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Biomedical subjects

J H Levy

Publications and source records attributed to J H Levy.

At least 55 records · Page 3Linked to original sources
PubMed1998

A bolus dose of 1.5 mg/kg amrinone effectively improves low cardiac output state following separation from cardiopulmonary bypass in cardiac surgical patients.

BACKGROUND: The aim of this study was to evaluate the efficacy of 1.5 mg/kg bolus of amrinone on low cardiac output (CO) state following emergence from cardiopulmonary bypass (CPB) in cardiac surgical patients. METHODS: Immediately after emergency from CPB, 14 patients with a cardiac index (CI) less than 2.2 l.min-1.m-2 despite administration of inotropes and nitroglycerin, received 1.5 mg/kg amrinone over 3 min without changing catecholamine infusion rates (amrinone group). Hemodynamics and left ventricular short axis views with transesophageal echocardiography were recorded at baseline, 3, 4, and 10 min following amrinone administration. Left ventricular filling volumes were maintained constant by volume reinfusion from the CPB reservoir. We matched the data of the amrinone group with the other 14 patients who did not receive amrinone (non-amrinone group) to evaluate the efficacy of amrinone in low CO state. RESULTS: At baseline, CI (1.8 +/- 0.1 l.min-1.m-2) in the amrinone group was significantly lower than CI (3.0 +/- 0.2) in the non-amrinone group. Following amrinone administration, CI and velocity of circumferential fibershortening corrected for heart rate (Vcfc) significantly increased, and systemic vascular resistance index and pulmonary vascular resistance index significantly decreased from the baseline within 10 min without changes in heart rate, mean arterial blood pressure, or pulmonary artery occlusion pressure, and became equivalent with those of the non-amrinone group. CONCLUSIONS: A 1.5 mg/kg amrinone loading dose to patients in a low CO state, despite catecholamine therapy immediately after emergence from CPB, effectively improves ventricular function when loading conditions are maintained constant.

Adult↗
PubMed1997

The inflammatory response to cardiopulmonary bypass.

The inflammatory response to cardiopulmonary bypass is the product of a complex interplay of humoral and cellular components. Contact activation cascades, the complement system, and cytokines comprise the humoral elements and interact in such a way as to propagate their own cascades and to activate the cellular elements. Neutrophils and endothelial cells are the cellular components and become involved after their "activation" by the humoral mediators. Neutrophil-endothelial cell adherence is the initial step of the cellular inflammatory response and is promoted by the expression of specific adhesion molecules on the surfaces of both of these cells leading to the emigration of neutrophils into the extravascular space where they release toxins that damage surrounding tissues. The resulting organ dysfunction produces the clinical picture referred to as the "postperfusion syndrome." Strategies to attenuate this response include the administration of corticosteroids, aprotinin, and anticytokine monoclonal antibodies, as well as various modifications of the bypass circuit. The existence of multiple pathways to trigger this inflammatory response hampers efforts at its attenuation and leaves much investigation to be done as the quest to understand the body's inflammatory response to cardiopulmonary bypass continues.

Adrenal Cortex Hormones↗
PubMed1997

Functional maturity of the coagulation system in children: an evaluation using thrombelastography.

There are quantitative deficiencies in the coagulation system for at least the first 6 mo of life. Clinical experience, however, does not indicate an increased risk of excessive bleeding during surgical procedures. Thrombelastography, a test providing a functional evaluation of coagulation, was used to assess the hemostatic system of pediatric patients under 2 yr of age. Thrombelastographic data were obtained from 237 healthy pediatric patients less than 2 yr of age undergoing elective noncardiac surgery. Five groups were distinguished: under 30 days, 1-3 mo, 3-6 mo, 6-12 mo, and 12-24 mo. Thrombelastography revealed no defects in coagulation when these groups were compared to each other or to adults, indicating a functionally intact hemostatic process even in neonates. Indeed, children less than 12 mo of age were found to initiate and develop clot faster than adults, with the coagulation process slowing to adult rates after 1 yr of age. In addition to defining functional integrity, our data represents a set of pediatric control thrombelastographic values that have not been previously reported and that may become important in understanding coagulation changes that accompany disease states and surgery in pediatric patients.

