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- Sodium Nitroprusside-Enhanced Cardiopulmonary Resuscitation Facilitates Intra-Arrest Therapeutic Hypothermia in a Porcine Model of Prolonged Ventricular Fibrillation. [JOURNAL ARTICLE]
- Crit Care Med 2014 Dec 18.
The aim of this study was to assess the effect of sodium nitroprusside-enhanced cardiopulmonary resuscitation on heat exchange during surface cooling. We hypothesized that sodium nitroprusside-enhanced cardiopulmonary resuscitation would decrease the time required to reach brain temperature less than 35°C compared to active compression-decompression plus impedance threshold device cardiopulmonary resuscitation alone, in the setting of intra-cardiopulmonary resuscitation cooling. We further hypothesized that the addition of epinephrine during sodium nitroprusside-enhanced cardiopulmonary resuscitation would mitigate heat exchange.Prospective randomized animal investigation.Preclinical animal laboratory.Female farm pigs (n = 28).After 10 minutes of untreated ventricular fibrillation, animals were randomized to three different protocols: sodium nitroprusside-enhanced cardiopulmonary resuscitation (n = 8), sodium nitroprusside-enhanced cardiopulmonary resuscitation plus epinephrine (n = 10), and active compression-decompression plus impedance threshold device alone (control, n = 10). All animals received surface cooling at the initiation of cardiopulmonary resuscitation. Sodium nitroprusside-enhanced cardiopulmonary resuscitation included active compression-decompression plus impedance threshold device plus abdominal binding and 2 g of sodium nitroprusside at 1, 4, and 8 minutes of cardiopulmonary resuscitation. No epinephrine was used during cardiopulmonary resuscitation in the sodium nitroprusside-enhanced cardiopulmonary resuscitation group. Control and sodium nitroprusside-enhanced cardiopulmonary resuscitation plus epinephrine groups received 0.5 g of epinephrine at 4.5 and 9 minutes of cardiopulmonary resuscitation. Defibrillation occurred after 10 minutes of cardiopulmonary resuscitation. After return of spontaneous circulation, an Arctic Sun (Medivance, Louiseville, CO) was applied at maximum cooling on all animals. The primary endpoint was the time required to reach brain temperature less than 35°C beginning from the time of cardiopulmonary resuscitation initiation. Data are presented as mean ± SEM.The time required to reach a brain temperature of 35°C was decreased with sodium nitroprusside-enhanced cardiopulmonary resuscitation versus control or sodium nitroprusside-enhanced cardiopulmonary resuscitation plus epinephrine (24 ± 6 in, 63 ± 8 in, and 50 ± 9 in, respectively; p = 0.005). Carotid blood flow was higher during cardiopulmonary resuscitation in the sodium nitroprusside-enhanced cardiopulmonary resuscitation group (83 ± 15 L/min vs 26 ± 7 L/min and 35 ± 5 L/min in the control and sodium nitroprusside-enhanced cardiopulmonary resuscitation plus epinephrine groups, respectively; p = 0.001).This study demonstrates that sodium nitroprusside-enhanced cardiopulmonary resuscitation facilitates intra-cardiopulmonary resuscitation hypothermia. The addition of epinephrine to sodium nitroprusside-enhanced cardiopulmonary resuscitation during cardiopulmonary resuscitation reduced its improvement in heat exchange.
- Laboratory Assessment of the Anticoagulant Activity of Dabigatran. [JOURNAL ARTICLE]
- Clin Appl Thromb Hemost 2014 Dec 18.
Our aim was to identify laboratory assays in order to assess the anticoagulant effects of dabigatran etexilate (DE).Twenty patients with nonvalvular atrial fibrillation treated on DE (110 mg per os twice daily) and 20 on acenocoumarol were studied. Conventional coagulation tests, endogenous thrombin potential (ETP), thromboelastometry (ROTEM), epinephrine-induced light transmission aggregometry (LTA), and Hemoclot Thrombin Inhibitors (HTI) were performed in all patients.In ROTEM analysis, the lysis index at 60 minutes was significantly lower in patients receiving DE (P = .011). In LTA, patients on DE showed decreased aggregation compared to those on acenocoumarol, marginally insignificant (P = .068). Regarding ETP, acenocoumarol affected thrombin generation more than dabigatran (area under the curve [AUC], P < .001), while statistically significant associations were detected between dabigatran levels, as determined by the HTI assay, and almost all parameters of ETP assay (AUC, P < .001).The role of ETP in estimating anticoagulant activity of dabigatran possibly requires further research.
