Effects of acute administration of selective serotonin reuptake inhibitors on sympathetic nerve activity.

Serotonergic mechanisms have an important function in the central control of circulation. Here, the acute effects of three selective serotonin (5-HT) reuptake inhibitors (SSRIs) on autonomic and cardiorespiratory variables were measured in rats. Although SSRIs require 2-3 weeks to achieve their full antidepressant effects, it has been shown that they cause an immediate inhibition of 5-HT reuptake. Seventy male Wistar rats were anesthetized with urethane and instrumented to record blood pressure, heart rate, renal sympathetic nerve activity (RSNA), and respiratory frequency. At lower doses, the acute cardiovascular effects of fluoxetine, paroxetine and sertraline administered intravenously were insignificant and variable. At middle and higher doses, a general pattern was observed, with significant reductions in sympathetic nerve activity. At 10 min, fluoxetine (3 and 10 mg/kg) reduced RSNA by -33 ± 4.7 and -31 ± 5.4%, respectively, without changes in blood pressure; 3 and 10 mg/kg paroxetine reduced RSNA by -35 ± 5.4 and -31 ± 5.5%, respectively, with an increase in blood pressure +26.3 ± 2.5; 3 mg/kg sertraline reduced RSNA by -59.4 ± 8.6%, without changes in blood pressure. Sympathoinhibition began 5 min after injection and lasted approximately 30 min. For fluoxetine and sertraline, but not paroxetine, there was a reduction in heart rate that was nearly parallel to the sympathoinhibition. The effect of these drugs on the other variables was insignificant. In conclusion, acute peripheral administration of SSRIs caused early autonomic cardiovascular effects, particularly sympathoinhibition, as measured by RSNA. Although a peripheral action cannot be ruled out, such effects are presumably mostly central.

Effects of acute administration of selective serotonin reuptake inhibitors on sympathetic nerve activity

Serotonergic mechanisms have an important function in the central control of circulation. Here, the acute effects of three selective serotonin (5-HT) reuptake inhibitors (SSRIs) on autonomic and cardiorespiratory variables were measured in rats. Although SSRIs require 2-3 weeks to achieve their full antidepressant effects, it has been shown that they cause an immediate inhibition of 5-HT reuptake. Seventy male Wistar rats were anesthetized with urethane and instrumented to record blood pressure, heart rate, renal sympathetic nerve activity (RSNA), and respiratory frequency. At lower doses, the acute cardiovascular effects of fluoxetine, paroxetine and sertraline administered intravenously were insignificant and variable. At middle and higher doses, a general pattern was observed, with significant reductions in sympathetic nerve activity. At 10 min, fluoxetine (3 and 10 mg/kg) reduced RSNA by -33±4.7 and -31±5.4%, respectively, without changes in blood pressure; 3 and 10 mg/kg paroxetine reduced RSNA by -35±5.4 and -31±5.5%, respectively, with an increase in blood pressure +26.3±2.5; 3 mg/kg sertraline reduced RSNA by -59.4±8.6%, without changes in blood pressure. Sympathoinhibition began 5 min after injection and lasted approximately 30 min. For fluoxetine and sertraline, but not paroxetine, there was a reduction in heart rate that was nearly parallel to the sympathoinhibition. The effect of these drugs on the other variables was insignificant. In conclusion, acute peripheral administration of SSRIs caused early autonomic cardiovascular effects, particularly sympathoinhibition, as measured by RSNA. Although a peripheral action cannot be ruled out, such effects are presumably mostly central.

Comparison of bispectral index and vital parameters in rabbits receiving propofol or isoflurane anesthesia

