[Effects of Electroacupuncture Stimulation of "Neiguan" (PC 6) at Different Frequencies on Plasma Vasoactive Substance Levels in Myocardial Ischemic Reperfusion Rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of "Neiguan" (PC 6) at different frequencies on plasma vasoactive substance levels in myocardial ischemia-reperfusion (MIR) injury rats, so as to explore its mechanisms underlying improvement of acute myocardial ischemia. METHODS: A total of 40 Wistar rats were randomized into control, model, high frequency (HF, 120 Hz) and low frequency (LF, 20 Hz) groups (n = 10 in each group). The MIR model was established by occlusion of the anterior descending branch (ADB) of the left coronary artery for 30 min, followed by reperfusion for 40 min. EA (3 V, 120 Hz or 20 Hz) was applied to bilateral "Neiguan" (PC 6) for 50 min immediately after occlusion of ADB. Subsequently, the contents of plasma endothelin (ET), atrial natriuretic peptide (ANP), thromboxane B 2 (TXB2) and 6-Keto-PGF1, were assayed by radioimmunoassay, and the content of serum nitric oxide (NO) was detected by nitrate reductase method. RESULTS: Compared with the control group, the contents of plasma ET, ANP and TXB2 in the model group were significantly increased (P < 0.05), and that of plasma 6-Keto-PGF1α in the model group was notably decreased (P < 0.05), but no significant change was found in serum NO level (P > 0.05). Compared with the model group, the contents of plasma ET, ANP and TXB2 were considerably decreased, and plasma 6-Keto-PGF1α and serum NO contents were obviously increased in both HF and LF groups (P < 0.05). No significant differences were found between the HF and LF groups in plasma ET , ANP, TXB2 and 6-Keto-PGF1α contents (P > 0.05), but the HF EA was markedly superior to the LF EA in up-regulating the content of serum NO (P < 0.05). CONCLUSION: EA stimulation of "Neiguan" (PC 6) can down-regulate the contents of plasma ET, ANP and TXB2 and up-regulate contents of plasma 6-Keto-PGF1α and serum NO in MIR rats, which may contribute to its effect in relieving acute ischemic myocardial injury. The effect of HF EA is better than LF EA in raising blood NO level.

Selepressin, a new V1A receptor agonist: hemodynamic comparison to vasopressin in dogs.

Selepressin is a new selective vasopressin V1a agonist for treatment of vasodilatory hypotension in shock. Its effect on coronary and aortic blood flow, hemodynamics, and electrocardiogram as an indication of drug safety in healthy dogs was compared with arginine vasopressin (AVP). Eight dogs were fasted, anesthetized, intubated, and ventilated. Following thoracotomy, coronary and aortic blood flows were monitored, left ventricular and peripheral arterial blood pressures were measured, and electrocardiogram was recorded. Selepressin or AVP was administered by dose-escalating infusions (1-300, 0.3-100 ng · kg(-1) · min(-1), respectively). Drug formulation analysis and plasma bioanalysis confirmed exposure. For each dose level, hemodynamic parameters, drug potency, and efficacy were determined. Selepressin and AVP induced a similar increase in mean blood pressure (+13% to 18%), a moderate decrease in aortic blood flow (-40% to 45%), and a slight decrease in coronary blood flow (-16% to 22%). These vasopressors displayed similar hemodynamic characteristics, with peripheral vasoconstriction and decreased aortic blood flow being more pronounced than the increase in coronary resistance and decrease in coronary blood flow. Importantly, selepressin bore no relevant coronary ischemic liability, suggesting that V1a receptor agonists are a potential pharmacological target for treatment of vasodilatory hypotension in shock.

High-dose ascorbic acid infusion abolishes chronic vasoconstriction and restores resting leg blood flow in healthy older men.

