Histopathologic consequences of hyperglycemic cerebral ischemia during hypothermic cardiopulmonary bypass in pigs.

BACKGROUND: This study examined whether 34 degrees C or 31 degrees C hypothermia during global cerebral ischemia with hyperglycemic cardiopulmonary bypass (CPB) in surviving pigs improves electroencephalographic (EEG) recovery and histopathologic scores when compared with normothermic animals. METHODS: Anesthetized pigs were placed on CPB and randomly assigned to 37 degrees C (n = 9), 34 degrees C (n = 10), or 31 degrees C (n = 8) management. After increasing serum glucose to 300 mg/dL, animals underwent 15 minutes of global cerebral ischemia by temporarily occluding the innominate and left subclavian arteries. Following reperfusion, rewarming, and termination of CPB, animals were recovered for 24 (37 degrees C animals) or 72 hours (34 degrees C and 31 degrees C animals). Daily EEG signals were recorded, and brain histopathology from cortical, hippocampal, and cerebellar regions was graded by an independent observer. RESULTS: Before ischemia, serum glucose concentrations were similar in the 37 degrees C (307+/-9 mg/dL), 34 degrees C (311+/-14 mg/dL), and 31 degrees C (310+/-15) groups. By the first postoperative day, EEG scores in 31 degrees C animals (4.2+/-0.6) had returned to baseline and were greater than those in the 34 degrees C (3.4+/-0.5) and 37 degrees C (2.5+/-0.4) groups (p < 0.05, respectively, between groups). Cooling to 34 degrees C showed selective improvement over 37 degrees C in hippocampal, temporal cortical, and cerebellar regions, but the greatest improvement in all regions occurred with 31 degrees C. Cumulative neuropathology scores in 31 degrees C animals (13.5+/-2.2) exceeded 34 degrees C (6.8+/-2.2) and 37 degrees C (1.9+/-2.1) animals (p < 0.05, respectively, between groups). CONCLUSIONS: Hypothermia during CPB significantly reduced the morphologic consequences of severe, temporary cerebral ischemia under hyperglycemic conditions, with the greatest protection at 31 degrees C.

The effects of chlorhexidine irrigation solution on contaminated bone-tendon allografts.

The purpose of this study was to determine an expedient and effective method for disinfecting contaminated human bone-tendon allografts. The first part of this study used beef muscle and cadaveric human tissues to determine the most effective solution and volume to decontaminate tissues inoculated with four different organisms: Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Of the solutions tested (benzalkonium chloride, castile soap, castile soap followed by benzalkonium chloride, triple antibiotic, chlorhexidine gluconate, and chlorhexidine gluconate/triple antibiotic), only the 4% chlorhexidine power irrigation solution and 4% chlorhexidine/triple antibiotic bath completely disinfected all tissues. Work in part 2 revealed that a 2% chlorhexidine irrigation solution was equally effective as the 4% solutions. Part 3 of the study involved human Achilles tendon-calcaneus allografts. We found similar results: 3 liters of 2% chlorhexidine power irrigation solution thoroughly removed all microorganisms from the contaminated tissues. All control allografts irrigated with normal saline solution alone revealed positive bacterial growth for all four organisms after 72 hours' growth on sheep blood agar. Total decontamination time was 10 to 12 minutes. Two percent chlorhexidine irrigation solution may be an effective method for decontaminating human bone-tendon allografts challenged with a polymicrobial inoculum. This method of disinfecting bone-tendon allografts is at least five times more expeditious than methods in previously reported studies.

Transient electroencephalographic suppression with initiation of cardiopulmonary bypass in pigs: blood versus nonblood priming.

Electroencephalographic (EEG) changes have been reported with cardiopulmonary bypass (CPB). We tested whether the type of priming solution (blood versus nonblood) affected the EEG. Twenty-six anesthetized pigs (29.5+/-1.6 kg) were cannulated for CPB primed with 1 liter plasmalyte and 500 ml 6% hetastarch (nonblood prime). EEG signals were recorded during the initiation of normothermic CPB. Three minutes later, animals were weaned from CPB and allowed to stabilize. CPB was reinstituted using the animals' hemodiluted blood as prime. We found that with nonblood prime, abrupt and marked EEG suppression lasting 12.6+/-0.7 s was found in all animals, followed by gradual resumption of baseline EEG activity. In contrast, CPB with blood prime caused no detectable EEG changes. We conclude that severe reductions in EEG activity occur after initiating CPB with nonblood prime; these reductions are not seen when using blood prime. The cause of EEG suppression is unknown, but may represent transient impairment of oxygen delivery to the brain caused by nonblood perfusion.

