Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Protamines”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 595 records · Page 33Linked to original sources
PubMedDate not supplied

[Interaction of fibrinogen and fibrin with protamine sulfate].

Fibrinogen and fibrin sedimentation by different protamine sulphate preparations have been studied. Ionic strength and protamine sulphate concentration are found to influence the sedimentation reaction (paracoagulation). High sedimentation activity is inherent in protamine sulphate preparations with the lower electrophoretic mobility, that is with the higher molecular weight. The protamine sulphate reaction with fibrinogen and fibrin is of electrostatic character as the long polycationic chain of protamine is coupled with the negatively charged loci either of fibrin or of fibrinogen molecules, thus evoking aggregation. In this case the fibrin molecules being brought together favour the specific mutual binding due to the active sites of polymerization, specific fibres or gel being formed.

Animals↗
PubMed1987

Comparison of two protocols for heparin neutralization by protamine after cardiopulmonary bypass.

Twenty patients undergoing cardiac operations were randomly assigned to two protocols for heparin neutralization by protamine after cardiopulmonary bypass. In all patients protamine chloride was given at a ratio of 1 unit of protamine to 1 unit of injected heparin. In Group I (10 patients) all protamine was infused within 10 minutes after termination of cardiopulmonary bypass. Group II (10 patients) received 75% of the calculated protamine dose within 10 minutes after termination of bypass and the remainder after transfusion of all blood in the heart-lung machine. Plasma heparin levels were significantly lower in Group II 5 minutes after transfusion of all blood in the heart-lung machine and were 0.13 units/ml (standard deviation 0.04) in Group I and 0.06 units/ml (standard deviation 0.05) in Group II (p less than 0.001) 60 minutes after bypass. Activated partial thromboplastin time mirrored the changes in plasma heparin, whereas activated clotting time (Hemochron) was too insensitive to detect these low plasma heparin levels. We conclude that the two-dose protocol resulted in more complete heparin neutralization than the one-dose protocol.

Cardiopulmonary Bypass↗
PubMed1988

Bovine protamine genes contain a single intron. The structures of the two alleles.

In a recent paper, we described the isolation of the first bovine protamine cDNA (BPK59), demonstrating that the gene was autosomal and single copy (Krawetz, S. A., Connor, W., and Dixon, G. H. (1987) DNA 6, 45-57). We have since utilized the BPK59 clone as a probe, to isolate both alleles of the protamine gene from a bovine genomic library constructed in Charon 28. The sequenced alleles are highly homologous and code for identical mRNAs. Unlike the trout protamine genes, the bovine gene is not contiguous as it possesses a single intron. This intron divides the highly variable mammalian carboxyl domain from the conserved protamine basic core. Three tandemly repeated CG-like ("enhancer") sequences upstream from the CAAT box have been identified, separated by a conserved spacer region. Their possible role in the transcription of this P1 gene is discussed. The bovine genome immediately surrounding (approximately equal to 20 kilobase pairs) the protamine gene has been mapped and reveals that the sequence flanking the 5' segment of the gene is unique, while the sequence flanking the 3' segment is repetitive.

Alleles↗
PubMed1986

Neutralization of a low molecular weight heparin (LHN-1) and conventional heparin by protamine sulfate in rats.

The neutralization of a low molecular weight heparin (LHN-1) and conventional heparin (CH) by protamine sulfate has been studied in vitro and in vivo. In vitro, the APTT activity of CH was completely neutralized in parallel with the anti-Xa activity. The APTT activity of LHN-1 was almost completely neutralized in a way similar to the APTT activity of CH, whereas the anti-Xa activity of LHN-1 was only partially neutralized. In vivo, CH 3 mg/kg and LHN-1 7.2 mg/kg was given intravenously in rats. The APTT and anti-Xa activities, after neutralization by protamine sulfate in vivo, were similar to the results in vitro. In CH treated rats no haemorrhagic effect in the rat tail bleeding test and no antithrombotic effect in the rat stasis model was found at a protamine sulfate to heparin ratio of about 1, which neutralized APTT and anti-Xa activities. In LHN-1 treated rats the haemorrhagic effect was neutralized when APTT was close to normal whereas higher doses of protamine sulfate were required for neutralization of the antithrombotic effect. This probably reflects the fact that in most experimental models higher doses of heparin are needed to induce bleeding than to prevent thrombus formation. Our results demonstrate that even if complete neutralization of APTT and anti-Xa activities were not seen in LHN-1 treated rats, the in vivo effects of LHN-1 could be neutralized as efficiently as those of conventional heparin. The large fall in blood pressure caused by high doses of protamine sulfate alone was prevented by the prior injection of LHN-1.

