The use of ultrasound to guide needle placement and monitor the spread of local anesthetic improves the success rate of interscalene brachial plexus block.

Carbon dioxide (CO2), the major product of metabolism, has a strong impact on cerebral blood vessels, a phenomenon known as cerebrovascular reactivity. Several vascular risk factors such as hypertension or diabetes dampen this response, making cerebrovascular reactivity a useful diagnostic marker for incipient vascular pathology, but its functional relevance, if any, is still unclear. Here, we found that GPR4, an endothelial H+ receptor, and endothelial Gαq/11 proteins mediate the CO2/H+ effect on cerebrovascular reactivity in mice. CO2/H+ leads to constriction of vessels in the brainstem area that controls respiration. The consequential washout of CO2, if cerebrovascular reactivity is impaired, reduces respiration. In contrast, CO2 dilates vessels in other brain areas such as the amygdala. Hence, an impaired cerebrovascular reactivity amplifies the CO2 effect on anxiety. Even at atmospheric CO2 concentrations, impaired cerebrovascular reactivity caused longer apneic episodes and more anxiety, indicating that cerebrovascular reactivity is essential for normal brain function. The site-specific reactivity of vessels to CO2 is reflected by regional differences in their gene expression and the release of vasoactive factors from endothelial cells. Our data suggest the central nervous system (CNS) endothelium as a target to treat respiratory and affective disorders associated with vascular diseases.

No abstract

Levobupivacaine is the isolated S(-)-stereoisomer of racemic bupivacaine. Important pharmacodynamic properties of levobupivacaine have not been determined for the femoral three-in-one block. In this randomized, controlled, double-blinded trial, we studied 60 ASA physical status I-III patients scheduled for surgery of the lower limb. A nerve-stimulator-guided three-in-one block was performed as supplemental analgesic therapy with 20 mL of bupivacaine 0.5% (n = 20), levobupivacaine 0.5% (n = 20), or levobupivacaine 0.25% (n = 20). Sensory onset time, quality of blockade, and duration of blockade were assessed by pinprick test in the central sensory innervation region of the femoral nerve (distribution of the anterior femoral cutaneous nerve). A rating scale from 100% (normal sensation) to 0% (no sensation at all) as compared with the contralateral leg was used. No significant difference in sensory onset time among the three local anesthetic solutions was observed (mean [95% confidence interval]): bupivacaine 0.5%, 27 min (20-33 min); levobupivacaine 0.5%, 24 min (18-30 min); and levobupivacaine 0.25%, 30 min (23-36 min) (P = 0.49). The analgesic quality of the blockade was also not significantly different among the three groups, whereas a complete sensory block was achieved in significantly fewer patients in the levobupivacaine 0.25% group (P = 0.02). The duration of blockade was significantly shorter with levobupivacaine 0.25% compared with the other groups: bupivacaine 0.5%, 1053 min (802-1304 min); levobupivacaine 0.5%, 1001 min (844-1158 min); and levobupivacaine 0.25%, 707 min (551-863 min) (P = 0.01). Levobupivacaine 0.5% is recommended instead of bupivacaine 0.5% for the three-in-one block.

Obesity is a global health problem and treatment options are still insufficient. When chronically treated with the angiotensin II receptor blocker telmisartan (TEL), rodents do not develop diet-induced obesity (DIO). However, the underlying mechanism for this is still unclear. Here we investigated whether TEL prevents leptin resistance by enhancing leptin uptake across the blood-brain barrier (BBB). To address this question, we fed C57BL/6 mice a high-fat diet (HFD) and treated them daily with TEL by oral gavage. In addition to broadly characterizing the metabolism of leptin, we determined leptin uptake into the brain by measuring BBB transport of radioactively labeled leptin after long-term and short-term TEL treatment. Additionally, we assessed BBB integrity in response to angiotensin II in vitro and in vivo. We found that HFD markedly increased body weight, energy intake, and leptin concentration but that this effect was abolished under TEL treatment. Furthermore, glucose control and, most importantly, leptin uptake across the BBB were impaired in mice on HFD, but, again, both were preserved under TEL treatment. BBB integrity was not impaired due to angiotensin II or blocking of angiotensin II receptors. However, TEL did not exhibit an acute effect on leptin uptake across the BBB. Our results confirm that TEL prevents DIO and show that TEL preserves leptin transport and thereby prevents leptin resistance. We conclude that the preservation of leptin sensitivity is, however, more a consequence than the cause of TEL preventing body weight gain.