Impact of stepwise hyperventilation on cerebral tissue oxygen saturation in anesthetized patients: a mechanistic study.

BACKGROUND: While the decrease in blood carbon dioxide (CO2 ) secondary to hyperventilation is generally accepted to play a major role in the decrease of cerebral tissue oxygen saturation (SctO2 ), it remains unclear if the associated systemic hemodynamic changes are also accountable. METHODS: Twenty-six patients (American Society of Anesthesiologists I-II) undergoing nonneurosurgical procedures were anesthetized with either propofol-remifentanil (n = 13) or sevoflurane (n = 13). During a stable intraoperative period, ventilation was adjusted stepwise from hypoventilation to hyperventilation to achieve a progressive change in end-tidal CO2 (ETCO2 ) from 55 to 25 mmHg. Minute ventilation, SctO2 , ETCO2 , mean arterial pressure (MAP), and cardiac output (CO) were recorded. RESULTS: Hyperventilation led to a SctO2 decrease from 78 ± 4% to 69 ± 5% (Δ = -9 ± 4%, P < 0.001) in the propofol-remifentanil group and from 81 ± 5% to 71 ± 7% (Δ = -10 ± 3%, P < 0.001) in the sevoflurane group. The decreases in SctO2 were not statistically different between these two groups (P = 0.5). SctO2 correlated significantly with ETCO2 in both groups (P < 0.001). SctO2 also correlated significantly with MAP (P < 0.001) and CO (P < 0.001) during propofol-remifentanil, but not sevoflurane (P = 0.4 and 0.5), anesthesia. CONCLUSION: The main mechanism responsible for the hyperventilation-induced decrease in SctO2 is hypocapnia during both propofol-remifentanil and sevoflurane anesthesia. Hyperventilation-associated increase in MAP and decrease in CO during propofol-remifentanil, but not sevoflurane, anesthesia may also contribute to the decrease in SctO2 but to a much smaller degree.

Impact of phenylephrine administration on cerebral tissue oxygen saturation and blood volume is modulated by carbon dioxide in anaesthetized patients.

BACKGROUND: Multiple studies have shown that cerebral tissue oxygen saturation (Sct(O(2))) is decreased after phenylephrine treatment. We hypothesized that the negative impact of phenylephrine administration on Sct(O(2)) is affected by arterial blood carbon dioxide partial pressure (Pa(CO(2))) because CO(2) is a powerful modulator of cerebrovascular tone. METHODS: In 14 anaesthetized healthy patients, i.v. phenylephrine bolus was administered to increase the mean arterial pressure ~20-30% during hypocapnia, normocapnia, and hypercapnia. Sct(O(2)) and cerebral blood volume (CBV) were measured using frequency domain near-infrared spectroscopy, a quantitative technology. Data collection occurred before and after each treatment. RESULTS: Phenylephrine caused a significant decrease in Sct(O(2)) during hypocapnia [ΔSct(O(2)) =-3.4 (1.5)%, P<0.001], normocapnia [ΔSct(O(2)) =-2.4 (1.5)%, P<0.001], and hypercapnia [ΔSct(O(2)) =-1.4 (1.5)%, P<0.01]. Decreases in Sct(O(2)) were significantly different between hypocapnia, normocapnia, and hypercapnia (P<0.001). Phenylephrine also caused a significant decrease in CBV during hypocapnia (P<0.01), but not during normocapnia or hypercapnia. CONCLUSION: The negative impact of phenylephrine treatment on Sct(O(2)) and CBV is intensified during hypocapnia while blunted during hypercapnia.

Effect of phenylephrine and ephedrine bolus treatment on cerebral oxygenation in anaesthetized patients.

