Experimental Renal Ischemia Research Articles

LIGHT deficiency attenuates acute kidney disease development in an in vivo experimental renal ischemia and reperfusion injury model.

Ischemia-reperfusion (I/R), a leading risk factor of acute kidney injury (AKI), is associated with high mortality and risk of progression to chronic kidney disease. However, the molecular mechanism of I/R-AKI remains not fully understood, which hinders its efficient clinical treatment. In this study, we observed that LIGHT deficiency remarkably attenuated I/R-AKI, as evidenced by rescued renal function, ameliorated tubular cell apoptosis, and alleviated inflammatory responses. Consistently, blocking LIGHT signaling with its soluble receptor fusion proteins (HVEM-IgG-Fc or LTβR-IgG-Fc) improved I/R renal dysfunction. RNA-sequencing and corresponding results indicated that LIGHT promoted oxidative stress and inflammation triggered by ischemic injury. Moreover, LIGHT signaling augmented ischemic stress-induced mitochondrial dysfunction characterized by an imbalance in mitochondrial fission and fusion, decreased mtDNA copies, impaired mitophagy, and increased mitochondrial membrane potential (ΔΨm). Mechanistically, LIGHT promoted mitochondrial fission by enhancing Drp1 phosphorylation (Ser616) and its translocation to the mitochondria. In conclusion, these results suggest that LIGHT-HVEM/LTβR signaling is critical for the I/R-AKI pathogenesis and it is further confirmed to be related to the increase in I/R-induced oxidative stress and mitochondria dysfunction, which may be the underlying mechanism of LIGHT signaling-mediated I/R-AKI.

Renal Fibrosis Is Significantly Attenuated Following Targeted Disruption of Cd40 in Experimental Renal Ischemia.

BackgroundRenal artery stenosis is a common cause of renal ischemia, contributing to the development of chronic kidney disease. To investigate the role of local CD40 expression in renal artery stenosis, Goldblatt 2‐kidney 1‐clip surgery was performed on hypertensive Dahl salt‐sensitive rats (S rats) and genetically modified S rats in which CD40 function is abolished (Cd40 mutant).Methods and ResultsFour weeks following the 2‐kidney 1‐clip procedure, Cd40 mutant rats demonstrated significantly reduced blood pressure and renal fibrosis in the ischemic kidneys compared with S rat controls. Similarly, disruption of Cd40 resulted in reduced 24‐hour urinary protein excretion in Cd40 mutant rats versus S rat controls (46.2±1.9 versus 118.4±5.3 mg/24 h; P<0.01), as well as protection from oxidative stress, as indicated by increased paraoxonase activity in Cd40 mutant rats versus S rat controls (P<0.01). Ischemic kidneys from Cd40 mutant rats demonstrated a significant decrease in gene expression of the profibrotic mediator, plasminogen activator inhibitor‐1 (P<0.05), and the proinflammatory mediators, C‐C motif chemokine ligand 19 (P<0.01), C‐X‐C Motif Chemokine Ligand 9 (P<0.01), and interleukin‐6 receptor (P<0.001), compared with S rat ischemic kidneys, as assessed by quantitative PCR assay. Reciprocal renal transplantation documented that CD40 exclusively expressed in the kidney contributes to ischemia‐induced renal fibrosis. Furthermore, human CD40‐knockout proximal tubule epithelial cells suggested that suppression of CD40 signaling significantly inhibited expression of proinflammatory and ‐fibrotic genes.ConclusionsTaken together, our data suggest that activation of CD40 induces a significant proinflammatory and ‐fibrotic response and represents an attractive therapeutic target for treatment of ischemic renal disease.

Ringer's ethyl pyruvate solution attenuates hypoperfusion and renal injury after multivisceral ischemia-reperfusion in rabbits.

Ringer's ethyl pyruvate solution (REPS) has been protective against experimental renal, intestinal, and spinal ischemia and may be useful for organ protection in major vascular surgery. The purpose of this study was to investigate whether REPS attenuates organ injury in a rabbit model of supraceliac aortic cross-clamp that simulates thoracoabdominal aortic surgery. Following the Institutional Animal Care and Use Committee's approval, 20 rabbits were undergone cross-clamping of the supraceliac thoracic aorta for 30min, and observed for 180min after reperfusion. Either REPS (33mg/kg/h of ethyl pyruvate) or Ringer's lactate solution were infused throughout the study period. Arterial pressure and aortic blood flow were continuously monitored. Blood lactate concentration, serum transaminase levels, neutrophil activation, and urinary N-acetyl-beta-glucosaminidase (NAG) activity were evaluated. After reperfusion, supraceliac aortic blood flow was significantly higher, and urinary NAG was significantly lower in animals that received REPS, while the other parameters were not significantly different. In conclusion, REPS attenuated the reduction of aortic blood flow and urinary NAG elevation after the cross-clamp of supraceliac aorta.

