Search PubMed⌕ Search

Biomedical subjects

J H Levy

Publications and source records attributed to J H Levy.

At least 37 records · Page 2Linked to original sources
PubMed2000

Weal and flare responses to intradermal rocuronium and cisatracurium in humans.

Thirty volunteers underwent intradermal skin testing with increasing concentrations of rocuronium and cisatracurium to evaluate weal and flare responses, and whether either agent would cause mast cell degranulation and sensitization upon re-exposure. We found that intradermal injection of rocuronium and cisatracurium at concentrations > 10(-4) M resulted in positive weal (>8 mm) responses, and positive flare responses at > 10(-4) and > 10(-5) M respectively. Only cisatracurium caused mild to moderate mast cell degranulation, and neither drug caused significant in vitro histamine release from whole blood collected from study subjects 4 weeks after skin testing. Skin testing with rocuronium and cisatracurium should be performed at concentrations < 10(-4) and < 10(-5) M respectively to avoid false-positive responses. The ability of these agents to produce positive weal and flare responses at relatively low concentrations may explain the high incidence of potential reactions reported.

Androstanols↗
PubMed2000

Pharmacokinetics of recombinant transgenic antithrombin in volunteers.

UNLABELLED: Adequate levels of antithrombin (AT) III are essential for anticoagulation during cardiopulmonary bypass. Levels of AT are often decreased in patients receiving heparin before surgery. In these patients supplementation with exogenous AT can suppress the coagulation pathway and possibly decrease the risk of postoperative coagulopathy. However, the pharmacokinetics of AT have not been extensively analyzed. In this study we investigated the pharmacokinetics of transgenic recombinant AT in healthy volunteers. The concentrations of AT, after initial doses given over 30 min, were best described by a weight-normalized two-compartment model. The fast compartment volume was 41.1 mL/kg and the volume of distribution was 115.4 mL/kg. Intercompartmental clearance was 0. 0763 mL. kg(-1). min(-1) and elimination clearance was 0.0383 mL. kg(-1). min(-1). These variables are equivalent to a distribution half-life of 196 min and an elimination half-life of 2568 min. Approximately 75% of the supplemental dose is removed from plasma by the initial distribution process. A single supplemental dose of transgenic recombinant antithrombin restoring levels to 120%-150% of normal can provide adequate levels for the usual duration of cardiopulmonary bypass. IMPLICATIONS: A single supplemental dose of transgenic recombinant antithrombin restoring levels to 120%-150% of normal can provide adequate levels for the usual duration of cardiopulmonary bypass.

Adult↗
PubMed2000

The in vitro effects of antithrombin III on the activated coagulation time in patients on heparin therapy.

UNLABELLED: Heparin requires antithrombin III (AT) to achieve anticoagulation, and patients on continuous small-dose heparin preoperatively experience decreased levels of AT-causing heparin resistance. When this occurs, 2-4 units of fresh frozen plasma ( approximately 1000 units of AT) are often administered to increase AT levels and restore heparin responsiveness. We evaluated purified human AT concentrate (Thrombate III; Bayer, Inc., Elkhart, IN) to restore in vitro anticoagulation responses in patients receiving heparin. Blood samples were obtained from cardiac surgery patients including 22 patients receiving heparin and 21 patients not receiving heparin preoperatively. Heparin was added to blood in final concentrations of 4.1, 5.4, and 6.8 U/mL (equivalent to 300, 400, and 500 U/kg), and kaolin-activated clotting times (ACTs) were determined with and without AT at a final concentration of 0.2 units/mL to mimic fresh frozen plasma administration. The mean duration of preoperative heparin therapy was 4.0 days (range 2-10 days). AT activity was 69% +/- 9% in patients receiving heparin and 92% +/- 8% in patients not receiving heparin (P < 0.01). Heparin >4.1 U/mL failed to further increase ACT values in all patients. Attempts to increase ACT in patients receiving heparin may require supplemental AT administration. Purified AT even in small doses significantly prolongs the ACT response to heparin. IMPLICATIONS: In vitro addition of antithrombin III (0.2 U/mL) to heparinized blood samples (4.1-6.8 units of heparin/mL) from patients on previous heparin therapy increases sensitivity to supplemental heparin as reflected by significantly prolonged activated clotting time.

Aged↗
PubMed2000

Rapid evaluation of coagulopathies after cardiopulmonary bypass in children using modified thromboelastography.