Age Factors↗
PubMed1997

The effect of milrinone on hemodynamics and left ventricular function after emergence from cardiopulmonary bypass.

Although milrinone effectively increases cardiac function, few studies have specifically evaluated its efficacy during cardiac surgery. We investigated the effects of milrinone on hemodynamics and left ventricular function in cardiac surgical patients who were already treated with catecholamines. Thirty-seven patients undergoing cardiac surgery were studied. Immediately after emergence from cardiopulmonary bypass (CPB), patients were randomly assigned to a control group (n = 10) or to one of these milrinone groups: milrinone 50 microg/kg intravenously (n = 8), 50 microg/kg + 0.5 microg x kg(-1) x min(-1) (n = 10), or 75 microg/kg + 0.75 microg x kg(-1) x min(-1) (n = 9). Hemodynamics and transesophageal echocardiogram were recorded while constant filling pressures were maintained by volume reinfusion from the CPB reservoir. Arterial blood samples were obtained for the measurement of milrinone plasma concentrations and to determine the dose response curve. In all three milrinone groups, cardiac index and velocity of circumferential fiber shortening (Vcfc) significantly increased from the baseline, and both were significantly higher at 5 and 10 min than those in the control group. The plasma concentration of milrinone with half of maximum increase in Vcfc was 139.3 ng/mL based on the dose-response curve. Thus, milrinone improves hemodynamics and left ventricular function when constant loading conditions are maintained.

Cardiac Surgical Procedures↗
PubMed1997

The vasodilator effects of clevidipine on human internal mammary artery.

UNLABELLED: Endothelial dysfunction and platelet activation with thromboxane release may contribute to spasm or alterations in internal mammary artery (IMA) graft flow during coronary artery surgery. Clevidipine, an ultrashort-acting dihydropyridine calcium channel blocker, is undergoing clinical development, but there are little data regarding its effects on human vasculature. We investigated the effects of clevidipine on human IMA obtained during surgery. After precontracting IMA segments with an analog of thromboxane (U46619, 10(-8) mol/L), acetylcholine and nitroglycerin were added cumulatively to examine endothelial function. Concentration-response curves to clevidipine were cumulatively obtained during submaximal contraction to the U46619 (10(-8) mol/L) in rings with and without endothelium. In the IMA samples with endothelium, acetylcholine did not completely reverse the U46619-mediated contraction, which implies impaired endothelial function (40% +/- 6% maximal response). Both clevidipine and nitroglycerin completely reversed U46619-induced contraction (clevidipine (50% effective concentration [EC50] = 3.88 +/- 0.84 x 10(-6) mol/L, nitroglycerin EC50 = 4.84 +/- 2.76 x 10(-8) mol/L). The responses to clevidipine were similar in preparations with or without intact endothelium. Clevidipine is an endothelium-independent arterial vasodilator that offers a potential therapeutic option in the treatment of perioperative arterial graft vasospasm and/or hypertension. IMPLICATIONS: Clevidipine is a new ultrashort-acting dihydropyridine calcium antagonist. In human internal mammary arteries precontracted with a thromboxane A2 analog, clevidipine was an effective vasodilator on vessel segments in the presence and in the absence of endothelium.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1997

Predicting and treating coagulopathies after cardiopulmonary bypass in children.