Comparison of the protective effects of selective endothelin-a receptor antagonist, ambrisentan, and dual endothelin-A/B receptor antagonist, bosentan, in experimental renal ischemia reperfusion injury.

This study aims to compare the protective effects of ambrisentan, a selective endothelin typeA receptor antagonist, and bosentan, a dual endothelin typeA/B receptor antagonist, on experimental renal ischemia reperfusion injury. The study sample consisted of 21 female rats, which were divided into 3 groups: Control, Ambrisentan and Bosentan. For the ischemia-reperfusion injury model, left‑kidney nephrectomy was performed after sacrificing the animals. In the immunohistochemical examination, caspase-3 was examined, and then the apoptotic index was determined. In the biochemical examination, the activities of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase, and the levels of nitrite (NOx), TNF-α, and IL-1β were determined. There were statistically significant differences between the groups in terms of total injury score grade in range of 0‒3 (p=0.001).The glomerular and tubular apoptotic indices were higher in the control group as compared to those of the ambrisentan and bosentan groups (p=0.001).There were no statistically significant differences in terms of SOD, CAT, GPx, MDA, IL-1β and TNF-α measurements among the groups (p>0.05). In the experimentally created renal ischemia reperfusion model, both ambrisentan and bosentan increased the NOx level, decreased the apoptosis, and protected the kidney from renal ischemia reperfusion injury. However, no significant superiority was found between ambrisentan and bosentan in terms of their protective effects (Tab. 3, Fig. 2, Ref. 31).

The role of L-arginine and aerobic exercise in experimental renal ischemia reperfusion injury in male and female rats

: Introduction: Renal ischemia/reperfusion (I/R) injury due to reactive oxygen species (ROS) formation is the main cause of acute kidney damage. Nitric oxide (NO) biosynthesis and oxidative stress are closely related to the pathogenesis of renal I/R injury. This study was undertaken to determine the effects of L-arginine (L-arg) as NO donor and aerobic exercise (EX) and also the combination of L-arg with EX on renal I/R injury in male and female rats. Methods: 54 male and female Wistar rats were divided into four groups in each gender as control, L-arginine (L-arg), treadmill exercise (EX), and L-arginine plus exercise (Larg & EX). After 8 weeks of EX, animals were exposed to 45 min of bilateral kidney ischemia followed by 24 hours of reperfusion. We assessed serum creatinine (Cr), Kidney tissue damage score (KTDS), kidney weight (KW), serum nitrite and malondialdehyde (MDA) levels. Results: L-arg, EX or combination of L-arg &EX caused a significant decrease in serum level of creatinine (Cr) (P groups and male L-arg treated group (P However, the kidney weight was decreased significantly in male rats (P post reperfusion, and such observation was not seen in female. No significant differences were detected in serum nitrite levels between the groups, but combination of L-arg &EX decreased the serum level of malondialdehyde (MDA) in female significantly (P Conclusion: Pretreatment with L-arg seems to have protective effects against renal I/R injury. The protective effect of exercise against renal I/R injury seems to be less than Larg but the reno-protective effect of EX increases when combined with L-arg.

CD47 regulates renal tubular epithelial cell self-renewal and proliferation following renal ischemia reperfusion

Defects in renal tubular epithelial cell repair contribute to renal ischemia reperfusion injury, cause acute kidney damage, and promote chronic renal disease. The matricellular protein thrombospondin-1 and its receptor CD47 are involved in experimental renal ischemia reperfusion injury, although the role of this interaction in renal recovery is unknown. We found upregulation of self-renewal genes (transcription factors Oct4, Sox2, Klf4 and cMyc) in the kidney of CD47(-/-) mice after ischemia reperfusion injury. Wild-type animals had minimal self-renewal gene expression, both before and after injury. Suggestive of cell autonomy, CD47(-/-) renal tubular epithelial cells were found to increase expression of the self-renewal genes. This correlated with enhanced proliferative capacity compared with cells from wild-type mice. Exogenous thrombospondin-1 inhibited self-renewal gene expression in renal tubular epithelial cells from wild-type but not CD47(-/-) mice, and this was associated with decreased proliferation. Treatment of renal tubular epithelial cells with a CD47 blocking antibody or CD47-targeting small interfering RNA increased expression of some self-renewal transcription factors and promoted cell proliferation. In a syngeneic kidney transplant model, treatment with a CD47 blocking antibody increased self-renewal transcription factor expression, decreased tissue damage, and improved renal function compared with that in control mice. Thus, thrombospondin-1 via CD47 inhibits renal tubular epithelial cell recovery after ischemia reperfusion injury through inhibition of proliferation/self-renewal.

