PubMed Health⌕ Search

Biomedical subjects

E B Grossbard

Publications and source records attributed to E B Grossbard.

13 recordsLinked to original sources
PubMed1998

Pharmacokinetics and biological actions of subcutaneously administered human brain natriuretic peptide.

Human brain natriuretic peptide (hBNP) has demonstrated favorable hemodynamic effects in patients with congestive heart failure; however, the peptidic nature of this compound has focused clinical testing on protocols involving intravenous delivery. We have studied subcutaneous delivery as an alternative method of administering hBNP. Administration of 30 microgram/kg hBNP by either subcutaneous or intravenous delivery protocols resulted in significant hBNP-immunoreactive material in the plasma with area under the plasma concentration-time curve values of 310 +/- 20 nmolxmins/liter and 187 +/- 47 nmolxmins/liter, respectively. Plasma cyclic GMP, a surrogate marker of activation of the biological receptor for hBNP, was elevated for a longer period of time following subcutaneous delivery compared with intravenous delivery. Subcutaneous delivery of 30 microg/kg hBNP resulted in natriuresis, diuresis and reduced systolic blood pressure in anesthetized normotensive rabbits, effects similar in magnitude yet prolonged in duration compared with those elicited by the same dose of hBNP delivered intravenously. Systolic blood pressure following hBNP treatment remained below base-line values for 50 and 150 min following intravenous and subcutaneous delivery protocols, respectively. These results suggests that subcutaneous delivery of hBNP may be a viable therapeutic alternative to intravenous modes of delivery.

Amino Acid Sequence↗
PubMed1997

Human brain natriuretic peptide reduces blood pressure in normotensive and acute norepinephrine-induced hypertensive rabbits.

Human brain natriuretic peptide (hBNP) is a cardiac-derived peptide hormone with potent hemodynamic and renal effects in dogs, monkeys, and humans, but not in rats. At present there is no small animal model to study the actions of hBNP. These studies describe the effects of hBNP in New Zealand White rabbits in normotensive and acute norepinephrine-induced hypertensive states. Intravenous administration of hBNP (1, 3, 10, and 30 microg/kg) to anesthetized rabbits resulted in a dose-dependent diuresis and natriuresis and a decrease in systolic blood pressure. Bolus administration of hBNP resulted in a time- and dose-dependent accumulation of plasma cyclic GMP, consistent with activation of a particulate guanylyl cyclase receptor. The hemodynamic actions of hBNP suggest clinical utility for the management of acute hypertension associated with numerous surgical procedures, a condition linked to catecholamine activation. In rabbits with norepinephrine-induced acute hypertension, bolus and continuous infusion of hBNP markedly reduced blood pressure. These studies demonstrate that the rabbit is a useful species to study the hemodynamic and renal effects of hBNP and that this peptide may have therapeutic utility for the acute reduction of hypertension associated with catecholamine activation.

Animals↗
PubMed1996

Hemodynamic effects of a single intravenous injection of synthetic human brain natriuretic peptide in patients with heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

Synthetic human brain natriuretic peptide (sBNP) is a polypeptide with the same amino acid sequence as the naturally occurring hormone. Preclinical studies have demonstrated that BNP has potent hemodynamic, diuretic, and natriuretic effects that might be beneficial in treating patients with heart failure. This study was a randomized, double-blind, placebo-controlled, ascending-dose trial of sBNP administered as a single intravenous bolus in 27 heart failure patients. Six groups of patients received sequentially increasing doses of sBNP (0.3, 1, 3, 10, 15, and 20 micrograms/kg, respectively) as a single intravenous injection, and hemodynamics were assessed by pulmonary artery monitoring catheter. The 10 and 15 micrograms/kg doses of sBNP resulted in significant reductions in pulmonary capillary wedge pressure (-73%, p < 0.001), mean pulmonary artery pressure (-41%, p < 0.001), mean arterial blood pressure (-28%, p = 0.001), and systemic vascular resistance (-53%, p = 0.004). Significant increases occurred in cardiac index (68%, p < 0.001) and stroke volume index (72%, p < 0.001). The magnitude and duration of hemodynamic changes were dose dependent. There were no adverse effects. sBNP injected as a single intravenous bolus in heart failure patients improves hemodynamics in a dose-related fashion. Further clinical investigations to determine the use of sBNP in decompensated heart failure are clearly warranted.

Cardiomyopathy, Dilated↗
PubMed1994

A perfluorochemical emulsion for prehospital resuscitation of experimental hemorrhagic shock: a prospective, randomized, controlled study.