UNLABELLED: Coagulopathies in children after cardiopulmonary bypass (CPB) are complex. There are very limited data correlating coagulation tests with postoperative bleeding. We evaluated coagulation changes after CPB and after the administration of coagulation products to 75 children. Baseline coagulation tests were obtained and repeated after protamine administration, after transfusion of individual coagulation products, and on arrival in the intensive care unit (ICU). Regression analysis demonstrated no baseline coagulation test to predict postoperative chest tube drainage. Weight and duration of CPB were determined to be the only predictors of bleeding. Further analyses demonstrated that children <8 kg had more bleeding and required more coagulation products than children >8 kg. Postprotamine platelet count and fibrinogen level correlated independently with 24-h chest tube drainage in children <8 kg, whereas postprotamine platelet count and thrombelastographic values did so in patients weighing >8 kg. Platelet administration alone was found to restore effective hemostasis in many patients. With ongoing bleeding, cryoprecipitate improved coagulation parameters and limited blood loss. Fresh-frozen plasma administration after platelets worsened coagulation parameters and was associated with greater chest tube drainage and more coagulation product transfusions in the ICU. Objective data to guide post-CPB component therapy transfusion in children are suggested. IMPLICATIONS: Children <8 kg can be expected to have more severe coagulopathies, require more coagulation product transfusions, and bleed more after cardiopulmonary bypass. Correlations between coagulation tests and postoperative chest tube drainage are defined. Platelets and, if necessary, cryoprecipitate optimally restore hemostasis. Fresh-frozen plasma offers no benefits in correcting postcardiopulmonary bypass coagulopathies in children.

Anticoagulants↗
PubMed1997

Prevention of chronic cerebral vasospasm in dogs with milrinone.

OBJECTIVE: Delayed cerebral ischemia resulting from vasospasm is a major cause of morbidity and death in patients with aneurysmal subarachnoid hemorrhage. Milrinone, because it inhibits Type IV cyclic adenosine monophosphate-specific phosphodiesterase enzyme in both cardiac and vascular smooth muscle, is a powerful inotrope and vasodilator, but it has little effect on heart rate or blood pressure. Because of these properties, milrinone is an attractive potential therapy after subarachnoid hemorrhage. The purpose of the present study was to investigate the effect of milrinone on chronic experimental cerebral vasospasm. METHODS: A double-hemorrhage canine model of vasospasm was used to study the efficacy of milrinone. Angiographic vasospasm and systemic hemodynamics were compared in a treatment group of animals that received a loading dose of milrinone (0.05 mg/kg, intravenously) and then slow-release (0.05 microgram/kg/min) milrinone pellets (n = 10) and a control group that received placebo pellets (n = 9), over an 8-day period after the initial subarachnoid hemorrhage. The hemorrhage was created by injection of 4 ml of autologous, nonheparinized, arterial blood into the cisterna magna on Days 1 and 3. Hemodynamic measurements, including cardiac output determinations, were made on Days 0, 1, 3, 6, and 8 with a pulmonary artery catheter, and angiographic vasospasm was assessed on Day 8 by comparison with baseline angiograms. RESULTS: Treatment with milrinone caused no significant changes in systemic hemodynamics. Angiographic vasospasm, however, was significantly reduced in the Day 8 angiograms for the treated group, compared with the control group (98.28 +/- 14.06 and 67.89 +/- 13.06% of original vessel cross-sectional area, respectively; P < 0.001). CONCLUSION: Milrinone is effective in preventing chronic cerebral vasospasm in a canine model of experimental chronic cerebral vasospasm. This effect is independent of changes in systemic hemodynamics. Milrinone and related drugs warrant further investigation for the treatment of cerebral vasospasm.

Animals↗
PubMed1997

Soluble intercellular adhesion molecule-1 in primary biliary cirrhosis: effect of ursodeoxycholic acid and immunosuppressive therapy.

OBJECTIVES: Soluble intercellular adhesion molecule-1 (sICAM-1) is thought to be released by a variety of cells at sites of inflammation, and their serum levels have been used as markers of inflammatory and immune activity. Our aim was to determine the effect of therapy with ursodeoxycholic acid alone and in combination with azathioprine and prednisone on serum sICAM-1 levels in primary biliary cirrhosis. DESIGN/METHODS: Twenty-four patients with primary biliary cirrhosis and 17 healthy subjects were studied. Primary biliary cirrhosis patients received ursodeoxycholic acid for 12 months and were then randomized in a double-blind fashion to receive prednisone and azathioprine, or placebo in addition to ursodeoxycholic acid. RESULTS: sICAM-1 levels were significantly higher in primary biliary cirrhosis patients than healthy subjects and fell by a median of 20% after 12 months' therapy with ursodeoxycholic acid (P<0.0004). Addition of azathioprine and prednisone to ursodeoxycholic acid resulted in a further reduction of sICAM-1 levels by a median of 25% (P< 0.01). Reductions in sICAM-1 were accompanied by improvement in liver function tests but not in the lymphocyte activation marker, soluble interleukin-2 receptor. CONCLUSION: sICAM-1 levels in primary biliary cirrhosis are reduced by ursodeoxycholic acid. Further reductions were achieved by adding prednisone and azathioprine. These reductions probably reflect an improvement in hepatobiliary excretion and a reduction in cellular production of sICAM-1.

