Search PubMed⌕ Search

Biomedical subjects

M Ramez Salem

Publications and source records attributed to M Ramez Salem.

At least 19 recordsLinked to original sources
PubMed2006

Isoflurane, but not sevoflurane, increases transendothelial albumin permeability in the isolated rat lung: role for enhanced phosphorylation of caveolin-1.

BACKGROUND: Caveolae mediated transendothelial transport of albumin has recently been shown to be the primary mechanism regulating microvascular endothelial albumin permeability. The authors investigated the effects of isoflurane and sevoflurane on pulmonary endothelial albumin permeability and assessed the potential role of the caveolae scaffold protein, caveolin-1, in these effects. METHODS: Isolated rat lungs and cultured rat lung microvessel endothelial cells (RLMVECs) were exposed to 1.0 or 2.0 minimum alveolar concentration (MAC) isoflurane or sevoflurane for 30 min. I-albumin permeability-surface area product and capillary filtration coefficient were determined in the isolated lungs. In RLMVECs, uptake and transendothelial transport of I-albumin were measured in the absence and presence of pretreatment with 2 mm methyl-beta-cyclodextrin, a caveolae-disrupting agent. Uptake of fluorescent-labeled albumin, as well as phosphorylation of Src kinase and caveolin-1, was also determined. In Y14F-caveolin-1 mutant (nonphosphorylatable) expressing RLMVECs, uptake of I-albumin and phosphorylation of caveolin-1 were evaluated. RESULTS: In the isolated lungs, 2.0 MAC isoflurane increased I-albumin permeability-surface area product by 48% without affecting capillary filtration coefficient. In RLMVECs, isoflurane more than doubled the uptake of I-albumin and caused a 54% increase in the transendothelial transport of I-albumin. These effects were blocked by pretreatment with methyl-beta-cyclodextrin. The isoflurane-induced increase in uptake of I-albumin in wild-type RLMVECs was abolished in the Y14F-caveolin-1 mutant expressing cells. Isoflurane also caused a twofold increase in Src and caveolin-1 phosphorylation. Neither 1.0 MAC isoflurane nor 1.0 or 2.0 MAC sevoflurane affected any index of albumin transport or phosphorylation of caveolin-1. CONCLUSION: Isoflurane, but not sevoflurane, increased lung transendothelial albumin permeability through enhancement of caveolae-mediated albumin uptake and transport in the isolated lung. This effect may involve an enhanced phosphorylation of caveolin-1.

Albumins↗
PubMed2005

Role of adenosine receptors in volatile anesthetic preconditioning against neutrophil-induced contractile dysfunction in isolated rat hearts.

BACKGROUND: The authors tested the hypothesis that adenosine receptors in polymorphonuclear neutrophils and the heart mediate the preconditioning effects of volatile anesthetics against neutrophil-induced contractile dysfunction. METHODS: Studies were conducted in buffer-perfused and paced isolated rat hearts. Left ventricular developed pressure served as index of contractility. Neutrophils and platelet-activating factor were added to perfusate for 10 min followed by 30 min of recovery. The effect of selective pretreatment of the neutrophils and the hearts with 1.0 minimum alveolar concentration isoflurane or sevoflurane on the neutrophil-induced contractile dysfunction was assessed. Studies were performed in the absence and presence of the nonselective adenosine receptor antagonist 8-phenyltheophylline (10 microM). Neutrophil retention was determined from difference between those administered and collected in coronary effluent and from myeloperoxidase concentration in myocardial samples. Superoxide production of neutrophils was measured by spectrophotometry. RESULTS: Under control conditions (no anesthetic pretreatment), activated neutrophils caused marked and persistent reductions in left ventricular developed pressure, associated with increases in neutrophil retention and myeloperoxidase activity. Pretreatment of the neutrophils or the heart with either isoflurane or sevoflurane abolished these effects. Pretreatment of the neutrophils also reduced the platelet-activating factor-induced increase in superoxide production by 29 and 33%, respectively. 8-Phenyltheophylline blunted the effects of anesthetic pretreatment of the neutrophils, whereas it did not alter the effects of anesthetic pretreatment of the heart. CONCLUSION: An activation of adenosine receptors in neutrophils, but not in the heart, plays a role in the preconditioning effects of volatile anesthetics against neutrophil-induced contractile dysfunction.

Anesthetics, Inhalation↗
PubMed2005

Isoflurane prevents platelets from enhancing neutrophil-induced coronary endothelial dysfunction.