Resting whole leg blood flow and vascular conductance decrease linearly with advancing age in healthy adult men. The potential role of age-related increases in oxidative stress in these changes is unknown. Resting leg blood flow during saline and ascorbic acid infusion was studied in 10 young (25 +/- 1 yr) and 11 older (63 +/- 2 yr) healthy normotensive men. Plasma oxidized LDL, a marker of oxidative stress, was greater in the older men (P < 0.05). Absolute resting femoral artery blood flow at baseline (iv saline control infusion) was 25% lower in the older men (238 +/- 25 vs. 316 +/- 38 ml/min; P < 0.05), and it was inversely related to plasma oxidized LDL (r = -0.56, P < 0.01) in all subjects. Infusion of supraphysiological concentrations of ascorbic acid increased femoral artery blood flow by 37% in the older men (to 327 +/- 52 ml/min; P < 0.05), but not in the young men (352 +/- 41 ml/min; P = 0.28), thus abolishing group differences (P = 0.72). Mean arterial blood pressure was greater in the older men at baseline (86 +/- 4 vs. 78 +/- 2 mmHg; P < 0.05), but it was unaffected by ascorbic acid infusion (P >/= 0.70). As a result, the lower baseline femoral artery blood flow in the older men was mediated solely by a 32% lower femoral artery vascular conductance (P < 0.05). Baseline femoral vascular conductance also was inversely related to plasma oxidized LDL (r = -0.65, P < 0.01). Ascorbic acid increased femoral vascular conductance by 36% in the older men (P < 0.05) but not in the young men (P = 0.31). In conclusion, ascorbic acid infused at concentrations known to scavenge reactive oxygen species restores resting femoral artery blood flow in healthy older adult men by increasing vascular conductance. These results support the hypothesis that oxidative stress plays a major role in the reduced resting whole leg blood flow and increased leg vasoconstriction observed with aging in men.

[Hemodynamic effects of local anesthetics with adrenaline during septal surgery]. / Nazal cerrahide adrenalinli lokal anestetiklerin hemodinamik etkileri.

OBJECTIVES: We investigated the hemodynamic effects of local anesthetics with adrenaline used before septal surgery. PATIENTS AND METHODS: In a prospective, controlled design, administration of local anesthetics was performed with and without adrenaline in 39 patients and 10 patients, respectively, undergoing septal surgery. Plasma adrenaline concentrations were measured before anesthesia, and after 2, 5, and 10 minutes from anesthesia. The patients were monitored with respect to pulse rate, electrocardiographic findings, and blood pressure. RESULTS: Preoperative plasma adrenaline levels were similar in patients receiving local anesthetics with or without adrenaline (0.8 nmol/l vs 0.7 nmol/l). Following adrenaline administration, adrenaline levels showed significant increases to 2.2, 1.9, and 1.7 nmol/l after 2, 5, and 10 minutes, respectively (p<0.001), whereas they remained similar in the control group. No side effects related to adrenaline use were detected. CONCLUSION: Despite systemic absorption of local injections, adrenaline-related side effects during septal surgery are extremely rare when the patients are closely monitored.

[Tumescent anaesthesia for dermatological surgery. Plasma concentrations of lidocaine and prilocaine]. / Tumeszenzlokalanästhesie bei dermatologischen Eingriffen. Plasmakonzentrationen von Lidocain und Prilocain.

BACKGROUND: Tumescent anaesthesia is currently used for several dermatological procedures. The objective of this study was to determine the plasma concentrations of local anaesthetics under real operating conditions with this anaesthetic technique. METHODS: A total of 31 patients received 3 different anaesthetic solutions with prilocaine and lidocaine for several surgical procedures. The concentrations of local anaesthetics, methemoglobin, epinephrine as well as the occurrence of adverse reactions were determined 30 min, 1 h, 3 h, 6 h, 12 h and 24 h after administration RESULTS: Maximum plasma concentrations of prilocaine were measured predominantly after 3 and 6 h, for lidocaine after 6 h. In two patients maximum plasma levels occurred 24 h after infiltration. Although toxic concentrations were not exceeded, side-effects could be observed in four patients. CONCLUSIONS: Even if the measured concentrations of local anaesthetics appeared to be safe, slight and moderate side-effects could be observed in 12.9% of cases. Maximum plasma levels of local anaesthetics may still occur 24 h after administration.

