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J L Fontana

Publications and source records attributed to J L Fontana.

9 recordsLinked to original sources
PubMed2001

Pyruvate improves cerebral metabolism during hemorrhagic shock.

Pyruvate (PYR) improves cellular and organ function hypoxia and ischemia by stabilizing the reduced nicotinamide adenine dinucleotide redox state and cytosolic ATP phosphorylation potential. In this in vivo study, we evaluated the effects of intravenous pyruvate on neocortical function, indexes of the cytosolic redox state, cellular energy state, and ischemia during a prolonged (4 h) controlled arterial hemorrhage (40 mmHg) in swine. Thirty minutes after the onset of hemorrhagic shock, sodium PYR (n = 8) was infused (0.5 g x kg(-1) x h(-1)) to attain arterial levels of 5 mM. The volume and osmotic effects were matched with 10% NaCl [hypertonic saline (HTS)] (n = 8) or 0.9% NaCl [normal saline (NS)] (n = 8). During the hemorrhage protocol, the time to peak hemorrhage volume was significantly delayed in the PYR group compared with the HTS and NS groups (94 +/- 5 vs. 73 +/- 6 and 72 +/- 4 min, P < 0.05). In addition to the early onset of the decompensatory phase of hemorrhagic shock, the complete return of the hemorrhage volume during decompensatory shock resulted in the death of five and four animals, respectively, in the HTS and NS groups. In contrast, in the PYR group, reinfusion of the hemorrhage volume was slower and all animals survived the 4-h hemorrhage protocol. During hemorrhage, the PYR group also exhibited improved cerebral cortical metabolic and function status. PYR slowed and reduced the rise in neocortical microdialysis levels of adenosine, inosine, and hypoxanthine and delayed the loss of cerebral cortical biopsy ATP and phosphocreatine content. This improvement in energetic status was evident in the improved preservation of the electrocorticogram in the PYR group. PYR also prevented the eightfold increase in the excitotoxic amino acid glutamate observed in the HTS group. The findings show that PYR administered after the onset of hemorrhagic shock markedly improves cerebral metabolic and functional status for at least 4 h.

Animals↗
PubMed1999

Hemodynamic changes induced by liposomes and liposome-encapsulated hemoglobin in pigs: a model for pseudoallergic cardiopulmonary reactions to liposomes. Role of complement and inhibition by soluble CR1 and anti-C5a antibody.

BACKGROUND: Intravenous administration of some liposomal drugs can trigger immediate hypersensitivity reactions that include symptoms of cardiopulmonary distress. The mechanism underlying the cardiovascular changes has not been clarified. METHODS AND RESULTS: Anesthetized pigs (n=18) were injected intravenously with 5-mg boluses of large multilamellar liposomes, and the ensuing hemodynamic, hematologic, and laboratory changes were recorded. The significant (P<0.01) alterations included 79+/-9% (mean+/-SEM) rise in pulmonary arterial pressure, 30+/-7% decline in cardiac output, 11+/-2% increase in heart rate, 236+/-54% increase in pulmonary vascular resistance, 71+/-27% increase in systemic vascular resistance, and up to a 100-fold increase in plasma thromboxane B2. These changes peaked between 1 and 5 minutes after injection, subsided within 10 to 20 minutes, were lipid dose-dependent (ED50=4. 5+/-1.4 mg), and were quantitatively reproducible in the same animal several times over 7 hours. The liposome-induced rises of pulmonary arterial pressure showed close quantitative and temporal correlation with elevations of plasma thromboxane B2 and were inhibited by an anti-C5a monoclonal antibody (GS1), by sCR1, or by indomethacin. Liposomes caused C5a production in pig serum in vitro through classic pathway activation and bound IgG and IgM natural antibodies. Zymosan- and hemoglobin-containing liposomes and empty liposomes caused essentially identical pulmonary changes. CONCLUSIONS: The intense, nontachyphylactic, highly reproducible, complement-mediated pulmonary hypertensive effect of minute amounts of intravenous liposomes in pigs represents a unique, unexplored phenomenon in circulation physiology. The model provides highly sensitive detection and study of cardiopulmonary side effects of liposomal drugs and many other pharmaceutical products due to "complement activation-related pseudoallergy" (CARPA).

