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Biomedical subjects

J H Levy

Publications and source records attributed to J H Levy.

At least 73 records · Page 4Linked to original sources
PubMed1995

Heparin neutralization by recombinant platelet factor 4 and protamine.

Protamine is the only available drug to reverse heparin-induced anticoagulation. Platelet factor 4 (PF4) is a basic polypeptide stored in platelets that reverses heparin. To investigate its potential as a reversal drug, we studied recombinant PF4 on anticoagulated blood obtained during cardiac surgery. Blood was obtained from 33 different venous reservoirs, and activated clotting time (ACT), heparin concentrations, and heparinase-ACT were determined. Anticoagulation was reversed by adding incremental PF4:heparin and protamine:heparin ratios to the heparinized blood, and the ACTs were determined (n = 21). Viscoelastic analysis of anticoagulation reversal was performed by adding protamine or PF4 at reversal ratios of 1.3:1 protamine:heparin, and 3.2:1 PF4:heparin using thromboelastography (n = 12). PF4 reversal ratios of 3:1 and 3.5:1 and protamine reversal ratios of 1:1, 1.5:1, 2:1 were not statistically different from heparinase-ACT values. There were no significant differences in viscoelastic measurements of clot formation between protamine and PF4. Recombinant PF4 at a 3.0:1 ratio reverses heparin-induced anticoagulation after cardiopulmonary bypass, and represents a potential alternative, especially for the protamine allergic patient.

Blood Coagulation↗
PubMed1995

The effects of milrinone on platelets in patients undergoing cardiac surgery.

Although amrinone produces thrombocytopenia, no information is available regarding the acute effects of milrinone on platelets. Therefore, we evaluated the effects of milrinone on platelet number and function in cardiac surgical patients. Twenty-seven patients were studied during cardiac surgery requiring cardiopulmonary bypass (CPB). Patients were randomized to receive no milrinone (n = 10), or milrinone (n = 17) at a loading dose of 50-75 micrograms/kg in the CPB circuit followed by 0.5-0.75 micrograms.kg-1.min-1 for 12-24 h. Bleeding times and blood samples for coagulation studies were obtained prior to induction, and at 2 and 24 h after CPB. In both groups, platelet counts decreased significantly from the baseline at 2 and 24 h after CPB, and bleeding time increased significantly from the baseline at 2 and 24 h after CPB. No significant thromboelastoplasty (TEG) changes were observed in either group, and there were no significant differences in platelet aggregation or chest tube drainage between the groups. Acute milrinone administration did not cause significant changes in platelet number or function in patients undergoing cardiac operations requiring CPB, beyond the usual adverse effects of cardiac surgery and CPB.

Adult↗
PubMed1995

New cardiac drugs.

The positive inotropic agents, including beta-adrenergic receptor agonists and PDE III inhibitors, are reviewed to explain their mechanisms of action, pharmacology, and clinical usage. New cardiotonic drugs, such as dopexamine and dobutamine (beta-adrenergic receptor agonists) and amrinone, milrinone, and enoximone (PDE III inhibitors), have important roles for the treatment of perioperative acute heart failure or acute deterioration of congestive heart failure. PDE III inhibitors have important roles as effective inodilator agents, and understanding their actions, pharmacology, and appropriate usage is important. Nicardipine, the first dihydropyridine calcium-channel blocker available for intravenous use, represents an arterial-specific vasodilator that offers an important therapeutic approach to treat perioperative hypertension.

Adrenergic beta-Agonists↗
PubMed1994

Soluble intercellular adhesion molecule-1 in primary biliary cirrhosis: relationship with disease stage, immune activity and cholestasis.