UNLABELLED: Complex coagulopathies follow cardiopulmonary bypass (CPB) in children. However, objective laboratory data that can be acquired rapidly to guide their management are lacking. Because thromboelastography has proven useful in this regard, we evaluated the use of celite or tissue factor (TF) activation and heparinase modification of blood samples to allow rapid determination of thromboelastogram data in children younger than 2 yr undergoing CPB. Celite or TF activation shortened the initiation of clotting and, thus, the time required for the important thromboelastogram alpha and maximum amplitude values to begin evolving. Although thromboelastogram alpha and maximum amplitude values were increased with these activators, correlations persisted between platelet count or fibrinogen level and each of these values. The additional use of heparinase allowed thromboelastograms to be obtained during CPB with values not different from those obtained without heparinase after protamine administration. Therefore, celite- or TF-activated, heparinase-modified thromboelastograms begun during CPB allow objective data to be available by the conclusion of protamine administration to help restore hemostasis after CPB in children. Thromboelastography identified transient fibrinolysis during CPB in some children that resolved by the conclusion of protamine administration. Future investigations of the effectiveness of modified thromboelastography-guided coagulopathy management after CPB in children are needed. IMPLICATIONS: Thromboelastography is useful in assessing the coagulopathies that follow cardiopulmonary bypass in children. Modifying blood samples with celite or tissue factor and heparinase allows thromboelastography begun before the termination of cardiopulmonary bypass to become a rapid point-of-care monitor to provide objective data for guiding blood component therapy to manage these coagulopathies.

Anticoagulants↗
PubMed2000

Mechanisms of nonimmunological histamine and tryptase release from human cutaneous mast cells.

BACKGROUND: If mast cells are stimulated they release multiple mediators that delineate markers for immunologic and nonimmunologic reactions; histamine and tryptase are the two best known. Although histamine can be assayed in plasma, it is a nonspecific marker with a very short half-life. Tryptase has a longer half-life, but its release has not been proven to be specific for anaphylaxis. The authors investigated the mechanisms of nonimmunologic histamine release from human cutaneous mast cells to understand the mechanisms of mediator release and to determine whether tryptase was specific for allergic mediated activation. METHODS: Dispersed mast cell suspensions isolated from neonatal foreskins underwent challenge with vancomycin, calcium ionophore A23187, morphine, and atracurium, and histamine tryptase release was measured. The effects of calcium and magnesium, along with phospholipase C and phospholipase A2 inhibitors, also were investigated. RESULTS: Tryptase and histamine both were released by the known nonimmunologic stimuli (pharmacologic agents used in the current study; r2 = 0.6). Furthermore, vancomycin- and atracurium-induced histamine release was calcium dependent. Phospholipase C and phospholipase A2 inhibitors decreased vancomycin-induced histamine release, but not calcium ionophore A23187-induced release. CONCLUSIONS: Tryptase is not a specific marker of mast cell activation (ie., anaphylaxis), and signaling mechanisms for mast cell activation involve activation of phospholipase C and phospholipase A2 pathways that are also involved in other cellular activation mechanisms.

Arachidonic Acid↗
PubMed2000

Perioperative blood pressure control: a prospective survey of patient management in cardiac surgery.

OBJECTIVE: To conduct a survey of current cardiac anesthetic practice in Europe and the United States, as a first step toward establishing guidelines for the management of perioperative hypertension. DESIGN: Prospective, multicenter study. SETTING: University hospitals. PARTICIPANTS: Unselected patients (n = 1,930) requiring cardiac surgery. INTERVENTIONS: Data extending from the preoperative evaluation to 120 hours or more after surgery were collected from all patients. MEASUREMENTS AND MAIN RESULTS: Only the data from patients undergoing coronary artery bypass surgery, valve surgery, or combined procedures were analyzed, leaving a final total of 1,660 patients from the original 1,930. Of these, 88% were treated at least once perioperatively to lower arterial blood pressure. Deepening of anesthesia was the most commonly used antihypertensive measure (68%), regardless of the ongoing anesthetic regimen, and was usually combined with vasodilator therapy, most frequently nitroglycerin (53%) or sodium nitroprusside (28%). Reported perioperative mean arterial pressure (MAP) was 15 to 20 mmHg lower than MAP before anesthesia induction, regardless of the use of antihypertensive therapy. The MAP at which antihypertensive treatment was initiated varied markedly among the various phases of surgery and showed no clear correlation with preoperative MAP. CONCLUSIONS: The results of this survey show that current anesthetic practice tries to prevent perioperative hypertension wherever possible during cardiac surgery. Blood pressure measurements taken before surgery have little influence on the development of hypertension intraoperatively, and the main determinants of perioperative blood pressure control and the need for therapeutic intervention are factors arising from the surgical procedure itself, such as aortic cross-clamping and activation of adrenergic mechanisms.