Prevention of hypertension and organ damage in 2-kidney, 1-clip rats by tetradecylthioacetic acid.

Dietary lipids are reported to affect the blood pressure in both humans and experimental animal models with hypertension. In the present study, 2-kidney, 1-clip (2K1C) hypertensive rats were treated with the modified fatty acid tetradecylthioacetic acid (TTA) from the time of clipping or after hypertension was established. TTA treatment attenuated the development of hypertension and reduced established 2K1C hypertension. The mRNA level of renin in the clipped kidney and the plasma renin activity were markedly reduced, and the plasma angiotensin II level tended to decrease after TTA treatment. In addition, TTA reduced the mRNA level of angiotensinogen in white adipose tissue. Prevention of organ damage was demonstrated by normal urinary excretion of protein, maintained serum albumin, lower heart weight, and clearly reduced vascular, glomerular, and tubulointerstitial damage in the nonclipped kidney. Renal function was not affected as estimated by unchanged plasma creatinine. Furthermore, the serum levels of triacylglycerol and cholesterol were reduced by TTA. The serum fatty acid composition was changed, resulting in a favorable increase of oleic acid. However, the levels of all of the omega-3 fatty acids and of linoleic acid were reduced, and no change was seen in the level of arachidonic acid, but the urinary excretion of 8-iso-prostaglandin F2alpha was declined. In conclusion, TTA attenuated the development of hypertension, reduced established hypertension, and prevented the development of organ damage in 2K1C rats, possibly by reducing the amounts of the vasoconstrictors angiotensin II and 8-iso-prostaglandin F2alpha and by inducing a favorable increase of oleic acid in serum.

Plasma catecholamine concentrations and hemodynamic responses to vasoconstrictor during conventional or Gow-Gates mandibular anesthesia.

OBJECTIVE: The literature supports that systemic responses to injected vasoconstrictors depend on the volume and concentration administered, patient's age and health status, as well as site of injection. Thus, the influence of mandibular anesthesia technique on hemodynamic and plasma responses to epinephrine-containing local anesthetics was investigated. STUDY DESIGN: Conventional or Gow-Gates anesthesia with 2% lidocaine and epinephrine, 1:100,000, was performed in 18 subjects who required third molar extraction. A control group of 9 subjects was submitted to conventional anesthesia with plain 3% mepivacaine. Blood pressure, heart rate, and plasma catecholamines were measured. RESULTS: Analysis of variance showed that plasma epinephrine level after conventional lidocaine anesthesia was significantly elevated (P < .01), while there was no difference between the Gow-Gates and control groups. The hemodynamic parameters did not demonstrate correlation to the injection technique. CONCLUSION: Presumably, there was less exogenous epinephrine absorption in the Gow-Gates technique than in the conventional mandibular anesthesia injection.

Effects of lidocaine with and without epinephrine on plasma epinephrine and lidocaine concentrations and hemodynamic values during third molar surgery.

Lidocaine with epinephrine is currently the most common local anesthetic agent used for impacted third molar surgery. The purpose of the present study was to define the adverse hemodynamic effects and plasma concentrations of lidocaine and epinephrine on 17 healthy patients during the impacted teeth operations. Arterial blood pressure (systolic blood pressure, diastolic blood pressure), heart rate, peripheral oxygen saturation range, and electrocardiography were measured by an automatic noninvasive pressure device and monitor. High-performance liquid chromatography was used to measure the changes of plasma concentrations of epinephrine and lidocaine from blood samples taken 5 different times during the operation. We concluded that lidocaine-epinephrine is effective local anesthetic and had no important adverse events in healthy patients during the third molar surgery.

Antioxidant restriction and oxidative stress in short-duration exhaustive exercise.