Animals↗
PubMed1987

Electrical charge and joint inflammation: suppression of cationic aBSA induced arthritis with the polycation protamine.

aBSA arthritis was elicited by intraarticular (i.a.) injection of 60 micrograms aBSA into the knee joint of mice immunized with aBSA in Freund's complete adjuvant. The chronicity of the joint inflammation appeared to depend on the excellent charge-mediated retention of aBSA in the joint. We examined whether arthritis induced with the positively charged aBSA (pl approximately 8.5) could be modulated with the competitive polycation protamine (pl approximately 10). Concomitant i.a. injection of aBSA (60 micrograms) with protamine (180 micrograms) strongly reduced the aBSA arthritis. Lower dosages of protamine were less effective. Protamine caused a strong reduction in the retention of aBSA in the joint, particularly at the cartilage level. Our data indicate that protamine exerts its effect on aBSA arthritis by interfering with anionic retention sites in the joint.

Animals↗
PubMed1985

Protamine: a review of its toxicity.

The prospective human studies considered above reveal that in some patients protamine is associated with decreases in SBP and SVR, especially when administered rapidly. Cardiac output increases reflexly, except perhaps in patients with less compliant ventricles, which are more dependent on preload to maintain stroke volume. In the latter, decreases in filling volume associated with protamine can lower CO. Regardless of the rate of administration, protamine does not produce predictable, acute increases in PAP, although increases in PAP may occur during idiosyncratic reactions (see the section on idiosyncratic reactions below). Left atrial or aortic administration of protamine may not confer protection from its hemodynamic or idiosyncratic sequelae (see below). Little evidence exists to conclude that protamine directly depresses contractility of the human heart.

Anaphylaxis↗
PubMed1973

Protamine--antagonist to heparin.

Protamine is used for titration of heparin in vitro for diagnosis of hemorrhagic states and for neutralization of heparin in vivo to terminate heparinization. The protamine equivalent varies with the heparin preparation, conditions of testing and, in vivo, with the amount of heparin present in the circulation. The latter depends on time after administration and the hemodynamic and metabolic state of the patient. Protamine, when injected rapidly, will release histamine and agglutinate platelets. Bleeding (spontaneous hemorrhage) demonstrates a multiple breakdown of hemostatic mechanisms due to surgical stress, drugs, exposure of the blood to foreign surfaces, etc. Simple rules for the amount of protamine required for an individual patient based on clinical judgement will be satisfactory in most cases. When hemostasis is not achieved, it must be appreciated that heparin and protamine are only part of a complex deteriorating situation.

Hemorrhage↗
PubMed1984

Differences in threshold for protamine toxicity in isolated atrial and ventricular tissue.

The inotropic and chronotropic effects of protamine sulfate on rabbit myocardium were studied using isolated preparations of atrial and ventricular tissue. Each tissue differed markedly in its susceptibility to depression of peak isometric developed tension. The threshold concentration for depression of tension was 0.022% for left atrium, 0.055% for right atrium, and 0.3% for right ventricular papillary muscle. Tension in the left atrial preparation increased 20% over control at a protamine concentration of 0.02%, but decreased to less than 30% of control at a concentration of 0.022%. Right atrial tissue tension decreased to 48% of control at a protamine concentration of 0.055% and then to 17% of control at a concentration of 0.6%. In papillary muscle, tension decreased to 64% of control at a concentration of 0.3% and then to 9% of control at a concentration of 0.35%. Thus a very steep dose-response curve was observed for each tissue. In the right atrium-sinoatrial node preparation, administration of protamine at concentrations of 0.05-0.06% produced intermittent atrial extrasystoles, but no significant change in overall rate of discharge. The narrow margin of safety of the protamine dose-response curve may provide a partial explanation for the precipitous nature of hypotensive episodes during clinical administration.