Comparison of castile soap, benzalkonium chloride, and bacitracin as irrigation solutions for complex contaminated orthopaedic wounds.

OBJECTIVE: The purpose of the present study was to determine the effects of cleaning a contaminated orthopaedic wound with different classes of wound irrigation solutions. STUDY DESIGN: Rats with a contaminated orthopaedic wound were randomized into treatment groups: normal saline (NS), castile soap (CS), benzalkonium chloride (BzC), bacitracin (Abx), or sequential irrigation with BzC, CS, and NS. INTERVENTION: Pseudomonas aeruginosa [P. aeruginosa; 1 x 10(6) colony-forming units (CFU)], or Staphylococcus aureus (S. aureus; 1 x 10(6) CFU) were placed into a paravertebral wound (containing a wire implant placed through a spinous process) and allowed to incubate for fifteen minutes. The wound was then irrigated with three liters of either NS, 0.05 percent CS, 0.03 percent BzC, Abx (33,000 units per liter) or underwent a sequential irrigation treatment (one liter each of BzC, CS, NS). MAIN OUTCOME MEASUREMENTS: The animals were observed daily for wound complications for fourteen days and then killed, and cultures of the wound were obtained. RESULTS: Pseudomonas aeruginosa: Both CS and the sequential irrigation treatment significantly lowered the rate of positive wound cultures when compared with NS (p < 0.05). Irrigation with BzC resulted in a higher rate of positive wound cultures and complications. The sequential irrigation treatment prevented the wound complications associated with irrigation with BzC alone. Staphylococcus aureus: Only BzC irrigation significantly lowered the rate of positive wound cultures when compared with NS (p < 0.05). CONCLUSION: The rate of positive wound cultures due to P. aeruginosa is effectively reduced by irrigation with CS alone or by the sequential irrigation treatment. When used alone, the antiseptic BzC results in a higher rate of positive wound cultures and wound complications. The wound complications seen with irrigation with BzC alone are prevented by the sequential irrigation treatment (BzC followed by CS and NS). The rate of positive wound cultures in this model due to S. aureus is not decreased by irrigation with CS; however, the rate of positive wound cultures is safely and effectively decreased with the use of BzC.

Sequential irrigation with common detergents: a promising new method for decontaminating orthopedic wounds.

This investigation sought to determine the capacity of irrigation solutions in decontaminating orthopedic wounds challenged with a polymicrobial inoculum. Rats were divided into two groups, a control group and a treatment group. After creation of a dorsolumbar incision and placement of a wire through the spinous process, rats were inoculated with Staphylococcus aureus and Pseudomonas aeruginosa. Wounds were irrigated with control or treated solutions. At 2 weeks, cultures were obtained. There were statistically significant differences between groups regarding total number of culture positive sites (P < 0.001), culture-positive animals (P = 0.02), and quantitative cultures (P < 0.02). Sequential irrigation with surfactants lowers bacteria counts recovered from polymicrobial wounds.

Lamotrigine attenuates cortical glutamate release during global cerebral ischemia in pigs on cardiopulmonary bypass.

BACKGROUND: The dose-response effects of pretreatment with lamotrigine (a phenyltriazine derivative that inhibits neuronal glutamate release) in a porcine cerebral ischemia model during cardiopulmonary bypass were studied. METHODS: Sagittal sinus catheters and cortical microdialysis catheters were inserted into anesthetized pigs. Animals undergoing normothermic cardiopulmonary bypass were pretreated with lamotrigine 0, 10, 25, or 50 mg/kg (n = 10 per group). Fifteen minutes of global cerebral ischemia was produced, followed by 40 min of reperfusion and discontinuation of cardiopulmonary bypass. Cerebral oxygen metabolism was calculated using cerebral blood flow (radioactive microspheres) and arterial-venous oxygen content gradients. Concentrations of microdialysate glutamate and aspartate were quantified; electroencephalographic signals were recorded. After cardiopulmonary bypass, blood and cerebrospinal fluid were sampled for S-100B protein, and a biopsy was performed on the cerebral cortex for metabolic profile. RESULTS: Lamotrigine caused dose-dependent reductions in systemic vascular resistance so that additional fluid was required to maintain venous return. Concentrations of glutamate and aspartate did not change during reperfusion after 50 mg/kg lamotrigine in contrast to fivefold and twofold increases, respectively, with lower doses. There were no intergroup differences in cerebral metabolism, electroencephalographic scores, cortical metabolites, brain lactate, or S-100B protein concentrations in the cerebrospinal fluid and blood. CONCLUSIONS: Lamotrigine 50 mg/kg significantly attenuated excitatory neurotransmitter release during normothermic cerebral ischemia during cardiopulmonary bypass without improving other neurologic parameters. Lamotrigine caused arterial and venous dilation, which limits its clinical usefulness.

