Response of protein synthesis to hypercapnia in rats: independent effects of acidosis and hypothermia.

Acute metabolic acidosis has been shown to inhibit muscle protein synthesis, although little is known on the effect of acidosis of respiratory origin. The aim of this study was to investigate the effect of acute respiratory acidosis on tissue protein synthesis. Rats (n = 8) were made acidotic by increasing the CO2 content of inspired air to 12% for 1 hour. Similar rats breathing normal air served as controls (n = 8). Muscle and liver protein synthesis rates were then measured with L-[ 2H5 ]phenylalanine (150 micromol per 100 g body weight, 40 mol%). The results show that protein synthesis is severely depressed in skeletal muscle (-44% in gastrocnemius, -39% in plantaris, and -24% in soleus muscles, P < .01) and liver (-20%, P < .001) in acidotic animals. However, because breathing CO2 -enriched air was found to lower body temperature by approximately 2 degrees C, in a second experiment (n = 10), the difference in body temperature between treated and control animals was minimized by gently wrapping rats breathing CO2 -enriched air in porous cloths. This second experiment confirmed that respiratory acidosis depresses protein synthesis in muscle (-22% in gastrocnemius, P < .001; -19% in plantaris, P < .01; and -4% in soleus, P = NS). However, no effect on liver protein synthesis could be detected, suggesting that liver protein synthesis may be sensitive to changes in body temperature but is not affected by acute respiratory acidosis for 1 hour. The results show that respiratory acidosis inhibits protein synthesis in skeletal muscle and indicates that acidosis, whether of metabolic or respiratory origin, may contribute to loss of muscle protein in patients with compromised renal or respiratory function.

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.

Acute metabolic acidosis inhibits muscle protein synthesis in rats.

In this study, we investigated the effect of acute metabolic acidosis on tissue protein synthesis. Groups of rats were made acidotic with intragastric administration of NH(4)Cl (20 mmol/kg body wt every 12 h for 24 h) or given equimolar amounts of NaCl (controls). Protein synthesis in skeletal muscle and a variety of different tissues, including lymphocytes, was measured after 24 h by injection of l-[(2)H(5)]phenylalanine (150 micromol/100 g body wt, 40 moles percent). Results show that acute acidosis inhibits protein synthesis in skeletal muscle (-29% in gastrocnemius, -23% in plantaris, and -17% in soleus muscles, P < 0.01) but does not affect protein synthesis in heart, liver, gut, kidney, and spleen. Protein synthesis in lymphocytes is also reduced by acidosis (-8%, P < 0.05). In a separate experiment, protein synthesis was also measured in acidotic and control rats by a constant infusion of l-[(2)H(5)]phenylalanine (1 micromol.100 g body wt(-1).h(-1)). The results confirm the earlier findings showing an inhibition of protein synthesis in gastrocnemius (-28%, P < 0.01) and plantaris (-19%, P < 0.01) muscles but no effect on heart and liver by acidosis. Similar results were also observed using a different model of acute metabolic acidosis, in which rats were given a cation exchange resin in the H(+) (acidotic) or the Na(+) (controls) form. In conclusion, this study demonstrates that acute metabolic acidosis for 24 h depresses protein synthesis in skeletal muscle and lymphocytes but does not alter protein synthesis in visceral tissues. Inhibition of muscle protein synthesis might be another mechanism contributing to the loss of muscle tissue observed in acidosis.

Prevention of postsurgery-induced abdominal adhesions by electrospun bioabsorbable nanofibrous poly(lactide-co-glycolide)-based membranes.

OBJECTIVES: The objective of this study was to evaluate the efficacy of nonwoven bioabsorbable nanofibrous membranes of poly(lactideco-glycolide) for prevention of postsurgery-induced abdominal adhesions. SUMMARY BACKGROUND DATA: Recent reports indicated that current materials used for adhesion prevention have only limited success. Studies on other bioabsorbable materials using a new fabrication technique demonstrated the promising potential of generating an improved and inexpensive product that is suitable for a variety of surgical applications. METHODS: All rats underwent a midline celiotomy. The cecum was identified and scored using an abrasive pad until serosal bleeding was noted on the anterior surface. A 1 x 1 cm of abdominal wall muscle was excised directly over the cecal wound. The celiotomy was then closed in 2 layers immediately (control) after a barrier was laid in between the cecum and the abdominal wall. All rats underwent a second celiotomy after 28 days to evaluate the extent of abdominal adhesions qualitatively and quantitatively. RESULTS: Cecal adhesions were reduced from 78% in the control group to 50% in the group using biodegradable poly(lactide-co-glycolide) (PLGA) nonwoven nanofibrous membranes (n = 10, P = 0.2) and to 22% in the group using membranes containing PLGA and poly(ethylene glycol)/poly(D,L-lactide) (PEG-PLA) blends (n = 9, P = 0.03). Electrospinning method also enabled us to load an antibiotic drug Cefoxitin sodium (Mefoxin; Merck Inc., West Point, PA) with high efficacy. The electrospun PLGA/PEG-PLA membranes impregnated with 5 wt% cefoxitin sodium, which amounts to approximately 10% of the systemic daily dose typically taken after surgery in humans, completely prevented cecal adhesions (0%) in rats. CONCLUSIONS: Electrospun nonwoven bioabsorbable nanofibrous membranes of poly(lactide-co-glycolide) were effective to reduce adhesions at the site of injury using an objective rat model. The membrane acted as a physical barrier but with drug-delivery capability. The combined advantages of composition adjustment, drug-loading capability, and easy placement handling (relatively hydrophobic) make these membranes potentially successful candidates for further clinical evaluations.