Animals↗
PubMed1984

Acute reaction to protamine. Its importance to surgeons.

Three open heart surgery patients developed noncardiogenic pulmonary edema after administration of protamine following cardiopulmonary bypass. A catastrophic series of events are characteristic of this reaction: 1) sudden onset; 2) severe bronchoconstriction with early extreme difficulty in ventilation; 3) hyperinflation of the lungs; 4) pulmonary hypertension with normal pulmonary wedge or left atrial pressures; 5) progression to fulminant noncardiogenic pulmonary edema; 6) significant mortality; and 7) ventilatory perfusion abnormalities in survivors. Review of the literature reveals three types of reactions to protamine injection of varying severity: 1) brief hypotension; 2) anaphylactoid generalized reaction; and 3) high protein noncardiogenic pulmonary edema with cardiopulmonary collapse. The severity of the reaction had no relation to the dose of protamine. Previous protamine exposure was documented in 14 of 35 cases. Awareness of this reaction is essential for prompt treatment if fulminant pulmonary edema occurs. Administration of epinephrine, steroids, vasopressors, and potassium replacement may be required. Needless use of protamine sulfate should be discouraged.

Acute Disease↗
PubMed1983

The detection of fibrinogen (or FgDP)-protamine sulphate complex in vitro and in the circulating blood.

In order to clarify the pathophysiological significance of the fibrinogen (FgDP)-protamine complex, the interaction between fibrinogen and protamine sulphate was studied in vitro and in vivo. Using the electrophoretic technique, an attempt was made to determine whether the complex could be detected in vitro and in the circulating blood. From the present studies, it has been clarified in in vitro experiments that the slower mobility of two peaks on immunoelectrophoresis represented a complex of protamine sulphate and fibrinogen (FgDP). Furthermore, the peak of slower mobility on crossed immunoelectrophoresis appeared in the circulating blood of a rabbit receiving administration of excess protamine sulphate. That is, in vivo experiments showed that a complex of protamine sulphate and fibrinogen (FgDP) could be detected in the circulating blood.

Animals↗
PubMed1980

A weak negative inotropic effect of protamine sulfate upon the isolated canine heart muscle.

The direct effect of protamine sulfate upon myocardial inotropism was studied using an isolated canine heart muscle preparation. Isometric force (F) was decreased to 87.6 +/- 1.2% of control values by a concentration of 50 x 10(-3) g/L protamine, which is approximately equal to the estimated serum concentration of protamine when administered clinically in doses of 4 mg/kg. The decrease in F was accompanied by a decrease in the maximum velocity of force development (dF/dt) but no alteration in time to peak force. Administration of the preservative of protamine sulfate did not alter F and dF/dt. This suggests that protamine produces a direct negative inotropic effect, mediated by a decrease in intensity but not by a decrease in duration of the active state.

Animals↗
PubMed1982

Effects of protamine sulfate on myocardial oxygen supply and demand in patients following cardiopulmonary bypass.

The effect of protamine sulfate on myocardial oxygen supply and demand was studied under clinical conditions in nine patients following cardiopulmonary bypass. Before surgery, the patients had severe coronary artery disease with good ventricular function. The patients required no vasoactive drugs, but only blood volume adjustments when weaned off bypass, and were hemodynamically stable at the time of study. The protamine dose of 196 mg (2.5 mg/kg) was infused over 4 +/- 1 minutes. Although modest variation in hemodynamic function occurred in individual patients after administration of protamine, there were no significant hemodynamic alterations for the group. No significant alteration in global myocardial metabolism was observed. Protamine caused a small decrease in measured coronary blood flow, resulting in a corresponding reduction in calculated myocardial oxygen consumption as coronary sinus oxygen content remained unaltered. Myocardial lactate extraction showed no significant alteration. It is concluded that protamine sulfate, given at rapid infusion rates in hemodynamically stable patients, is not associated with an adverse alteration in hemodynamics or global myocardial metabolism.

Aged↗
PubMed1994

[Effectiveness of preventing hypotension with H1/H2 antagonists before protamine administration].