Adult↗
PubMed1996

Aprotinin in primary valve replacement and reconstruction: a multicenter, double-blind, placebo-controlled trial.

BACKGROUND: Patients having cardiac operations often require blood transfusions. Aprotinin reduces the need for blood transfusions during coronary artery bypass graft operations. To determine the safety and effectiveness of aprotinin in reducing the use of allogeneic blood and postoperative mediastinal chest tube drainage, we studied 212 patients undergoing primary sternotomy for valve replacement or repair. METHODS: This study was multicenter, randomized, prospective, double-blind, and placebo-controlled. Patients received high-dose aprotinin (n = 71), low-dose aprotinin (n = 70), or placebo (n = 71). The study medication was given as a loading dose followed by a continuous infusion and pump prime dose. Heparin administration was standardized. Transfusions, postoperative mediastinal shed blood, and adverse events were tracked. RESULTS: Demographic profiles were similar among the treatment groups. Aprotinin did not decrease the percentage of patients receiving transfusions when compared with placebo (high-dose aprotinin, 63%, p = 0.092; low-dose aprotinin, 52%, p = 0.592; placebo, 48%). Aprotinin was associated with a reduction in the volume of mediastinal shed blood (high-dose aprotinin vs placebo, p = 0.002; low-dose aprotinin vs placebo, p = 0.017). Adverse events were equally distributed among the treatment groups except for postoperative renal dysfunction (high-dose aprotinin, 11%; low-dose aprotinin, 7%; placebo, 0%; p = 0.01). A disproportionate number of patients in the high-dose aprotinin group with postoperative renal dysfunction also had diabetes mellitus. CONCLUSIONS: Aprotinin treatment in this population did not reduce allogeneic blood use, although there were significant reductions in the volume of mediastinal shed blood.

Aprotinin↗
PubMed1996

The in vitro effects of phosphodiesterase inhibitors on the human internal mammary artery.

The internal mammary artery (IMA) is the preferred conduit for myocardial revascularization, but it changes diameter in response to injury or thromboxane release to decrease myocardial blood supply. Papaverine, a phosphodiesterase (PDE) inhibitor, is injected in the IMA bed during surgery to prevent spasm. We evaluated the ability of papaverine and cyclic adenosine monophosphate PDE Type III (cAMP-PDE) inhibitors (amrinone, enoximone, and milrinone) in vitro to reverse the constriction of human IMA rings, induced by a thromboxane A2 analog, U46619, and evaluated amrinone's ability to modify the constricting effect of norepinephrine (NE). All cAMP-PDE inhibitors produced complete relaxation of U46619-induced contractions. The contractions necessary to produce 50% relaxation (EC50) were within therapeutic ranges. The vasodilatory potency of amrinone was greater after NE than after U46619 (EC50, 1.9 +/- 0.5 vs 4.3 +/- 2.2 x 10(-5)M; mean +/- SD; P < 0.05). Response to constriction after a submaximal dose of NE was attenuated to 38% (P < 0.001) from that observed in the control rings by a pretreatment with amrinone. These results suggest that cAMP-PDE inhibitors have the potential utility to reverse IMA spasm, and represent a potential therapeutic modality for IMA spasm after myocardial revascularization.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1996

Heparin neutralization with methylene blue, hexadimethrine, or vancomycin after cardiopulmonary bypass.

