Search PubMed⌕ Search

Biomedical subjects

Y Gozal

Publications and source records attributed to Y Gozal.

At least 19 recordsLinked to original sources
PubMed2005

Isoflurane does not mimic ischaemic preconditioning in decreasing hydroxyl radical production in the rabbit.

BACKGROUND: Reactive oxygen species are an important mediator in isoflurane-induced myocardial preconditioning. However, hydroxyl radicals are also released during reperfusion after regional ischaemia. The purpose of the present study was to test whether ischaemic preconditioning and isoflurane would influence the production of hydroxyl radicals during reperfusion. METHODS: After i.v. administration of salicylate 100 mg kg(-1) and a 30 min stabilization period, New Zealand White rabbits were subjected to 40 min of regional myocardial ischaemia and 2 h of reperfusion. Ischaemic preconditioning was elicited by 5 min ischaemia followed by 10 min reperfusion (before the 40 min ischaemia). In another group, isoflurane (2.1%) was administered for 30 min, followed by 15 min washout, before the long ischaemia. Area at risk and infarct size were assessed by blue dye injection and tetrazolium chloride staining. We quantified the level of OH-mediated conversion of salicylate to its dihydrobenzoate derivatives (2,3- and 2,5-DHBAs). Normalized values of the DHBAs (ng DHBA per mg salicylate) were calculated. RESULTS: Mean (se) infarct size was 57 (6)% of the risk area in the untreated controls. This was significantly smaller in the ischaemic preconditioning and isoflurane groups: 22 (5) and 23 (6)% respectively. At 10 min of reperfusion, ischaemic preconditioning limited the mean increase in 2,3-DHBA to 24% from baseline, compared with 81% in control and 74% in the isoflurane group. Normalized 2,5-DHBA was maximally increased by 75% in the untreated group, 4 min after reperfusion. Ischaemic preconditioning significantly inhibited this increase (24% increase from baseline, P<0.01). However, the increase observed in the isoflurane group was not different from control (71%). CONCLUSIONS: As already known, ischaemic preconditioning and isoflurane markedly reduced infarct size. However, only ischaemic preconditioning decreased postischaemic production of hydroxyl radicals. These different effects suggest different protective mechanisms at the cellular level.

Anesthetics, Inhalation↗
PubMed2005

Ischaemic preconditioning but not isoflurane prevents post-ischaemic production of hydroxyl radicals in a canine model of ischaemia-reperfusion.

BACKGROUND AND OBJECTIVE: Isoflurane has been shown to mimic ischaemic preconditioning (IPC). The protective effect of IPC, or applying isoflurane or perfusion with the 'push-pull' complex zinc-desferrioxamine (Zn-DFO) in the canine heart, was investigated. METHODS: Thirty minutes after salicylate administration (100 mg kg(-1)) the heart was exposed. All dogs were subjected to a 10 min left anterior descending artery occlusion followed by 2 h of reperfusion. In Group I (n = 9) isoflurane (2.5%) was administered 10 min prior to and during ischaemia. In Group II (n = 8), IPC was elicited by 5 min coronary artery occlusion, followed by 5 min of reperfusion, prior to the 10 min ischaemia. In Group III (n = 9) Zn-DFO (2.5 mg kg(-1)) was given 10 min prior to ischaemia. The effects of these interventions were compared to control (n = 10). Coronary sinus blood concentrations of salicylate, 2,3-dihydroxybenzoic acid (DHBA), lactate, pH and oxygen content were monitored. RESULTS: In the control group, 2,3-DHBA increased by 32% above the pre-ischaemic value (P < 0.05). In contrast, in the IPC hearts, a significant decrease in the production of 2,3-DHBA was observed (40% lower than baseline, P < 0.01). In the isoflurane group only a 13% (and non-significant) decrease was noticed. In the Zn-DFO group a 33% decrease was found (P < 0.01). The increase in lactate concentrations in the IPC and Zn-DFO groups was significantly smaller than that of control and isoflurane groups. CONCLUSIONS: IPC protected the heart against the deleterious effects of reperfusion, possibly by amelioration of the level of oxygen-derived reactive species, and the complete inhibition of reactive hydroxyl radical production. Isoflurane did not prove to be as effective in reducing the free radical damage.

