Ischemia with intermittent reperfusion reduces functional and morphologic damage following renal ischemia in the rat

Attempts to minimize ischemic injury by interrupting a given ischemic period might be compromised if repeated bouts of reperfusion injury occurred. To determine whether intermittent ischemia improved or worsened functional and morphologic outcome of renal ischemia, halothaneanesthetized rats underwent a right nephrectomy and placement of a snare about the left renal vascular pedicle at 37° C. Eleven animals underwent 45 minutes of continuous renal ischemia (C-ISC), whereas 10 animals received 45 minutes of vessel occlusion interrupted (I-ISC) at 15 and 30 minutes by snare release and 5 minutes of reperfusion. A group of three sham rats underwent the above procedure but did not have the snare tightened. Blood samples were drawn preoperatively and 24, 48, and 72 hours postoperatively for creatinine analysis. At 72 hours the animals were sacrificed and their kidneys morphologically evaluated. The C-ISC group had a significantly higher mean postoperative plasma creatinine ( p <0.01) as well as significantly higher plasma creatinine levels at 24 ( p <0.005) and 48 hours ( p <0.05) than did the I-ISC group. The C-ISC group also demonstrated significantly greater histologic damage than the I-ISC group ( p <0.002) when assessed by a pathologist blinded to the intervention. Sham rats did not demonstrate functional or morphologic damage. These data demonstrate a significantly improved outcome when 45 minutes of renal ischemia is interrupted by periods of reperfusion. We are led to conclude that in this setting reperfusion injury did not overwhelm the salutary effects of interrupting the 45-minute ischemic event.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41372/1/10016_2005_Article_BF02001009.pd

Hyperglycemia exacerbates and insulin fails to protect in acute renal ischemia in the rat

Hyperglycemia worsens ischemic injury in several ischemic models. To determine whether renal lactate accumulation was associated with hyperglycemia-exacerbated postischemic renal dysfunction and mortality, halothane-anesthetized rats underwent right nephrectomy and 45 min of left renal artery and vein occlusion. Prior to ischemia, rats received saline (n = 22), glucose (2 g/kg, n = 22), or insulin (4 U/kg, n = 18). Sham-operated glucose-treated rats (2 g/kg, n = 4) underwent right nephrectomy and no vascular occlusion. As anticipated, glucose pretreatment elevated plasma glucose, while insulin pretreatment lowered plasma glucose; both were significantly different from values in saline controls. Creatinine was unchanged in sham-operated rats but was significantly higher in glucose-treated rats at 24 and 48 hr postischemia compared to saline controls. No statistical differences in creatinine were found when comparing saline controls to insulin-treated rats. Eighteen percent of glucose-treated rats survived to 72 hr postocclusion, while 45% of insulin-treated rats, 73% of saline control rats, and 100% of sham-operated rats survived this period. In a separate but identical treatment protocol, renal tissue was serially sampled and lactate content was determined in rats pretreated with saline (n = 7), glucose (n = 6) or insulin (n = 6) or sham-operated (n = 2) and receiving identical operation. Tissue lactate concentration did not change during serial sampling in the sham group. During ischemia, lactate was significantly higher in glucose-treated rats and significantly lower in insulin-treated rats as compared to saline controls. The adverse effects of exogenous glucose and attendant hyperglycemia on renal function during normothermic renal ischemia are demonstrated. Increased anaerobic metabolism of glucose with marked lactate accumulation may increase the severity of injury. However, a direct link between tissue lactate and ischemic damage is not fully supported since insulin reduced renal lactate but failed to lessen morbidity and mortality.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27924/1/0000348.pd

Infusion of five percent dextrose increases mortality and morbidity following six minutes of cardiac arrest in resuscitated dogs