Optimizing Mouse Surgery with Online Rectal Temperature Monitoring and Preoperative Heat Supply. Effects on Post-Ischemic Acute Kidney Injury.

Body temperature affects outcomes of tissue injury. We hypothesized that online body core temperature recording and selective interventions help to standardize peri-interventional temperature control and the reliability of outcomes in experimental renal ischemia reperfusion injury (IRI). We recorded core temperature in up to seven mice in parallel using a Thermes USB recorder and ret-3-iso rectal probes with three different protocols. Setup A: Heating pad during ischemia time; Setup B: Heating pad from incision to wound closure; Setup C: A ventilated heating chamber before surgery and during ischemia time with surgeries performed on a heating pad. Temperature profile recording displayed significant declines upon installing anesthesia. The profile of the baseline experimental setup A revealed that <1% of the temperature readings were within the target range of 36.5 to 38.5°C. Setup B and C increased the target range readings to 34.6 ± 28.0% and 99.3 ± 1.5%, respectively. Setup C significantly increased S3 tubular necrosis, neutrophil influx, and mRNA expression of kidney injury markers. In addition, using setup C different ischemia times generated a linear correlation with acute tubular necrosis parameters at a low variability, which further correlated with the degree of kidney atrophy 5 weeks after surgery. Changing temperature control setup A to C was equivalent to 10 minutes more ischemia time. We conclude that body temperature drops quickly in mice upon initiating anesthesia. Immediate heat supply, e.g. in a ventilated heating chamber, and online core temperature monitoring can help to standardize and optimize experimental outcomes.

Content of Total Homocysteine and Major Aminothiols in Rats with Experimental Renal Ischemia

The contents of total homocysteine, cysteine, and glutathione in blood plasma and tissue of rats with renal ischemia were measured by HPLC. Our study was performed on the "two-kidney, one-clip (0.13 mm)" model. The concentrations of homocysteine and cysteine in blood plasma from treated rats were higher than in sham-operated animals (control; by 36 and 14%, respectively). Homocysteine level in the intact and clipped kidneys of treated rats was 40% higher than in the control. However, no differences were found in homocysteine level in the ischemic and intact kidneys of treated animals. Cysteine concentration in the clipped kidney was lower than in the kidneys of intact and sham-operated animals (by 1.6 and 1.5 times, respectively). Glutathione concentration in the ischemic kidney did not differ from the control. No differences were revealed in the content of aminothiols in liver samples from rats of the treatment and control groups. Our results suggest that functional inactivation of one kidney is accompanied by impairment of homocysteine catabolism (trans-sulfonation).

Trimetazidine reduces early and long-term effects of experimental renal warm ischemia: A dose effect study

Renal ischemia reperfusion (IR) injury (IRI) is an important mechanism of acute renal failure (ARF) and a crucial factor of tissue damage during vascular surgery. IR may lead to tissue destruction and influence the early and long-term outcome of organs. The anti-anginal medication trimetazidine (TMZ) is a drug, the protective effects of which have been already assessed during cold preservation and warm ischemia (WI). The objective of this dose-effect study was to assess the role of TMZ in severe renal WI model. We have used an established WI pig kidney model associated with a uninephrectomy condition and studied the dose-dependent role of TMZ (1, 5, and 10 mg/Kg, i.v. for 24 hours before WI) against deleterious effects of WI (60 minutes of WI followed by reperfusion) compared with sham-operated (control) and uninephrectomized animals (unif). Direct effect of TMZ was determined using different variables: renal function (creatinine clearance; C(cr)) and indirectly, the consequences on inflammation (cells infiltration), rate of apoptosis, fibrosis development, and renal epithelial cells change into myofibroblast, which defined epithelial to mesenchymal transition (alpha-smooth muscle actin [alpha-SMA] and vimentin expression). TMZ (5 or 10 mg/Kg) significantly increased C(cr) and reduced the inflammatory response prevalent in ischemic kidney injury and rate of apoptosis expression. In addition, the limitation of initial IRI was correlated with an earlier and greater expression of hypoxia-inducible transcription factor-1alpha (HIF-1alpha), which is a hypoxia marker during kidney regeneration. A reduction of the tubulointerstitial development of fibrosis and a limitation of the alpha-smooth muscle actin expression (alpha-SMA) was observed with TMZ treatment. At 3 months, vimentin expression was increased in WI groups without TMZ or low TMZ dose treatment compared with 5 or 10 mg/Kg treated groups. Collectively, these data suggest that TMZ made the warm ischemic kidneys more resistant to the deleterious impact of a single episode of IR and could have a role in preserving the ischemic kidney from long-term damage.