We evaluated whether platelets can enhance polymorphonuclear neutrophil-induced coronary endothelial dysfunction, and, after observing this, whether isoflurane can prevent the effect. Neutrophils, coronary artery segments, and platelets were obtained from 25 healthy dogs. Coronary artery rings were exposed to neutrophils activated with platelet-activating factor (1.0 microM), and after washing and preconstriction with U46619, were evaluated for concentration-related responses to acetylcholine, an endothelium-dependent vasorelaxing drug. Superoxide production by activated neutrophils was measured spectrophotometrically. Adherence of the activated neutrophils to the endothelium of coronary segments was assessed by direct counting of neutrophils labeled with fluorescent dye. Measurements were performed in absence and presence of isoflurane (1 minimum alveolar concentration) both with and without platelets. The presence of platelets enhanced the neutrophil-induced rightward shift in the concentration-vasorelaxation response curve to acetylcholine (the concentration of acetylcholine required to elicit 50% of maximal relaxation (-log M) was increased from 6.78 +/- 0.7 to 5.26 +/- 0.6), and it increased superoxide oxide production from 45.0 +/- 4.2 to 54.3 +/- 4.2 nM O2-/5 x 10(6) neutrophils and adherence of activated neutrophils from 204 +/- 10 to 268 +/- 5 neutrophils/mm2. Isoflurane abolished these effects of platelets. In conclusion, platelets enhanced the ability of neutrophils to cause coronary endothelial dysfunction. This effect was prevented by isoflurane. This may be attributable to an inhibitory action on superoxide production by the neutrophils leading to reduced expression of endothelial adhesion molecules and, in turn, reduced neutrophil adherence.

Acetylcholine↗
PubMed2004

Isoflurane preserves central nervous system blood flow during intraoperative cardiac tamponade in dogs.

PURPOSE: The present study tested the hypothesis that the anesthetic technique will influence the changes in regional blood flow (RBF) during intraoperative cardiac tamponade. METHODS: Twenty-four dogs were divided into three equal groups: Group I, anesthesia was maintained with ketamine (25 mg.kg(-1).hr(-1)); Group II, with fentanyl and midazolam (F-M; 10 mug.kg(-1).hr(-1) and 0.5 mg.kg(-1).hr(-1), respectively); Group III with 1 minimum alveolar concentration (MAC; 1.4%) isoflurane. Radioactive microspheres were used to measure RBF in myocardium, brain, spinal cord, abdominal viscera, skeletal muscle and skin. Cardiac output (CO) was measured by thermodilution and arterial pressure with a catheter situated in the thoracic aorta. Catheters were introduced into the pericardial cavity to infuse isotonic saline and to measure intrapericardial pressure (IPP). Measurements were obtained under control conditions and during tamponade, as defined by an increase in IPP sufficient to reduce mean arterial pressure by 40%. RESULTS: Tamponade caused decreases in CO and RBF that were comparable under the three anesthetics, except that RBF in subcortical regions of the brain and in the spinal cord were maintained under isoflurane but decreased under ketamine or F-M. CONCLUSIONS: In dogs, intraoperative cardiac tamponade caused comparable changes in RBF under the different anesthetic techniques except that autoregulation was effective in maintaining RBF within the central nervous system only under isoflurane anesthesia. Our findings provide no compelling reason to recommend one anesthetic over the others for maintenance of anesthesia in situations with increased risk for intraoperative cardiac tamponade. However, they cannot be extrapolated to anesthesia induction in the presence of cardiac tamponade.

Analgesics↗
PubMed2004

Isoflurane and sevoflurane precondition against neutrophil-induced contractile dysfunction in isolated rat hearts.

BACKGROUND: The authors tested the hypothesis that pretreatment with isoflurane or sevoflurane can protect the heart against neutrophil-induced contractile dysfunction. METHODS: Studies were conducted in buffer-perfused and paced isolated rat hearts. Left ventricular developed pressure served as an index of contractility. Pretreatment consisted of administration of 1.0 minimum alveolar concentration isoflurane or sevoflurane for 15 min followed by a 10-min washout and was performed in the absence and presence of the adenosine triphosphate-sensitive potassium channel inhibitor glibenclamide (10 microM). Polymorphonuclear neutrophils and platelet-activating factor were then added to the perfusate for 10 min, followed by 30 min of recovery. Neutrophil retention was assessed from the difference between those administered and collected in coronary effluent and measurements of myeloperoxidase in myocardial samples. Isolated hearts were also used to assess the effect of volatile anesthetic pretreatment on cardiac dysfunction caused by enzymatically generated superoxide. In additional studies, the authors evaluated the effect of volatile anesthetic pretreatment on the adherence of neutrophils to isolated rat aortic segments. RESULTS: Platelet-activating factor-stimulated neutrophils caused marked and persistent reductions (> 50%) in left ventricular developed pressure. Pretreatment with either isoflurane or sevoflurane abolished these effects, as well as the associated increases in neutrophil retention. Glibenclamide did not alter these actions of the anesthetics. Pretreatment with either volatile anesthetic attenuated the reductions in left ventricular developed pressure caused by exogenous superoxide and abolished the increases in neutrophil adherence in the aortic segments. CONCLUSION: Isoflurane and sevoflurane preconditioned the heart against neutrophil-induced contractile dysfunction. This action was associated with an inhibition to neutrophil adherence and likely involved an increased resistance of the myocardium to oxidant-induced injury; the adenosine triphosphate-sensitive potassium channels played no apparent role.

