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At least 307 records · Page 17Linked to original sources
PubMed1987

Nucleotide sequence of a bovine protamine cDNA.

The nucleotide sequence of a 441-base cDNA encoding the bovine protamine has been determined. This insert, isolated from a bovine spermatid-specific cDNA library, encodes a polypeptide of 50 amino acids of which 26 are arginine, 7 are cysteine, and 2 are tyrosine. The insert contains the complete 3'-noncoding region of 150 bases and most of the 5'-noncoding region. The predicted amino-acid sequence of bovine protamine is about 96% homologous to ram protamine, 76% to boar protamine, 64% to mouse protamine 1 and 52% to human protamine 1 and contains the central, highly basic domain of four arginine clusters found in the trout protamines. Our results show that bovine protamine is 50 amino-acid residues in length and not 47 residues as previously published (Coelingh, J.P. et al. (1972) Biochim. Biophys. Acta 285, 1-14).

Animals↗
PubMed1999

Effects of protamine on nitric oxide level in the pulmonary circulation.

Protamine reversal of heparin anticoagulation often causes systemic hypotension by releasing nitric oxide (NO) from vascular endothelium. We investigated the hypothesis that protamine prevents severe pulmonary vasoconstriction by increasing NO. Twenty patients undergoing elective coronary artery bypass graft surgery were included in the study. Nitrite and nitrate levels--as end-metabolites of NO--were measured in blood samples obtained before and after protamine administration. Mean arterial pressure, heart rate, mean pulmonary artery pressure, central venous pressure and left atrial pressure were noted as hemodynamic data. Nitrite levels were 4.64 +/- 0.67 mumol in the right atrium and 4.84 +/- 0.95 mumol in the left atrium before protamine administration. The difference was insignificant statistically. These measurements were 4.85 +/- 0.92 in the right atrium and 5.28 +/- 0.66 mumol in the left atrium after protamine administration. This increase was significant (p < 0.05). The measurements of nitrate levels were completely parallel with those of nitrite. Mean arterial pressures were 78.9 +/- 7.59 mm-Hg before protamine and 74.1 +/- 8.55 mm-Hg after protamine (p = 0.03). The changes in other hemodynamic parameters were not significant. Protamine augments NO production and prevents the pulmonary circulation from possible vasoconstriction.

Aged↗
PubMed1999

Protamine enhances the efficiency of liposome-mediated gene transfer in a cultured human hepatoma cell line.

Protamine, used clinically as an antidote for heparin, is a small protein with high arginine content and is potent in folding DNA. Protamine and DNA can form a compact structure, protecting DNA from digestion by intracellular enzymes. Protamine may, therefore, enhance the efficiency of gene transfer. In this study, we tested the ability of protamine to improve liposome-mediated gene transfer efficiency in a human hepatoma cell line. The results of a preliminary gel retardation assay indicated that 10 micrograms was the minimal amount of protamine sulfate needed to completely bind 5 micrograms of a plasmid containing a reporter gene, green fluorescent protein (GFP). For transfection assays, protamine (0, 10, 50, 100, and 500 micrograms) was added to a DNA-liposome mixture (5 micrograms DNA and 20 micrograms of a mixed formulation of 2,3-dioleyloxy-N-[2(sperminecarboxamido)ethyl]-N, N-dimethyl-1-propanaminium trifluoroacetate and dioleoylphosphatidylethanolamine) to transfect cultured Huh7 cells. Transfected cells (those expressing GFP) were counted by using flow cytometry. The expression index (EI) was calculated as the transfection efficiency (% of transfected cells) with protamine divided by the transfection efficiency with DNA and liposome only. Our results show that protamine sulfate (in a range of 10-100, 10 micrograms being most efficient) addition to the liposome-DNA mixture significantly increases the EI, and transfection efficiency of GFP in Huh7 cells.

Animals↗
PubMed2001

A four-year experience with patient individualized heparin and protamine dosing using the Hemochron RxDx system.