Acute Renal Failure: Much More Than a Kidney Disease

Acute renal failure is a frequent clinical problem with an increasing incidence, an unacceptably high mortality rate that has not improved in more than 40 years, and no specific treatment, yet renal failure is not the usual cause of death. The role of inflammation has been documented in both acute renal injury and cardiac dysfunction. Several investigators have shown that congestive heart failure is associated with increased mortality in patients with acute renal failure. This article reviews some of the cardiac and other distant organ effects of acute renal injury that may be important in the morbidity and mortality observed clinically. Cardiac changes after experimental renal ischemia include cytokine induction, leukocyte infiltration, cell death by apoptosis, and impaired function. I propose that the extrarenal effects of kidney injury must be considered in designing therapies. Acute renal failure has systemic consequences and must be thought of as more than a kidney disease.

Evaluating the Efficacy of Single Daily Dose of 1200mg of N-Acetyl-Cysteine in Preventing Contrast Agent-Associated Nephrotoxicity

Background: Renal toxicity of contrast media remains an up-to-date challenge. N-Acetylcysteine is an antioxidant agent which efficacy has been proved in various models of experimental renal ischemia and therefore proposed in the prevention of renal failure due to intravenous iodine contrast media. Effects of prophylactic administration of N-acetylcysteine to prevent contrast agent-associated nephrotoxicity (CAN) are controversial. Aims: This study was designed to evaluate the efficacy of 1200mg once daily administration of NAC on the day before and on the day of imaging on preventing CAN. Methods: Seventy patients with renal insufficiency (creatinine level ≥1.3 mg/dl), referred to our institution for abdominal or chest CT scanning, were randomly assigned to receive either only 0.9 saline 1 hour before contrast dye administration (control group) or 0.9% saline intravenously 1 hour before CT scan and NAC 1200mg single daily dose one the day before imaging and at contrast media injection day (case group). Both groups were comparable in demographics, disease states, drug regimens, and risk factors for developing contrast-agent-induced nephrotoxicity. There were no significant differences between the two groups in type of CT scan, or volume and concentration of contrast used. All patients received 140ml IOHEXOL (300mg I/ml) before CT scanning. CAN was defined as a rise in serum creatinine of 0.5 mg/dl within 48-72 hours after dye injection. Results: Seventy patients (35 in each group) completed the study. In the case group, the median of Scr concentrations before receiving the contrast agent, 24,48 and 72 hours afterward were 1.43, 1.41, 1.51, 1.45 mg/dl respectively. The median of Scr concentrations in the control group before administration of the contrast agent, 24, 48, 72 hours afterward were 1.31, 1.41, 1.48, and 1.61 mg/dl, respectively. The median change in Scr concentrations was greater in the control group than in the case group (p = 0.04). Increase of at least 25% of the creatinine concentration from baseline 72h after the procedure occurred in 12/35 patients (34%) in the control group and 5/35 patients (14.2%) in case group. The percentage of patients developing acute renal failure was significantly greater in the control group than in the case group (P = 0.021). Conclusion: The use of prophylactic oral NAC combined with IV hydration, significantly reduced the rise in Scr levels within 48-72h after the administration of contrast media.

NO bioavailability, endothelial dysfunction, and acute renal failure: new insights into pathophysiology

This brief overview sketches current evidence of imbalance between inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS), role of oxidant stress, and generation of peroxynitrite in the pathophysiology of acute ischemic renal injury. The development of endothelial cell dysfunction at early stages of experimental acute renal ischemia is the focus of the review, with the results of recent studies on amelioration of renal injury by the infused endothelial cells engrafting in the renal microcirculation. Finally, this article provides some future perspectives on the potential usefulness of endothelial progenitor cells in the prevention and treatment of acute renal failure.

