Resonant and notch behavior in intracranial pressure dynamics.

OBJECT: The intracranial pulse pressure is often increased when neuropathology is present, particularly in cases of increased intracranial pressure (ICP) such as occurs in hydrocephalus. This pulse pressure is assumed to originate from arterial blood pressure oscillations entering the cranium; the fact that there is a coupling between the arterial blood pressure and the ICP is undisputed. In this study, the nature of this coupling and how it changes under conditions of increased ICP are investigated. METHODS: In 12 normal dogs, intracarotid and parenchymal pulse pressure were measured and their coupling was characterized using amplitude and phase transfer function analysis. Mean intracranial ICP was manipulated via infusions of isotonic saline into the spinal subarachnoid space, and changes in transfer function were monitored. RESULTS: Under normal conditions, the ICP wave led the arterial wave, and there was a minimum in the pulse pressure amplitude near the frequency of the heart rate. Under conditions of decreased intracranial compliance, the ICP wave began to lag behind the arterial wave and increased significantly in amplitude. Most interestingly, in many animals the pulse pressure exhibited a minimum in amplitude at a mean pressure that coincided with the transition from a leading to lagging ICP wave. CONCLUSIONS: This transfer function behavior is characteristic of a resonant notch system. This may represent a component of the intracranial Windkessel mechanism, which protects the microvasculature from arterial pulsatility. The impairment of this resonant notch system may play a role in the altered pulse pressure in conditions such as hydrocephalus and traumatic brain swelling. New models of intracranial dynamics are needed for understanding the frequency-sensitive behavior elucidated in these studies and could open a path for development of new therapies that are geared toward addressing the pulsation dysfunction in pathological conditions, such as hydrocephalus and traumatic brain injury, affecting ICP and flow dynamics.

Rosiglitazone, a PPAR-gamma ligand, reduces burn progression in rats.

Burns induce the activation of an inflammatory cascade that generates reactive oxygen radicals and lipid peroxidation leading to burn wound progression and extension. Peroxisome proliferation-activated receptor-gamma is a nuclear hormone receptor that is activated by transcription factors and plays an important role in the regulation of cellular proliferation and inflammation. We hypothesized that treatment of burns with rosiglitazone, a peroxisome proliferation-activated receptor-gamma ligand, would reduce burn wound progression. This is a randomized controlled study of 20 Sprague-Dawley rats. Two burns were created on each animal's dorsum using a brass comb with four rectangular prongs preheated in boiling water and applied for 30 seconds resulting in four rectangular 10 x 20 mm full thickness burns separated by three 5 x 20 mm unburned interspaces (zone of ischemia). Animals were randomized to rosiglitazone 4 mg/kg or vehicle by oral gavage 30 minutes after injury and at 24 and 48 hours after injury. Wounds were observed at 1, 2, 3, and 4 days after injury for visual evidence of necrosis in the unburned interspaces. Full thickness biopsies from the interspaces were evaluated with hematoxylin and eosin staining 7 days after injury for evidence of necrosis. The percentage of interspaces that progressed to necrosis was compared with chi tests. Forty comb burns with 120 unburned interspaces were evenly distributed between rosiglitazone and vehicle. The number of interspaces that progressed to full thickness necrosis at 1, 2, 3, 4, and 7 days after injury in the rosiglitazone and vehicle groups were 9/60 (15%) versus 13/60 (21%) (P = .48), 16/60 (27%) versus 15/60 (20%) (P = 1.00), 24/60 (40%) versus 46/60 (77%) (P = .001), 35/60 (58%) versus 53/60 (88%) (P = .001), and 43/60 (72%) versus 54/60 (90%) (P = .02), respectively. Treatment with oral rosiglitazone reduces the percentage of unburned skin interspaces that progress to full necrosis in a rat comb burn model.

Validation of a porcine comb burn model.

OBJECTIVE: A brass comb burn model that creates 3 full-thickness burns separated by 3 interspaces of unburned skin representing the zone of ischemia has been described in rats. We evaluated this model in pigs. METHODS: Design--observational. Subjects--6 pigs (20-25 kg). Interventions--4 burns created on each animal on the dorsum using a brass comb with 4 rectangular prongs preheated in boiling water and applied for 30 seconds resulting in 4 rectangular 10 x 20-mm full-thickness burns separated by three 5 x 20-mm unburned interspaces. Outcomes--wounds observed at 1, 2, 3, and 7 days for evidence of necrosis in unburned interspaces. Full-thickness biopsies from interspaces were evaluated with hematoxylin-eosin staining 7 days after injury for evidence of necrosis. Data analysis--the percentages of interspaces progressing to necrosis were analyzed with descriptive statistics. RESULTS: Twenty-four comb burns with 72 unburned interspaces were created evenly distributed between the animals. The percentages of interspaces that progressed to full-thickness necrosis at 1, 2, 3, and 7 days after injury were 88.9% (64/72; 95% confidence interval [CI], 79.6%-94.3%), 88.9% (64/72; 95% CI, 79.6%-94.3%), 88.9% (64/72; 95% CI, 79.6%-94.3%), and 97.7% (70/72; 95% CI, 90.4%-99.2%), respectively. There was perfect agreement between gross inspection and histomorphology. CONCLUSIONS: The comb burn model in swine results in the progression of most unburned ischemic interspaces to full-thickness necrosis within 1 to 7 days.

