ARG and IP+L-NAME groups. Significant preservation of NOx was observed during reperfusion in the IP+ARG group compared with the GI group. CONCLUSIONS: Inhibition of NO synthase with L-NAME had little impact on ischaemic preconditioning, suggesting that endogenous NO is not a major mediator of ischaemic preconditioning. Nevertheless, enhancement of the effects of ischaemic preconditioning can be achieved with L-arginine, a precursor of NO, improving post-ischaemic functional recovery and infarct size in the isolated rat heart.     

Effects of diltiazem on postischaemic renal cortical microcirculation in the pig

Diltiazem--a calcium entry blocker--was tested in a porcine model under continuous chlormethiazole-pancuronium anaesthesia as protection against renal failure following 60 min of renal ischaemia. Fourteen pigs were randomly allocated to one experimental (diltiazem and ischaemia) and one control group (only ischaemia) (n = 7 in each). Diltiazem was administered as a continuous intravenous infusion started before the ischaemic insult. In two additional animals diltiazem was given but ischemia was not induced. The postischaemic renal cortical microcirculation was simultaneously investigated in four different regions in the left kidney during the first 4 h of reperfusion. Laser Doppler flowmetry (LDF) was performed in two different regions and measurement of tissue oxygenation was done in two other regions. In the two animals treated with diltiazem without ischaemia, only minor variations in central haemodynamic and renal microcirculatory parameters were evident. In the control group (ischaemia), superficial renal cortical blood flow (Qsrc) decreased from 49 +/- 11 (s.d.) arbitrary units at baseline to 24 +/- 4 arb. units 4 h after start of reperfusion (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Dexmedetomidine protects against myocardial ischaemia/reperfusion-induced renal damage in rats

Background

Myocardial ischaemia/reperfusion (MI/R) may induce renal damage. Our aim was to investigate the effects of dexmedetomidine (DEX) administration at two different timings either before or after ischaemia on renal damage induced by MI/R.

Role of PI3-kinase/Akt signalling pathway in renal function and cell proliferation after renal ischaemia/reperfusion injury in mice

BACKGROUND: PI3K/Akt pathway has been shown to play a critical role in the regulation of mitogenic signalling, apoptosis, cell proliferation and survival in a variety of cells and tissues. The aim of the present study was to investigate the role of PI3K/Akt pathway in the renal ischaemia/reperfusion. METHODS: Four experimental groups, sham-operative mice, vehicle-delivered and wortmannin-treated ischaemic/reperfusion injury mice, wortmannin-treated normal mice were designed to examined serum blood urea nitrogen level, renal injury, proliferating cell nuclear antigen protein and Akt phosphorylation status at 30 min, 90 min, 24 h, 48 h of reperfusion after ischaemic treatment. Wortmannin or its vehicle was given intraperitoneally at 4 h before surgery. Blood urea nitrogen was measured, and immunohistochemistry and western blotting were used to detect the components of PI3K/Akt pathway in the ischaemic/reperfusion injury kidney. RESULTS: PI3-kinase inhibitor wortmannin imposes a deleterious effect on serum blood urea nitrogen level, renal function after renal ischaemia/reperfusion injury in mice. The renal cell proliferation increased after ischaemia/reperfusion injury in mouse, which could be inhibited by wortmannin. Phosphorylation of Akt was increased after ischaemia/reperfusion in the mouse kidney, and reduced by wortmannin administration. CONCLUSION: This primary study suggests that PI3-kinase/Akt signalling pathway play an important role in the regulation of the renal repair after ischaemia/reperfusion injury.     