Animals↗
PubMed1999

The anesthetic and physiologic effects of an intravenous administration of a halothane lipid emulsion (5% vol/vol)

UNLABELLED: The i.v. administration of < or = 9 mL of nonvaporized liquid halothane causes significant pulmonary damage, cardiovascular decompensation, and death. To determine whether liquid halothane mixed in a lipid emulsion would alter these toxic effects, six swine were evaluated in a randomized cross-over study. The pulmonary, analgesic, hemodynamic, and histopathologic effects of liquid halothane (25 mL) mixed with a liquid carrier (475 mL, Liposyn III 20%) and administered by constant infusion were compared with halothane administered by a calibrated vaporizer. Three swine received the halothane lipid emulsion (HLE), followed by inhaled halothane. Three additional swine received inhaled halothane, followed by the HLE. There were no changes in pulmonary compliance or arterial blood gases during or after the administration of equivalent volumes of halothane (13.75 mL) either by infusion of HLE or by inhalation of halothane. The end-tidal halothane concentration for the minimum alveolar anesthetic concentration was 0.79% +/- 0.08% during HLE administration and 1.13% +/- 0.12% for inhaled halothane (P < 0.001). Hemodynamic variables and blood halothane levels by gas chromatography were measured at end-tidal concentrations of 0.6%, 1.2%, and 1.8%. Blood halothane levels (mg/mL) were significantly higher (P < 0.05) after the administration of HLE at end-tidal halothane concentrations of 1.2% (0.49 +/- 0.19 vs 0.82 +/- 0.18) and 1.8% (0.79 +/- 0.17 vs 1.29 +/- 0.34). When compared at equivalent blood levels, HLE caused fewer changes in the left ventricular end-diastolic pressure, mean arterial pressure, and dP/dt than inhaled halothane. There was no evidence of pulmonary histopathologic damage 4-8 h after the infusion of 500-700 mL of HLE. This novel method of delivery of a volatile anesthetic seems to lack the toxicity of direct i.v. administration of liquid halothane. It may be a useful alternative to traditional administration via a vaporizer. IMPLICATIONS: Halothane causes pulmonary dysfunction and death when given i.v. in liquid form. Six swine received a halothane lipid emulsion i.v. to evaluate the anesthetic and physiologic effects. No pulmonary toxicity or deaths were associated with the halothane lipid emulsion. The anesthetic profile was similar to delivery of halothane via a vaporizer.

Anesthetics, Inhalation↗
PubMed1999

Intravenous pyruvate prolongs survival during hemorrhagic shock in swine.

Pyruvate improves cellular and organ function during hypoxia and ischemia and stabilizes the NADH redox state and cytosolic ATP phosphorylation potential. In this in vivo study, we evaluated the effects of intravenous pyruvate on cardiovascular and neocortical function, indexes of the cytosolic redox state (lactate/pyruvate ratio, L/P) and cellular energy state (adenosine and degradative products hypoxanthine and inosine, ADO + HX + Ino) during controlled arterial hemorrhage (40 mmHg) in sedated swine (45 kg). Na+ pyruvate was infused 1 h before (1 g. kg(-1). h(-1)) and 2 h during (0.5 g. kg(-1). h(-1)) hemorrhage to attain arterial pyruvate levels of 6 mM. Volume (0.9% NaCl) and osmotic (10% NaCl) effects were matched in controls. Time to peak hemorrhage (57 min) and peak hemorrhage volume (43 ml/kg) were similar in all groups. The volume and osmotic groups experienced spontaneous cardiovascular decompensation between 60 and 90 min, with an average time until death of 82.7 +/- 5.5 and 74.8 +/- 8.2 min. In contrast, survival in the pyruvate group was 151.2 +/- 10.0 min (P < 0.001). During hemorrhage, the pyruvate group had better cardiovascular and cerebrovascular function with significantly higher systemic and cerebral oxygen consumption and less attenuation of the amplitude and frequency of the electrocorticogram. In addition, pyruvate prevented metabolic acidosis and stabilized the L/P. Pyruvate slowed the rise in neocortical microdialysis levels of ADO + HX + Ino, and prevented the net efflux of ADO + HX + Ino into the sagittal sinus. The findings reveal considerable metabolic and functional enhancement by pyruvate during severe hemorrhagic shock with a 75-min delay in spontaneous cardiovascular decompensation and death.

Animals↗
PubMed1996

Profound normovolemic hemodilution: hemostatic effects in patients and in a porcine model.