There are no clinically available alternatives for reversing heparin in protamine-allergic patients. This study examined the ability of methylene blue, hexadimethrine, and vancomycin to reverse circulating heparin so that these compounds can be carefully examined in future placebo-controlled studies in humans. Heparin activity in blood obtained from extracorporeal circuits was reversed by adding protamine (13.5, 27.0, 81.1, 135.1, and 270.3 micrograms/mL), methylene blue (13.5, 27.0, 135.1, 202.7, 270.3, 337.8, 405.4, 473.0, 540.5, and 810.8 micrograms/mL), hexadimethrine (6.8, 13.5, 20.3, 27.0, 81.1, and 135.1 micrograms/mL), or vancomycin (13.5, 27.0, 135.1, 270.3, 540.5, and 810.8 micrograms/mL), and activated clotting times (ACTs) were measured with kaolin (n = 18). Heparinase-ACT was obtained to determine complete reversal. Heparin concentrations were 3.3 +/- 0.3 U/mL with ACT values of 485 +/- 97 s. The ACT at a protamine concentration of 81.1 micrograms/mL and at hexadimethrine concentrations of 81.1 and 135.1 micrograms/mL was not statistically different from heparinase-ACT; however, methylene blue or vancomycin did not reverse the anticoagulation at any concentrations. Hexadimethrine can reverse heparin-induced anticoagulation after cardiopulmonary bypass as well as protamine, although methylene blue or vancomycin did not neutralize heparin in vitro.

Blood Coagulation↗
PubMed1996

Heparinase I (neutralase) reversal of systemic anticoagulation.

BACKGROUND: Protamine causes multiple adverse reactions. Heparinase I, a specific enzyme that inactivates heparin, is a possible alternative to protamine. In this study, the authors examined the efficacy of heparinase I to reverse heparin-induced anticoagulation in vitro and compared heparinase I to protamine as an antagonist of heparin-induced anticoagulation in dogs. METHODS: In the in vitro study, blood was obtained from the extracorporeal circuits of 12 patients, and activated clotting times were determined after adding different concentrations of heparinase I. In the in vivo study, 24 anesthetized dogs received 300 units/kg heparin injected intravenously for 5 s, then 10 min later, 3.9 mg/kg protamine, 5-41 micrograms/kg heparinase I, or the vehicle (n = 4/group) were administered intravenously, and activated clotting times and hemodynamics were measured. RESULTS: In the in vitro study, heparin concentrations of 3.3 +/- 1.0 (mean +/- SD) units/ml (approximately 0.033 mg/ml; n = 12) were reversed in the blood of patients by heparinase I at concentrations > 0.490 microgram/ml. In the canine study, heparinase at all doses studied and protamine effectively reversed the anticoagulating effects of heparin within 10 min of administration. Protamine produced adverse hemodynamic effects, whereas heparinase or its vehicle produced no significant change in arterial pressure. CONCLUSION: Both heparinase I and protamine effectively reversed heparin anticoagulation. However, as opposed to protamine, heparinase I did not produce any significant hemodynamic changes when given as a bolus to dogs.

Anesthesia↗
PubMed1996

The human inflammatory response.

Inflammation is a protective response of vascularized tissue normally elicited toward nonself-determinants or tissue injury. Inflammation functions as part of normal host surveillance mechanisms to destroy or quarantine both harmful agents and damaged tissue. Most forms of inflammation are exaggerated out of proportion to the stimulus, because humoral amplification systems recruit additional components of the immune system initiating the production of proinflammatory mediators, including cytokines synthesized by activated macrophages. These act as secondary messengers to induce synthesis and expression of specific adhesion molecules on endothelial cells and white cells. Polymorphonuclear leukocytes play a central role in the acute inflammatory response. Anaphylaxis, an immediate hypersensitivity reaction to substances administered in the perioperative period, serves as a useful model for some of the problems of acute inflammation because there are important interrelationships with the cardiovascular system, endothelium, and coagulation. Mast cells and basophils produce the acute inflammation associated with anaphylaxis mediated by immunoglobulin E (IgE) antibodies, whereas the immunoglobulin G (IgG)-antigen interaction activates the complement cascade to generate anaphylatoxins, specifically C5a. Activation of white cells causes release of proteolytic enzymes, production of oxygen-derived free radicals, and the synthesis of a variety of lipid mediators. Protamine sulfate is one of the most common causes of life-threatening anaphylactic reactions during cardiac surgery. Differing responses occur, dependent on the presence of either IgE or IgG antibodies with the activation of the mast cell or the complement system, respectively. The many different amplifying pathways that can be recruited during anaphylaxis and the array of mediators involved are important when therapeutic intervention is considered. The challenge for the future will be to identify a pharmacologic agent that will arrest the inflammatory cascade and thus prevent further amplification and resultant host injury.