-Arginine given after ischaemic preconditioning can enhance cardioprotection in isolated rat hearts

Objective: Ischaemic or pharmacological preconditioning with -arginine has been reported to be insufficient for optimal cardioprotection. The ability of nitric oxide (NO) to enhance ischaemic preconditioning was assessed, and the role of -arginine-induced ischaemic preconditioning in myocardial protection was determined. Methods: Isolated rat hearts were prepared and divided into six groups: control hearts (control, n=6) were perfused without global ischaemia at 37°C for 160 min; global ischaemia hearts (GI, n=6) were subjected to ischaemia for 20 min and reperfusion for 120 min; ischaemic preconditioned hearts (IP, n=6) received 2 min of zero-flow global ischaemia followed by 5 min reperfusion, before 20 min of global ischaemia; -arginine hearts (ARG, n=6) received 1 mmol/l -arginine for 5 min, before 20 min of global ischaemia; ischaemic preconditioning plus nitro- -arginine methyl ester hearts (IP+ -NAME, n=6) received 2 min of ischaemic preconditioning and 5 min reperfusion with 3 mmol/l -NAME in Krebs–Henseleit buffer, before 20 min of global ischaemia; and ischaemic preconditioning plus -arginine hearts (IP+ARG, n=6) received 2 min of ischaemic preconditioning and 5 min reperfusion with 1 mmol/l -arginine in Krebs–Henseleit buffer. Haemodynamic parameters and coronary flow were recorded continuously. Nitrites and nitrates (NOx) were measured 5 and 60 min after reperfusion, and infarct size was also determined. Results: In the IP+ARG group, significant amelioration and preservation of left ventricular peak developed pressure and coronary flow was observed compared with the GI, IP, ARG and IP+ -NAME groups. Infarct size in the IP+ARG group was reduced significantly compared with that in the GI, IP, ARG and IP+ -NAME groups. Significant preservation of NOx was observed during reperfusion in the IP+ARG group compared with the GI group. Conclusions: Inhibition of NO synthase with -NAME had little impact on ischaemic preconditioning, suggesting that endogenous NO is not a major mediator of ischaemic preconditioning. Nevertheless, enhancement of the effects of ischaemic preconditioning can be achieved with -arginine, a precursor of NO, improving post-ischaemic functional recovery and infarct size in the isolated rat heart.     

Ischaemic preconditioning protects the rat kidney from reperfusion injury.

OBJECTIVE: To examine the possible role of ischaemic preconditioning (IPC), an adaptive pathophysiological phenomenon that increases tolerance to ischaemia-reperfusion (I-R) injury, in renal protection when rats are presented with an I-R challenge. MATERIALS AND METHODS: Female Wistar rats (n=36) were divided randomly into four groups: (A) sham-operated controls; (B) IPC only; (C) renal ischaemia (RI) only; and (D) IPC+RI. The left kidney in groups B and D was preconditioned with four cycles of renal artery occlusion lasting 4 min, each occlusion separated by 11 min of reperfusion. The ischaemic insult, applied in groups C and D, comprised 40 min of sustained left renal artery occlusion. In Group D, the IPC cycle was completed 5 min before the start of the ischaemic insult. Differential left renal function was calculated by 99mTc-labelled dimercaptosuccinic acid scintigraphy at 0, 2 and 9 days after treatment, and expressed as a percentage of the total renal uptake. RESULTS: The mean (sem) maximum decrease in left renal function, to 14.5 (4.3)% of the total, occurred on day 2 in Group C. The equivalent value in Group D showed relative preservation of function, at 36.0 (3.5)% (P=0.001 compared with Group C). The mean left renal function improved by day 9, to 39.6 (6.7)% (Group C) and 48.6 (1.5)% (Group D). The mean left renal function in Group B (50.5-53.9%) did not differ from that in controls (49.4-51.4%). CONCLUSION: An IPC regimen applied 5 min before RI in the rat significantly protects it from the functional impairment associated with ischaemia and reperfusion.     

Adenosine triphosphate regeneration and function in the rat kidney following warm ischaemia.