BACKGROUND: How phenylephrine and ephedrine treatments affect global and regional haemodynamics is of major clinical relevance. Cerebral tissue oxygen saturation (Sct(O2) )-guided management may improve postoperative outcome. The physiological variables responsible for Sct(O2) changes induced by phenylephrine and ephedrine bolus treatment in anaesthetized patients need to be defined. METHODS: A randomized two-treatment cross-over trial was conducted: one bolus dose of phenylephrine (100-200 µg) and one bolus dose of ephedrine (5-20 mg) were given to 29 ASA I-III patients anaesthetized with propofol and remifentanil. , mean arterial pressure (MAP), cardiac output (CO), and other physiological variables were recorded before and after treatments. The associations of changes were analysed using linear-mixed models. RESULTS: The CO decreased significantly after phenylephrine treatment [▵CO = -2.1 (1.4) litre min(-1), P<0.001], but was preserved after ephedrine treatment [▵CO = 0.5 (1.4) litre min(-1), P>0.05]. The was significantly decreased after phenylephrine treatment [▵ = -3.2 (3.0)%, P<0.01] but preserved after ephedrine treatment [▵ = 0.04 (1.9)%, P>0.05]. CO was identified to have the most significant association with (P<0.001). After taking CO into consideration, the other physiological variables, including MAP, were not significantly associated with (P>0.05). CONCLUSIONS: Associated with changes in CO, decreased after phenylephrine treatment, but remained unchanged after ephedrine treatment. The significant correlation between CO and implies a cause-effect relationship between global and regional haemodynamics.

The effect of coenzyme Q10 in patients with congestive heart failure.

BACKGROUND: Coenzyme Q10 is commonly used to treat congestive heart failure on the basis of data from several unblinded, subjective studies. Few randomized, blinded, controlled studies have evaluated objective measures of cardiac performance. OBJECTIVE: To determine the effect of coenzyme Q10 on peak oxygen consumption, exercise duration, and ejection fraction. DESIGN: Randomized, double-blind, controlled trial. SETTING: University and Veterans Affairs hospitals. PATIENTS: 55 patients who had congestive heart failure with New York Heart Association class III and IV symptoms, ejection fraction less than 40%, and peak oxygen consumption less than 17.0 mL/kg per minute (or <50% of predicted) during standard therapy were randomly assigned. Forty-six patients completed the study. INTERVENTION: Coenzyme Q10, 200 mg/d, or placebo. MEASUREMENTS: Left ventricular ejection fraction (measured by radionuclide ventriculography) and peak oxygen consumption and exercise duration (measured by a graded exercise evaluation using the Naughton protocol) with continuous metabolic monitoring. RESULTS: Although the mean (+/-SD) serum concentration of coenzyme Q10 increased from 0.95+/-0.62 microg/mL to 2.2+/-1.2 microg/mL in patients who received active treatment, ejection fraction, peak oxygen consumption, and exercise duration remained unchanged in both the coenzyme Q10 and placebo groups. CONCLUSION: Coenzyme Q10 does not affect ejection fraction, peak oxygen consumption, or exercise duration in patients with congestive heart failure receiving standard medical therapy.

[3H]8-OH-DPAT labels the 5-hydroxytryptamine uptake recognition site and the 5-HT1A binding site in the rat striatum.

The binding of [3H]8-hydroxy-2-(di-N-propylamino)-tetralin ([ 3H]8-OH-DPAT) to rat hippocampal and striatal membranes has been compared. In the hippocampus, low concentrations of [3H]8-OH-DPAT bound to a single, high affinity site which was sensitive to inhibition by spiperone, buspirone and ergotamine but not by mianserin, quipazine or (-)-propranolol. This is consistent with a selective labeling of the 5-HT1A receptor. In the striatum, [3H]8-OH-DPAT bound to two sites with high and low affinity (KD's 1.18 and 109 nM). The high affinity component was blocked by low concentrations of buspirone, spiperone and ergotamine. The low affinity component was blocked only by high concentrations of buspirone and spiperone, and was not displaced by ergotamine at concentrations up to 1 microM. The ergotamine-resistant component of striatal [3H]8-OH-DPAT binding was blocked by low concentrations of the 5-HT uptake inhibitors fluvoxamine and paroxetine, and by relatively low concentrations of 5-HT itself. Thus [3H]8-OH-DPAT labels the 5-HT transporter in the rat striatum. Unlike [3H]imipramine binding, the binding of [3H]8-OH-DPAT to the 5-HT transporter was independent of external sodium ions. It is therefore suggested that 8-OH-DPAT acts as substrate for the 5-HT transporter and labels the 5-HT recognition site of the transporter complex.