Blood Pressure↗
PubMed2000

Management strategies for high-risk cardiac surgery: improving outcomes in patients with heart failure.

BACKGROUND: Surgical heart failure management is the fastest growing aspect of cardio-vascular surgery. Advances in cardiac surgical techniques have changed the number and types of operations permitted physicians and thus broadened the complexity of patients recommended for operation. METHODS: Surgeons, anesthesiologists and cardiologists face hemodynamic and patho-physiological challenges that can be optimally overcome only by modifying treatment strategies. Because many treatment standards are still evolving in this rapidly advancing field, a team of cardiovascular surgeons and anesthesiologists convened to share clinical experience and impressions and discuss practical issues related to high-risk patients undergoing heart surgery. RESULTS: Heart failure pathophysiology, surgical heart failure management, including mitral reconstruction and left ventricular remodeling, cardiopulmonary bypass weaning, inotropic support, transesophageal echocardiography and acute cardiovascular collapse after cardiac surgery are discussed. CONCLUSION: This article is intended to guide clinicians to improve patient care and outcomes in this special population by providing specific guidance on the appropriate use of inotropic and mechanical support in patients undergoing high-risk procedures using innovative techniques.

Cardiac Surgical Procedures↗
PubMed1999

Fenoldopam: a new parenteral antihypertensive: consensus roundtable on the management of perioperative hypertension and hypertensive crises.

A panel of clinicians from anesthesiology, surgery, nephrology, hypertension, cardiology, and pharmacology was convened to discuss pharmacologic therapeutics in the management of hypertensive crisis and perioperative hypertension. The panel discussed the advantages and limitations of currently available parenteral drugs, and assessed the potential use of fenoldopam mesylate, a drug in clinical development since 1981, and recently approved by the U.S. Food and Drug Administration (FDA). Fenoldopam is a dopamine receptor (DA1 selective) agonist that is a systemic and renal vasodilator. It was concluded that fenoldopam offers significant advantages as a parenterally administered agent for the management of blood pressure in both hypertensive emergencies and in the perioperative setting.

Acute Disease↗
PubMed1999

The effects of rapacuronium on histamine release and hemodynamics in adult patients undergoing general anesthesia.

UNLABELLED: Neuromuscular blocking drugs may have variable effects on heart rate (HR) and blood pressure. Rapacuronium is a rapid-acting, steroidal-derived neuromuscular blocking drug whose hemodynamic effects have not been characterized. We studied the effects of 1, 2, and 3 mg/kg rapacuronium on histamine release, HR, and blood pressure in 47 ASA physical status II or III adult patients after the induction of anesthesia with etomidate/fentanyl/N2O. Plasma histamine concentrations were measured before induction and immediately before and 1, 3, and 5 min after the rapid administration of rapacuronium. Mean arterial pressure (MAP) decreased after rapacuronium administration, but there were no significant differences among the groups for changes in HR or MAP, and there was no correlation between changes in MAP or HR and increases in histamine levels. There were no changes in HR or MAP among five patients who had significant (> or = 1 ng/mL) increases in histamine from baselin. Seven patients had bronchospasm without increases in plasma histamine levels. Rapacuronium 2-3 mg/kg increased plasma histamine levels. However, clinically significant histamine-related sequelae did not occur in this population with 1- to 3-mg/kg doses of rapacuronium, and cardiovascular changes were not directly correlated with histamine release. Rapacuronium administration can produce hypotension via mechanisms that do not seem to be related to histamine release. IMPLICATIONS: Rapacuronium, a new steroidal-derived muscle relaxant, may release histamine and produce slight changes in blood pressure and heart rate after administration.

Adult↗
PubMed1999

Adenosine A(3)-receptor stimulation attenuates postischemic dysfunction through K(ATP) channels.

