The mid-point transverse process to pleura (MTP) block: a new end-point for thoracic paravertebral block.

Current descriptions of thoracic paravertebral block techniques require the needle tip to be anterior to the superior costotransverse ligament. We hypothesised that an injection point midway between the posterior border of the transverse process and the pleura would result in spread to the paravertebral space. We completed bilateral injections of 5 ml methylene blue 0.2% midway between the posterior border of the transverse process and the pleura at T2, T4, T6, T8 and T10 in three unembalmed cadavers. The presence of methylene blue dye at the nerve root in the paravertebral space, the corresponding intercostal nerve and sympathetic chain at the level of injection, and at additional levels, was examined. We identified the superior costotransverse ligament, pleural displacement and spread to the erector spinae plane. We describe two case reports using this technique in patients. Our cadaver results and clinical cases demonstrate that, with the exception of cadaver 1, an injection point midway between the posterior border of the transverse process and pleura consistently achieved spread of dye at least to the paravertebral space at the level of injection, and frequently to adjacent levels. This may be a plausible explanation for the landmark technique's inability to reliably achieve a multilevel block. We describe a new ultrasound-guided technique for a single level paravertebral block.

Effects of 11ß-hydroxysteroid dehydrogenase-1 inhibition on hepatic glycogenolysis and gluconeogenesis.

The aim of this study was to determine the effect of prolonged 11ß-hydroxysteroid dehydrogenase-1 (11ß-HSD1) inhibition on basal and hormone-stimulated glucose metabolism in fasted conscious dogs. For 7 days prior to study, either an 11ß-HSD1 inhibitor (HSD1-I; n = 6) or placebo (PBO; n = 6) was administered. After the basal period, a 4-h metabolic challenge followed, where glucagon (3×-basal), epinephrine (5×-basal), and insulin (2×-basal) concentrations were increased. Hepatic glucose fluxes did not differ between groups during the basal period. In response to the metabolic challenge, hepatic glucose production was stimulated in PBO, resulting in hyperglycemia such that exogenous glucose was required in HSD-I (P < 0.05) to match the glycemia between groups. Net hepatic glucose output and endogenous glucose production were decreased by 11ß-HSD1 inhibition (P < 0.05) due to a reduction in net hepatic glycogenolysis (P < 0.05), with no effect on gluconeogenic flux compared with PBO. In addition, glucose utilization (P < 0.05) and the suppression of lipolysis were increased (P < 0.05) in HSD-I compared with PBO. These data suggest that inhibition of 11ß-HSD1 may be of therapeutic value in the treatment of diseases characterized by insulin resistance and excessive hepatic glucose production.

Physiologic action of glucagon on liver glucose metabolism.

Glucagon is a primary regulator of hepatic glucose production (HGP) in vivo during fasting, exercise and hypoglycaemia. Glucagon also plays a role in limiting hepatic glucose uptake and producing the hyperglycaemic phenotype associated with insulin deficiency and insulin resistance. In response to a physiological rise in glucagon, HGP is rapidly stimulated. This increase in HGP is entirely attributable to an enhancement of glycogenolysis, with little to no acute effect on gluconeogenesis. This dramatic rise in glycogenolysis in response to hyperglucagonemia wanes with time. A component of this waning effect is known to be independent of hyperglycemia, though the molecular basis for this tachyphylaxis is not fully understood. In the overnight fasted state, the presence of basal glucagon secretion is essential in countering the suppressive effects of basal insulin, resulting in the maintenance of appropriate levels of glycogenolysis, fasting HGP and blood glucose. The enhancement of glycogenolysis in response to elevated glucagon is critical in the life-preserving counterregulatory response to hypoglycaemia, as well as a key factor in providing adequate circulating glucose for working muscle during exercise. Finally, glucagon has a key role in promoting the catabolic consequences associated with states of deficient insulin action, which supports the therapeutic potential in developing glucagon receptor antagonists or inhibitors of glucagon secretion.

Regulation of sarcoendoplasmic reticulum Ca2+-ATPase (SERCA) in turtle muscle and liver during acute exposure to anoxia.

The freshwater turtle Trachemys scripta elegans naturally tolerates extended periods of anoxia during winter hibernation at the bottom of ice-locked ponds. Survival in this anoxic state is facilitated by a profound depression of metabolic rate. As calcium levels are known to be elevated in anoxic turtles, and ion pumping is an ATP-expensive process, we proposed that activity of the sarcoendoplasmic reticulum Ca(2+)-ATPase (SERCA) would be reduced in muscle and liver of T. s. elegans during acute (up to 20 h) exposure to anoxia. SERCA activity decreased approximately 30% in liver and approximately 40% in muscle after 1 h anoxia exposure and was approximately 50% lower after 20 h of anoxia exposure in both tissues, even though SERCA protein levels did not change. SERCA kinetic parameters (increased substrate K(m) values, increased Arrhenius activation energy) were indicative of a less active enzyme form under anoxic conditions. Interestingly, the less active SERCA in anoxic turtles featured greater stability than the enzyme from normoxic animals as determined by both kinetic analysis (effect of low pH and low temperatures on K(m) MgATP) and conformational resistance to urea denaturation. The quick time course of deactivation and the stable changes in kinetic parameters that resulted suggested that SERCA was regulated by a post-translational mechanism. In vitro experiments indicated that SERCA activity could be blunted by protein phosphorylation and enhanced by dephosphorylation in a tissue-specific manner.