PubMed Health⌕ Search

Biomedical subjects

Richard J Levy

Publications and source records attributed to Richard J Levy.

9 recordsLinked to original sources
PubMed2006

Clinical implications of mitochondrial dysfunction.

Mitochondria produce metabolic energy, serve as biosensors for oxidative stress, and eventually become effector organelles for cell death through apoptosis. The extent to which these manifold mitochondrial functions are altered by previously unrecognized actions of anesthetic agents seems to explain and link a wide variety of perioperative phenomena that are currently of interest to anesthesiologists from both a clinical and a scientific perspective. In addition, many surgical patients may be at increased perioperative risk because of inherited or acquired mitochondrial dysfunction leading to increased oxidative stress. This review summarizes the essential aspects of the bioenergetic process, presents current knowledge regarding the effects of anesthetics on mitochondrial function and the extent to which mitochondrial state determines anesthetic requirement and potential anesthetic toxicity, and considers some of the many implications that our knowledge of mitochondrial dysfunction poses for anesthetic management and perioperative medicine.

Aged↗
PubMed2006

A child with anterior mediastinal mass supported with veno-arterial extracorporeal membrane oxygenation.

OBJECTIVE: To demonstrate the utility of rescue with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and to demonstrate the feasibility of administration of chemotherapy during VA-ECMO in a child with an anterior mediastinal mass. DESIGN: Case report. SETTING: Large, tertiary care, pediatric intensive care unit. PATIENT: One patient with cardiopulmonary collapse in the setting of a new diagnosis of an anterior mediastinal mass. INTERVENTIONS: Cardiopulmonary support with VA-ECMO; administration of chemotherapy during VA-ECMO. MEASUREMENTS AND MAIN RESULTS: Successful rescue with VA-ECMO and successful chemotherapy while on VA-ECMO. CONCLUSIONS: VA-ECMO can be successfully used to support patients with cardiopulmonary failure during initial diagnosis of an anterior mediastinal mass. In addition, we have demonstrated that successful chemotherapy can be administered while the patient is supported on VA-ECMO.

Antineoplastic Agents↗
PubMed2005

Chronic hypoxemia increases myocardial cytochrome oxidase.

OBJECTIVE: Cyanotic patients have potentially decreased tissue oxygen tension. Cytochrome oxidase catalyzes the reduction of oxygen and is integral to adenosine triphosphate production. Cytochrome oxidase subunit I, the active site, is encoded by mitochondrial DNA. Using a newborn swine model of chronic hypoxemia, we evaluated ventricular cytochrome oxidase subunit I mRNA and protein expression and assessed cytochrome oxidase activity. METHODS: Thirty-two newborn piglets underwent thoracotomy and placement of a pulmonary artery-to-left atrium shunt or sham operation. Two weeks later, partial pressure of arterial oxygen, hematocrit, and left ventricular shortening fraction values were compared with baseline values. Northern blot hybridization and protein immunoblotting for ventricular cytochrome oxidase subunit I were performed. Cytochrome oxidase kinetic activity was measured. Heme a,a3 content and turnover number were determined. Significance was assessed with a t test. RESULTS: Baseline partial pressure of arterial oxygen and hematocrit values were similar. Hypoxemic piglets had a lower partial pressure of arterial oxygen of 38 +/- 10 mm Hg (P < .001) and higher hematocrit value of 31.4% +/- 2.9% (P < .001) compared with a partial pressure of arterial oxygen of 140 +/- 47 mm Hg and hematocrit value of 24.6% +/- 3.9% after the sham operation. Baseline and postprocedure left ventricular shortening fraction were similar within and between groups. Chronic hypoxemia increased right ventricular and left ventricular cytochrome oxidase I mRNA and protein by more than 1.4-fold. Cytochrome oxidase activity increased significantly in hypoxemia by 2.5-fold compared with that seen after the sham operation. Heme a,a3 content and turnover number increased by 1.5-fold during hypoxemia. CONCLUSIONS: Chronic hypoxemia increases cytochrome oxidase I message, protein expression, and activity. The increase in kinetics was due to increased enzyme content and catalytic activity. This is a possible adaptive mechanism that might preserve organ function during chronic hypoxemia.

Animals↗
PubMed2005

Evidence of myocardial hibernation in the septic heart.

OBJECTIVE: Myocardial hibernation is an adaptive response to ischemia and hypoxia. Hibernating cardiomyocytes are reversibly hypocontractile and demonstrate characteristic metabolic and ultrastructural changes. These include a switch in primary substrate utilization from fatty acids to glucose, up-regulation of the myocardial specific glucose transporters (GLUT1 and GLUT4), and glycogen deposition within and between cardiomyocytes. We hypothesized that myocardial hibernation may underlie sepsis-associated myocardial depression. DESIGN: Prospective observational study aimed at identifying the characteristic changes of hibernation in the septic heart. SETTING: University hospital-based laboratory. SUBJECTS: Forty-three C57Bl6 male mice. INTERVENTIONS: Mice underwent cecal ligation and double puncture, sham operation, or no operation and were evaluated 48 hrs after the procedure. MEASUREMENTS AND MAIN RESULTS: Using novel, clinically relevant technology such as magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography imaging, we found septic mice to have diminished cardiac performance, increased myocardial glucose uptake, increased steady-state levels of myocardial GLUT4, and increased deposits of glycogen, recapitulating the changes during hibernation. Importantly, these changes occurred in the setting of preserved arterial oxygen tension and myocardial perfusion. CONCLUSIONS: Sepsis-associated cardiac dysfunction may reflect hibernation. Furthermore, such down-regulation of cellular function may underlie sepsis-induced dysfunction in other organ systems.