Anesthetics, Inhalation↗
PubMed2005

Isoflurane-induced myocardial preconditioning is dependent on phosphatidylinositol-3-kinase/Akt signalling.

BACKGROUND: Isoflurane and other volatile anaesthetics have a cardioprotective effect and limit myocardial infarct size to the same extent as ischaemic preconditioning. Phosphatidylinositol-3-kinase (PI3K) was found to play a key role in myocardial protection by ischaemic preconditioning. The aim of the present investigation was to evaluate whether isoflurane-induced myocardial preconditioning is dependent on PI3K signalling. METHODS: Using a model of regional myocardial ischaemia and reperfusion, New Zealand White rabbits were subjected to 40 min of regional myocardial ischaemia followed by 120 min of reperfusion. The rabbits were randomly assigned to one of the following six experimental groups: sham-operated controls (n=5); ischaemia and reperfusion controls (n=8); isoflurane preconditioning (n=8); a PI3K inhibitor, wortmannin (0.6 mg kg(-1) i.v.) + isoflurane (n=8); and wortmannin+ischaemia and reperfusion (n=8). An additional control group of sham operation+ wortmannin (n=5) was also included. Myocardial injury was assessed by measuring the serum concentration of the MB fraction of creatine kinase (CK-MB) and infarct size was assessed by 2,3,5-triphenyl tetrazolium chloride staining. Phosphorylation of Akt, a downstream target of PI3K, was assessed by western blotting. RESULTS: Isoflurane preconditioning was seen as reduced infarct size compared with control animals: 24 (4) and 41 (5)% respectively (P<0.05). Wortmannin inhibited this cardioprotective effect with myocardial infarct size at 44 (3)% (not significant). Akt phosphorylation was increased after isoflurane preconditioning, but administration of wortmannin blocked this effect. CONCLUSIONS: Our data demonstrate that isoflurane protects the heart against ischaemia and decreases myocardial infarction by activation of PI3K.

Androstadienes↗
PubMed2004

Complicated endoscopic pediatric procedures using deep sedation and general anesthesia are safe in the endoscopy suite.

BACKGROUND: Complicated upper and lower endoscopic procedures of the gastrointestinal tract are performed in children for a variety of diagnostic and therapeutic reasons. Unlike adult patients, who receive conscious sedation, children usually require deep sedation (DS) or general anesthesia (GA). The aim of this study is to assess the safety parameters of complicated endoscopic procedures under DS or GA performed in children in the endoscopy suite rather than in the operating theatre. METHODS: Between May 1997 and December 2002, 296 patients (mean age 4.5 years, range 3 weeks to 16 years), defined as ASA I-III, underwent either DS or GA for endoscopic foreign body extraction, endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous endoscopic gastrostomy (PEG) insertion. ASA physical status I was found in 15%, II in 57% and III in 28%. The pathologies included neuromuscular diseases, genetic syndromes, nesidioblastosis, biliary atresia, hematologic, respiratory (cystic fibrosis) and cardiac disorders. Propofol was the drug of choice (63%) followed by a combination of propofol and midazolam (16%). RESULTS: Transient desaturation (O2 saturation <90%) was the only complication recorded in 21/296 (7.09%) patients. Only two patients with severe respiratory underlying disease were hospitalized for follow-up for a 24-h period. CONCLUSIONS: The use of DS and GA for complicated endoscopies in a moderately high-risk pediatric population was found to be safe. The very low complication rate found in this study suggests that complicated pediatric patients can be managed successfully outside the operating theatre, provided that all the safety criteria for ambulatory DS or anesthesia are present.

Adolescent↗
PubMed2004

[The use of conscious sedation versus general anesthesia in modern dentistry: rising ethical dilemmas].