- Restoration of Glucose Counterregulation by Islet Transplantation in Long-Standing Type 1 Diabetes. [JOURNAL ARTICLE]
- Diabetes 2014 Dec 18.
Patients with long-standing type 1 diabetes (T1D) may exhibit defective glucose counterregulation and impaired hypoglycemia symptom recognition that substantially increase their risk for experiencing severe hypoglycemia. To determine whether intrahepatic islet transplantation improves endogenous glucose production (EGP) in response to hypoglycemia in T1D patients experiencing severe hypoglycemia, we studied subjects (n=12) longitudinally with ∼30 years disease duration before and 6 months after intrahepatic islet transplantation using stepped hyperinsulinemic-hypoglycemic and paired hyperinsulinemic-euglycemic clamps with infusion of 6,6-(2)H2-glucose, and compared results to those from a nondiabetic control group (n=8). Following islet transplantation, HbA1c was normalized and time spent hypoglycemic (<70 mg/dl) was nearly abolished as indicated by continuous glucose monitoring. In response to insulin-induced hypoglycemia, C-peptide (absent prior to transplant) was appropriately suppressed, glucagon secretion was recovered, and epinephrine secretion was improved after transplantation. Corresponding to these hormonal changes, the EGP response to insulin-induced hypoglycemia, absent before, was normalized following transplantation, with a similar effect seen for autonomic symptoms. Since the ability to increase EGP is ultimately required to circumvent the development of hypoglycemia, these results evidence that intrahepatic islet transplantation can restore glucose counterregulation in long-standing T1D, and support its consideration as treatment for patients with hypoglycemia unawareness experiencing severe hypoglycemia.
- Hormonal and Metabolic Responses to Endurance Exercise in Children With Prader-Willi Syndrome and Non-Syndromic Obesity. [JOURNAL ARTICLE]
- Metabolism 2014 Dec 2.
Excess adiposity affects endocrine and metabolic function at rest and during exercise. This study evaluated the endocrine and metabolic responses to exercise in syndromic (Prader-Willi syndrome) and non-syndromic pediatric obesity.Eleven PWS (10.9±1.6y, 45.4±9.5% body fat), 12 lean (9.4±1.2y, 17.5±4.6% body fat), and 12 obese (9.2±1.2y, 39.9±6.8% body fat) children completed ten two-minute cycling exercise bouts, separated by one-minute rest. Blood samples were obtained at rest pre-exercise (PRE), immediately post-exercise (IP), and 15, 30 and 60minutes into recovery. Samples were analyzed for hormones and metabolites.Growth hormone increased in response to exercise in lean and obese but not PWS (IP>PRE; IP: lean>obese). Epinephrine increased with exercise in lean (IP>PRE), while norepinephrine increased in lean and obese (IP>PRE) but not PWS; no differences were observed between lean and obese groups at IP. No other significant hormonal group interactions existed. Glucose, lactate, free fatty acid, glycerol and ketone responses were similar among groups.PWS children exhibited altered stress hormone responses to exercise. However, glucose-regulating hormones and metabolic responses to exercise appeared normal.
- Outcomes of extremely preterm infants after delivery room cardiopulmonary resuscitation in a population-based cohort. [JOURNAL ARTICLE]
- J Perinatol 2014 Dec 18.