Intercellular adhesion molecule-1, strongly expressed on the interlobular and proliferating bile ducts in primary biliary cirrhosis, is important in the migration and adhesion of inflammatory cells from the circulation to these structures. A soluble form has been found to be elevated in serum in primary biliary cirrhosis. Our aim was to check on the role of soluble intercellular adhesion molecule-1 in primary biliary cirrhosis with particular reference to its specificity by comparison with other disease control groups and to assess its relationship with stage of disease activity, circulating lymphocyte activation and cholestasis. Soluble intercellular adhesion molecule-1 (enzyme-linked immunosorbent assay) and liver biochemistry were measured in 41 patients with primary biliary cirrhosis, 9 with primary sclerosing cholangitis, 12 with alcoholic liver disease and 17 healthy controls. In subgroups of patients with primary biliary cirrhosis, lymphocyte activation and hepatic bile acid uptake and excretory rates were determined. Soluble intercellular adhesion molecule-1 was significantly higher in all three disease groups. Levels in primary biliary cirrhosis and primary sclerosing cholangitis were similar and significantly higher than alcoholic liver disease. Soluble intercellular adhesion molecule-1 expression was greater in late primary biliary cirrhosis than early disease and correlated with histological progression. Correlations were also found with alkaline phosphatase, gamma-glutamyl transpeptidase and conjugated bilirubin. A trend toward an inverse correlation with hepatic excretory rate was found, but no correlation was detected with circulating lymphocyte interleukin-2 receptor expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Astigmatic changes after cataract surgery with 5.1 mm and 3.5 mm sutureless incisions.

We evaluated postoperative keratometric astigmatism in 80 eyes that had phacoemulsification and intraocular lens implantation through sutureless corneal incisions. The eyes were separated into two groups based on the use of rigid ovoid or foldable silicone lenses inserted through 5.1 mm corneal lip incisions or 3.5 mm lip incisions, respectively. In the early postoperative period (one to three months), vector analysis showed less induced astigmatism in the 3.5 mm group than in the 5.1 mm group. Uncorrected visual acuity during the postoperative period was also better in the smaller incision group.

Adult↗
PubMed1994

Pharmacokinetics of aprotinin in preoperative cardiac surgical patients.

BACKGROUND: Aprotinin, a polypeptide protease inhibitor, reduces bleeding and transfusion requirements during cardiac surgery. To investigate aprotinin's pharmacokinetics, we administered therapeutic doses to patients scheduled to undergo cardiac surgery. METHODS: Preoperative doses of 500,000 and 1,000,000 kallikrein inhibitor units (KIU) were administered as an infusion over 30 min to 28 patients, and plasma concentrations were measured for 48 h. Aprotinin concentrations were determined using a sandwich-enzyme-linked immunosorbent assay. A three-compartment model was fit to the measured aprotinin concentrations using extended nonlinear least-squares regression. RESULTS: Plasma aprotinin concentrations at the end of the 30-min infusion were 147 +/- 61 KIU/ml for the 1,000,000-KIU dose and 60 +/- 19 KIU/ml for the 500,000-KIU dose. Elimination clearance was 35.5 ml/min, and volume of distribution at steady state was 26.5 l. CONCLUSIONS: A 2,000,000-KIU dose is needed to produce the plasma concentration of 200 KIU/ml associated with kallikrein inhibition. Plasma concentrations in excess of 50 KIU/ml, the concentration required to inhibit plasmin, can be achieved by a significantly smaller dose. Based on the derived pharmacokinetic parameters, an infusion model was developed to appropriately administer and maintain effective plasma concentrations of aprotinin, depending on the plasma concentration desired and the target proteases to be inhibited.

Aged↗
PubMed1994

Pharmacokinetics of intravenous milrinone in patients undergoing cardiac surgery.

