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)     

Postischaemic regional microvascular variations in the porcine renal cortex

Regional microcirculatory differences in the superficial renal cortex were studied before and during 4 h following 60 min of renal ischaemia in seven pigs under continuous intravenous chlormethiazole-pancuronium anaesthesia. Superficial renal cortical blood flow (Qsrc) was measured by laser Doppler flowmetry (LDF) in two different regions. In two other different regions tissue oxygenation (PtO2) was measured by surface electrodes. Thus, microcirculatory measurements were simultaneously carried out in each animal in four different regions of the left kidney. After 60 min of renal ischaemia, pronounced renal cortical microcirculatory disturbances were found. The regional microcirculatory differences were notable, especially after ischaemia. On average, Qsrc was 49 +/- 11 (s.d.) arbitrary units at baseline and decreased to 24 +/- 4 arb. units 4 h after start of reperfusion (P less than 0.05). Before ischaemia the average difference between Qsrc simultaneously measured in two different parts of the renal cortex was 26 +/- 15% of the mean of both measurements, and it was 30 +/- 22% 4 h after start of reperfusion (n.s.). Mean PtO2 (m-PtO2) was on average 4.5 +/- 1.3 kPa at baseline and 2.4 +/- 1.5 kPa 4 h after start of reperfusion (P less than 0.05). The average difference between m-PtO2 simultaneously measured in two different parts of the renal cortex at baseline was 24 +/- 13% of the mean of both measurements and 57 +/- 49% 4 h after start of reperfusion (n.s.). In each of the two measured regions of the renal cortex m-PtO2 was calculated from 160 small tissue volumes distributed within a surface area of about 1 mm2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Variations in superficial renal cortical blood flow and tissue oxygenation: an experimental porcine model

Renal cortical microcirculation and its relation to inulin clearance, central haemodynamics and pulmonary gas exchange were studied in eight pigs under continuous intravenous chlormethiazole-pancuronium anaesthesia. The animals were studied during six consecutive 30-min periods. Four of the animals were also studied 19 h after the first period. In the superficial renal cortex, regional blood flow (Qsrc) was measured by laser Doppler flowmetry (LDF) and tissue oxygenation (PtO2) by surface microelectrode technique. Central haemodynamics and pulmonary gas exchange values were distributed within normal ranges. The importance of stable central haemodynamics in order to perform accurate microcirculatory measurements in the renal cortex was documented. A significant relation between Qsrc and pulmonary capillary wedge pressure (PCWP) was found (P less than 0.0001) despite the fact that PCWP was distributed within a range of only 0.7 kPa (all values were well within the normal range for pigs). No other relationships were found between central haemodynamics or pulmonary gas exchange variables and renal microcirculatory parameters. Concerning renal microcirculation and inulin clearance, at least 2-3 h may be required for stabilization after surgery. The average temporal variability between measurements performed every 30 min in each animal was 6 +/- 7% (s.d.) in the LDF values and 21 +/- 21% in the PtO2 values (mean PtO2). No correlations were found between Qsrc or PtO2 and inulin clearance. Since the haemodynamic parameters, pulmonary gas exchange variables and haematocrit were distributed within narrow ranges, we regard the temporal microcirculatory variability obtained here as normal in this experimental situation, and consider the porcine model well suited for further studies concerning renal microcirculation.     

Low arginine plasma levels do not aggravate renal blood flow after experimental renal ischaemia/reperfusion.

BACKGROUND: Ischaemic renal dysfunction is present in many clinical settings, including cardiovascular surgery. Renal hypoperfusion seems to be the most important pathophysiologic mechanism. Arginine plasma levels are rate limiting for NO synthesis, and low arginine plasma levels are seen after major vascular surgery. OBJECTIVE: to establish the effects of low arginine plasma levels on renal blood flow after renal ischaemia/reperfusion. DESIGN: Wistar rats were used in this unilateral renal ischaemia/reperfusion model. After 70 min of ischaemia, the kidney was reperfused for 150 min. Arginase infusion was used to lower arginine plasma levels. Blood flow measurement was performed at the end of the experiment using radiolabelled microspheres. Additional experiments were performed for histopathology. RESULTS: Arginase efficiently decreased arginine plasma levels to about 50% of normal. There was a lower blood flow in the ischaemic kidney than the contralateral (non-ischaemic) kidney. Lowering arginine plasma levels did not reduce renal blood flow in the ischaemic kidney. Renal histopathology was not influenced by lowered arginine plasma levels. CONCLUSIONS: Lowering arginine plasma levels did not affect blood flow or histology following renal ischaemia and reperfusion.     