PURPOSE: To determine the effect of dietary antioxidant restriction on oxidative stress, antioxidant defenses, and exercise performance in athletes. Oxidative stress has been shown to increase during exercise. To alleviate oxidative stress, a high intake of antioxidant rich foods or supplements may be required in trained athletes. METHODS: Plasma oxidative stress and antioxidant defenses were examined in 17 trained athletes who underwent two separate exercise tests. Before the initial exercise test participants followed their habitual (high) antioxidant (H-AO) diets. Then they followed a 2-wk restricted-antioxidant (R-AO) diet before the second exercise test. Blood was taken at rest, after submaximal and high-intensity exhaustive exercise, and after 1 h of recovery. RESULTS: The R-AO diet induced a threefold reduction in antioxidant intake when compared with habitual-antioxidant (H-AO) diets. F(2)-isoprostane concentration (marker of oxidative stress) was significantly higher after submaximal exercise (38%), exhaustion (45%), and 1 h of recovery (31%) when following the R-AO diet compared with the H-AO diet. Rate of perceived exertion was increased on the R-AO diet whilst exercise time to exhaustion was not affected. Total antioxidant capacity and circulating antioxidant concentrations, although not significantly different, tended to be lower when following the R-AO diet. CONCLUSION: Athletes regularly participating in up to 40 min of acute high-intensity exercise may require higher intakes of exogenous antioxidants to defend against increased oxidative stress during exercise, which can be met through an adequate intake of high-antioxidant foods. Thus, there seems no valid reason to recommend antioxidant supplements to athletes participating in acute high-intensity exercise events up to 40 min in duration, except in those known to be consuming a low-antioxidant diet for prolonged periods.

Ephedrine-induced cardiac ischemia: exposure confirmed with a serum level.

The temporal association of symptoms consistent with ephedrine toxicity after ingestion of ephedrine-containing dietary supplements is heavily relied upon to confirm exposure. Few reports in the literature attempt to associate toxicity with serum levels of these drugs. We report a case of ephedrine-induced cardiac ischemia confirmed by a plasma level. A 22-year-old woman ingesting an ephedrine- and caffeine-containing product for 2 days presented with multiple symptoms, including palpitations, nausea, tremulousness, abdominal pain, and vomiting. The initial electrocardiogram (ECG) revealed a normal sinus rhythm with 1 mm of ST segment depression in leads V3 and V4, along with inverted T waves in leads V1-V4. Her symptoms and ST segment depression resolved over several hours with medical management. The amplitude of her T wave inversions notably diminished with therapy; however, they did not completely resolve. Troponins at presentation and the following morning were negative, and an echocardiogram showed only trace tricuspid regurgitation. A serum ephedrine level, drawn approximately 6 to 7 hr after ingestion, was 150 ng/mL. She was discharged from the hospital after being instructed to avoid ephedrine-containing products.

Circulating angiotensin II activates neurones in circumventricular organs of the lamina terminalis that project to the bed nucleus of the stria terminalis.

The aim of this study was to determine, in conscious rats, whether elevated concentrations of circulating angiotensin II activate neurones in both the subfornical organ and organum vasculosum of the lamina terminalis (OVLT) that project to the bed nucleus of the stria terminalis (BNST). The strategy employed was to colocalize retrogradely transported cholera toxin B subunit (CTB) from the BNST, with elevated levels of Fos protein in response to angiotensin II. Circulating angiotensin II concentrations were increased by either intravenous infusion of angiotensin II or subcutaneous injection of isoproterenol. Neurones exhibiting Fos in response to angiotensin II were present in the subfornical organ, predominantly in its central core but with some also seen in its peripheral aspect, the dorsal and lateral margins of the OVLT, the supraoptic nucleus and the parvo- and magnocellular divisions of the paraventricular nucleus. Fos-labelling was not apparent in control rats infused with isotonic saline intravenously or injected with either CTB or CTB conjugated to gold particles (CTB-gold) only. Of the neurones in the subfornical organ that were shown by retrograde labelling to project to BNST, approximately 50% expressed Fos in response to isoproterenol. This stimulus also increased Fos in 33% of neurones in the OVLT that project to BNST. Double-labelled neurones were concentrated in the central core of the subfornical organ and lateral margins of the OVLT in response to increased circulating angiotensin II resulting from isoproterenol treatment. These data support a role for circulating angiotensin II acting either directly or indirectly on neurones in subfornical organ and OVLT that project to the BNST and provide further evidence of functional regionalization within the subfornical organ and the OVLT. The function of these pathways is yet to be determined; however, a role in body fluid homeostasis is possible.