We tested the hypothesis that selective adenosine A(3)-receptor stimulation reduces postischemic contractile dysfunction through activation of ATP-sensitive potassium (K(ATP)) channels. Isolated, buffer-perfused rat hearts (n = 8/group) were not drug pretreated (control) or were pretreated with adenosine (20 microM), 2-chloro-N(6)-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (Cl-IB-MECA; A(3) agonist, 100 nM), Cl-IB-MECA + 8-(3-noradamantyl)-1,3-dipropylxanthine (KW-3902; A(1) antagonist, 5 microM), Cl-IB-MECA + glibenclamide (Glib; K(ATP)-channel blocker, 0. 3 microM), or Glib alone for 12 min before 30 min of global normothermic ischemia followed by 2 h of reperfusion. After 2 h of reperfusion, left ventricular developed pressure (LVDP, %baseline) in control hearts was depressed to 34 +/- 2%. In hearts pretreated with Cl-IB-MECA, there was a statistically significant increase in LVDP (50 +/- 6%), which was reversed with coadministration of Glib (37 +/- 1%). Control hearts also showed similar decreases in left ventricular peak positive rate of change in pressure (dP/dt). Therefore, the A(3) agonist significantly attenuated postischemic cardiodynamic injury compared with the control, which was reversed by Glib. Cumulative creatine kinase (CK in U/min) activity was most pronounced in the control group (10.4 +/- 0.6) and was significantly decreased by Cl-IB-MECA (7.5 +/- 0.4), which was reversed by coadministration of Glib (9.4 +/- 0.2). Coronary flow was increased during adenosine infusion (160% of baseline) but not during Cl-IB-MECA infusion. Effects of Cl-IB-MECA were not reversed by the specific A(1) antagonist KW-3902. We conclude that cardioprotection afforded by A(3)-receptor stimulation may be mediated in part by K(ATP) channels. Cl-IB-MECA may be an effective pretreatment agent that attenuates postischemic cardiodynamic dysfunction and CK release without the vasodilator liability of other adenosine agonists.

Adenosine↗
PubMed1999

Hemostatic agents and their safety.

The pharmacologic management of hemostasis in patients undergoing cardiopulmonary bypass may be accompanied by adverse responses. Evaluating the safety profile of hemostatic agents (eg, lysine analogs, aprotinin, protamine, or even donor blood) should be done objectively. Subsequent to early anecdotal reports, the safety profile of aprotinin, a broad-spectrum serine protease inhibitor, has been thoroughly evaluated in multiple double-blind, placebo-controlled, multicenter studies. Although associated with decreased fibrinolysis, aprotinin has not been associated with an increased risk of post-cardiopulmonary bypass myocardial infarction, graft closure, stroke, or increased risk of renal dysfunction from US studies. As with any polypeptide, there is a risk of anaphylaxis, which is influenced not only by prior exposure but also by time since prior exposure. In a similar fashion, after early anecdotal reports, evaluations involving large numbers of patients have helped define adverse reactions to protamine. Adverse reactions to blood products also must be considered in any safety comparisons involving hemostatic agents.

Aminocaproic Acid↗
PubMed1998

Hematologic and economic impact of aprotinin in reoperative pediatric cardiac operations.

BACKGROUND: Aprotinin consistently reduces blood loss and transfusion requirements in adults during and after cardiac surgical procedures, but its effectiveness in children is debated. We evaluated the hemostatic and economic effects of aprotinin in children undergoing reoperative cardiac procedures with cardiopulmonary bypass. METHODS: Control, low-dose aprotinin, and high-dose aprotinin groups were established with 15 children per group. Platelet counts, fibrinogen levels, and thromboelastographic values at baseline and after protamine sulfate administration, number of blood product transfusions, and 6-hour and 24-hour chest tube drainage were used to evaluate the effects of aprotinin on postbypass coagulopathies. Time needed for skin closure after protamine administration and lengths of stay in the intensive care unit and the hospital were recorded prospectively to determine the economic impact of aprotinin. RESULTS: Coagulation tests performed after protamine administration rarely demonstrated fibrinolysis but did show significant decreases in platelet and fibrinogen levels and function. The thromboelastographic variables indicated a preservation of platelet function by aprotinin. Decreased blood product transfusions, shortened skin closure times, and shortened durations of intensive care unit and hospital stays were found in the aprotinin groups, most significantly in the high-dose group with a subsequent average reduction of nearly $3,000 in patient charges. CONCLUSIONS: In children undergoing reoperative cardiac surgical procedures, aprotinin is effective in attenuating postbypass coagulopathies, decreasing blood product exposure, improving clinical outcome, and reducing patient charges.

Adolescent↗
PubMed1998

Analyses of coronary graft patency after aprotinin use: results from the International Multicenter Aprotinin Graft Patency Experience (IMAGE) trial.