OBJECTIVE: To evaluate the efficacy of a novel, oxygen-transporting perfluorochemical emulsion as a prehospital therapy, using a canine hemorrhagic shock model based on compromised tissue oxygenation. DESIGN: Prospective, randomized, controlled study. SETTING: HemaGen animal laboratory. SUBJECTS: Sixteen healthy, adult male grade beagles (weight 8 to 14 kg). INTERVENTIONS: Administration of lactated Ringer's solution (n = 8), 15 mL/kg and perfluorochemical emulsion admixed with physiologic salts (n = 8), 15 mL/kg. MEASUREMENTS AND MAIN RESULTS: PaO2 increased significantly (p < .01) in the perfluorochemical-treated animals for 2 hrs after resuscitation. Mixed venous PO2 returned to preshock values in the perfluorochemical-treated dogs for 60 mins after fluid administration (p < .01). Normalization of hemodynamic variables was not observed in either group. Although not statistically significant, survival of the lactated Ringer's solution-treated animals was 63% compared with 100% for the perfluorochemical-treated dogs at 3 hrs after resuscitation. CONCLUSIONS: Resuscitation with a perfluorochemical emulsion augmented oxygen transport and restored global tissue oxygenation after massive hemorrhage, which translated into improved survival when compared with the group receiving an equal volume of lactated Ringer's solution.

Animals↗
PubMed1990

Low incidence of antibodies to recombinant human tissue-type plasminogen activator in treated patients.

Sera from over 1,600 patients who received recombinant human tissue plasminogen activator (rt-PA) during clinical trials were assessed for the presence of antibodies to this therapeutic agent. The rt-PA was administered by a variety of dosage regimens for several different indications. Two different forms of rt-PA were used; one was predominantly two chain form, and the other was a predominantly one chain form. A sensitive radioimmunoprecipitation assay was used to measure antibodies to rt-PA in patients' serum before and after treatment. Of 932 patients tested with this assay, 929 were negative for antibodies to t-PA. Three patients developed low titers after treatment. Additional serum samples were obtained from these three patients within 2 years after rt-PA therapy and were negative for antibodies to t-PA. With the limited number of positive samples, no correlation could be found with dose or type of rt-PA, dosing regimen or clinical diagnosis. The virtual absence of antibody formation was confirmed in an additional 754 patients using a novel competitive two-site ELISA. It can be concluded that a single infusion of rt-PA was virtually unassociated with antibody formation, suggesting that repeat treatments could be given when necessary without the risk of immunologic complications as are seen with streptokinase or its derivatives.

Animals↗
PubMed1987

A multicenter, randomized, placebo-controlled trial of a new form of intravenous recombinant tissue-type plasminogen activator (activase) in acute myocardial infarction.

A new, predominantly single chain preparation of recombinant tissue-type plasminogen activator was evaluated to determine coronary thrombolytic efficacy in 100 patients with acute myocardial infarction. At 3.6 +/- 1.2 hours (mean +/- SD) from symptom onset, patients received either intravenous tissue plasminogen activator (1.25 mg/kg body weight over 3 hours) or placebo on a 3:1 randomized, double-blind basis. Coronary angiography, performed 68 +/- 13 minutes after initiation of the study drug infusion, demonstrated patency of the infarct-related artery in 40 (57%) of 70 patients in the tissue plasminogen activator group compared with 3 (13%) of 23 patients in the placebo group (p less than 0.001). Patients in the placebo group were then eligible to receive intracoronary streptokinase. At 90 minutes the patency was observed in 49 (69%) of 71 tissue plasminogen activator patients compared with 5 (24%) of 21 placebo patients (p less than 0.001). At 120 minutes patency was observed in 59 (79%) of 75 patients of the tissue plasminogen activator group and in 10 (40%) of 25 in the intracoronary streptokinase/placebo group. A nadir value of less than 100 mg/dl fibrinogen occurred in 8 (11%) of 73 patients receiving tissue plasminogen activator versus 8 (40%) of 20 patients treated with intracoronary streptokinase (p = 0.002). Moderate or severe bleeding episodes occurred in 39% of patients treated with tissue plasminogen activator compared with 32% of patients who received placebo/intracoronary streptokinase (p = NS). Thus, this tissue plasminogen activator preparation achieves a high rate of recanalization and, at the doses employed, exhibits increased fibrinogen sparing compared with intracoronary streptokinase.

Angiography↗
PubMed1987

Recombinant tissue plasminogen activator: a brief review.