BACKGROUND: Milrinone is a phosphodiesterase inhibitor with positive inotropic and vasodilator effects that are useful in the treatment of ventricular dysfunction after cardiac surgery. However, the pharmacokinetics of the drug have been investigated only in healthy volunteers and in patients with chronic congestive heart failure. This study investigates the pharmacokinetics of milrinone in adult cardiac surgical patients after cardiopulmonary bypass. METHODS: Milrinone was administered to 25 patients just before or immediately after separation from cardiopulmonary bypass. Arterial blood was sampled over the next 16 h and milrinone plasma concentrations were determined by high-performance liquid chromatography. Data were analyzed by extended nonlinear least-squares regression. The relation between milrinone plasma concentration and hemodynamic effect was examined in an additional 11 patients who had cardiac indices less than 2.5 l.min-1.m-2 immediately after separation from cardiopulmonary bypass. Milrinone was administered and plasma concentrations were related to changes in cardiac index during the next 10 min. RESULTS: A milrinone dose of 50 micrograms/kg in conjunction with an infusion of 0.5 micrograms.kg-1.min-1 consistently maintained plasma concentrations in excess of 100 ng/ml. A triexponential equation describing the plasma concentration as a function of time was used to describe the data. Central-compartment volume was 102 ml/kg, volume of distribution was 1,698 ml/kg, and elimination clearance was 1.88 ml.kg-1.min-1. Pharmacokinetic parameters were independent of dose. The relation between plasma concentration and percentage increase in cardiac index could be described by a sigmoidal curve with the plasma concentration associated with a 50% increase in cardiac index equal to 167 ng/ml. CONCLUSIONS: A milrinone dose of 50 micrograms/kg with an infusion at 0.5 micrograms.kg-1.min-1 maintains plasma concentrations at or above the threshold of therapeutic effects.

Aged↗
PubMed1994

Determination of the hemodynamics and histamine release of rocuronium (Org 9426) when administered in increased doses under N2O/O2-sufentanil anesthesia.

The cardiovascular effects, histamine release potential, and pharmacodynamics of rocuronium were determined in adult patients randomized to receive rapid (5 s) intravenous (i.v.) bolus doses of 600, 900, or 1200 micrograms/kg (2.0, 3.0, and 4.0 times the ED95) with maintenance doses of 150 micrograms/kg. There were no statistically significant hemodynamic effects (heart rate, blood pressure, mean arterial pressure [MAP] or electrocardiogram [ECG]) after administration of rocuronium. There were no increases in plasma histamine levels at 1, 3, and 5 min after the rapid i.v. bolus of rocuronium as determined by a new radioimmunoassay (RIA) with a sensitivity for histamine quantification of 0.05 ng/mL. Endotracheal intubation was successfully performed 6 min after rocuronium administration (and after plasma samples were obtained). The mean +/- SD clinical durations of 600-, 900-, and 1200-micrograms/kg intubating doses of rocuronium under N2O/O2-sufentanil anesthesia were 45 +/- 20 min, 66 +/- 16 min, and 85 +/- 22 min, respectively. We conclude that rocuronium can be administered safely over a wide range of doses (2-4 x ED95), with minimum hemodynamic effects or histamine release.

Adult↗
PubMed1994

Amrinone: its effect on vascular resistance and capacitance in human subjects.

Reports evaluating amrinone's effects in normal (intact) human subjects are complex and difficult to interpret because of the drug's diverse effects on myocardial function, resistance vessels, and vascular capacitance. In this study, 1.5 mg/kg of amrinone was administered as an intravenous bolus to cardiac surgical patients during constant flow cardiopulmonary bypass to determine its isolated effects on venous capacitance and vascular resistance. We noted a significant decrease in vascular resistance up to 8 min after injection and a 460 +/- 160 ml (mean +/- SD) decrease in venous reservoir volume 10 min after injection. Amrinone has potent venous and arterial vasodilating properties that make it a unique drug for treating congestive heart failure in addition to its reported positive inotropic effects.

Amrinone↗
PubMed1994

Treatment of postoperative hypertension after coronary artery bypass surgery. Double-blind comparison of intravenous isradipine and sodium nitroprusside.

