Non-alpha-adrenergic effects on systemic vascular conductance during lower-body negative pressure, static exercise and muscle metaboreflex activation.

AIM: This study tested the hypothesis that non-α-adrenergic mechanisms contribute to systemic vascular conductance (SVC) in a reflex-specific manner during the sympathoexcitatory manoeuvres. METHODS: Twelve healthy subjects underwent lower-body negative pressure (LBNP, -40 mmHg) as well as static handgrip exercise (HG, 20% of maximal force) followed by post-exercise forearm circulatory occlusion (PECO, 5 min each) with and without α-adrenergic blockade induced by phentolamine (PHE). Aortic blood flow, finger blood pressure and superficial femoral artery blood flow were measured to calculate cardiac output, SVC and leg vascular conductance (LVC) during the last minute of each intervention. RESULTS: Mean arterial pressure (MAP) decreased more during LBNP with PHE compared with saline (-7 ± 7 vs. -2 ± 5%, P = 0.016). PHE did not alter the MAP response to HG (+20 ± 12 and +24 ± 16%, respectively, for PHE and saline) but decreased the change in MAP during PECO (+12 ± 7 vs. +21 ± 14%, P = 0.005). The decrease in SVC and LVC with LBNP did not differ between saline and PHE trials (-13 ± 10 vs. -17 ± 10%, respectively, for SVC, P = 0.379). In contrast, the SVC response to HG increased from -9 ± 12 with saline to + 5 ± 15% with PHE (P = 0.002) and from -16 ± 15 with saline to +1 ± 16% with PHE during PECO (P = 0.003). LVC responses to HG or PECO were not different from saline with PHE. CONCLUSIONS: Non-α-adrenergic vasoconstriction was present during LBNP. The systemic vasoconstriction during static exercise and isolated muscle metaboreflex activation, in the absence of leg vasoconstriction, was explained by an α-adrenergic mechanism. Therefore, non-α-adrenergic vasoconstriction is more emphasized during baroreflex, but not metaboreflex-mediated sympathetic activation.

Adrenergic and myogenic regulation of viscoelasticity in the vascular bed of the human forearm.

This study tested the hypothesis that the compliance (C) and viscoelasticity (K) of the forearm vascular bed are controlled by myogenic and/or α-adrenergic receptor (αAR) activation. Heart rate (HR) and waveforms of brachial artery blood pressure (Finometer) and forearm blood flow (Doppler ultrasound) were measured in baseline conditions and during infusion of noradrenaline (NA; αAR agonist), with and without phentolamine (αAR antagonist; n = 10; 6 men and 4 women). These baseline and αAR-agonist-based measures were repeated when the arm was positioned above or below the heart to modify the myogenic stimulus. A lumped Windkessel model was used to quantify the values of forearm C and K in each set of conditions. Baseline forearm C was inversely, and K directly, related to the myogenic load (P < 0.001). Compared with saline infusion, C was increased, but K was unaffected, with phentolanine, but only in the 'above' position. Compliance was reduced (P < 0.001) and K increased (P = 0.06) with NA infusion (main effects of NA) across arm positions; phentolamine minimized these NA-induced changes in C and K for both arm positions. Examination of conditions with and without NA infusion at similar forearm intravascular pressures indicated that the NA-induced changes in C and K were due largely to the concurrent changes in blood pressure. Therefore, within the range of arm positions used, it was concluded that vascular stiffness and vessel wall viscoelastic properties are acutely affected by myogenic stimuli. Additionally, forearm vascular compliance is sensitive to baseline levels of αAR activation when transmural pressure is low.

The importance of kinin antagonist treatment timing in closed head trauma.

BACKGROUND: Giving LF 16-0687 Ms (a bradykinin B2 receptor antagonist) 1 hour after closed head trauma (CHT) previously was reported to decrease brain edema at 24 hours and improve neurologic severity score (NSS) at 7 days. It is not certain whether a greater benefit could be achieved by treatment sooner after CHT. METHODS: To examine the latter possibility we studied a surrogate condition for the earliest possible administration of LF 16-0687 Ms after CHT, e.g., we examined brain edema and NSS when LF 16-0687 Ms was given 15 min before CHT in rats. RESULTS: LF 16-0687 Ms decreased brain water content (80.0 +/- 1.4%, mean +/- SD) at 24 hours and improved NSS (2 +/- 3, median +/- range) at 7 days after CHT in comparison to that with CHT + saline (82.9 +/- 1.3% and 8 +/- 4). CONCLUSION: Similarity of the present results to those previously reported indicates that the benefit of giving LF 16-0687 Ms 1 hour after CHT appears to represent the maximal benefit afforded by this drug.

The effect of treatment with albumin, hetastarch, or hypertonic saline on neurological status and brain edema in a rat model of closed head trauma combined with uncontrolled hemorrhage and concurrent resuscitation in rats.