Tissue levels of adonosine triphosphate (ATP) have been measured in rat kidneys following periods of warm ischaemia: (1) immediately after the ischaemic period and (2) after the kidney had been reperfused with blood for 10 min. ATP levels at the end of the period of ischaemia are similar for ischaemic periods of 10 to 60 min and give no indication of the kidneys subsequent functional ability. The amount of ATP regenerated in 10 min of reperfusion correlates both with the duration of the period of ischaemia and with the subsequent functional ability of the kidney.     

The impact of warm ischaemia on renal function after laparoscopic partial nephrectomy

Authors from Cleveland assessed the impact of warm ischaemia on renal function, using their large database of laparoscopic partial nephrectomies for tumour. While agreeing that renal hilar clamping is essential for precise excision of the tumour, and other elements of the operation, the authors indicate that warm ischaemia may potentially damage the kidney. However, they found that there were virtually no clinical sequelae from warm ischaemic of up to 30 min. They also found that advancing age and pre-existing renal damage increased the risk of postoperative renal damage. OBJECTIVE: To assess the effect of warm ischaemia on renal function after laparoscopic partial nephrectomy (LPN) for tumour, and to evaluate the influence of various risk factors on renal function. PATIENTS AND METHODS: Data were analysed from 179 patients undergoing LPN for renal tumour under warm ischaemic conditions, with clamping of the renal artery and vein. Renal function was primarily evaluated in two groups of patients: 15 with tumour in a solitary kidney, who were evaluated by serial serum creatinine measurements; and 12 with two functioning kidneys undergoing unilateral LPN, and evaluated by renal scintigraphy before and 1 month after LPN to quantify differential renal function. Also, in all 179 patients, mean serum creatinine data at baseline, 1 day after LPN, at hospital discharge, and at the last follow-up were provided as supportive evidence. Logistic regression analyses were used to assess the effect of various risk factors on renal function after LPN, i.e. patient age, baseline serum creatinine, tumour size, solitary kidney status, duration of warm ischaemia, pelvicalyceal suture repair, urine output and intravenous fluids during LPN. RESULTS: In the group of patients with a solitary kidney the mean warm ischaemia time was 29 min, kidney parenchyma excised 29%, and serum creatinine at baseline, discharge, the peak after LPN and at the last follow-up (mean 4.8 months) 1.3, 2.3, 2.8, and 1.8 mg/dL, respectively. One patient (6.6%) required temporary dialysis. In the second group, assessed by renal scintigraphy, the function of the operated kidney was reduced by a mean of 29%, commensurate with the amount of parenchyma excised. For all 179 patients, a combination of age > or = 70 years and a serum creatinine level after LPN of > or = 1.5 mg/dL correlated with a higher serum creatinine after LPN. On logistic regression, baseline serum creatinine and solitary kidney status were the only variables significant for serum creatinine status after LPN. CONCLUSIONS: The bloodless field provided by renal hilar clamping is important for precise tumour excision, pelvicalyceal suture repair and securing parenchymal haemostasis during LPN. However, renal hilar clamping causes warm ischaemia. These data indicate that the clinical sequelae of warm ischaemic renal injury of approximately 30 min are minimal. Advancing age and pre-existing azotaemia increase the risk of renal dysfunction after LPN, especially when the warm ischaemia exceeds 30 min.     

Renal hyaluronan accumulation and hyaluronan synthase expression after ischaemia-reperfusion injury in the rat.