Conscious sedation and general anesthesia have been in the use of the dental profession since the first half of the 19th century. Although seemingly appealing to use due to alleviation of pain and anxiety induced by the dental treatment, the alteration of consciousness level of dental patients is not without risk. Morbidity and mortality due to dental treatment performed under general anesthesia were investigated at the last decades of the 20th century. The mortality rates found in these investigations were surprisingly high comparing to researches of morbidity and mortality due to other medical procedures, performed under general anesthesia. Therefore, although general anesthesia is sometimes the only way to treat certain patients, maintaining strict indications for dental treatment under general anesthesia is necessary. Conscious sedation was found as a safer alternative for achieving a level of consciousness enabling dental treatment in those patients who are unable to receive treatment in normal dental clinic settings. We therefore believe that conscious sedation should be the golden standard for the treatment of those patients. The practicing of dentistry in patients who have need of dental treatment under special settings such as general anesthesia and sedation raises ethical dilemmas to the caregiver. The following review will summarize the available data on morbidity and mortality due to dental treatment given under general anesthesia and conscious sedation. The ethical questions arising from their practicing will be discussed and some answers shall be proposed.

Anesthesia, Dental↗
PubMed2002

Manipulations in glycogen metabolism and the failure to influence infarct size in the ischaemic rabbit heart.

BACKGROUND AND OBJECTIVE: Myocardial ischaemic preconditioning is characterized by a reduction in the rate of glycolysis. Brief myocardial ischaemia also reduces the glycogen content of the heart. The first objective was to determine whether augmenting glucose oxidation by activation of the pyruvate dehydrogenase complex would prevent the infarct limitation of ischaemic preconditioning. The second part of the study evaluates whether glycogen depletion before ischaemia mimics the infarct-limiting effect of ischaemic preconditioning. METHODS: Dichloroacetate (300 + 150 mg kg(-1)), an activator of the pyruvate dehydrogenase complex, was administered intravenously in the anaesthetized open-chest rabbit. All animals underwent 45 min of regional ischaemia and 3 h of reperfusion. Ischaemic preconditiong was elicited by 5 min of coronary occlusion. Control rabbits, those with ischaemic preconditioning with no dichloroacetate, received a saline vehicle. An isolated perfused rabbit heart model was employed to test the second hypothesis. Hearts were depleted of glycogen by perfusing them with a substrate-free buffer. Infarction was assessed by triphenyl tetrazolium chloride and area at risk determined with fluorescent particles. RESULTS: (a) Pyruvate dehydrogenase complex activation experiments. Treatment with dichloroacetate alone did not alter infarct size (58 +/- 7% control vs. 60 +/- 5% dichloroacetate). Addition of dichloroacetate did not attenuate the infarct-limiting effect of ischaemic preconditioning as evidenced by a similar reduction in infarct size in the ischaemic preconditioning group (22 +/- 5%) and in the ischaemic preconditioning + dichloroacetate group (27 +/- 7%). (b) Glycogen depletion experiments. Compared with control hearts with a normal glycogen content (4.84 +/- 0.15 mg g(-1) wet weight), glycogen depleted and ischaemic preconditioning hearts had reduced glycogen content before ischaemia (2.15 +/- 0.26, 1.62 +/- 0.17 mg g(-1) wet weight, respectively; P < 0.01). Glycogen depletion did not reduce infarct size: 25.0 +/- 4.5% cf. 27.9 +/- 3.4% in the control group. However, ischaemic preconditioning resulted in a significant reduction of infarct size (11.5 +/- 2.3% vs. 27.9 +/- 3.4% control; P < 0.01). CONCLUSIONS: Augmentation of oxidative glycolysis by dichloroacetate in in situ rabbit hearts does not alter the effect of ischaemic preconditioning, and glycogen depletion in the isolated rabbit heart does not influence infarct size after subsequent coronary occlusion.

Analysis of Variance↗
PubMed2001

Propofol does not modify the hemodynamic status of children with intracardiac shunts undergoing cardiac catheterization.