Heterogeneous 3H-rauwolscine binding sites in rat cortex: two alpha 2-adrenoceptor subtypes or an additional non-adrenergic interaction?

Ligand binding and isolated tissue data have provided evidence for the existence of two, tissue-specific, alpha 2-adrenoceptor subtypes in various rodent and non-rodent species. Thus it has been proposed that the complex binding of alpha 2-antagonists to rat cortical membranes is due to the presence of both subtypes in this tissue. We have previously shown that the alpha 2-antagonist 3H-rauwolscine binds to two sites on rat cortical membranes: a high affinity component characterised pharmacologically as an alpha 2-binding site, and a low affinity, spiperone-sensitive, serotonergic-like component. By the use of computerised non-linear curve-fitting, and the inclusion of (in the incubation buffer of displacement experiments) a concentration of spiperone previously shown to selectively occlude the low affinity component of the 3H-rauwolscine saturation isotherm, we have determined the rank order of affinity at each of the two sites. Whereas the rank order of affinity at the high affinity site retains the pharmacological profile of a single, monophasic alpha 2-binding site, that at the low affinity component is markedly different and is similar to that at the putative 5HT1A subtype. These data, together with the additional, functional serotonergic interactions of rauwolscine and yohimbine, indicate that there is no evidence to support the existence of heterogeneous alpha 2-binding sites, as measured by 3H-rauwolscine binding, on rat cortical membranes. Furthermore, we present evidence that the specific, low affinity serotonergic interaction of 3H-rauwolscine could be avoided by a more judicial estimation of specific binding.

Diuretic-induced CNS magnesium alteration and digoxin intoxication.

Male Wistar rats were injected intraperitoneally for 3 consecutive days with hydrochlorothiazide (HCTZ; 15 mg/kg), chlorothiazide (CTZ; 100 mg/kg), bendroflumethiazide (BFTZ; 1.5 mg/kg), chlorthalidone (CHLOR; 15 mg/kg), methyclothiazide (METH; 1.0 mg/kg) or metolazone (MET; 1.5 mg/kg). Magnesium content was measured in the hypothalamus, medulla oblongata, cerebral cortex, heart, skeletal muscle and serum. Although there was no consistent alteration of Mg in the serum, skeletal muscle and heart, there was a significant effect on hypothalamic and medullary Mg. Compared to a control value of 17.20 +/- 1.24 mEg/kg in the hypothamus there was a decrease by HCTZ (26%; p less than 0.01), CTZ (24%; p less than 0.01) and BFTZ (30%; p less than 0.01). Similarly, there was a decrease by HCTZ (22%; p less than 0.01), CTZ (30%; p less than 0.01) and BFTZ (25%; p less than 0.01) on Mg in medulla. In contrast MET increases Mg in hypothalamus (31%; p less than 0.01) and medulla (26%; p less than 0.01). Furthermore, digoxin infusion (0.051 ml/min) in animals pretreated with HCTZ induced arrhythmias earlier than in animals receiving digoxin alone (30 vs. 60 min; p less than 0.01). The effects of digoxin toxicity in HCTZ-pretreated animals were partially reversed by CNS administration of 50 micrograms of Mg. These findings strongly suggest that thiazide-induced depletion of Mg in the CNS predisposes to digoxin intoxication.

Stereoselective blockade of central [3H]5-hydroxytryptamine binding to multiple sites (5-HT1A, 5-HT1B and 5-HT1C) by mianserin and propranolol.

The interaction of the enantiomers of mianserin and propranolol with the binding of [3H]5-hydroxytryptamine ([3H]5-HT) to the 5-HT1A, 5-HT1B and 5-HT1C sites, and with the binding of [3H]ketanserin to the 5-HT2 site, has been evaluated in rat brain membranes. A stereoselective interaction at the 5-HT1A, 5-HT1B and 5-HT1C sites was demonstrated for both compounds, with (+)-mianserin being a more potent displacer than (-)-mianserin and (-)-propranolol being more potent than (+)-propranolol. Only mianserin interacted in a stereoselective manner with the 5-HT2 site, (+)-mianserin being the more potent isomer. The stereoselective association of mianserin and propranolol with the 5-HT1A, 5-HT1B and 5-HT1C sites may prove useful in the characterization of these sites.