Cardiac surgical case histories, collected over 4 years at Huntsville Hospital in Alabama, were reviewed for 2,293 patients. Patients were separated into two dosing groups for both heparin and protamine, hospital empirically dosed and Hemochron RxDx dosed. Review of the heparin dosing information found that incomplete data were collected for 47 patients, leaving 2,246 patients eligible to be evaluated for heparin dose comparison. Both RxDx recommended and empirically calculated doses were recorded, as well as the actual dose given. Of the 2,246 patients, 1671 were administered heparin according to the RxDx calculated dose, and the remaining 575 patients were dosed according to the hospital's empirical protocol. The average RxDx calculated heparin dose was 17% greater then the empirically calculated heparin dose (350 U/kg) (p < .001). Anticoagulation to target ACT (480 sec) was achieved in 92% of the patients dosed according to the RxDx recommended dose; whereas, in the empirically dosed patient group only 80% of the patients reached the target ACT after initial heparin bolus dose. Incomplete protamine dosing data was recorded for 336 patients, leaving a total of 1,957 patients available for protamine dose evaluation. All patients had an RxDx protamine calculation, empirical protamine calculation, and actual amount of protamine dosed recorded. Of the 1,953 patients, 1,764 were dosed according to the RxDx recommended dose, with the remaining 189 patients dosed empirically (1 mg protamine/100 U of heparin). In both the RxDx and the empirical groups, 96% of the patients returned to baseline following initial protamine infusion. The overall RxDx dose (293 mg) was 16% lower than the average empirical dose (348 mg). The RxDx system has been shown to be an effective method for determining patient-specific dosing for both heparin and protamine. This long-term clinical experience demonstrates the consistency and reliability of patient maintenance using this individualized dosing system, which has been shown, in other independent evaluations, to lead to improved patient outcomes.

Analysis of Variance↗
PubMedDate not supplied

Altered protamine 2 expression is uncommon in donors of known fertility, but common among men with poor fertilizing capacity, and may reflect other abnormalities of spermiogenesis.

During the spermatid elongation stage of spermiogenesis approximately 85% of sperm nuclear histones are replaced by protamines. Protamines increase the packing ratio of sperm chromatin, presumably facilitating sperm motility and function. In this study we evaluated the incidence of abnormal protamine expression in 75 patients undergoing in vitro fertilization (IVF) and 50 donors of known fertility by isolation of sperm nuclear proteins, quantitative gel electrophoresis, and Western blot analysis. In addition, we evaluated the relationship between abnormal protamine expression and semen quality, sperm penetration ability, chromatin stability, and IVF outcome. Seventeen percent (13/75) of IVF patients had no measurable protamine 2 (P2) versus 0% (0/50) of donors of known fertility (P < .005). Sperm penetration rates were decreased in 12 of 13 patients without P2, and mean penetration rates (4.6 +/- 1.2 vs 32.8 +/- 2.9, P < .005), normal morphology (22.4 +/- 3.6 vs 48.7 +/- 4.2, P < .05), and progressive motility (22.3 +/- 2.5 vs 35.4 +/- 2.1, P < .05) were all significantly decreased compared with patients with measurable P2. The mean sperm concentration was not significantly different. The presence of protamine precursor bands was also associated with a diminished penetration capacity (18.4 +/- 2.8 vs 36.7 +/- 3.0, P < .05). Sperm chromatin decondensation following exposure to heparin sulfate was significantly increased in patients without a measurable P2 band. Twelve patients with no measurable P2 underwent intracytoplasmic sperm injection (ICSI), with 6 patients (6/12, 50%) becoming pregnant. ICSI fertilization and subsequent embryo cleavage were not different in patients without P2 compared with other patients undergoing ICSI. These data indicate that abnormal sperm protamine levels are a common defect in infertility patients, but not in donors of known fertility. It appears that abnormal protamine levels may reflect defects of late spermiogenesis, including sperm penetration capacity.

Anticoagulants↗
PubMed2004

[Effect of casein and protamine on the enzymatic degradation and the orally hypoglycemic action of insulin].