Humans↗
PubMed1996

Pharmacodynamics and pharmacokinetics of milrinone administration to increase oxygen delivery in critically ill patients.

OBJECTIVES: The positive inotropic and vasodilator actions of phosphodiesterase (PDE) inhibitor drugs may offer therapeutic alternatives to beta-agonists in critically ill patients. We hypothesized that milrinone administration would increase cardiac index (CI) and oxygen delivery (Do2) in ICU patients, and that a pharmacokinetic model previously developed in cardiac surgery patients may be used to predict milrinone plasma concentrations in a medical-surgical ICU population. SETTING: ICU in two tertiary-care, university medical centers. DESIGN AND INTERVENTIONS: A prospective, open-label, multicenter, dose-escalating study in three successive groups of eight ICU patients who received a 10-min loading dose of milrinone (25 micrograms/kg [LOW], 50 micrograms/kg [MED], and 75 micrograms/kg [HIGH]). In addition, all patients then received a milrinone infusion of 0.5 microgram/kg/min for 1 h. MEASUREMENTS: Hemodynamic measurements included heart rate (HR); mean arterial, pulmonary artery, central venous, and pulmonary artery occlusion pressures; and thermodilution cardiac output. Oxygen transport indexes included arterial and venous blood oxygen tensions to determine Do2 and oxygen consumption (Vo2). Data were analyzed by univariate repeated measures analysis of covariance, with baseline values utilized as covariate regressors. RESULTS: Twenty-four adult ICU patients 20 to 84 years of age completed the study. The three groups did not differ, except that the patients in the MED group were significantly older (67 +/- 4 years, mean +/- SEM) compared with either the patients in the LOW (48 +/- 7 years) or HIGH (47 +/- 6 years) group. While HR did not change in the LOW group (90 +/- 4 to 93 +/- 3 beats/min), HR increased significantly in the HIGH group (94 +/- 5 to 112 +/- 8 beats/min) (baseline to 60 min infusion time points). All milrinone doses increased both CI and Do2. At the end of the 10-min loading dose, CI increased 0.3 L/min/m2 in the LOW group, 1.1 L/min/m2 in the MED group, and 0.9 L/min/m2 in the HIGH group. Do2 increased 8% in the LOW group, 33% in the MED group, and 23% in the HIGH group, similar to the changes in CI. Mixed venous oxygen saturation increased 3 to 5% during the 10-min loading dose of milrinone. During this same time period, mean arterial pressure decreased 6 to 16% and pulmonary artery pressures decreased 9 to 15%. Peak plasma milrinone concentrations increased as a function of the loading dose (159 +/- 9 ng/mL in the LOW group, 302 +/- 33 ng/ml in the MED group, and 411 +/- 45 ng/mL in the HIGH group). However, milrinone concentrations were similar in all three groups after the 1-h infusion; 113 +/- 14 ng/ml (LOW), 147 +/- 22 ng/mL (MED), and 119 +/- 14 ng/ml (HIGH). In all patients with final plasma milrinone concentrations greater than 100 ng/mL (15/23), the CI increased by at least 0.4 L/min/m2 (range, 0.4 to 1.8 L/min/m2). CONCLUSIONS: Our study confirms that a milrinone loading dose of 50 micrograms/kg/min followed by an infusion of 0.5 microgram/kg/min achieves adequate plasma concentrations of 100 ng/mL or greater, which significantly increases both CI and Do2. In addition, a previously established pharmacokinetic model of milrinone disposition is confirmed in this mixed ICU population.