BACKGROUND: Hyaluronan (HA) is a connective tissue component with unique water binding and pro-inflammatory properties. It has been suggested that HA is involved in normal renal water handling but also in several pathological conditions such as organ rejection and ischaemia-reperfusion (IR) injury. METHODS: In anaesthetized normal rats we investigated if renal cortical HA accumulation and the intrarenal distribution and expression of HA synthases (Has 1, 2 and 3) correlate with renal dysfunction after renal IR injury. After 20, 30 or 45 min of unilateral renal ischaemia and 72 h of reperfusion, renal function and cortical HA content were measured. Has 1, 2 and 3 mRNA were determined in control and IR kidneys subjected to 45 min ischaemia and 72 h reperfusion. RESULTS: IR kidneys had reduced urine concentrating ability, potassium excretion, glomerular filtration rate (GFR) and renal blood flow. On average, IR kidneys had more than 10 times higher amounts of cortical HA than the contralateral control kidney and their water content was elevated while medullary HA was largely unaffected. Has 2 expression in the cortex was heavily up-regulated in IR kidneys while Has 3 remained at control levels. Has 1 could never be detected. There was a direct correlation between the amount of cortical HA and the time period of ischaemia and also between the cortical amount of HA and depression of functional parameters. CONCLUSIONS: IR injury depresses parameters of renal function, which coincides with an elevated cortical HA content and Has 2 expression. The enhanced Has 2 expression indicates that the cortical HA accumulation is primarily dependent on increased HA synthesis and not impaired degradation/elimination. The water binding and pro-inflammatory properties of HA may contribute to renal dysfunction after IR.     

Evaluation of a preservation solution containing fructose-1,6-diphosphate and mannitol using the isolated perfused rat kidney. Comparison with Euro-Collins and University of Wisconsin solutions

The renal preservation ability of a flushing solution (F-M)with fructose-1,6-diphosphate (1 g/dl) and mannitol (2 g/dl)during cold ischaemia was studied with the isolated perfusedrat kidney model and compared with the Euro-Collins (EC) andUniversity of Wisconsin (UW) solutions. Kidneys were storedin hypothermia for 4 and 18 h after initial flushing with thesolution being tested, and then reperfused at 37°C in anisolated perfusion circuit for 90 min with a Krebs-Henseleitsolution containing 4.5% albumin. Forty-four kidneys were studied and divided in a control groupand six study groups according to the cold ischaemia time andflushing solution used. Renal functional parameters of plasmaflow rate (PFR), renal vascular resistance (RVR), urine flowrate (UFR) glomerular filtration rate (GFR), fractional (FRNa)and net (TNa) sodium reabsortion were assessed during reperfusion.Conventional histology and malon-dialdehyde tissue levels (MDA)were also evaluated. Our results show that PFR, RVR, and UFR were similar in allstudy groups. After 4 and 18 h of cold ischaemia, GFR, FRNaand TNa were better, and conventional histology worse in F-Mthan in EC flushed kidneys. After 4 and 18 h of cold ischaemia,GFR, FRNa and TNa, in fact, were not different between F-M andUW flushed kidneys. After 4 h of cold ischaemia, conventionalhistology was similar in F-M and UW flushed kidneys. Nevertheless,after 18 h of cold ischaemia, UW flushed kidneys showed worsehistological parameters than F-M flushed kidneys. After 4 hof cold ischaemia, MDA was similar in kidneys flushed with thethree solutions. After 18 h of cold ischaemia MDA was higherin EC than in F-M or UW flushed kidneys. In summary, our newly developed cold storage solution showspromising results in renal preservation and its ability to preserveis at least as good as UW solution assessed in the isolatedperfused rat kidney.     

Effects of propofol on the systolic and diastolic performance of the postischaemic,reperfused myocardium in rabbits

