Contribution of α2-adrenoceptors and Y1 neuropeptide Y receptors to the blunting of sympathetic vasoconstriction induced by systemic hypoxia in the rat

There is evidence that sympathetically evoked vasoconstriction in skeletal muscle is blunted in systemic hypoxia, but the mechanisms underlying this phenomenon are not clear. In Saffan-anaesthetized Wistar rats, we have studied the role of α2-adrenoceptors and neuropeptide Y (NPY) Y1 receptors in mediating vasoconstriction evoked by direct stimulation of the lumbar sympathetic chain by different patterns of impulses in normoxia (N) and systemic hypoxia (H: breathing 8% O2). Patterns comprised 120 impulses delivered in bursts over a 1 min period at 40 or 20 Hz, or continuously at 2 Hz. Hypoxia attenuated the evoked increases in femoral vascular resistance (FVR) by all patterns, the response to 2 Hz being most affected (40 Hz bursts: N = 3.25 ± 0.75 arbitrary resistance units (RU); H = 1.14 ± 0.29 RU). Yohimbine (Yoh, α2-adrenoceptor antagonist) or BIBP 3226 (Y1-receptor antagonist) did not affect baseline FVR. In normoxia, Yoh attenuated the responses evoked by high frequency bursts and 2 Hz, whereas BIBP 3226 only attenuated the response to 40 Hz (40 Hz bursts: N + Yoh = 2.1 ± 0.59 RU; N + BIBP 3226 = 1.9 ± 0.4 RU). In hypoxia, Yoh did not further attenuate the evoked responses, but BIBP 3226 further attenuated the response to 40 Hz bursts. These results indicate that neither α2-adrenoceptors nor Y1 receptors contribute to basal vascular tone in skeletal muscle, but both contribute to constrictor responses evoked by high frequency bursts of sympathetic activity. We propose that in systemic hypoxia, the α2-mediated component represents about 50% of the sympathetically evoked constriction that is blunted, whereas the contribution made by Y1 receptors is resistant. Thus we suggest the importance of NPY in the regulation of FVR and blood pressure increases during challenges such as systemic hypoxia

Action of ryanodine on neurogenic responses in rat isolated mesenteric small arteries

1. Rat mesenteric arteries (∼250 μm) were set up in a single-channel isometric myograph designed to allow fluorescence measurements concurrent with field stimulation of intramural nerves. Vessels were loaded with 6 μM fura-2AM for 2 h and simultaneous recordings of neurogenic contraction (force) and intracellular calcium [Ca(2+)](i) were obtained. In other experiments, arteries were loaded with 1 μCi ml(−1) [(3)H]-noradrenaline (NA) for 30 min in order to measure release of [(3)H]-NA in response to field stimulation to examine whether ryanodine directly inhibited neuronal release of NA. 2. Arteries were activated by single intermittent field stimulation or continuously to excite intrinsic sympathetic nerves, or by cumulative addition of noradrenaline (1 nM–10 μM) to the bathing solution. 3. Pre-incubation with ryanodine markedly inhibited the contraction and [Ca(2+)](i) release in response to single-pulse nerve stimulation. Ryanodine also inhibited an early phasic component of the response to continuous field stimulation and reduced the rate of rise in force in response to continuous field stimulation. However, stable maximal contraction and [Ca(2+)](i) in response to continuous field stimulation as well as maximal responses to exogenous NA were unaffected. Release of [(3)H]-NA in response to single intermittent field stimulation was not affected by ryanodine when compared to vehicle. 4. Our results suggest that brief intermittent activation of intramural sympathetic nerves increases [Ca(2+)](i) and contracts small arteries primarily by releasing Ca(2+) from a ryanodine-sensitive intracellular store. In contrast, the stable rise in tone and [Ca(2+)](i) resulting from continuous nerve stimulation may largely depend on sources of Ca(2+) other than the ryanodine-sensitive intracellular store

Survival after primary breast cancer surgery following propofol or sevoflurane general anesthesia—A retrospective, multicenter, database analysis of 6305 Swedish patients

Background: Retrospective studies indicate that the choice of anesthetic can affect long-term cancer survival. Propofol seems to have an advantage over sevoflurane. However, this is questioned for breast cancer. We gathered a large cohort of breast cancer surgery patients from seven Swedish hospitals and hypothesized that general anesthesia with propofol would be superior to sevoflurane anesthesia regarding long-term breast cancer survival. Methods: We identified all patients who were anaesthetized for breast cancer surgery between 2006 and 2012. The patients were matched to the Swedish Breast Cancer Quality Register, to retrieve tumor characteristics, prognostic factors, and adjuvant treatment as well as date of death. Overall survival between patients undergoing sevoflurane and propofol anesthesia was analyzed with different statistical approaches: (a) multiple Cox regression models adjusted for demographic, oncological, and multiple control variables, (b) propensity score matching on the same variables, but also including the participating centers as a cofactor in a separate analysis. Results: The database analysis identified 6305 patients. The 5-year survival rates were 91.0% and 81.8% for the propofol and sevoflurane group, respectively, in the final model (P =.126). Depending on the statistical adjustment method used, different results were obtained, from a non-significant to a "proposed" and even a "determined" difference in survival that favored propofol, with a maximum of 9.2 percentage points higher survival rate at 5 years (hazard ratio 1.46, 95% CI 1.10-1.95). Conclusions: It seems that propofol may have a survival advantage compared with sevoflurane among breast cancer patients, but the inherent weaknesses of retrospective analyses were made apparent

Survival after primary breast cancer surgery following propofol or sevoflurane general anesthesia—A retrospective, multicenter, database analysis of 6305 Swedish patients

Background: Retrospective studies indicate that the choice of anesthetic can affect long-term cancer survival. Propofol seems to have an advantage over sevoflurane. However, this is questioned for breast cancer. We gathered a large cohort of breast cancer surgery patients from seven Swedish hospitals and hypothesized that general anesthesia with propofol would be superior to sevoflurane anesthesia regarding long-term breast cancer survival. Methods: We identified all patients who were anaesthetized for breast cancer surgery between 2006 and 2012. The patients were matched to the Swedish Breast Cancer Quality Register, to retrieve tumor characteristics, prognostic factors, and adjuvant treatment as well as date of death. Overall survival between patients undergoing sevoflurane and propofol anesthesia was analyzed with different statistical approaches: (a) multiple Cox regression models adjusted for demographic, oncological, and multiple control variables, (b) propensity score matching on the same variables, but also including the participating centers as a cofactor in a separate analysis. Results: The database analysis identified 6305 patients. The 5-year survival rates were 91.0% and 81.8% for the propofol and sevoflurane group, respectively, in the final model (P =.126). Depending on the statistical adjustment method used, different results were obtained, from a non-significant to a "proposed" and even a "determined" difference in survival that favored propofol, with a maximum of 9.2 percentage points higher survival rate at 5 years (hazard ratio 1.46, 95% CI 1.10-1.95). Conclusions: It seems that propofol may have a survival advantage compared with sevoflurane among breast cancer patients, but the inherent weaknesses of retrospective analyses were made apparent