Intérêt de la N’acétylcystéine dans la néphroprotection de la toxicité rénale des produits de contraste iodés

Renal toxicity of contrast agents remains an up-to-date challenge. N’Acetyl cystein is an antioxyde agent which efficacy has been proved in various models of experimental renal ischemia and therefore proposed in the prevention of renal failure due to intravenous iodine contrast media. The author of this review reports and comments these studies in order to better define indications of N’Acetyl cystein in this clinical context.

Urinary heat shock protein-72 excretion in clinical and experimental renal ischemia.

Renal ischemia not only causes injury but also induces repair mechanisms, such as the cellular induction of the 72-kilodalton heat shock protein HSP-72. The aim of this study was to determine whether HSP-72 is excreted in urine after ischemic renal injury. The first urine of six pediatric allograft recipients was examined for proteinuria and urinary HSP-72 excretion. Sprague-Dawley rats were treated with renal ischemia or hyperthermia and renal cortex and urinary HSP-72 levels were determined. HSP-72 was excreted in the first urine of renal allografts. In rats, renal HSP-72 was induced both by renal ischemia or hyperthermia. However, only renal ischemia resulted in urinary excretion of HSP-72. Urinary excretion of HSP-72 indicates an increased renal stress response and loss of tubular cell integrity after clinical and experimental renal ischemia.

Renal cortical perfusion in rabbits: visualization with color amplitude imaging and an experimental microbubble-based US contrast agent.

To evaluate an experimental microbubble-based ultrasound (US) contrast agent (Imagent US, formulation AF0150) in the kidney to help identify focal perfusion abnormalities. Six incremental doses (0.007-0.2 mL/kg) of contrast material were injected intravenously in six New Zealand rabbits (3.1-3.5 kg), with experimental focal renal ischemia in five kidneys. Unenhanced and contrast material-enhanced color amplitude and gray-scale images of the kidney were analyzed for changes in mean pixel intensity. Kidneys were harvested and examined pathologically. On contrast-enhanced color amplitude images, mean pixel intensity increased significantly in cortex and medulla at every dose level (P < .0005) (with doses as low as 0.007 mL/kg), and differences were significant in cortical peak intensity and duration of enhancement with incremental increases in dose (P < .006). On contrast-enhanced gray-scale images, renal cortical enhancement reached statistical significance only at the highest dose (0.2 mL/kg). Duration of gray-scale tissue enhancement was not dose related. Color mean pixel intensity markedly increased in areas of normally perfused kidney (P = .002) but remained essentially unchanged in ischemic areas (P = .34). Color Doppler and gray-scale images enhanced with this microbubble-based US contrast agent depict renal cortical perfusion clearly in rabbits.

Effect of a 21-Aminosteroid, U74006F, on Lipid Peroxidation and Glomerulotubular Function Following Experimental Renal Ischemia

In order to investigate the capacity of the 21-aminosteroid, U74006F, to mitigate ischemic/reperfusion injury (IRI), we studied lipid peroxidation and glomerulotubular function in a rat model of IRI. U74006F, superoxide dismutase (SOD), and their respective vehicles were administered preischemia and prereperfusion to Brown Norway rats subjected to 45 or 60 min of bilateral normothermic ischemia. Lipid peroxidation was assessed by assay of thiobarbituric acid reactive products (TBA-RP) in a forced peroxidation reaction with t-butylhydroperoxide while renal function was assessed by timed determinations of serum creatinine, creatinine clearance, urine volume, and fractional excretion of sodium (FeNa +). Twenty-four hours following a 60-min ischemic insult and uninephrectomy, the glomerular filtration rate (GFR) was markedly reduced in the IRI + vehicle group compared to controls as reflected by a significant elevation in mean serum creatinine (0.138 ± 0.018 vs 0.045 ± 0.002 μmole/liter, P < 0.05) and a significant reduction in mean creatinine clearance (0.200 ± 0.076 vs 1.130 ± 0.153 ml/min, P < 0.05). Neither U74006F nor SOD afforded protection against this marked fall in GFR. In contrast, U74006F significantly attenuated both the diuresis (UVol) and the increase in fractional excretion of filtered sodium (FeNa +) seen post-IRI. At 24 hr post-IRI, mean UVol was 22.50 ± 4.57 ml/day and FeNa + 1.35 ± 0.16% in the IRI + vehicle group compared to 11.48 ± 2.00 ml/day and 0.82 ± 0.22%, respectively, in the IRI + U74006F group ( P < 0.05). While SOD also proved partially protective of tubular function, the effect was not as pronounced as that observed with U74006F. At 15 min postreperfusion following a 45-min ischemic insult, lipid peroxidation was markedly increased as compared to non-IRI controls as assessed by the production of TBA-RP. U74006F, but not SOD, significantly attenuated the elevation in TBA-RP compared to vehicle ( P < 0.05). We conclude that U74006F affords partial protection from IRI-induced tubular injury, but not impaired glomerular filtration function, and that this may, in part, be related to a reduction in membrane lipid peroxidation.