Immobility and cardiovascular stability are required for cardiac catheterization. Pediatric patients need a type of sedation that also allows spontaneous ventilation without supplemental oxygen. Propofol has been adequate in hemodynamically stable patients with congenital heart disease undergoing cardiac catheterization. However, mild systemic hypotension caused by propofol may increase a preexisting right-to-left shunt. The aim of this study is to evaluate, in pediatric patients scheduled for cardiac catheterization, the effects of propofol on systemic and pulmonic circulations. Fifteen patients aged 18 months to 9 years were studied. After a fast of 4-6 hours for solid food, the patient arrived at the cardiac catheterization suite, where an IV catheter was placed. Usual monitoring was used. For sedation, without supplemental oxygen, patients received 1 mg/kg of fentanyl followed by propofol (1-2 mg/kg) titrated to immobility during preparation of the groin. A continuous infusion of propofol (100 mg/kg/min) was also started to obtain immobility during the procedure. Hemodynamic data, including systemic venous, pulmonary artery and vein, aortic saturations, and pressures, were recorded; Qp and Qs were calculated. The same set of data was re-corded 4 minutes after discontinuation of propofol and when the patient was responding to tactile stimuli. Despite lower pressures during propofol infusion, as compared with those pressures measured after discontinuation of propofol, the extent of the intracardiac shunt remained unchanged. Propofol seems to be an adequate sedative agent for pediatric patients undergoing cardiac catheterization, including those with intracardiac shunts.

Anesthetics, Intravenous↗
PubMed2000

The effect of clonidine premedication on hemodynamic responses to microlaryngoscopy and rigid bronchoscopy.

The usual hemodynamic response to laryngoscopy and bronchoscopy is an increase in heart rate and arterial blood pressure. Previous work has reported that 10%-18% of the patients develop ischemic ST segment changes during the procedure. Therefore, we performed a prospective, randomized, double-blinded study in 36 patients scheduled for elective microlaryngeal and bronchoscopic surgical procedures to evaluate the effects of 300-microg oral clonidine premedication (n = 18) or placebo (n = 18) on the hemodynamic alterations and the incidence of perioperative myocardial ischemic episodes. Myocardial ischemia was assessed by using continuous electrocardiographic monitoring, beginning 30 min before, and lasting until 24 h after the operation. During the procedure, patients receiving placebo exhibited a significant increase (mean +/- SD) in arterial blood pressure (the systolic increasing from 137+/-11 to 166+/-17 mm Hg, the diastolic increasing from 80+/-11 to 97+/-14 mm Hg) and heart rate (increasing from 79+/-15 to 97+/-12 bpm) compared with the baseline and with the clonidine group. A dose of 300-microg clonidine blunted the hemodynamic response to endoscopy. Ventricular arrhythmias were more frequent in patients who were not premedicated with clonidine. Two patients in the control group, but none in the clonidine group, had evidence of myocardial ischemia. These data should encourage routine premedication with clonidine in patients undergoing microlaryngoscopic and bronchoscopic procedures.

Adrenergic alpha-Agonists↗
PubMed2000

Perioperative myocardial ischemia in cataract surgery patients: general versus local anesthesia.

Patients having cataract surgery are usually elderly and have risk factors for ischemic heart disease. We sought to determine the incidence of perioperative myocardial ischemia in patients having cataract surgery and compare the influence of local anesthesia (LA) and general anesthesia (GA). Eighty-one patients undergoing cataract surgery with at least two risk factors for ischemic heart disease were monitored continuously for 24 h by using electrocardiogram leads II and V5 and a Holter recorder (Medilog 4500, Oxford Ltd, UK). Patients were randomly allocated to two groups, either LA (n = 39) or GA (n = 42). In the LA group, a peribulbar block was performed, whereas a similar block was performed in the GA group after tracheal intubation. The study demonstrated that cataract patients suffered from a frequent incidence of perioperative myocardial ischemia (31%). There was no difference in the incidence rate between the groups: 12 of 39 in the LA group and 13 of 42 in the GA group (P: = NS). However, the number of ischemic episodes was significantly increased in the GA group (18 vs. 13 in the LA group) (P<0.05), and there were significantly more intraoperatively in the GA group (8 vs. 1) (P<0.01). All intraoperative ischemic events were associated with tachycardia (> or =20% of baseline), whereas postoperative ischemic changes were mostly independent of heart rate. Only one of the ischemic patients (in the GA group) was admitted as a result of intractable chest pain. There were significantly less intraoperative episodes in the LA group, suggesting that LA may be safer than GA in patients during this type of surgery.