The triphasic pattern of skeletal muscle blood flow in reperfusion injury: an experimental model with implications for surgery on the acutely ischaemic lower limb

A new model of acute lower limb ischaemia has been developed in the rat hind limb. The model has been used to examine the influence on skeletal muscle blood flow of increasing periods of ischaemia and reperfusion. Following restoration of blood flow after 2-6h ischaemia initial gastrocnemius muscle blood flow was reduced. The severity of initial low reflow, indicated by mean perfusion ratios at 0 and 10 min, correlated with the duration of preceding ischaemia (r = 0.83, p less than 0.05) and was greatest in limbs subjected to 6h ischaemia (p less than 0.01 vs. controls at 0, 10 and 60 min after revascularisation). After 60-240 min, reperfusion muscle blood flow returned to normal in limbs subjected to 3, 4 or 5 h ischaemia. In contrast, peak muscle blood flow in limbs that had been ischaemic for 6 h occurred after 120 min, although perfusion remained less than that measured in control limbs (p less than 0.05:6 h ischaemia, 120 min vs. control)-(relative reperfusion). Limbs reperfused after 6 h ischaemia demonstrated a subsequent decline in muscle blood flow between 120 min and 240 min following revascularisation (p less than 0.05). In addition, muscle blood flow at 240 min was no different to that in a totally ischaemic limb (p less than 0.01 vs. controls; ns vs. ischaemic limb) thus representing reperfusion injury.     

Mesna: a novel renoprotective antioxidant in ischaemic acute renal failure.

BACKGROUND: Reactive oxygen species (ROS) play a key role in renal ischaemia-reperfusion injury. After establishing the in vitro anti-oxidative potential of mesna, a sulfhydryl-containing compound, its effect on kidney function and morphology in a rat model of ischaemic acute renal failure (ARF) was examined. METHODS: Mesna (180 mg/kg) was administered at different time points relative to ischaemia and/or reperfusion onset. Kidney function was assessed by glomerular filtration rate (GFR) and fractional sodium excretion (FE(Na)) before a 45-min period of unilateral renal artery clamping and following 90 min of reperfusion. Mesna was administered by bolus, 30 min before the induction of ischaemia, 5 min before ischaemia, 5 min before reperfusion, and 5 min after the onset of reperfusion. RESULTS: Mesna improved function of the ischaemic kidney at each administration. When mesna was administered 5 min before the onset of reperfusion, GFR reached 90-100% of its pre ischaemic value and FE(Na) was improved by 75%. The beneficial effect of mesna was also demonstrated by light and electron microscopy. Kidneys treated with mesna 5 min before reperfusion resembled ischaemic non-reperfused kidneys and showed subtle morphological and ultrastructural changes compared with ischaemic-reperfused kidneys. Mesna had no haemodynamic effect on renal blood flow and did not induce any osmotic diuresis. CONCLUSIONS: We suggest that mesna acts as an antioxidant. Its antioxidant potential together with optimal protection achieved when administered 5 min before reperfusion, supports the conclusion that mesna scavenges ROS generated at the onset of reperfusion, thus diminishing reperfusion injury and organ damage.     

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.     

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.     

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.     

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.     

Failure of verapamil to protect from ischaemic renal damage

To reassess the reported protective effects of verapamil in renal ischaemia, we perfused the left kidney of uninephrectomized female Wistar rats with verapamil (0.1 and 1.0 mg/kg) immediately prior to clamping the renal artery for 60 min. When compared to controls, both doses of verapamil failed to afford protection with respect to urine flow, plasma creatinine, creatinine clearance or histology 24 and 48 h after ischaemia, whereas the purine nucleotide inosine (200 mg/kg) was partially protective: mean plasma creatinine 48 h after ischaemia (+/- SEM) was 547 +/- 54 mumol/l in controls, 686 +/- 38 mumol/l with 0.1 mg/kg verapamil, 491 +/- 68 mumol/l with 1.0 mg/kg verapamil and 374 +/- 45 mumol/l with inosine (p less than 0.05 vs. controls). Using the same model, the effect of verapamil 1.0 mg/kg on renal blood flow, creatinine clearance, urine flow and arterial pressure was studied in the first 2 h after ischaemia. Although significant amounts of verapamil were present in the kidney during ischaemia as evidenced by decreases in systemic blood pressure and in renal vascular resistance after unclamping the renal artery, the early course of renal failure was not altered when compared to controls. In conclusion, we have been unable to confirm earlier reports of a protective effect of verapamil in this rat model of ischaemic renal failure. If there is such an effect, its demonstration appears to depend on very specific experimental circumstances. Based on the results of this and other studies, verapamil is unlikely to afford an impressive overall benefit in the clinical setting of ischaemic renal failure.     