Background: Reflexes, muscle tonus, heart rate, respiratory frequency and blood pressure are parameters that can be used to evaluate the depth of anesthesia. Bispectral index (BIS) was developed with the objective of evaluating quantitatively the sedative and hypnotic effects of anesthetic drugs. It is widely used to assess central nervous system depression levels. The objective of this study was to compare changes in BIS and several vital parameters during general anesthesia achieved with either propofol or isoflurane, following premedication with dexmedetomidine. Materials, Methods & Results: Adult female New Zealand rabbits (Mean ± SD body weight 3.6 ± 0.4 kg) were procured from a commercial source certified for medical experimentation. The animal number in each of the two study groups was four, for a total of eight. The animals were checked before the study to ascertain their good health. The animals, randomly allocated to either of two study groups, were given dexmedetomidine, 20 µg/kg i.v. Induction was realized by means of propofol, 8 mg/kg i.v. in the propofol group (n = 4), and by administration through a glove mask of isoflurane, 4%, in the isoflurane group (n = 4). Anesthesia maintenance was assured by propofol, 0.6 mg/kg/min or 2% isoflurane with oxygen, respectively. Both anesthetic applications were well tolerated by the rabbits. Before premedication (T0), at the time points of 1 (T1) and 5 min (T2) after dexmedetomidine injection, 1 min into anesthesia induction (T3), and 10 (T4), 30 (T5) and 60 min (T6) after start of maintenance, the following were recorded: BIS, systolic, diastolic and mean arterial blood pressure, heart rate and Anesthesia Score (AS). Blood gas analysis, serum sodium and potassium, blood glucose level, hemoglobin and hematocrit were measured at time points T0 and T6. MAP dropped significantly lower in the propofolgroup at times T2, T3 and T4 (P < 0.05). Under BIS monitoring, BIS values were also found to be relatively lower in the propofol group at times T1, T2 and T4, corresponding in this to AS. At T4, the BIS values were, respectively, 69.5 ± 6.24 and 68.25 ± 3.59 in the isoflurane and propofol groups (P < 0.05). In summary, premedication with dexmedetomidine did not, differently than with humans, assure deep sedation; BIS values, in parallel with our AS evaluation, reached levels of deep anesthesia in the maintenance stage both in the propofol and isoflurane groups. BGA results in arterial blood (pH, PaO2, PaCO2, BE, HCO3) as well as hematocrit (Hct), Na+, K+, glucose, hemoglobin (Hb) were recorded and reported in Table 2. A significant increase in pH was noted at T6 (P < 0.05) in the propofol groups compared to animals given isoflurane (7.39 ± 0.01 vs 7.35 ± 0.003, respectively), all measurements remaining within the normal values. Discussion: Vital parameters showed parallelism with the values of both our AS and BIS in this study, in which we administered general anesthesia with either propofol or isoflurane to rabbits premedicated with dexmedetomidine. Publications on humans show that surgical anesthesia is realized at BIS values under 60; BIS fell in rabbits in parallel to MBP at 10, 30 and 60 min of anesthesia, and AS also showed that the depth of anesthesia was adequate. No surgery having been performed in this study, we think that the parameters noted in this paper should be investigated in future studies that include surgery.

The effect of acute magnesium loading on the maximal exercise performance of stable chronic obstructive pulmonary disease patients.

OBJECTIVE: The potential influence of magnesium on exercise performance is a subject of increasing interest. Magnesium has been shown to have bronchodilatatory properties in asthma and chronic obstructive pulmonary disease patients. The aim of this study was to investigate the effects of acute magnesium IV loading on the aerobic exercise performance of stable chronic obstructive pulmonary disease patients. METHODS: Twenty male chronic obstructive pulmonary disease patients (66.2 + 8.3 years old, FEV1: 49.3+19.8%) received an IV infusion of 2 g of either magnesium sulfate or saline on two randomly assigned occasions approximately two days apart. Spirometry was performed both before and 45 minutes after the infusions. A symptom-limited incremental maximal cardiopulmonary test was performed on a cycle ergometer at approximately 100 minutes after the end of the infusion. RESULTS: Magnesium infusion was associated with significant reductions in the functional residual capacity (-0.41 l) and residual volume (-0.47 l), the mean arterial blood pressure (-5.6 mmHg) and the cardiac double product (734.8 mmHg.bpm) at rest. Magnesium treatment led to significant increases in the maximal load reached (+8 w) and the respiratory exchange ratio (0.06) at peak exercise. The subgroup of patients who showed increases in the work load equal to or greater than 5 w also exhibited significantly greater improvements in inspiratory capacity (0.29 l). CONCLUSIONS: The acute IV loading of magnesium promotes a reduction in static lung hyperinflation and improves the exercise performance in stable chronic obstructive pulmonary disease patients. Improvements in respiratory mechanics appear to be responsible for the latter finding.

The effect of acute magnesium loading on the maximal exercise performance of stable chronic obstructive pulmonary disease patients

OBJECTIVE: The potential influence of magnesium on exercise performance is a subject of increasing interest. Magnesium has been shown to have bronchodilatatory properties in asthma and chronic obstructive pulmonary disease patients. The aim of this study was to investigate the effects of acute magnesium IV loading on the aerobic exercise performance of stable chronic obstructive pulmonary disease patients. METHODS: Twenty male chronic obstructive pulmonary disease patients (66.2 + 8.3 years old, FEV1: 49.3+19.8%) received an IV infusion of 2 g of either magnesium sulfate or saline on two randomly assigned occasions approximately two days apart. Spirometry was performed both before and 45 minutes after the infusions. A symptom-limited incremental maximal cardiopulmonary test was performed on a cycle ergometer at approximately 100 minutes after the end of the infusion. ClinicalTrials.gov: NCT00500864 RESULTS: Magnesium infusion was associated with significant reductions in the functional residual capacity (-0.41 l) and residual volume (-0.47 l), the mean arterial blood pressure (-5.6 mmHg) and the cardiac double product (734.8 mmHg.bpm) at rest. Magnesium treatment led to significant increases in the maximal load reached (+8 w) and the respiratory exchange ratio (0.06) at peak exercise. The subgroup of patients who showed increases in the work load equal to or greater than 5 w also exhibited significantly greater improvements in inspiratory capacity (0.29 l). CONCLUSIONS: The acute IV loading of magnesium promotes a reduction in static lung hyperinflation and improves the exercise performance in stable chronic obstructive pulmonary disease patients. Improvements in respiratory mechanics appear to be responsible for the latter finding.