OBJECTIVE: We examined the effects of aprotinin on graft patency, prevalence of myocardial infarction, and blood loss in patients undergoing primary coronary surgery with cardiopulmonary bypass. METHODS: Patients from 13 international sites were randomized to receive intraoperative aprotinin (n = 436) or placebo (n = 434). Graft angiography was obtained a mean of 10.8 days after the operation. Electrocardiograms, cardiac enzymes, and blood loss and replacement were evaluated. RESULTS: In 796 assessable patients, aprotinin reduced thoracic drainage volume by 43% (P < .0001) and requirement for red blood cell administration by 49% (P < .0001). Among 703 patients with assessable saphenous vein grafts, occlusions occurred in 15.4% of aprotinin-treated patients and 10.9% of patients receiving placebo (P = .03). After we had adjusted for risk factors associated with vein graft occlusion, the aprotinin versus placebo risk ratio decreased from 1.7 to 1.05 (90% confidence interval, 0.6 to 1.8). These factors included female gender, lack of prior aspirin therapy, small and poor distal vessel quality, and possibly use of aprotinin-treated blood as excised vein perfusate. At United States sites, patients had characteristics more favorable for graft patency, and occlusions occurred in 9.4% of the aprotinin group and 9.5% of the placebo group (P = .72). At Danish and Israeli sites, where patients had more adverse characteristics, occlusions occurred in 23.0% of aprotinin- and 12.4% of placebo-treated patients (P = .01). Aprotinin did not affect the occurrence of myocardial infarction (aprotinin: 2.9%; placebo: 3.8%) or mortality (aprotinin: 1.4%; placebo: 1.6%). CONCLUSIONS: In this study, the probability of early vein graft occlusion was increased by aprotinin, but this outcome was promoted by multiple risk factors for graft occlusion.

Adult↗
PubMed1998

Protamine reversal of heparin affects platelet aggregation and activated clotting time after cardiopulmonary bypass.

UNLABELLED: Bleeding after cardiopulmonary bypass (CPB) is related to multiple factors. Excess protamine weakens clot structure and decreases platelet function; therefore, an increased activated clotting time (ACT) after protamine reversal of heparin may be misinterpreted as residual heparin anticoagulation. We evaluated the effects of protamine, recombinant platelet factor 4 (rPF4), and hexadimethrine on ACT in blood obtained after CPB. In addition, we examined the effect of protamine on in vitro platelet aggregation. Incremental doses of protamine, rPF4, and hexadimethrine were added to heparinized blood from CPB, and ACTs were performed. Incremental concentrations of protamine were added to heparinized platelet-rich plasma, and aggregometry was induced by adenosine diphosphate (ADP) and collagen. The mean heparin concentration at the end of CPB was 3.3 U/mL. Protamine to heparin ratios >1.3:1 produced a significant prolongation of the ACT that was not seen with rPF4 and was observed only with 5:1 hexadimethrine to heparin ratios. ADP-induced platelet aggregation was reduced with protamine administration > or =1.3:1. Excessive protamine reversal of heparin prolongs ACT and alters ADP-induced platelet aggregation in a dose-dependent manner in vitro. Additional protamine administered to treat a prolonged ACT may further increase clotting time, reduce platelet aggregation, and potentially contribute to excess bleeding after CPB. IMPLICATIONS: We found that excess protamine prolonged the activated clotting time and altered platelet function after cardiopulmonary bypass, whereas heparin antagonists, such as recombinant platelet factor 4 and hexadimethrine, exhibited a wider therapeutic range without adversely affecting the activated clotting time. Approaches to avoid excess protamine or use of alternative heparin antagonists after cardiopulmonary bypass may be beneficial.

Adenosine Diphosphate↗
PubMed1998

A comparative evaluation of the effects of multiple vasodilators on human internal mammary artery.

BACKGROUND: Vasospasm of arterial grafts represents an unpredictable complication of coronary artery surgery and may compromise myocardial revascularization, and treatment is based on empirical therapy with nitroglycerin. Because of the potential for tolerance to nitroglycerin to occur, the authors studied different vasodilators acting through separate pathways on segments of human internal mammary artery. METHODS: Isolated vascular rings were precontracted with norepinephrine (1 microM), KCl, or the thromboxane A2 analogue (U46619, 10 nm). Nitroglycerin (a nitrovasodilator), milrinone (a type III phosphodiesterase inhibitor), papaverine (a phosphodiesterase inhibitor), prostaglandin E1, and isradipine (a dihydropyridine calcium channel blocker) were added in a cumulative fashion. RESULTS: The analysis of the concentration-response curves showed that vasodilators induced 90-100% relaxation of the constricted segments with norepinephrine or the thromboxane A2 analogue, except prostaglandin E1, which produced 73% relaxation at maximal concentrations. The effective concentrations of vasodilator agent that caused 50% relaxation for nitroglycerin and milrinone were within the range of the reported therapeutic concentrations in plasma. Isradipine was also effective at reversing receptor-mediated contraction (maximal relaxation=100% in internal mammary artery contracted with norepinephrine; maximal relaxation=0% in internal mammary artery contracted with the thromboxane A2 analogue). CONCLUSIONS: Vasodilator drugs acting through multiple pathways are effective at reversing in vitro vasoconstriction.

Dose-Response Relationship, Drug↗