UNLABELLED: In rats subjected to closed head trauma (CHT) plus uncontrolled hemorrhage, giving 0.3 mL of 0.9% saline per 0.1 mL of blood lost did not restore mean arterial blood pressure (MAP) or improve neurological severity score (NSS). In CHT without hemorrhage, giving 20% albumin or 10% hetastarch improved NSS. We hypothesized that these latter treatments would also improve NSS after CHT plus uncontrolled hemorrhage. Rats were randomly assigned to one of seven groups. Experimental conditions were CHT (yes or no), uncontrolled hemorrhage (yes or no), and fluid given to replace blood loss (none; 10% hetastarch, 20% albumin, or 3% saline [0.1 mL per 0.1 mL of blood lost]; or 0.9% saline [0.3 mL per 0.1 mL of blood lost]). NSS (0--25 scale, where 0 = no impairment) was determined at 1, 4, and 24 h, and brain water content was determined at 24 h after CHT. NSS (median +/- range) at 24 h was 11 +/- 6 when no fluid was given; 16 +/- 5 with 10% hetastarch; 14 +/- 5 with 20% albumin; 12 +/- 4 with 3% saline; and 13 +/- 4 with 0.9% saline given (not significant). In addition, brain water content and MAP did not differ among the groups receiving CHT with or without uncontrolled hemorrhage. In our model of CHT plus uncontrolled hemorrhage in rats, giving 10% hetastarch, 20% albumin, 3% saline, or 0.9% saline failed to improve NSS, brain water content, or MAP. IMPLICATIONS: In previous studies of closed head trauma (CHT) without hemorrhage, giving 20% albumin or 10% hetastarch improved neurological severity scores (NSSs). We hypothesized that these treatments also might be beneficial in CHT plus uncontrolled hemorrhage. We found that giving 10% hetastarch, 20% albumin, 3% saline, or 0.9% saline failed to improve NSS, brain water content, or mean arterial blood pressure.

Raised interleukin-6 levels in obese patients.

OBJECTIVE: Obese patients demonstrate a variety of biochemical, metabolic, and pulmonary abnormalities. Inflammatory mediators such as tumor necrosis factor-alpha and interleukin-6 (IL-6) may have a direct effect on glucose and lipid metabolism. Hypoxemia in itself induces release of IL-6. The aim of this study was to examine the relationship between IL-6 levels in healthy volunteers (control group) and three different groups of obese patients: patients without obstructive sleep apnea syndrome (OSAS), patients with OSAS, and patients with obesity hypoventilation syndrome (OHS) (daytime baseline oxygen saturation of <93%). RESEARCH METHODS AND PROCEDURES: We measured serum IL-6 levels in 25 obese patients (body mass index of >35 kg/m2) and 12 healthy women. RESULTS: The results demonstrate statistically significant differences in serum IL-6 levels between the control group (1.28 +/- 0.85 pg/mL) and obese patients without OSAS (7.69 +/- 5.06 pg/mL, p < 0.05) and with OSAS (5.58 +/- 0.37 pg/mL, p < 0.0005). In the patients with OHS, IL-6 concentrations were highest (43.13 +/- 24.27 pg/mL). DISCUSSION: We conclude that serum IL-6 is increased in obese patients. The highest IL-6 levels were found in the patients with OHS.

Ketamine attenuates the interleukin-6 response after cardiopulmonary bypass.

UNLABELLED: Cardiopulmonary bypass (CPB) has been proposed as a model for studying the inflammatory cascade associated with the systemic inflammatory response syndrome. Serum interleukin-6 (IL-6) concentration seems to be a good indicator of activation of the inflammatory cascade and predictor of subsequent organ dysfunction and death. Prolonged increases of circulating IL-6 are associated with morbidity and mortality after cardiac operations. In the present study, we compared the effects of adding ketamine 0.25 mg/kg to general anesthesia on serum IL-6 levels during and after elective coronary artery bypass grafting (CABG). Thirty-one patients undergoing elective CABG were randomized to one of two groups and prospectively studied in a double-blind manner. The patients received either ketamine 0.25 mg/kg or a similar volume of isotonic sodium chloride solution in addition to large-dose fentanyl anesthesia. Blood samples for analysis of serum IL-6 levels were drawn before the operation; after CPB; 4, 24, and 48 h after surgery; and daily for 6 days beginning the third day postoperatively. Ketamine suppressed the serum IL-6 response immediately after CPB and 4, 24, and 48 h postoperatively (P < 0.05). During the first 7 days after surgery, the serum IL-6 levels in the ketamine group were significantly lower than those in the control group (P < 0.05). On Day 8 after surgery, IL-6 levels were no different from baseline values in both groups. A single dose of ketamine 0.25 mg/kg administered before CPB suppresses the increase of serum IL-6 during and after CABG. IMPLICATIONS: In this randomized, double-blind, prospective study of patients during and after coronary artery bypass surgery, we examined whether small-dose ketamine added to general anesthesia before cardiopulmonary bypass suppresses the increase of the serum interleukin-6 (IL-6) concentration. Serum IL-6 levels correlate with the patient's clinical course during and after coronary artery bypass. Ketamine suppresses the increase of serum IL-6 during and after coronary artery bypass surgery.