Aged↗
PubMed1998

ST segment changes following retinal surgery.

STUDY OBJECTIVE: To describe the perioperative cardiac morbidity in adult patients undergoing retinal surgery using continuous Holter monitoring. DESIGN: Prospective study. SETTING: University hospital. PATIENTS: 56 patients scheduled for elective retinal surgery with local anesthesia. INTERVENTIONS: Patients were monitored continuously for 24 hours using a Holter recorder. Blood samples for creatine phosphokinase (CPK) and serum myocardial creatine phosphokinase (CPK-MB) were taken preoperatively and 24 hours postoperatively. The characteristics of myocardial ischemia were compared according to the number of risk factors for ischemic heart disease. MEASUREMENTS AND MAIN RESULTS: The overall incidence of perioperative myocardial ischemia was high: 26.7% (n = 15). These patients exhibited 41 episodes of ischemia with mean ST segment change from baseline of 2.2+/-0.7 mm. However, almost all (93.3%) ischemic episodes were silent. Patients with two risk factors or more had 77% more episodes of ischemia than patients with one risk factor (p < 0.005), and the duration of ischemia was 47+/-22.5 minutes compared with 34.8+/-27.5 minutes (p = NS). The first episode of ischemia occurred an average of 10 hours after surgery. No patient had intraoperative evidence of ischemia. Half of the ischemic episodes were associated with an increase in heart rate. No patient had evidence of acute myocardial infarction. CONCLUSION: Retinal surgery with local anesthesia is accompanied by a high incidence of postoperative myocardial ischemia. No negative outcome was correlated to the occurrence of postoperative myocardial ischemia. The significance of these findings has yet to be evaluated.

Aged↗
PubMed1997

Halothane prevents postischemic production of hydroxyl radicals in the canine heart.

BACKGROUND: Recent studies indicate that during regional myocardial ischemia and subsequent reperfusion, volatile anesthetics may provide protection against free radical-related injury. The effect of halothane on free radical production during ischemia and reperfusion, in the canine heart, was investigated. The level of hydroxyl radical (.OH)-mediated conversion of salicylate to its dehydroxybenzoate derivatives (2,3-DHBA and 2,5-DHBA) was monitored. METHODS: Under general anesthesia, the heart was exposed through median sternotomy. Salicylate (100 mg/kg given intravenously) was administered 30 min before left anterior descending artery occlusion. Six dogs were studied using inhaled halothane (1.6%) 10 min before and during the 10-min ischemic period, followed by 50 min of reperfusion, and then they were compared with seven other dogs used as controls. Blood concentrations of salicylate, 2,3-DHBA and 2,5-DHBA, K+, lactate, oxygen content, and pH were monitored. RESULTS: An acute increase in the normalized concentrations of 2,3-DHBA and 2,5-DHBA was observed in the control animals during reperfusion. In contrast, halothane inhalation completely inhibited the production of both metabolites (P < 0.02), but 2,5-DHBA concentrations in the halothane-treated group were even less than the basal level (P < 0.05). The increase in lactate concentrations in the experimental animals was significantly less than that of controls (P < 0.05) and followed the same time-dependent pattern as the changes in K+ and pH. Halothane significantly decreased (P < 0.0001) the difference in oxygen content between coronary sinus and aortic root blood, suggesting decreased oxygen utilization during reperfusion. CONCLUSIONS: Halothane completely inhibited the production of .OH, and its administration may protect the heart from the deleterious effect of oxygen-derived reactive species, with attenuation of the metabolic response to ischemia.

Anesthetics, Inhalation↗