Anesthetics, Inhalation↗
PubMed2004

The neuromuscular effects and tracheal intubation conditions after small doses of succinylcholine.

UNLABELLED: Succinylcholine 1.0 mg/kg usually produces excellent tracheal intubation conditions in 60 s. Recovery of respiratory muscle function after this dose, however, is not fast enough to forestall oxyhemoglobin desaturation when ventilation cannot be assisted. In this study, we investigated whether smaller doses of succinylcholine can produce satisfactory intubation conditions fast enough to allow rapid sequence induction with a shorter recovery time. Anesthesia was induced with fentanyl/propofol and maintained by propofol infusion and N(2)O in O(2). After the induction, 115 patients were randomly allocated to five groups according to the dose of succinylcholine (0.3 mg/kg, 0.4 mg/kg, 0.5 mg/kg, 0.6 mg/kg, or 1.0 mg/kg). Evoked adductor pollicis responses to continuous 1-Hz supramaximal ulnar nerve stimulation were recorded using acceleromyography. Tracheal intubation conditions were graded 60 s after succinylcholine administration. Onset time, maximal twitch depression, time to initial twitch detection after paralysis, and to 10%, 25%, 50%, and 90% twitch height recovery were recorded. Time to initial diaphragmatic movement as well as time to resumption of regular spontaneous respiratory movements were calculated. Onset times ranged between 82 s and 52 s, decreasing with increasing doses of succinylcholine but not differing between 0.6 and 1 mg/kg. Maximum twitch depression was similar after 0.5, 0.6, and 1 mg/kg (98.2%-100%). Recoveries of twitch height and apnea time were dose-dependent. Intubation conditions were often unacceptable after 0.3- and 0.4-mg/kg doses. Acceptable intubation conditions were achieved in all patients receiving a 0.5, 0.6, and 1 mg/kg dose of succinylcholine. Intubation conditions in patients receiving 0.6 and 1 mg/kg were identical, whereas times to T(1) = 50% and 90% and time to regular spontaneous reservoir bag movements were significantly shorter in the 0.6-mg/kg dose group (5.78, 7.25, and 4.0 min, respectively) versus patients receiving 1 mg/kg (8.55, 10.54, and 6.16 min, respectively). The use of 0.5 to 0.6 mg/kg of succinylcholine can produce acceptable intubation conditions 60 s after administration. The conditions achieved after 0.6 mg/kg are similar to those after 1.0 mg/kg. These smaller doses are associated with faster twitch recovery and shorter apnea time. IMPLICATIONS: In normal healthy patients, succinylcholine 0.6 mg/kg produces clinical intubation conditions identical to the traditional 1.0-mg/kg dose but is associated with a shorter recovery time.

Adult↗
PubMed2003

Does the choice of intravenous induction drug affect intubation conditions after a fast-onset neuromuscular blocker?

STUDY OBJECTIVES: To compare intubation conditions and hemodynamic effects resulting from thiopental-rapacuronium, propofol-rapacuronium, and etomidate-rapacuronium intravenous (IV) induction. DESIGN: Randomized, blinded study. SETTING: Operating suites of a large university-affiliated medical center. PATIENTS: 60 ASA physical status I and II adult patients without airway abnormalities, who were scheduled for elective surgery requiring endotracheal intubation. Patients were randomly allocated to receive IV thiopental sodium 5 mg/kg (Group 1), propofol 2 mg/kg (Group 2), or etomidate 0.3 mg/kg (Group 3) followed by rapacuronium 1.5 mg/kg. Fifty seconds later, an anesthesiologist, who had no knowledge of the induction drug used, entered the operating room and attempted laryngoscopy and intubation. MEASUREMENTS: Intubation conditions were graded as excellent, good, poor, or impossible according to Good Clinical Research Practice criteria. Arterial blood pressure and heart rate changes accompanying both induction techniques were also monitored and recorded. MAIN RESULTS: All patients were intubated within 55 to 70 seconds. Clinically acceptable intubation conditions were not statistically different among the three groups. Moderate tachycardia after induction was seen in all three groups, and blood pressure was significantly lower in Group 2 than in Groups 1 or 3. CONCLUSIONS: Clinically acceptable intubation conditions are similar after either thiopental, propofol, or etomidate when a fast-onset neuromuscular blocking drug (rapacuronium 1.5 mg/kg) is used to facilitate tracheal intubation.