Intra- and post-operative assessment of renal cortical perfusion by laser Doppler flowmetry in renal transplantation in the rat

Renal blood flow (RBF) in the period immediately following transplantation has an important prognostic value. Here we report for the first time on the use of laser Doppler flowmetry (LDF) for the measurement of renal cortical perfusion (RCP) during all the important steps in renal transplantation. Left orthotopic kidney transplantation was performed in Lewis rats (n = 14) after 2 h of cold ischaemia and preservation in EuroCollins solution. Under baseline conditions, RCP in the donor and recipient kidneys were similar with a coefficient of variability of 11 and 12%, respectively. There was a progressive increase in RCP during the first 60 min after transplantation with a return to normal values 2 weeks later. In conclusion, LDF provides a rapid and continuous measure of RCP without interference to the operative site and may prove a useful tool for the measurement of RBF during kidney transplantation.     

Effects of fluid and dobutamine treatment on renal function during partial superior mesenteric artery occlusion and reperfusion

OBJECTIVE: We compared the effects of dobutamine, fluid resuscitation and their combination on renal function during experimental intestinal ischaemia and reperfusion. MATERIALS AND METHODS: Superior mesenteric artery (SMA) blood flow was reduced to 30% from the baseline for 120 minutes in 24 anaesthetized pigs (ischaemic group); 24 pigs (sham group) served as non-ischaemic controls. The animals were further assigned into four treatment arms. In the control arms, the animals were given only basic fluid therapy. In the fluid therapy arms, pulmonary capillary wedge pressure (PCWP) was maintained at 10 mmHg with intravenous fluids. In the dobutamine treatment arm, dobutamine hydrochloride was infused at a dose of 10 microg/min/kg. In the combined dobutamine-fluid therapy arms, dobutamine at 10 microg/min/kg was given and PCWP was maintained at 10 mmHg with fluids. At 120 minutes, the occluder was released in all study groups and the animals were followed for an additional 60 minutes. Renal function was evaluated by means of serum and urine creatinine. urine volume and creatinine clearance. Systemic and regional haemodynamics as well as intramucosal pH, intramucosal-arterial pCO2 gradient, and portal venous-arterial lactate gradient were measured. RESULTS: In the ischaemic groups, diuresis increased and serum and urine creatinine decreased significantly in fluid (p < 0.01, p < 0.01 and p < 0.05, respectively) and dobutamine-fluid (p < 0.01, p < 0.001 and p < 0.001, respectively) treated groups during SMA ischaemia. After SMA reperfusion, diuresis decreased in control group (p < 0.05) and in animals treated with dobutamine alone (p < 0.01). In addition, urine creatinine increased in dobutamine treated group (p < 0.05), and creatinine clearance decreased in control group (p < 0.01). Renal function and diuresis during the SMA occlusion and reperfusion did not differ between ischaemic and sham groups. All fluid treated groups had lower serum creatinine during SMA occlusion than control groups (p < 0.001). CONCLUSIONS: Intestinal ischaemia caused by partial SMA occlusion did not influence renal function. On the contrary, SMA reperfusion resulted in a significant impairment of renal function both in ischaemic and sham operated animals. The impairment was most obvious in control groups and in animals treated with dobutamine alone.     

The sequential change of local cerebral blood flow and local cerebral glucose metabolism after focal cerebral ischaemia and reperfusion in rat and the effect of MK-801 on local cerebral glucose metabolism