The aim of this study was to assess the effect of dextrose administration during and following cardiac resuscitation on mortality and morbidity. Thirty-one dogs anesthetized with halothane were subjected to six minutes of ventricular fibrillation and were resuscitated with open chest cardiac message. All dogs were successfully resuscitated. Thirteen received no dextrose infusion and were fully ambulatory, eating and drinking at 24 hours. Ten of the 18 dogs receiving an infusion of 5% dextrose died before 24 hours and the eight that survived were profoundly impaired. Significantly greater neurologic deficits were recorded for dogs with higher blood glucose concentrations. We conclude that the inclusion of dextrose in fluids used in resuscitation increases mortality and morbidity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26775/1/0000328.pd

Morphometric evaluation of brain infarcts in rats and gerbils

The Levine rat prepartion, the gerbil stroke model, and appropriate control animals were used to determine if the 2,3,5-triphenyltetrazolium chloride (TTC) would selectively identify noninfarcted versus infarcted cerebral tissue. The TTC is frequently used to quantify infarcted myocardial tissue and has been shown to have great specificity, reproducibility, and efficacy. The TTC produces a red product upon reaction with the respiratory enzymes (dehydrogenases) present in non-infarcted tissues. Irreversibly damaged tissues, lacking dehydrogenases, do not form red reaction products. Six gerbil brains and seven rat brains were incubated with the TTC, and the unreacted areas were macroscopically identified. The brains were fixed and sectioned for routine hematoxylin and eosin staining to determine the specificity of the TTC. The TTC was found to react selectively only with non-infarcted cerebral tissue. The gross brain sections were evaluated by macroscopic morphometric analysis, and the unreacted area was always ipsilateral to ligation and correlated with histologic identification of infarct. The brains from neurologically intact animals demonstrated neither macroscopic nor histological evidence of infarction. This technique allows macroscopic quantification of infarct size by planimetry. The average area of infarct for the neurologically impaired rats was 34.7% and it was 31.4% for the impaired gerbils. The percentage of surface area of each infarcted slice was found to correlate with the severity of the neurologic deficit. We conclude that the TTC staining is effective for macroscopically delineating cerebral infarcts in rats and gerbils, thus permitting quantification of infarct size.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25989/1/0000055.pd

Delayed Onset Hypertension with Infrarenal Aortic Cross-Clamping in Dogs

The time course and mechanism of systemic hypertension associated with infrarenal aortic cross-clamping were investigated in 31 chloralose-anesthetized dogs after ligating the tail artery, the paired infrarenal lumbar arteries, and the circumflex iliac arteries bilaterally. Cardiac output, renal blood flow, and suprarenal and infrarenal mean arterial blood pressure were continuously monitored. Infrarenal aortic clamping (90 min) in the standard group (n = 6) consistently decreased infrarenal blood pressure from 90 +/- 6 to 13 +/- 1 mm Hg within 1 min, while suprarenal blood pressure gradually increased over 20-30 min from 88 +/- 7 to 144 +/- 8 mm Hg, where it remained until declamp. The SHAM group (identical operation and instrumentation, without aortic clamping) (n = 5) showed no statistically significant changes. After 90 min of clamp total peripheral and renal resistance nearly doubled but no statistically significant changes in cardiac output, heart rate, central venous pressure, renal blood flow, renin, or glomerular filtration rate were detected. Upon declamping, pressures returned to control levels within 20 min. Groups with bilateral nephrectomy (n = 9) or unilateral iliac artery clamping (n = 7) produced similar time courses and patterns of hemodynamic change. Ablation of afferent nerves from the left hind limb (n = 4) eliminated the hypertension produced by left iliac artery clamping. The substantial delay (20-30 min) to the onset and full development of suprarenal hypertension, with near immediate infrarenal hypotension, is not consistent with a direct mechanical impedance effect. Hypertension in the presence of a bilateral nephrectomy or unilateral iliac artery clamping combined with its full reversal by nerve section strongly suggests that this is a reflex hypertension. This reflex mechanism of hypertension development has implications for intra- or perioperative events associated with hypertension management.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31805/1/0000751.pd