Objective:To describe the relationship of delivery room cardiopulmonary resuscitation (DR-CPR) to short-term outcomes of extremely preterm infants.Study design:This was a cohort study of 22 to 27+6/7 weeks gestational age (GA) infants during 2005 to 2011. DR-CPR was defined as chest compressions and/or epinephrine administration. Multivariable logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) associated with DR-CPR; analysis was stratified by GA.Result:Of the 13 758 infants, 856 (6.2%) received DR-CPR. Infants 22 to 23+6/7 weeks receiving DR-CPR had similar outcomes to non-recipients. Infants 24 to 25+6/7 weeks receiving DR-CPR had more severe intraventricular hemorrhage (OR 1.36, 95% CI 1.07, 1.72). Infants 26 to 27+6/7 weeks receiving DR-CPR were more likely to die (OR 1.81, 95% CI 1.30, 2.51) and have intraventricular hemorrhage (OR 2.10, 95% CI 1.56, 2.82). Adjusted hospital DR-CPR rates varied widely (median 5.7%).Conclusion:Premature infants receiving DR-CPR had worse outcomes. Mortality and morbidity varied by GA.Journal of Perinatology advance online publication, 18 December 2014; doi:10.1038/jp.2014.222.
- DUSP3 Phosphatase Deficiency or Inhibition Limit Platelet Activation and Arterial Thrombosis. [JOURNAL ARTICLE]
- Circulation 2014 Dec 17.
-A limitation of current antiplatelet therapies is their inability to separate thrombotic events from bleeding occurrences. Better understanding of the molecular mechanisms leading to platelet activation is of importance for the development of improved therapies. Recently, protein tyrosine phosphatases (PTPs) have emerged as critical regulators of platelet function.-This is the first report implicating the dual-specificity phosphatase 3 (DUSP3) in platelet signaling and thrombosis. This phosphatase is highly expressed in human and mouse platelets. Platelets from DUSP3-deficient mice displayed a selective impairment of aggregation and granule secretion mediated through the collagen receptor glycoprotein VI (GPVI) and the C-type lectin-like receptor 2 (CLEC-2). DUSP3-deficient mice were more resistant to collagen- and epinephrine-induced thromboembolism, compared to wild-type mice, and showed severely impaired thrombus formation upon ferric chloride-induced carotid artery injury. Intriguingly, bleeding times were not altered in DUSP3-deficient mice. At the molecular level, DUSP3 deficiency impaired Syk tyrosine phosphorylation, subsequently reducing phosphorylation of PLCγ2 and calcium fluxes. To investigate DUSP3 function in human platelets, a novel small-molecule inhibitor of DUSP3 was developed. This compound specifically inhibited collagen and CLEC-2-induced human platelet aggregation, thereby phenocopying the effect of DUSP3 deficiency in murine cells.-DUSP3 plays a selective and essential role in collagen- and CLEC-2-mediated platelet activation and thrombus formation in vivo. Inhibition of DUSP3 may prove therapeutic for arterial thrombosis. This is the first time a PTP, implicated in platelet signaling, has been targeted with a small-molecule drug.
- Intrapleural Epinephrine Irrigation for Massive Malignant Hemothorax. [JOURNAL ARTICLE]
- Thorac Cardiovasc Surg 2014 Dec 17.
Massive malignant hemothorax (MMH) is a rare and serious complication encountered in the field of oncology and can be life threatening. It is often difficult and complex to manage. Herein, we present cases of four patients who had MMH and in whom a hemothorax was successfully stopped via continuous intrapleural irrigation with epinephrine (5-mg epinephrine/1,000-mL normal saline, infused at 100 mL/h) instead of a conventional surgical approach. Although no patient deaths were attributed to intractable bleeding, two deaths were related to multiple organ failure. Despite the limited number of cases, this method was a convenient, effective, and inexpensive alternative to open surgical or thoracoscopic drainage for MMH.
- Hemodynamic Changes by Drug Interaction of Adrenaline With Chlorpromazine. [JOURNAL ARTICLE]
- Anesth Prog 2014; 61(4):150-154.