BACKGROUND AND OBJECTIVE: The effect of propofol on myocardial dysfunction during ischaemia and reperfusion is controversial yet important because of its frequent use in cardiac anaesthesia. Although animal studies suggest a free radical-scavenging potential, the cardioprotective properties of propofol have not been demonstrated consistently in vivo. Previous studies focused on systolic function while diastolic function may be a more sensitive marker of ischaemic injury. The main aim was to document the effect of propofol on diastolic function in isolated, blood perfused rabbit hearts subjected to moderate global ischaemia and reperfusion. METHODS: Propofol 168 micromol L(-1), or the equivalent of its vehicle, Intralipid, was administered to 34 paced parabiotic Langendorff blood-perfused isolated rabbit hearts before and after 30 min of global normothermic ischaemia. Recovery of systolic function was quantified with the maximum rate of rise of left ventricular pressure. Diastolic performance was assessed using the time constant of the decline in left ventricular pressure (tau) and chamber stiffness (VdP/dV at 12 mmHg). RESULTS: Recovery of systolic function during reperfusion was comparable in the two groups. There was no difference in left ventricular pressure between the two groups at any time during the experiments. Chamber stiffness increased significantly during ischaemia and reperfusion in the control group (from 34 +/- 9 to 54 +/- 8 mmHg during ischaemia, and 43 +/- 5 mmHg after 30 min reperfusion; mean +/-95% confidence interval) but not in the propofol-treated group (29 +/- 5, 36 +/- 8 and 30 +/- 8 at baseline, ischaemia and 30 min reperfusion, respectively). CONCLUSIONS: Propofol has no protective effect on active relaxation or on systolic function in the present model, but it reduces ischaemic and postischaemic chamber stiffness.     

A comparative study of several agents alone and combined in protection of the rodent kidney from warm ischaemia: Methylprednisolone,propranolol, furosemide,mannitol, and adenosine triphosphate-magnesium chloride

Summary The effect of 60 min of in situ warm ischaemia (37°C) on renal function was investigated in the rat model. In addition, the effect of pretreatment with intravenously administered furosemide, mannitol, propranolol, methylprednisolone, and adenosine triphosphate-magnesium chloride (ATP-MgCl₂), singly or in combination, was studied. The ischaemic kidney was effectively protected by the administration of methylprednisolone alone but not by furosemide, mannitol, ATP-MgCl₂, or propranolol singly or in combination. These results demonstrate that rat kidneys subjected to 60 min of warm ischaemia can be safely protected with methylprednisolone pretreatment (3mg/100 g of body weight) 30 min before warm ischaemia.     

Nigella sativa protects against ischaemia/reperfusion injury in rat kidneys.

BACKGROUND: Renal ischaemia followed by reperfusion leads to acute renal failure in both native kidneys and renal allografts, which is a complex pathophysiologic process involving hypoxia and free radical (FR) damage. The oil of Nigella sativa (NSO) has been subjected to considerable pharmacological investigations that have revealed its antioxidant activity in different conditions. But there is no previously reported study about its effect on ischaemia/reperfusion (I/R) injury of kidneys. The aim of this study was to investigate the possible effects of NSO in I/R-induced renal injury in rats. METHODS: Thirty healthy male Wistar albino rats were randomly assigned to one of the following groups: control, sham, I/R, NSO+I/R, I/R+NSO and NSO. I/R, NSO+I/R and I/R+NSO rats were subjected to bilateral renal ischaemia followed by reperfusion and then all the rats were killed and kidney function tests, serum and tissue oxidants and antioxidants were determined and histopathological examinations were performed. RESULTS: Pre- and post-treatment with NSO produced reduction in serum levels of blood urea nitrogen (BUN) and creatinine caused by I/R and significantly improved serum enzymatic activities of superoxide dismutase (SOD) and glutathion peroxidase (GSH-Px) and also tissue enzymatic activities of catalase (CAT), SOD and GSH-Px. NSO treatment resulted in lower total oxidant status (TOS) and higher total antioxidant capacity (TAC) levels and also significant reduction in serum and tissue malondialdehyde (MDA), nitric oxide (NO) and protein carbonyl content (PCC) that were increased by renal I/R injury. The kidneys of untreated ischaemic rats had a higher histopathological score, while treatment with NSO nearly preserved the normal morphology of the kidney. CONCLUSIONS: In view of previous observations and our data, with the potent FR scavenger and antioxidant properties, NSO seems to be a highly promising agent for protecting tissues from oxidative damage and preventing organ damage due to renal I/R.