Thrombolytic therapy has received renewed attention with the demonstration that early treatment of acute myocardial infarction with plasminogen activators can reduce mortality. Tissue plasminogen activator (t-PA) is a protein with attributes that may allow for greater efficacy and safety. Recombinant DNA technology has enabled the production of sufficient t-PA, called rt-PA (Activase), for substantial clinical evaluation. The results suggest that Activase is a significant advance in thrombolytic therapy.

Humans↗
PubMed1986

Recombinant human tissue-type plasminogen activator for thrombolysis in peripheral arteries and bypass grafts.

Recombinant human tissue-type plasminogen activator (rt-PA) was infused intraarterially at 0.1 mg/kg/h for 1-6 1/2 hours in 25 patients with lower extremity thromboembolic occlusions (13 thrombosed arteries, 12 thrombosed bypass grafts). Occlusion duration ranged from 1 hour to 21 days. Thrombolysis occurred in 23 of 25 patients (92%). Time to lysis varied from 1 to 6.5 hours, with an average time of 3.6 hours. Twenty of 23 patients (87%) in whom thrombolysis was successful benefited clinically from thrombolytic therapy. Twelve of 23 patients (52%) required secondary procedures to maintain arterial segment patency. In 15 of 25 patients (60%) fibrinogen levels were maintained above 50% of baseline values. No major complications directly attributable to rt-PA infusions occurred. rt-PA is a potent, relatively fibrin-specific thrombolytic agent that can achieve rapid thrombolysis while usually avoiding the profound systemic fibrinogenolysis associated with currently available thrombolytic agents.

Adult↗
PubMed1986

Acute coronary reocclusion after thrombolysis with recombinant human tissue-type plasminogen activator: prevention by a maintenance infusion.

Twenty-nine patients with acute myocardial infarction were treated with recombinant human tissue-type plasminogen activator (rt-PA). The incidence of acute coronary reocclusion and its prevention by a maintenance infusion of rt-PA were studied. Intravenous rt-PA was given at a rate of 0.4 to 0.75 mg/kg over 60 to 120 min after angiographic documentation of complete coronary occlusion. Reperfusion was accomplished within 1 hr in 24 of 29 patients (83%) and was associated with a decrease of the plasma fibrinogen level by 20%. In a first group of 13 patients, 11 of whom were successfully reperfused, prevention of reocclusion was attempted with heparin anticoagulation. However, acute reocclusion within 1 hr after cessation of rt-PA was demonstrated angiographically in five of these patients (45%). Quantitative angiographic analysis indicated that acute reocclusion only occurred in patients with 80% or greater residual stenosis. In patients with less than 80% residual stenosis, heparin anticoagulation was sufficient to maintain patency during the hospital stay in four of five patients. In a second group of patients (n = 16), 13 of whom underwent reperfusion with intravenous rt-PA, seven demonstrated a residual stenosis of 80% or greater. These patients were given heparin and, in addition, 10 mg of rt-PA per hour for 4 hr. None developed acute angiographic reocclusion or clinical signs of reocclusion during the hospital stay. Repeat angiography at 10 to 14 days confirmed persistent patency in six of the seven patients. The maintenance infusion resulted in only a moderate additional drop in fibrinogen, while a steady-state plasma rt-PA level of 750 +/- 250 ng/ml was maintained.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗
PubMed1986

Thrombolysis with recombinant human tissue-type plasminogen activator in patients with peripheral artery and bypass graft occlusions.

Thirty-three patients with thrombosed peripheral arteries and bypass grafts, as confirmed by angiography, were treated with recombinant human tissue-type plasminogen activator (rt-PA). Twenty-six patients were treated with a dose of 0.1 mg/kg/hr and seven patients with 0.05 mg/kg/hr. Thrombus lysis and clinical improvement occurred in 22 of 26 (85%) patients in the 0.1 mg/kg/hr group. In seven of seven (100%) patients in the 0.05 mg/kg/hr group angiographic as well as clinical improvement were observed. Fifteen of the 33 patients required anticoagulation to maintain patency. Sixteen required secondary procedures to maintain patency. One (3%) patient required a blood transfusion for a hematoma at the catheter entry site. Three other patients developed small hematomas that were controlled without transfusion or intervention. Sixty-one percent of patients treated with the 0.01 mg/kg/hr dose and 86% of patients treated with the 0.05 mg/kg/hr dose maintained fibrinogen levels greater than 50% of their initial values. Infusion durations ranged from 1 to 6 hr (mean 3.9 hr). rt-PA appears to be a potent and selective thrombolytic agent that rapidly and safely lyses thrombi in peripheral arteries and occluded bypass grafts.

Adult↗