Summary In order to investigate the time course change of local cerebral blood flow (1CBF) and local cerebral glucose metabolism (1CGM) and the effect of MK-801 (dizocilpine), an NMDA receptor antagonist on glucose metabolism in a middle cerebral artery occlusion-reperfusion model,¹⁴C-Iodo-antipyrine and¹⁴C-Deoxyglucose autoradiographic method have been used. The 1CBF was reduced to 0–10% of the control level in the ischaemic core and to 12–40% in the ischaemic penumbra between 60 and 120 min after the onset of the ischaemia. In the ischaemic core, the marked hyperfusion appeared at 15 min and maintained about 30 to 45 min following reperfusion. In the ischaemic penumbra, the hyperfusion during reperfusion was not found. Hypermetabolism occurred at 30 min and reached to the peak at 60 min after the middle cerebral artery (MCA) occlusion both in the ischaemic core and in the penumbra. The shift from hyper- to hypometabolism was observed during the ischaemia. The reperfusion following 2 hours of MCA occlusion facilitated the decrease of cerebral glucose metabolism in the ischaemic region. The pretreatment of MK-801 (0.4 mg/kg) inhibited both increased glucose metabolism during the ischaemia and decreased glucose metabolism during the reperfusion. The effect of limiting decreased glucose metabolism during the reperfusion by MK-801 was remarkable in the ischaemic penumbra. These findings support the hypothesis that excitation-induced hypermetabolism play a major role in the ischaemic insult following focal cerebral vascular occlusion.     

An experimental model for unilateral ischaemic acute renal failure in dog

We determined the recovery of unilateral ischaemic acute renal failure in both ischaemic and non-ischaemic canine kidneys. Split renal clearance studies were repeated for seven weeks after 90 minutes of left renal artery clamping. Clearance of inulin and para-aminohippuric acid in the ischaemic kidneys dropped significantly for 3 weeks. Significant increase of the fractional excretion of sodium in those kidneys was observed at only 1 week after ischaemia. In the contralateral non-ischaemic kidneys, these indices did not change significantly throughout the experiments. This animal model of acute renal failure would be helpful in testing possible preventive measures and therapy for human acute renal failure.     

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.     

Blood lipid profile in ischaemia reperfusion injury

BACKGROUND: Lipid components are considered to play an important role in ischaemia reperfusion injury although the mechanism of their action remains unknown. Accumulation of lipid metabolites in ischaemic tissues is a consistent observation, but exactly how these lipids are cleared from the tissues by the circulating blood during reperfusion is still open to speculation. In the present study, levels of blood lipids (fatty acids, phospholipids, triglycerides, cholesterol, lysolecithin and lysolecithin platelet activating factor (lyso PAF)) and the enzyme phospholipase A2 were determined in an experimental animal model (dogs) of ischaemic reperfusion injury. METHODS: The injury was induced by 4 h of aortic clamping followed by 2 h of reperfusion (unclamping). Blood samples were collected before clamping and at predetermined time intervals (0, 15, 60 and 120 min) after the release of clamp. The lipid contents were analysed and compared with sham-treated control dogs. RESULTS: The results showed significantly elevated levels of triglycerides and phospholipase A2, during ischaemia and reperfusion in experimental animals indicating tissue damage in the ischaemic phase continuing into the reperfusion phase and the risk of systemic damage from these toxic substances. Total fatty acid content in the circulating blood showed decreasing trends during the same time interval, which suggested possible reduced clearance of accumulated fatty acids from the affected tissues. Serum cholesterol, phospholipids, lyso PAF and lysolecithin did not show any significant variation compared with control dogs. CONCLUSIONS: It is possible that the delayed clearance of fatty acids may be due to the presence of fatty acids binding proteins in the ischaemic tissue, which trap these fatty acids in the tissues during ischaemic reperfusion injury. The prolonged retention of the accumulated fatty acids in the tissues in association with elevated triglycerides and phospholipase A2 activity may contribute to ischaemia reperfusion injury.     

Effects of experimental lower-limb ischaemia-reperfusion injury on the mesenteric microcirculation

BACKGROUND: Ischaemia-reperfusion (I-R) of the leg is associated with functional and structural changes in the intestine. This study assessed whether acute hind-limb I-R in rats induced a reduction in perfusion and/or signs of an inflammatory response in the intestine. METHODS: Rats were subjected to 2 h of unilateral hind-limb ischaemia followed by 2 h of reperfusion (I-R group, n = 9) or to a sham procedure (control group, n = 9). Mesenteric microvascular diameters, red blood cell velocity, blood flow and leucocyte-vessel wall interactions during reperfusion were measured using intravital microscopy. RESULTS: Blood pressure and heart rate decreased from 30 min of reperfusion onwards in the I-R group compared with controls. From 15 min after the start of reperfusion, mesenteric arteriolar and venular red blood cell velocity and blood flow decreased by 40-50 per cent. Microvascular diameters and leucocyte-vessel wall interactions did not change. CONCLUSION: Restoration of blood flow to an acutely ischaemic hind limb led to a significant decline in the splanchnic microcirculatory blood flow. There were, however, no signs of an early inflammatory response in the gut.     

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.     

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.