A novel TGF-beta antagonist speeds reepithelialization and reduces scarring of partial thickness porcine burns.

Scar formation after thermal injury is common and results in significant aesthetic and functional impairment. Transforming growth factor beta (TGF-beta) plays a significant role in scar formation. We tested the hypothesis that a novel TGF-beta peptantagonist would reduce scar formation and wound contraction in partial thickness burns by using a randomized controlled experiment. The subjects include two domestic pigs (20-25 kg). Forty burns were created on the animal's dorsum using an aluminum bar preheated to 80 degrees C and applied for 20 seconds resulting in a partial thickness thermal burn extending half way down the dermis. Burns were treated every other day for 1 week, then twice weekly for 3 weeks with a topical TGF-beta antagonist or its vehicle. Full thickness biopsies were obtained from all burns at 7, 10, and 14 days after injury. The wounds were completely excised after 28 days for histological assessment. Wound sections were stained with H&&E and evaluated by a dermatopathologist masked to treatment assignment for reepithelialization and depth of scar formation. We also determined the number of wounds at 28 days that healed with contracted, hour-glass shaped scars. Data were compared with chi and t-tests. Twenty burns were treated with TGF-beta antagonist and 20 with control vehicle. TGF-beta antagonist increased the percentage of completely reepithelialized wounds at 14 days (90 vs 45%, P = .002) and reduced the percentage of contracted wounds (35 vs 65%, P = .02) and full thickness scars (10 vs 60%, P = .002) at 28 days. Treatment of partial thickness porcine burns with the TGF-beta antagonist speeds reepithelialization and reduces scar formation and wound contraction in partial thickness porcine burns.

The effects of brain natriuretic peptide on scar formation in incisional rat wounds.

BACKGROUND: Brain natriuretic peptide (BNP) is a peptide that reduces scar formation in the heart by blocking transforming growth factor-beta (TGF-beta). Although TGF-beta is known to play a role in scar formation in the myocardium, little is known about the effects of BNP on cutaneous wound healing. OBJECTIVES: The objective was to determine if the administration of BNP in healing cutaneous wounds reduces the amount of scarring. METHODS: This was a laboratory investigation using 40 wild-strain rats. Three full-thickness 1-cm incisional wounds were created on each animal and randomized to intradermal BNP, saline, or no treatment. Wounds were excised at 3, 7, 14, 31, and 60 days and examined histologically for scar surface area and collagen architecture. Those wounds excised at 30 days were subjected to a measure of tensile strength and those excised at 60 days were evaluated prior to excision for cosmesis using a scar evaluation scale. The proportion of wounds healing without visually apparent scar was the main outcome. Groups were compared with Fisher's exact and Kruskal-Wallis tests. RESULTS: Wounds treated with BNP were more likely to heal without an apparent scar when compared to those treated with saline or control (37.5% vs. 0%, p = 0.03). There were no between-group differences in the surface area of the scars or the collagen architecture. Incisional tensile strength was also similar across treatments. CONCLUSIONS: Treatment of rat incisions with BNP reduced the number of visually apparent scars but did not affect the histologic appearance of the scars or the incisional tensile strength.

Curcumin reduces burn progression in rats.

OBJECTIVES: Cutaneous burns are dynamic injuries with a central zone of necrosis surrounded by a zone of ischemia. Conversion of this ischemic zone to full necrosis over the days following injury is due in part to highly reactive oxygen radicals. Curcumin is a component of the Oriental spice turmeric that has been shown to have antioxidant and antiapoptotic properties. The authors hypothesized that treatment of burns with curcumin would reduce the conversion of the ischemic zone to full necrosis. METHODS: This was a randomized controlled experiment. Twenty Sprague-Dawley rats were used. Two burns were created on each animal's dorsum using a brass comb with four rectangular prongs preheated in boiling water and applied for 30 seconds, resulting in four rectangular 10 x 20-mm full-thickness burns separated by three 5 x 20-mm unburned interspaces (zone of ischemia). Animals were randomized to curcumin or vehicle by oral gavage 30 minutes before injury and at 24, 48, and 72 hours after injury. Wounds were observed at one, two, and three days after injury for visual evidence of necrosis in the unburned interspaces. Full-thickness biopsy specimens from the interspaces were evaluated with hematoxylin and eosin staining seven days after injury for evidence of necrosis. The percentage of interspaces that progressed to necrosis was compared with chi-square tests. RESULTS: Forty comb burns with 120 unburned interspaces were created, evenly distributed between curcumin and vehicle alone. The percentage of interspaces that progressed to full-thickness necrosis at one, two, three, and seven days after injury in the curcumin and vehicle groups were 30% versus 63% (p = 0.003), 30% versus 70% (p < 0.001), 63% versus 95% (p = 0.02), and 63% versus 95% (p = 0.02), respectively. CONCLUSIONS: Pretreatment of rats with oral curcumin followed by once-daily oral treatment for three days reduced the percentage of unburned skin interspaces that progressed to full necrosis.