Adult↗
PubMed2003

Neutrophils pretreated with volatile anesthetics lose ability to cause cardiac dysfunction.

BACKGROUND: Volatile anesthetics can precondition the myocardium against functional depression and infarction following ischemia-reperfusion. Neutrophil activation, adherence, and release of superoxide play major roles in reperfusion injury. The authors tested the hypothesis that pretreatment of neutrophils with a volatile anesthetic, i.e., simulated preconditioning, can blunt their ability to cause cardiac dysfunction. METHODS: Studies were performed in 60 buffer-perfused and paced isolated rat hearts. Left ventricular developed pressure served as an index of myocardial contractility. Polymorphonuclear neutrophils and/or drugs were added to coronary perfusate for 10 min, followed by 30 min of recovery. Platelet-activating factor was used to stimulate neutrophils. Pretreatment of neutrophils consisted of incubation with 1.0 minimum alveolar concentration (MAC) isoflurane or sevoflurane for 15 min, followed by washout. Additional studies were performed with 0.25 MAC isoflurane. Effects of superoxide dismutase were compared to those of volatile anesthetics. Superoxide production was measured by spectrophotometry. Neutrophil adherence to coronary vascular endothelium was estimated from the difference between neutrophils administered and recovered in coronary venous effluent. RESULTS: Activated neutrophils caused marked, persistent reduction (> 50%) in left ventricular developed pressure. Isoflurane and sevoflurane at 1.0 MAC and superoxide dismutase abolished this effect. Isoflurane and sevoflurane reduced superoxide production of activated neutrophils by 29% and 33%, respectively, and completely prevented the platelet-activating factor-induced increases in neutrophil adherence. Isoflurane at 0.25 MAC blunted, but did not abolish, the neutrophil-induced decreases in left ventricular developed pressure. CONCLUSION: Neutrophils pretreated with 1.0 MAC isoflurane or sevoflurane lost their ability to cause cardiac dysfunction, while those pretreated with a concentration of isoflurane as low as 0.25 MAC were partially inhibited. This action of the volatile anesthetics was associated with reductions in superoxide production and neutrophil adherence to the coronary vascular endothelium. Our findings suggest that inhibitory actions on neutrophil activation and neutrophil-endothelium interaction may contribute to the preconditioning effects of volatile anesthetics observed in vivo during myocardial ischemia-reperfusion.

Anesthetics, Inhalation↗
PubMed2003

The relationship of posttetanic count and train-of-four responses during recovery from intense cisatracurium-induced neuromuscular blockade.

UNLABELLED: Posttetanic count (PTC) has been used to quantify intense degrees of nondepolarizing neuromuscular blockade. Our objective in the present investigation was to discern whether PTC correlates with recovery from intense cisatracurium-induced neuromuscular blockade under both inhaled and IV anesthesia. In 60 patients, anesthesia was induced with propofol 2 mg/kg and fentanyl 1.5 micro g/kg IV. Recovery from intense neuromuscular blockade induced by cisatracurium (0.15 mg/kg) was studied in 2 groups. Group 1 (n = 30) had anesthesia maintained with propofol 100-200 micro g x kg(-1) x min(-1) and 60% N(2)O in O(2), whereas Group 2 (n = 30) had anesthesia maintained with isoflurane (end-tidal concentration 0.8%) and 60% N(2)O in O(2). Neuromuscular functions were monitored using acceleromyography. Cycles of posttetanic stimulation were repeated every 6 min with train-of-four (TOF) stimulation in between. Measurement included times to posttetanic responses and to the first response to TOF stimulation (T(1)), as well as the correlation between PTC and T(1). In Group 1, the mean times to PTC(1) and T(1) were 35.6 +/- 7.5 and 46.9 +/- 6.5 min, respectively. Corresponding times in Group 2 were 39.5 +/- 6.8 and 56.7 +/- 5.4 min, respectively. There was a good time correlation, r = 0.919 for propofol (Group 1) and r = 0.779 for isoflurane (Group 2), between PTC and T(1) recovery in both groups. The PTC when T(1) appeared ranged between 8 and 9 in Group 1 and 8 and 14 in Group 2. Conforming to original observations with other neuromuscular blocking drugs, there is a correlation between PTC and TOF recovery from intense cisatracurium-induced neuromuscular blockade allowing better monitoring of this intense degree of blockade during both IV (propofol) and isoflurane anesthesia. IMPLICATIONS: Monitoring posttetanic count during intense neuromuscular blockade allows the clinician to estimate the intensity of the blockade and estimate recovery time. The relationship between posttetanic count and train-of-four recovery from intense cisatracurium-induced neuromuscular blockade was documented under both IV and inhaled anesthesia.