Previous systematic investigations of the hemostatic effects of normovolemic hemodilution (NHD) have not explored the influence of hematocrits less than 20% in humans or animals. However, clinical interest in maximizing the perioperative conservation of erythrocytes may involve profound NHD beyond traditionally accepted empiric end points. We report here on coagulation data in eight healthy adolescent patients undergoing profound NHD in concert with surgical correction of idiopathic scoliosis, and in 29 swine undergoing experimental stepwise NHD until death. Blood was replaced with 5% albumin in 0.9% saline in our patients, and with 5% albumin in lactated Ringer's solution in our pigs. A 75% blood volume exchange in our patients yielded a platelet count (PLT) of 158 +/- 26 x 10(3)/microL, fibrinogen concentration (FIB), 50 +/- 7 mg/dL, prothrombin time (PT), 25.4 +/- 2.6 s, activated partial thromboplastin time (aPTT), 87 +/- 15s, and a nadir hemoglobin of 2.8 +/- 0.2 g/dL; however, global oxygen delivery as assessed by body oxygen consumption remained adequate. Coagulation during the experimental porcine hemodilution was assessed by measuring PLT, FIB, PT, and aPTT, as well as by measurement of coagulation factor activities. In neither species did clinically significant thrombocytopenia (PLT < 100 x 10(3)/ microL) become manifest prior to clinical or other laboratory evidence of coagulopathy. Rather, a combined deficiency of coagulation factors explains the coagulopathy developing during NHD in both patients and swine. Abnormal hemostasis develops prior to compromise of global tissue oxygenation, assessed by mixed venous oxygen saturation and total body oxygen consumption, during NHD in healthy patients anesthetized as described. Therefore, NHD may be more limited by preservation of normal coagulation than of global oxygen delivery and consumption.

Adolescent↗
PubMed1995

Oxygen consumption and cardiovascular function in children during profound intraoperative normovolemic hemodilution.

The clinically acceptable limit of acute normovolemic, normothermic hemodilution, a standard procedure in scoliosis surgery, is not yet well defined. Eight ASA class I patients undergoing idiopathic scoliosis correction were administered a standard anesthetic with 100% oxygen and controlled ventilation. Hemodilution was accomplished by exchanging whole blood for 5% albumin in 0.9% saline. Blood gases, acid-base status, and circulatory variables were recorded prior to and after hemodilution, and every 30 min throughout surgery. The impact of hemodilution was judged by mixed venous oxygen saturation which was maintained at > or = 60%, while intravascular volume was maintained with the 5% albumin solution. Reinfusion of the autologous blood was completed by the end of surgery. In the eight controlled cases in which normovolemic hemodilution was studied, hemoglobin levels decreased from 10.0 +/- 1.6 g/dL to 3.0 +/- 0.8 g/dL. Mixed venous oxygen saturation decreased from 90.8% +/- 5.4% to 72.3% +/- 7.8%. Oxygen extraction ratio increased from 17.3% +/- 6.2% to 44.4% +/- 5.9%. Oxygen delivery decreased from 532.1 +/- 138.1 mL.min-1.m-2 to 260.2 +/- 57.1 mL.min-1.m-2, while global oxygen consumption did not decrease and plasma lactate did not appreciably increase. Central venous pressure increased and peripheral resistance decreased during hemodilution. Cardiac index increased, heart rate remained essentially constant, and left ventricular stroke work index did not decrease significantly. No patients suffered clinically adverse outcomes. Global oxygen transport and myocardial work can be maintained at extreme normovolemic anemia. Our evidence suggests that stages of normovolemic hemodilution more severe than previously reported may be clinically acceptable for young, healthy patients during normocarbic anesthesia.

Adaptation, Physiological↗
PubMed1993

Anesthetic considerations for neonatal and infant patients.

Selected topics in anesthesia that are intended to assist the perioperative nurse in caring for the neonate and infant during surgery are addressed in this article. Issues discussed include airway management, physiological differences between infants and adults, fluid management, and monitoring.

Anesthesia↗
PubMedDate not supplied

A modified wake-up test for use in very young children undergoing spinal surgery.

In a consecutive series of five very young children undergoing hemivertebrectomy and fusion, a modified intraoperative wake-up test was used to confirm neurologic integrity. Standard leads attached to a nerve stimulator and positioned over the plantar aspect of each foot were used to apply tetanic electrical stimulation at the time of intraoperative wake-up. Four children responded vigorously with flexion and extension of the knees and ankles after only minimal delay. One neurologically intact child did not respond because of technical issues. This report describes our favorable preliminary experience with this technique.

Anesthesia Recovery Period↗