AIM: To study the protection of casein and protamine against degradation of insulin (INS) by proteolysis enzymes and the effect of these two kinds of protein on the hypoglycemic action of INS solution and enteric-microspheres after administrated orally to rats. METHODS: HPLC was used to determine the remained INS in the solution of alpha-chymotrypsin and trypsin with or without casein or protamine; INS solution and enteric-microspheres were prepared and adiministrated orally to rats together with the absorption enhancer sodium N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC). At the same time, casein or protamine or both of these two kinds of protein were administrated together in order to study their influence on the hypoglycemic effect of INS and microspheres. RESULTS: Casein had a good protection against degradation of INS by alpha-chymotrypsin, but protamine had no protection effect. However, the degradation of INS by trypsin is concerned, the protection effect of protamine on INS was better that of casein. Both of protamine and casein can increase the hypoglycemic effect of INS solution and enteric-microspheres. Co-administrated these two kinds of protein had a better effect. In addition, co-administrated with SNAC, casein and protamine, INS enteric-microspheres had a longer and more potent hypoglycemic effect than that of the solution. CONCLUSION: Casein and protamine can increase the stability of INS in the intestinal fluid by the mechanism of competition and combine with proteolysis enzymes, which will benefit to INS oral administration.

Administration, Oral↗
PubMed1992

Heparin-mediated reductions of the toxic effects of protamine sulfate on rabbit myocardium.

Protamine sulfate causes direct myocardial suppression when used to reverse heparin anticoagulation. Protamine's excessive positive charge accompanying its surface arginine groups appears to be responsible for this toxicity. This study was designed to assess the hypothesis that negatively charged heparin given after protamine exposure may enhance the recovery of protamine-induced myocardial dysfunction. Isolated rabbit hearts (n = 20) were perfused with physiologic saline solution at 80 to 90 mm Hg containing high dose protamine, 250 micrograms/ml, until heart contraction essentially ceased (baseline). Hearts were then randomly reperfused for 15 minutes with either physiologic saline solution (group I, n = 10) or heparin plus physiologic saline solution (group II, n = 10) at a dose of 0.1 IU/1.0 microgram of previously administered protamine. Developed left ventricular blood pressure, heart rate, pulmonary artery PaO2, contractility (+dp/dt), oxygen extraction (AvO2), oxygen consumption (VO2), and rate x pressure product were assessed. A protective, beneficial response accompanied heparin administration (group II) in all functions assessed except blood pressure. Maximum changes, comparing group I with II, were heart rate (beats/min) -72 versus -1, p less than 0.001; +dp/dt -64% versus -51%, p less than 0.01; PaO2 +86% versus +9%, p less than 0.001; AvO2 -37% versus -4%, p less than 0.001; VO2 -50% versus -28%, p less than 0.008; and rate x pressure product -73% versus -51%, p less than 0.001. These data suggest a separation of protamine's hemodynamic effects (blood pressure) and metabolic effects (VO2). Furthermore, these data support the tenet that heparin is able to markedly lessen the toxic myocardial effects of protamine.

Animals↗
PubMed2006

[A case of anaphylactic shock in an elderly man following protamine sulfate administration during emergent off-pump coronary artery bypass grafting].

An 80-year-old diabetic man undergoing emergent off-pump coronary artery bypass grafting for acute myocardial infarction developed anaphylactic shock immediately following administering a small dose of protamine sulfate. Preoperative examination revealed atrial fibrillation, severe three-vessel coronary artery disease and impaired left ventricular function with ejection fraction of 40% and severe septal as well as apical hypokinesis and akinesis. After successful completion of coronary bypass grafting, a total of 40 mg of protamine sulfate was given through the central venous line. Three minutes after protamine administration, profound hypotension occurred. Pulmonary artery pressure was low and the left ventricle was almost empty by transesophageal echocardiography. Hypotension was refractory to rapid administration of 2 l of crystalloid and albumin, and repeated administrations of phenylephrine. Blood pressure finally returned towards baseline after infusion of norepinephrine 0.2 microg x kg(-1) x min(-1) and epinephrine 0.1 microg x kg(-1) x min(-1). Hemoconcentration and impaired oxygenation were also noted. The situation suggested anaphylactic shock due to protamine. He had diabetes mellitus for 20 years and been treated by protamine containing insulin. Postoperative interview revealed that the patient had experienced urticaria over the abdominal area with neutral protamine hagedorn (NPH) insulin administration. This history suggested that the patient had been sensitized by protamine before surgery. Although it is rare to experience anaphylactic shock due to protamine, it is important to elicit the detailed allergic history to insulin in diabetic patients. Because anaphylactic shock still carries high mortality even in a patient without cardiac disease, we were lucky to save this elderly patient with acute myocardial infarction and compromised left ventricular function.