Benzalkonium chloride. A potential disinfecting irrigation solution for orthopaedic wounds.

The efficacy of benzalkonium chloride was evaluated as an irrigating solution for the eradication of Staphylococcus aureus from a contaminated orthopaedic wound. Thirty Sprague Dawley rats were randomized into two groups. A stainless steel wire was placed in a lumbar spinous process, and the wound was inoculated with 10(7) or 10(6) colony forming units of Staphylococcus aureus. The wound was irrigated with 1 L of normal saline or 0.1% benzalkonium chloride solution. The animals were sacrificed, and cultures were obtained. Rats inoculated with 10(7) colony forming units of Staphylococcus aureus and irrigated with benzalkonium chloride had a significant decrease in the total number of positive cultures, deep wound cultures, and stainless steel wire cultures. Rats inoculated with 10(6) colony forming units of Staphylococcus aureus and irrigated with benzalkonium chloride also had a significant decrease in the total number of positive cultures, deep wound cultures, and stainless steel wire cultures. In a parallel noninoculation study, histologic evaluation of tissues did not show toxicity in the rats irrigated with benzalkonium chloride. This study shows that benzalkonium chloride is more effective than normal saline as an irrigating agent for eradicating Staphylococcus aureus from a contaminated orthopaedic wound.

Hypothermic modulation of cerebral ischemic injury during cardiopulmonary bypass in pigs.

BACKGROUND: The aim of this study was to determine whether progressive levels of hypothermia (37, 34, 31, or 28 degrees C) during cardiopulmonary bypass (CPB) in pigs reduce the physiologic and metabolic consequences of global cerebral ischemia. METHODS: Sagittal sinus and cortical microdialysis catheters were inserted into anesthetized pigs. Animals were placed on CPB and randomly assigned to 37 degrees C (n = 10), 34 degrees C (n = 10), 31 degrees C (n = 11), or 28 degrees C (n = 10) management. Next 20 min of global cerebral ischemia was produced by temporarily ligating the innominate and left subclavian arteries, followed by reperfusion, rewarming, and termination of CPB. Cerebral oxygen metabolism (CMRO2) was calculated by cerebral blood flow (radioactive microspheres) and arteriovenous oxygen content gradient. Cortical excitatory amino acids (EAA) by microdialysis were measured using high-performance liquid chromatography. Electroencephalographic (EEG) signals were graded by observers blinded to the protocol. After CPB, cerebrospinal fluid was sampled to test for S-100 protein and the cerebral cortex was biopsied. RESULTS: Cerebral oxygen metabolism increased after rewarming from 28 degrees C, 31 degrees C, and 34 degrees C CPB but not in the 37 degrees animals; CMRO2 remained lower with 37 degrees C (1.8 +/- 0.2 ml x min[-1] x 100 g[-1]) than with 28 degrees C (3.1 +/- 0.1 ml x min[-1] x 100 g[-1]; P < 0.05). The EEG scores after CPB were depressed in all groups and remained significantly lower in the 37 degrees C animals. With 28 degrees C and 31 degrees C CPB, EAA concentrations did not change. In contrast, glutamate increased by sixfold during ischemia at 37 degrees C and remained significantly greater during reperfusion in the 34 degrees C and 37 degrees C groups. Cortical biopsy specimens showed no intergroup differences in energy metabolites except two to three times greater brain lactate in the 37 degrees C animals. S-100 protein in cerebrospinal fluid was greater in the 37 degrees C (6 +/- 0.9 microg/l) and 34 degrees C (3.5 +/- 0.5 microg/l) groups than the 31 degrees C (1.9 +/- 0.1 microg/l) and 28 degrees C (1.7 +/- 0.2 microg/l) animals. CONCLUSIONS: Hypothermia to 28 degrees C and 31 degrees C provides significant cerebral recovery from 20 min of global ischemia during CPB in terms of EAA release, EEG and cerebral metabolic recovery, and S-100 protein release without greater advantage from cooling to 28 degrees C compared with 31 degrees C. In contrast, ischemia during 34 degrees C and particularly 37 degrees C CPB showed greater EAA release and evidence of neurologic morbidity. Cooling to 31 degrees C was necessary to improve acute recovery during global cerebral ischemia on CPB.