BACKGROUND: Hypertension commonly occurs after cardiac surgery and requires therapy to prevent the potentially deleterious effects. METHODS AND RESULTS: After coronary artery bypass graft surgery (CABG), 177 patients with elevated blood pressure > or = 90 mm Hg during the initial 6-hour postsurgical period were selected for this random blinded, parallel study to receive intravenous infusions of either isradipine (n = 90) or sodium nitroprusside (n = 87). Isradipine produced a statistically significant decrease in mean arterial pressure (MAP, delta-23 mmHg) during a 90-minute treatment period. Target MAP (< or = 85 mmHg or a decrease of 10 mmHg, if baseline MAP was between 90 and 95 mmHg) was achieved in 94% of patients 30 minutes after initiation of isradipine infusion (total mean dose, 411 micrograms); target MAP was achieved in 75% of nitroprusside-treated patients (total mean dose, 1708 micrograms). The mean time to control MAP was 18 minutes for isradipine compared with 24 minutes for nitroprusside. Global smoothness in MAP control was graded on a scale of 0 (not controlled) to 5 (excellent). Approximately 76% of isradipine-treated patients received a rating of > or = 3 (mean score, 3.5); 40% of the sodium nitroprusside-treated patients achieved a score of > or = 3 (mean score, 2.0). Both isradipine and nitroprusside produced statistically significant reductions in systolic and diastolic blood pressures, a decrease in systemic vascular resistance, and increases in heart rate, cardiac index, and stroke volume index. Isradipine produced no significant decreases in pulmonary artery occlusion wedge pressure compared with nitroprusside. CONCLUSIONS: Intravenous isradipine was effective and well tolerated in patients with hypertension after CABG and offers an additional therapeutic option to treat patients after cardiac surgery.

Coronary Artery Bypass↗
PubMed1993

Support of the perioperative failing heart with preexisting ventricular dysfunction: currently available options.

Perioperative support of the patient with preexisting biventricular failure requires simultaneous optimal manipulation of heart rate and rhythm, loading conditions, and contractility. Patients with preexisting ventricular dysfunction will have alterations in beta-adrenergic receptors, resulting in decreased responsiveness to catecholamines. Even patients with previously normal ventricular function can develop ventricular dysfunction caused by reperfusion injury and other potentially damaging effects of extracorporeal circulation. The mainstay of therapeutic agents used to allow separation from cardiopulmonary bypass are catecholamines, which stimulate alpha- and beta-adrenergic receptors. Submaximal responses to beta 1-adrenergic stimulation can occur in the down-regulated heart. The phosphodiesterase inhibitors provide both inotropic support and vasodilatation, which improves both systolic and diastolic function and bypasses beta-adrenergic receptors. When administered in combination, catecholamine and cyclic-AMP-specific phosphodiesterase inhibitors can have additive effects to restore beta 1-adrenergic responsiveness. Combination therapy provides an important therapeutic option to facilitate separation from cardiopulmonary bypass. Pharmacologic intervention for right ventricular dysfunction focuses on reversal of pulmonary vasoconstriction with nitrates, beta 2-adrenergic agents, phosphodiesterase inhibitors and prostaglandin E1.

Cardiac Output, Low↗
PubMed1993

Pharmacologic and mechanical methods of discontinuing extracorporeal circulation in patients with heart failure.

Separation from EC requires simultaneous optimal manipulation of heart rate and rhythm, loading conditions, afterload, and contractility. Patients with preexisting ventricular dysfunction will have alterations in beta-adrenergic receptors and responsiveness to catecholamines, but patients with previously normal ventricular function can also develop ventricular dysfunction. Catecholamines, by stimulating beta-adrenergic receptors, decrease systolic function to allow separation from EC. The phosphodiesterase inhibitors provide both inotropic support and vasodilation, to improve both systolic and diastolic function. When administered in combination, catecholamines and cyclic-AMP-specific phosphodiesterase inhibitors can have additive effects to restore beta 1-adrenergic responsiveness. Combination therapy provides an important support during biventricular dysfunction and facilitates separation from EC. Finally, mechanical support provides a therapeutic option when pharmacologic therapy is ineffective.

Cardiac Output, Low↗