Adult↗
PubMed2002

Tracheal intubation conditions and cardiovascular effects after modified rapid-sequence induction with sevoflurane-rapacuronium versus propofol-rapacuronium.

STUDY OBJECTIVES: To compare intubation conditions and hemodynamic effects resulting from rapid-sequence induction of anesthesia with sevoflurane-rapacuronium and propofol-rapacuronium. DESIGN: Randomized, blinded study. SETTING: Operating suites of a large university-affiliated medical center. PATIENTS: 40 ASA physical status I and II adult patients without airway abnormalities who were scheduled for elective surgery requiring endotracheal intubation. INTERVENTIONS: Patients were randomly allocated to receive either sevoflurane inhalational induction (Group 1) or propofol (2 mg/kg) intravenous induction (Group 2). Group 1 patients were coached on how to perform vital capacity breathing and the anesthesia machine was primed with sevoflurane 8%, N2O:O2 3.5:1.5 L/min. In both groups, when loss of consciousness was established, rapacuronium 1.5 mg/kg was administered. After 50 seconds, an anesthesiologist blinded to the study entered the room and attempted laryngoscopy and intubation. MEASUREMENTS: Intubation conditions were graded as excellent, good, poor, or impossible according to Good Clinical Research Practice (GCRP) criteria. Arterial blood pressure and heart rate changes accompanying both induction techniques were also monitored and recorded. MAIN RESULTS: All patients were successfully intubated within 60 seconds. Clinically acceptable intubating conditions (excellent or good scores) were obtained in 19 of 20 Group 1 patients and in 19 of 20 Group 2 patients. Moderate tachycardia was encountered in both groups and mild systolic hypotension in the Group 2 patients. There were no complications. CONCLUSIONS: Modified rapid-sequence inhalational induction using sevoflurane and rapacuronium produced clinically acceptable intubation conditions within 60 seconds of muscle relaxant administration. The intubation conditions were similar to those produced after intravenous propofol and rapacuronium.

Adolescent↗
PubMed2002

Isoflurane inhibits neutrophil-endothelium interactions in the coronary circulation: lack of a role for adenosine triphosphate-sensitive potassium channels.

UNLABELLED: Isoflurane protects myocardium during ischemia-reperfusion via a mechanism involving the adenosine triphosphate-sensitive potassium channels. We tested the hypothesis that an inhibition of the neutrophil-endothelium interactions by isoflurane contributes to this effect. Polymorphonuclear neutrophils and coronary artery segments were obtained from 35 healthy dogs. Superoxide production by neutrophils, stimulated with platelet-activating factor (PAF; 1.0 microM), was measured spectrophotometrically. Adherence of PAF-activated neutrophils to the endothelium of coronary segments was assessed by direct counting of neutrophils labeled with fluorescent dye. Coronary artery rings were exposed to PAF-activated neutrophils, and, after washing and preconstriction with U46619, they were evaluated for vasorelaxation responses to acetylcholine (endothelium dependent) and sodium nitroprusside (endothelium independent). Measurements were performed in the absence and presence of isoflurane (1 and 2 minimum alveolar anesthetic concentration) both with and without glibenclamide (10 microM). Isoflurane inhibited superoxide production and adherence by neutrophils and abolished neutrophil-induced reductions in coronary vascular relaxation responses to acetylcholine. Glibenclamide did not alter the effects of isoflurane on neutrophils or coronary artery endothelium. In conclusion, isoflurane had an inhibitory action on neutrophil-endothelium interactions and neutrophil-mediated coronary endothelial dysfunction--effects that may be involved in its cardioprotective action in vivo. These inhibitory actions of isoflurane were not mediated by adenosine triphosphate-sensitive potassium channels. IMPLICATIONS: Isoflurane inhibited neutrophil-endothelium interactions and the inflammatory response in vitro via a pathway independent of the adenosine triphosphate-sensitive potassium channels. This action could be involved in the cardioprotection by isoflurane observed in vivo.

Acetylcholine↗