Aged, 80 and over↗
PubMed1989

A facile colorimetric protamine titration method.

On the basis of the reversible, competitive binding of protamine and azure A dye to heparin, a facile, colorimetric protamine titration method was developed. The method uses azure A dye as the titration indicator and has thus replaced the time-consuming clotting assay in the traditional protamine titration method with a rapid colorimetric assay. It offers the same accuracy in estimating the titration end point as the traditional titration method but allows the processing time to be significantly shortened. With the use of a premade diagnostic kit containing a fixed amount of azure A dye and various amounts of protamine, the titration end point can be determined in less than 5 minutes. This new colorimetric protamine titration method should provide clinicians with an easy and reliable means to accurately estimate the protamine dose required for heparin neutralization. It should also assist medical laboratories in preparing plasma samples that are free of heparin interference for routine coagulation tests. In a reverse manner, the colorimetric assay can also be used with a heparin titration procedure to quickly assess the heparin dose required for protamine reversal. For patients who have received overdoses of protamine, the availability of a facile heparin titration method may offer the prospect of exercising a heparin "back titration."

Azure Stains↗
PubMed1989

Protamine-induced reductions of endothelial cell ATP.

Protamine, a polycationic protein used to reverse heparin anticoagulation, is frequently associated with decreased oxygen consumption, systemic hypotension, pulmonary artery hypertension, and bradycardia. This investigation examines the hypothesis that these events reflect toxic effects of protamine on endothelial cells. Cultured bovine pulmonary artery endothelium was exposed to protamine (12.5 to 500 micrograms/ml, corresponding to clinical doses 0.75 to 30 mg/kg), either alone (n = 6) or 3 minutes after exposure to heparin, 0.1 IU/microgram protamine (n = 6). ATP was measured 1 to 180 minutes after protamine by a luciferase-luciferin assay and cell viability determined by trypan blue exclusion. Ultrastructure was assessed by transmission electron microscopy. Polylysine, 25 micrograms/ml, a cytotoxic polycationic agent, was also studied. Dose-dependent reductions in ATP (range, -11% to -51%) and ATP per viable cell (up to -41%) occurred. Decreases in ATP did not occur until after 30 minutes with protamine alone, compared with differences as early as 1 minute after protamine with prior heparin. Progressive mitochondrial injury was noted evident by swollen cristae, vacuolization, and eventual disruption. Polylysine caused similar changes. Protamine decreases endothelial cell ATP and prior heparin exposure accelerates this effect. The toxicity may reside in the positive charges on these molecules and mitochondrial damage may account for reductions in cellular ATP and systemic oxygen consumption.

Adenosine Triphosphate↗
PubMed1988

The pulmonary microcirculation of the rat: differential ultrastructural responses of the endothelia to protamine sulfate.

Protamine sulfate is used clinically to reverse the anti-coagulant effects of heparin and in certain cases high protein, non-cardiogenic pulmonary edema develops. In the present study an initial stage of edema formation, namely, interstitial fluid accumulation around partially muscular extra-alveolar microvessels was observed in rats in situ after right ventricular injections of protamine. In addition, the endothelium of these microvessels displayed marked increases in plasmalemmal vesicles; however, disruption of the endothelium was not observed. Further, endothelial vesicle densities were unchanged and perivascular cuffs were not observed in either the nonmuscular extra-alveolar microvessels or the alveolar capillaries. Left ventricular injections of protamine failed to elicit the ultrastructural responses to protamine. Predosing the pulmonary microcirculation with heparin also served to prevent protamine-induced changes in the partially muscular microvessels. If it is assumed that heparin lowers the threshold for protamine-mediated responses in patients who develop edema, inhibition of protamine-induced changes by heparin predosing cannot be explained by the present data. Although evidence of increased endothelial vesiculation in the partially muscular microvessels was obtained, relative contributions of vesicles or of the junctional clefts to efflux from the pulmonary microvessels is not known. Thus, the mechanisms associated with a reduction of endothelial selectivity to macromolecular efflux after protamine administration remain to be defined.

Animals↗
PubMed1988

The binding mode of a mammalian (boar) protamine to DNA.