Vitamin E supplementation decreases basal levels of F(2)-isoprostanes and prostaglandin f(2alpha) in rats.

Lipid peroxidation is thought to be an important factor in the pathophysiology of a number of diseases and in the process of aging. We investigated the effects of supplementation with vitamin E on lipid peroxidation in rats. Both free radical-induced nonenzymatic- and cyclooxygenase-catalyzed enzymatic lipid peroxidation were investigated by measuring the levels of F(2)-isoprostanes (8-iso-PGF(2alpha)) and PGF(2alpha)-metabolite (15-K-DH-PGF(2alpha)), respectively, in blood, urine and liver. Samples were collected from control rats (n = 6) and from rats supplemented with vitamin E in the diet for 3 wk (n = 8, 20 g/kg diet of DL-alpha-tocopherol hydrogen succinate). Plasma alpha-tocopherol concentration and antioxidative capacity were greater in the vitamin E-supplemented rats than in the control rats (17.9 +/- 1.7 vs. 50.4 +/- 10.4 micromol/L, P < 0.001 and 181 +/- 6 vs. 275 +/- 27 micromol/L trolox equivalents, P < 0.001). Urine 8-iso-PGF(2alpha) tended to be lower in the vitamin E-supplemented rats (0.72 +/- 0.40 vs. 0.34 +/- 0.19 nmol/mmol creatinine, P = 0.056). Urine 15-K-DH-PGF(2alpha) was lower due to vitamin E supplementation (0.97 +/- 0.38 vs. 0.56 +/- 0. 21 nmol/mmol creatinine, P < 0.05), as was liver-free 8-iso-PGF(2alpha) concentration (0.47 +/- 0.11 vs. 0.18 +/- 0.04 nmol/g, P < 0.001). Supplementation with vitamin E did not affect plasma 8-iso-PGF(2alpha) or 15-K-DH-PGF(2alpha) concentrations, liver total 8-iso-PGF(2alpha) or plasma malondialdehyde levels. Thus, vitamin E supplementation reduced urine basal levels of biomarkers of both nonenzymatic and enzymatic lipid peroxidation. In liver, vitamin E reduced the basal level of free 8-iso-PGF(2alpha) but not total 8-iso-PGF(2alpha).

Plasma catecholamine and haemodynamic responses to surgical endodontic anaesthetic protocols.

The effects of varying clinically relevant patterns of anaesthetic-vasoconstrictor combinations used for periradicular surgery on plasma concentrations of catecholamines and haemodynamic responses was studied in the canine model. Five mongrel dogs were anaesthetized with sodium pentobarbitol. A femoral cannula was inserted to measure central blood pressure and an ECG was used to monitor heart rate and any associated arrhythmias. Femoral venous blood samples were drawn before initial injection and at 3 and 10 min after injections. Plasma catecholamine concentrations were determined using high pressure liquid chromatography (HPLC). Injection protocols used three time periods, 30, 60 and 90 s, with solutions containing 1:100,000 and 1:50,000 adrenaline. No significant changes in heart rates or presence of arrhythmias were noted over the experimental protocol. Catecholamine levels in pico moles mL-1 were within the normal range at the 3-min sample level. At the 10-min sample time there was a more erratic range of concentrations, with most samples within the normal range. This may have been due to endogenous release of catecholamines in specific animals. The data identified trends in both the haemodynamic parameters and plasma catecholamine levels that can legitimately support the careful use of higher levels of a vasoconstrictor when patient profiles and surgical needs dictate.