Animals↗
PubMed2005

Evaluation of tissue saturation as a noninvasive measure of mixed venous saturation in children.

BACKGROUND: Mixed venous saturation (S & OV0456;o2) is an important measurement that helps guide the care of critically ill patients. Invasive S & OV0456;o2 assessment in infants and children is often avoided because of the inherent risks. A noninvasive tissue saturation (S to 2) monitor has recently been developed that uses near-infrared spectroscopy to measure oxyhemoglobin saturation in muscle. In adult and animal studies, S to 2 correlated with oxygen delivery and S & OV0456;o2. There has been no evaluation in pediatric patients. OBJECTIVE: To evaluate tissue saturation as a noninvasive measure of mixed venous saturation in children. DESIGN: A prospective observational study. SETTING: Catheterization laboratory in a tertiary care children's medical center. PATIENTS: We studied 98 children (49 without intracardiac mixing and 49 with intracardiac mixing) <or=12 yrs of age who underwent cardiac catheterization. Under general anesthesia, we compared S to 2 measured over the deltoid muscle with superior vena cava saturation in both groups and S to 2 with pulmonary artery saturation in patients without intracardiac mixing. Paired measurements were analyzed for bias, precision, and correlation via Bland-Altman plot and linear regression. RESULTS: No meaningful correlation was found between S to 2 and superior vena cava saturation or pulmonary artery saturation. Bland-Altman analyses of S to 2 with superior vena cava saturation yielded bias values of -6.67 +/- 37.33% in patients with intracardiac mixing and -0.82 +/- 41.31% in patients without mixing. Bland-Altman analysis of S to 2 with pulmonary artery saturation yielded a bias of 3.61 +/- 41.32% in patients without mixing. Differences between noninvasive and invasive measurements were greatest in smaller children. CONCLUSION: Noninvasive tissue saturation over the deltoid does not correlate with S & OV0456;o2 in children. It is possible that more precise probe spacing, coupled with optimal muscle-mass location, could result in more accurate measures in future investigations.

Cardiac Catheterization↗
PubMed2004

Competitive and noncompetitive inhibition of myocardial cytochrome C oxidase in sepsis.

Sepsis is the most common cause of death in intensive care units worldwide. The basic pathophysiologic defect in sepsis, causing functional abnormalities in many organ systems, remains elusive. One potential cause is disruption of oxidative phosphorylation in mitochondria. Here, we report that oxidation of cytochrome c by myocardial cytochrome c oxidase, the terminal oxidase in the electron transport chain, is competitively inhibited early in experimental sepsis (cecal ligation with single or double 23-gauge puncture) in mice. In severe sepsis (cecal ligation and double puncture, 75% mortality at 48 h), inhibition becomes noncompetitive by 48 h. The development of noncompetitive inhibition is associated with a decrease in heme a,a3 content, which is the key active site in the functional subunit (I) and catalyzes the reduction of molecular oxygen. In addition, there are persistently decreased steady-state levels of subunit I mRNA and protein after cecal ligation and double puncture. Both loss of heme and loss of subunit I could explain the observed irreversible inhibition of cytochrome c oxidase. Noncompetitive inhibition of cytochrome c oxidase may interrupt oxidative phosphorylation, leading to sepsis-associated cardiac depression. Importantly, this abnormality may underlie sepsis-associated dysfunction in other organ systems.

Animals↗
PubMed2004

An evaluation of a noninvasive cardiac output measurement using partial carbon dioxide rebreathing in children.

Cardiac output (CO) is an important hemodynamic measure that helps to guide the therapy of critically ill patients. Invasive CO assessment in infants and children is often avoided because of the inherent risks. A noninvasive CO monitor that uses partial rebreathing has been recently developed to determine CO via the Fick principle for carbon dioxide. There have been no clinical studies confirming its accuracy in pediatric patients. This is a prospective observational study of 37 children <12 yr of age who underwent cardiac catheterization. Under general anesthesia via an endotracheal tube without a leak, we made multiple CO measurements using thermodilution and compared them with noninvasively determined CO measurements. Paired measurements were analyzed for bias, precision, and correlation via Bland-Altman plot and linear regression. Noninvasive measurements showed a linear correlation with thermodilution CO assessment with an r value of 0.83 (P < 0.03). Bland-Altman analysis yielded a bias of -0.27 L/min and a precision +/-1.49 L/min. Cardiac index measurements demonstrated a decreased r value of 0.67 (P = 0.15) and a bias of -0.18 L . min(-1) . m(-2) and precision of +/-2.13 L . min(-1) . m(-2). Differences between partial rebreathing measurements and thermodilution measurements were largest in children with a body surface area of </=0.6 m(2) ventilated with tidal volumes <300 mL. Based on these findings, noninvasive CO measurement using partial rebreathing may be clinically acceptable in children with >0.6 m(2) body surface area and >300 mL tidal volume.

Anesthesia, General↗