Adult↗
PubMed1995

A multicenter, double-blind, placebo-controlled trial of aprotinin for reducing blood loss and the requirement for donor-blood transfusion in patients undergoing repeat coronary artery bypass grafting.

BACKGROUND: Aprotinin is a serine protease inhibitor that reduces blood loss and transfusion requirements when administered prophylactically to cardiac surgical patients. To examine the safety and dose-related efficacy of aprotinin, a prospective, multicenter, placebo-controlled trial was conducted in patients undergoing repeat coronary artery bypass graft (CABG) surgery. METHODS AND RESULTS: Two hundred eighty-seven patients were randomly assigned to receive either high-dose aprotinin, low-dose aprotinin, pump-prime-only aprotinin, or placebo. Drug efficacy was determined by the reduction in donor-blood transfusion up to postoperative day 12 and in postoperative thoracic-drainage volume. The percentage of patients requiring donor-red-blood-cell (RBC) transfusions in the high- and low-dose aprotinin groups was reduced compared with the pump-prime-only and placebo groups (high-dose aprotinin, 54%; low-dose aprotinin, 46%; pump-prime only, 72%; and placebo, 75%; overall P = .001). The number of units of donor RBCs transfused was significantly lower in the aprotinin-treated patients compared with placebo (high-dose aprotinin, 1.6 +/- 0.2 U; low-dose aprotinin, 1.6 +/- 0.3 U; pump-prime-only, 2.5 +/- 0.3 U; and placebo, 3.4 +/- 0.5 U; P = .0001). There was also a significant difference in total blood-product exposures among treatment groups (high-dose aprotinin, 2.2 +/- 0.4 U; low-dose aprotinin, 3.4 +/- 0.9 U; pump-prime-only, 5.1 +/- 0.9 U; placebo, 10.3 +/- 1.4 U). There were no differences among treatment groups for the incidence of perioperative myocardial infarction (MI). CONCLUSIONS: This study demonstrates that high- and low-dose aprotinin significantly reduces the requirement for donor-blood transfusion in repeat CABG patients without increasing the risk for perioperative MI.

Aged↗
PubMed1995

Soluble E-selectin and vascular cell adhesion molecule-1 (VCAM-1) in primary biliary cirrhosis.

BACKGROUND/AIMS: E-selectin and vascular cell adhesion molecule-1, important in leucocyte adhesion, have recently been detected in soluble form in the circulation. However, their clinical significance remains unclear. Our aims were to determine whether the levels of these molecules are increased in primary biliary cirrhosis, and to relate these to histological disease stage, biochemical measures of liver damage and to lymphocyte activation. METHODS: We studied 42 patients with primary biliary cirrhosis, nine with primary sclerosing cholangitis, 14 with alcoholic liver disease and 17 healthy subjects. Circulating E-selectin and vascular cell adhesion molecule-1 levels were measured by enzyme-linked immunosorbent assay. In subgroups of patients with primary biliary cirrhosis, hepatic bile acid uptake and excretory rates and T-cell activation were also determined. RESULTS: Soluble E-selectin and vascular cell adhesion molecule-1 levels were significantly elevated in primary biliary cirrhosis compared to healthy controls. However, there was no difference between primary biliary cirrhosis and other liver disease groups. In primary biliary cirrhosis, both adhesion molecules correlated with disease stage, but differed in their relationships with specific liver function tests. They did not correlate with either hepatic bile acid uptake or excretion, or lymphocyte activation. CONCLUSIONS: We conclude that soluble E-selectin and vascular cell adhesion molecule-1 are elevated in chronic liver diseases. In primary biliary cirrhosis, they reflect the stage of disease and may reflect the degree of leucocyte adhesion and migration.

Adult↗