Involvement of reactive oxygen species in kidney damage.

There is considerable evidence suggesting that reactive oxygen species (ROS) are implicated in the pathogenesis of ischemic, toxic, and immunologically-mediated renal injury. In experimental renal ischemia, ROS sources include the electron transport chain, oxidant enzymes (xanthine oxidase), phagocytes, and auto-oxidation of epinephrine. ROS cause lipid peroxidation of cell and organelle membranes and, hence, disruption of the structural integrity and capacity for cell transport and energy production, especially in the proximal tubule segment. In experimental immune glomerulonephritis, ROS are generated by both infiltrating blood-borne cells (polymorphonuclear leukocytes and monocytes) and resident glomerular cells, mainly mesangial cells. Their formation results in morphologic lesions and in modifications of glomerular permeability to proteins through activation of proteases and reduction of proteoglycan synthesis. Additionally, they promote a reduction in glomerular blood flow and glomerular filtration rate through liberation of vasoconstrictory bioactive lipids (prostaglandins, thromboxane, and platelet activating factor) and, possibly, inactivation of relaxing nitric oxide. Further studies are needed to address the role of ROS in human glomerular diseases.

Intermediary Metabolism in Renal Proximal Tubules in the Recovery Phase of Experimental Renal Ischemia in Dogs

Intermediary metabolism has been studied in a viable suspension of renal proximal tubules isolated from dogs before and after 48 h of a 60 min period of renal ischemia by clamping the renal artery. The study consisted in measurements of tubular uptake/production of glucose, lactate, glutamine, glutamate, alpha-ketoglutarate, alanine, ammonium, and oxygen, using as substrates either glutamine 1 or 5 mM (+ glutamate 0.1 or 0.5 mM) or lactate 1 or 5 mM (+ pyruvate 0.1 or 0.5 mM). The combination of glutamine + lactate was also studied. Data revealed that the gluconeogenic ability of the postischemic tubules was maintained, with the exception of glutamine 5 mM as substrate (8.5 +/- 2.1 vs 15.4 +/- 2.1 mumol/min/g in control tubules). The production of NH4 was also decreased only with this substrate (from 214 +/- 15 to 165 +/- 9 mumol/min/g). Lactate extraction was decreased in the postischemic tubules, but the difference was only significant when lactate + glutamine 1 mM was used as substrate (72 +/- 12 vs 44 +/- 6 mumol/g/min). Postischemic tubules showed a greater oxygen consumption when either glutamine or lactate 1 mM were used, but lower ouabain-inhibitable O2 consumption when these substrates were used at 5 mM. These data revealed a modification of the metabolic profile of proximal tubules during the recovery of transient renal ischemia.

Improved neurological outcome in experimental focal cerebral ischemia treated with propranolol.

Propranolol has been shown to exert a protective effect in experimental myocardial, renal, and early acute focal cerebral ischemia. However, propranolol was not found to reduce infarct size in nitrous oxide-anesthetized, paralyzed, mechanically ventilated cats subjected to 6 hours of acute focal ischemia. The objective of the current investigation was to study further the effects of racemic (d,l)-propranolol on the evolution of acute focal cerebral ischemia in awake, conscious cats. Adult cats were anesthetized with halothane and underwent the implantation of an occluding device around the right middle cerebral artery. After a 48-hour recovery period, the right middle cerebral artery was occluded for 6 hours and then reopened, allowing reperfusion for an additional 6 hours. Neurological examinations were conducted every 2 hours throughout each experiment. Ten cats received d,l-propranolol (2 mg/kg) 1 hour before occlusion, immediately before occlusion, and every 2 hours throughout each experiment. Eleven cats serving as controls were not treated. The neurological examination significantly improved over time in the treated group when compared to the untreated group (P = 0.01). Carbon filling defects, gross brain swelling, and infarct size were reduced in treated cats. The results of this study suggest that propranolol does have beneficial effects in acute focal cerebral ischemia.

Morphological assessment of structural changes in arteries and arterioles of the kidney in experimental renal ischemia

Morphological assessment of structural changes in arteries and arterioles of the kidney in experimental renal ischemia