The binding modes of mammalian and fish protamines to DNA were studied by reconstitution experiments from dansylated protamines and DNA, using fluorescence spectroscopy, thermal denaturation and sedimentation. Both boar and fish protamines showed strong positive cooperativity in binding to DNA. Binding parameters of the protamines were determined in 0.1 M NaCl, 50 mM Tricine-HCl, pH 7.4, at 37 degrees C: in the boar protamine, the cooperative binding constant (Kc) = 3.4 X 10(6) M-1 and the cooperative factor (q) = 667, in the fish protamine, Kc = 1.8 X 10(7) M-1 and q = 304. The boar protamines bound to DNA with two functional domains, but the fish protamines bound directly to DNA as a single linear molecule.

Animals↗
PubMed1986

Attenuation of hemodynamic and hematologic effects of heparin-protamine sulfate interaction after aortic reconstruction in a canine model.

This investigation documented the effect of protamine sulfate pretreatment on the adverse hemodynamic and hematologic sequela of rapid intravenous protamine administration in heparinized dogs having undergone prior implantation of aortic prostheses. Fourteen dogs underwent infrarenal aortic replacement with 6 mm inner diameter by 7 cm knitted Dacron double-velour grafts. Carotid arterial, central venous, and pulmonary arterial catheters were placed for continuous hemodynamic monitoring. All dogs were adequately anticoagulated with heparin (150 IU/kg) and reversed with protamine (1.5 mg/kg/10 sec) after graft insertion. Pretreatment regimens studied included normal saline (n4), protamine 0.75 mg/kg (n5), and protamine 2.25 mg/kg in three divided doses of 0.75 mg/kg each (n5). All pretreatment agents were administered 3 minutes before heparinization. Blood pressure (BP), heart rate (HR), pulmonary artery pressure (PAP) and cardiac output (CO) were measured. Hematologic assessments included platelet count (PC), leukocyte count, thrombin clotting time, and total hemolytic complement. Significant salutory effects were associated with protamine pretreatment regarding BP, HR, PAP, CO, and PC. It is concluded that adverse hemodynamic effects of protamine reversal are blocked and certain hematologic effects are reduced with protamine pretreatment before heparinization and its reversal in this canine experimental model.

Animals↗
PubMed1985

Protamine-induced fatal anaphylaxis. Prevalence of antiprotamine immunoglobulin E antibody.

Protamine is used widely to reverse the anticoagulant effects of heparin and to delay the absorption of insulin. Although adverse reactions to protamine are reported infrequently and are usually mild, we recently observed the first fatal case of type I anaphylaxis resulting from protamine. This patient had previously been sensitized to protamine during cardiac catheterization and had high levels of protamine-specific immunoglobulin E in the serum. In a prospective study, we found that 10 of 19 diabetic patients (53%) who had received insulin containing insulin also had high levels of antiprotamine immunoglobulin E. In contrast, none of 27 nondiabetic healthy normal controls or 10 diabetics who had never received protamine or protamine-containing insulin had levels of antiprotamine immunoglobulin E over background. This study underscores the risks of routinely administering protamine to susceptible individuals and the need for alternative therapies.

Adolescent↗
PubMed1986

Hemodynamic changes after the administration of protamine.

Hemodynamic changes associated with the administration of protamine were studied in 30 dogs divided into three equal groups. Protamine (1 mg X kg-1 X min-1 for 4 min) was administered 10 min after 4 mg X hg-1 heparin was given via a left atrial (LA) line in group A, via a central vein in group B, and via a peripheral vein in group C. Protamine given through the central venous pressure (CVP) line resulted in an immediate and significant decrease in mean arterial pressure (MAP) to 60 +/- 4.5 mm Hg (P less than 0.025) from 72 +/- 7 mm Hg immediately after the protamine and to 58 +/- 5 mm Hg (P less than 0.025) 5 min later and with an increase in cardiac index (CI) to 3.7 +/- 0.3 L X min-1 X m-2 from 2.8 +/- .25 L X min-1 X m-2 immediately after the protamine (P less than 0.005), followed by a decrease back to 2.7 +/- 0.3 L X min-1 X m-2 5 min later. Mean arterial pressure and CI remained unchanged after administration of protamine via the peripheral vein or the left atrium. Systemic vascular resistance (SVR) decreased significantly only after administration of protamine via the CVP and was statistically unchanged when administered via the peripheral and LA line. Plasma histamine levels increased significantly after administration of protamine through the central line but remained unchanged after administration via a peripheral vein or the left atrium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Cardiovascular effects of protamine sulfate are dependent on the presence and type of circulating heparin.