Regional perfusion abnormalities with phenylephrine during normothermic bypass.

BACKGROUND: Hypotension and vasopressors during cardiopulmonary bypass may contribute to splanchnic ischemia. The effect of restoring aortic pressure on visceral organ, brain, and femoral muscle perfusion during cardiopulmonary bypass by increasing pump flow or infusing phenylephrine was examined. METHODS: Twelve anesthetized swine were stabilized on normothermic cardiopulmonary bypass. After baseline measurements, including regional blood flow (radioactive microspheres), aortic pressure was reduced to 40 mm Hg by decreasing the pump flow. Next, aortic pressure was restored to 65 mm Hg either by increasing the pump flow or by titrating phenylephrine. The animals had both interventions in random order. RESULTS: At 40 mm Hg aortic pressure, perfusion to all visceral organs and femoral muscle, but not to the brain, was significantly reduced. Increasing pump flow improved perfusion to the pancreas, colon, and kidneys. In contrast, infusing phenylephrine (2.4 +/- 0.6 micrograms.kg-1.min-1) increased aortic pressure but failed to improve splanchnic perfusion, so that significant perfusion differences existed between the pump flow and phenylephrine intervals. CONCLUSIONS: Increasing systemic pressure during cardiopulmonary bypass with phenylephrine causes significantly lower values of splanchnic blood flow than does increasing the pump flow. Administering vasoconstrictors during normothermic cardiopulmonary bypass may mask substantial hypoperfusion of splanchnic organs despite restoration of perfusion pressure.

Bone mineral density in elite junior Olympic weightlifters.

The purpose of this study was to examine the relationship of bone mineral density (BMD) to muscular strength in highly trained young male athletes in order to gain insights concerning the influence of heavy resistance training on BMD. Twenty-five elite junior weightlifters (age, 17.4 +/- 1.4 yr) and 11 age-matched controls (16.9 +/- 1.1 yr) volunteered for this investigation. Measurements of BMD (g.cm-2) utilizing dual energy x-ray absorptiometry were obtained for the lumbar spine (L2-4) and the proximal femur (neck; trochanter, Ward's triangle). The BMD values for the junior lifters were found to be significantly greater at all sites for the junior weightlifters compared with their age-matched control group. The BMD values of the spine and femoral neck of the junior weightlifters when compared with adult reference data (i.e., 20-39 yr old men) were found to be significantly greater. Both simple and multiple regression analyses demonstrated significant relationships of BMD with strength accounting for 30-65% of the variance. These data suggest that in elite junior weightlifters, muscle strength, highly specific to the sport of weightlifting, has a major influence on BMD due to the influence of the chronic overloads experienced in training.

Acute hormonal responses in elite junior weightlifters.

To date, no published studies have demonstrated resistance exercise-induced increases in serum testosterone in adolescent males. Furthermore, few data are available on the effects of training experience and lifting performance on acute hormonal responses to weightlifting in young males. Twenty-eight junior elite male Olympic-style weightlifters (17.3 +/- 1.4 yrs) volunteered for the study. An acute weightlifting exercise protocol using moderate to high intensity loads and low volume, characteristic of many weightlifting training sessions, was examined. The exercise protocol was directed toward the training associated with the snatch lift weightlifting exercise. Blood samples were obtained from a superficial arm vein at 7 a.m. (for baseline measurements), and again at pre-exercise, 5 min post-, and 15 min post-exercise time points for determination of serum testosterone, cortisol, growth hormone, plasma beta-endorphin, and whole blood lactate. The exercise protocol elicited significant (p less than or equal to 0.05) increases in each of the hormones and whole blood lactate compared to pre-exercise measures. While not being significantly older, subsequent analysis revealed that subjects with greater than 2 years training experience exhibited significant exercise-induced increases in serum testosterone from pre-exercise to 5 min post-exercise (16.2 +/- 6.2 to 21.4 +/- 7.9 nmol.l-1), while those with less than or equal to 2 years training showed no significant serum testosterone differences. None of the other hormones or whole blood lactate appear to be influenced by training experience.(ABSTRACT TRUNCATED AT 250 WORDS)