Abstract Adrenaline (epinephrine) is included in dental local anesthesia for the purpose of vasoconstriction. In Japan, adrenaline is contraindicated for use in patients receiving antipsychotic therapy, because the combination of adrenaline and an antipsychotic is considered to cause severe hypotension; however, there is insufficient evidence supporting this claim. The purpose of the present study was to clarify the changes in hemodynamics caused by drug interaction between adrenaline and an antipsychotic and to evaluate the safety of the combined use of adrenaline and an antipsychotic in an animal study. Male Sprague-Dawley rats were anesthetized with sodium pentobarbital. A catheter was inserted into the femoral artery to measure blood pressure and pulse rate. Rats were pretreated by intraperitoneal injection of chlorpromazine or chlorpromazine and propranolol, and after 20 minutes, saline or 1 of 3 different doses of adrenaline was administered by intraperitoneal injection. Changes in the ratio of mean arterial blood pressure and pulse rate were measured after the injection of adrenaline. Significant hypotension and tachycardia were observed after the injection of adrenaline in the chlorpromazine-pretreated rats. These effects were in a dose-dependent manner, and 100 μg/kg adrenaline induced significant hemodynamic changes. Furthermore, in the chlorpromazine and propranolol-pretreated rats, modest hypertension was induced by adrenaline, but hypotension and tachycardia were not significantly shown. Hypotension was caused by a drug interaction between adrenaline and chlorpromazine through the activation of the β-adrenergic receptor and showed a dose-dependent effect. Low-dose adrenaline similar to what might be used in human dental treatment did not result in a significant homodynamic change.
- G-CSF induces up-regulation of CXCR4 expression in human hematopoietic stem cells by beta-adrenergic agonist. [JOURNAL ARTICLE]
- Hematology 2014 Dec 17.
Introduction C-X-C chemokine receptor type 4/stromal-derived factor-1 (CXCR4/SDF-1) axis dynamically mediates hematopoietic stem cell trafficking in the bone marrow (BM). Granulocyte colony-stimulating factor (G-CSF) as the most effective mobilizing agent induces SDF-1 secretion from BM stromal cells into circulation that recruit CXCR4(+) cells such as hematopoietic stem cells (HSCs) into circulation. However, the direct effect of G-CSF on CXCR4 expression of HSC remains unknown. The nervous system regulates HSC migration with effecting on adrenergic receptors. On the other hand, interaction of G-CSF and catecholamines has been demonstrated; hence, we examined the direct effect of G-CSF and catecholamine on CXCR4 expression. Material and methods After enrichment of CD34(+) HSCs from the cord blood with MACs, these cells were exposed to G-CSF (100 ng/ml), epinephrine (10 µM), isoproterenol (10 µM), and propranolol (1 µM) separately and together. Results Our results showed that G-CSF had no direct effect on CXCR4 expression on human CD34(+) cells in vitro and treating HSCs with epinephrine leads to significantly increased CXCR4 in 1, 3, and 5 hours. Epinephrine and G-CSF-induced up-regulation of CXCR4 mRNA is dependent on beta receptors, so incubation of HSCs with propranolol led to inhibition of such increased expression. In addition, isoproterenol and agonist of beta receptors would significantly increase the expression of CXCR4 approximately 4- and 12-fold after 1-hour incubation, respectively. Discussion Co-stimulation of enriched HSCs with G-CSF and isoproterenol resulted to a further enhanced CXCR4 levels. In general, G-CSF-induced CXCR4 expression is the indirect mechanism and is specifically regulated through beta-adrenergic receptors.
- Efficacy of lidocaine with or without epinephrine in rigid nasal endoscopy. [Journal Article]
- Am J Rhinol Allergy 2014 Nov; 28(6):520-2.
This study evaluates if there is any benefit of adding epinephrine to lidocaine in patients undergoing diagnostic rigid nasal endoscopy. A prospective, randomized, double-blinded study was performed.Seventy patients were randomized to receive either 2% lidocaine or 2% lidocaine with 0.2% epinephrine before rigid nasal endoscopy examination. Patients were asked to report the intensity of pain and discomfort they experienced using visual analog scale. An endoscopist recorded the ease to perform the procedure using the same scale. Intranasal structures visualized were also reported.There were no significant differences in pain, discomfort or ease of exam, or in the percentage of visualized nasal structures between the two groups. In the whole series, there were no significant differences in the studied variables based on gender or indication to perform endoscopy.Adding epinephrine to lidocaine has no advantages in patients undergoing diagnostic rigid nasal endoscopy.