Man's response to clinical doses of protamine is highly variable. We investigated the influence of circulating heparin in nine swine (mean age 6 weeks, weight 10 kg). Through a sternotomy we implanted an electromagnetic flow probe around the pulmonary artery for cardiac output determination and catheters into the ascending aorta, pulmonary artery, right atrium, and left atrium for pressure monitoring. Each animal was allowed to recover and was studied awake on 3 consecutive days. Protamine, 3 mg/kg, beef lung heparin, 300 U/kg, and pork mucosal heparin, 300 U/kg, followed by protamine, were given in rotation by intravenous bolus. Protamine alone had no effect. Beef lung heparin followed by protamine induced a marked increase in pulmonary artery pressure (mean 38 +/- 3 to 51 +/- 5 mm Hg in 3 minutes). Pulmonary vascular resistance doubled (mean 0.12 +/- 0.01 to 0.23 +/- 0.04 R within 4 minutes), returning to normal within 15 minutes. Cardiac index and aortic pressure changed minimally. Pork mucosal heparin followed by protamine induced a similar but greater increase in mean pulmonary arterial pressure; however, cardiac index fell significantly (p less than 0.05, 207 +/- 16 to 117 +/- 16 ml/kg/min-1 at 1 minute) despite a regular rhythm and adequate left atrial filling pressure. Thus cardiac contractility was depressed. Systemic hypotension occurred in three of nine pigs. Both mean pulmonary vascular resistance and systemic vascular resistance increased (0.12 +/- 0.01 to 0.67 +/- 0.25 R and 0.40 +/- 0.04 to 1.09 +/- 0.25 R, respectively), significantly (p less than 0.05) more with pork than beef heparin. These data demonstrate that cardiovascular response to protamine neutralization varies significantly in regard to the type of heparin used. Furthermore, circulating heparin is required to produce those effects previously attributed to protamine alone.

Animals↗
PubMed1983

Hemodynamic changes during protamine administration.

Hemodynamic responses to intravenous protamine sulfate in 40 patients were evaluated. The dose of protamine administered was calculated as adequate to reverse residual heparin as measured by the activated clotting time (ACT). Thirty patients (n = 30) received protamine at a rate of 0.5 mg/kg/min and the remainder (n = 10) received protamine at a rate of 1 mg/kg/min. Hemodynamic measurements were made before protamine, at 5-min intervals during administration, and 5 min after completion of the infusion. No statistically significant changes in cardiac output, systemic arterial blood pressure, or vascular resistance were seen when protamine was administered to patients with good left ventricular function after cardiopulmonary bypass. However, in patients with poor left ventricular function after cardiopulmonary bypass, protamine infusion was associated with systemic vasodilation that was only partially compensated for by an increase in cardiac index, resulting in a 12% decrease in mean blood pressure (P less than 0.05). Thus protamine should be administered cautiously to patients who have poor left ventricular function after cardiopulmonary bypass.

Adult↗
PubMed1984

Protamine-induced circulatory changes.

The effects of rapid protamine administration via the left and right atria were compared. Preliminary studies first confirmed the safety of protamine administration via these routes, although decreases of up to 20 mm Hg were seen in the systolic blood pressure following protamine injection via the right atrium. Seventeen patients undergoing coronary artery bypass graft were studied, of whom nine received protamine via the right atrium and eight via the left atrium. Measurements of arterial pressure, left and right atrial pressure, cardiac output, and calculation of systemic vascular resistance and left ventricular stroke work index were made before and after protamine administration. Plasma histamine levels were measured in left atrial blood samples in 10 patients, before and after protamine injection. No significant change occurred after injection via the left atrial route, whereas a significant decrease in the systolic blood pressure and systemic vascular resistance with a transient increase in the cardiac index occurred after protamine administration via the right atrium. Plasma histamine levels were significantly higher after right atrial injection. It is concluded that histamine is released as protamine traverses the lungs following right atrial injection and produces peripheral vasodilation. Possible mechanisms for histamine release are discussed.

Aged↗