BACKGROUND: This prospective randomized study was undertaken to evaluate the effects of prophylactic administration of H1/H2 receptor blockers on histamine release and hemodynamic changes after administration of protamine in two groups of patients (n = 20) undergoing elective coronary artery bypass graft surgery. PATIENTS AND METHODS: Group 1 (n = 10) patients were pretreated intravenously with 1 mg/kg ranitidine and 0.1 mg/kg dimetinden 15 min before termination of the extracorporeal circulation; group 2 patients (n = 10) received no medication. After termination of the extracorporeal circulation, heparin was neutralized by administration of 350 U/kg protamine, injected during 4 min via a peripheral vein. Hemodynamic measurements were carried out before the administration of protamine and at 1-min intervals up to 10 min after the injection. Before administration of protamine and 2, 4, 6, 8, and 10 min thereafter, plasma histamine levels were measured using central venous blood samples. RESULTS: In group 1 patients, who were treated prophylactically with H1/H2 receptor blockers, the plasma histamine concentration was 0.21 +/- 0.15 ng/ml (mean +/- SD) and reached a peak value of 0.30 +/- 0.17 ng/ml within 4 min. In group 2 patients, the plasma histamine concentration increased from 0.17 +/- 0.15 to 0.26 +/- 0.24 ng/ml after 10 min. The hemodynamic reactions were comparable in both groups (group 1: decrease in systolic arterial pressure from 118 +/- 16 to 104 +/- 15 mm Hg; group 2: from 111 +/- 19 to 108 +/- 21 mm Hg; differences statistically not significant). The Spearman rank correlation revealed no statistically significant relationship between the slight plasma histamine release and clinically severe decreases of blood pressure that were observed in single patients. CONCLUSION: Histamine release appears unlikely as the mechanism of protamine-induced hypotension. Therefore, general prophylaxis using H1/H2 receptor antagonists does not seem to be justified and cannot be recommended.

Aged↗
PubMed1993

Protamine-induced acute lung injury and the protective effect of agents that increase cAMP.

Polycations, such as protamine sulfate and polylysine, have been implicated in acute lung injury. We studied the vascular effect of protamine sulfate and the protective effect of agents that increase cAMP in isolated rat lungs perfused with a cell- and plasma-free solution. Protamine sulfate (3 mg) markedly increased pulmonary artery pressure (PAP) from 15.6 +/- 0.5 to 30.8 +/- 1.2 mmHg (P < 0.01) and lung weight gain (LWG) by 7.8 +/- 1.5 g within 30 min (P < 0.001). The protective effects of pharmacological agents that increase intracellular cAMP were investigated. These agents included dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP, a cAMP analogue), aminophylline and pentoxifylline (both are phosphodiesterase inhibitors). Pretreatment with these agents 5 min before protamine administration largely attenuated the increases in PAP and LWG. Because DBcAMP, aminophylline and pentoxifylline all share the effects of increasing intracellular cAMP and were effective on the protamine-induced lung changes, the intracellular level of cAMP could be a major determinant of lung injury. Since there is no blood in the perfusate, the mechanism of cAMP on cellular components in the blood such as neutrophils, can be ruled out. The endothelial cells are likely to be the target cells because charge interaction is believed to occur on the endothelial surface. This result will be very important in the elucidation of the protective effect of cAMP in acute lung injury.

Aminophylline↗
PubMed1976

[Effect of protamine sulphate on erythrocyte agglutination by anti-rh antisera. Cause of time-dependence (author's transl)].

The effect of protamine sulphate on Rh antisera causes agglutination also in saline milieu and is time-dependent. Synchronous to the serologically demonstrable decrease of the protamine concentration a normalization of the immunoelectrophoretic picture (especially of the albumin arc) and a decline of the precipitate formation by heparin occur. These effects are based on enzymatic degradation of protamine by a protaminolytic enzyme contained in human serum. This enzyme could not be inhibited by sodium fluoride, sodium azide, ammonium oxalate, EDTA or alpha, alpha'-dipyridyl to a serologically desired degree. The change of the behaviour with regard to agglutination of human erythrocytes in the system Rh antibody - protamine sulphate results primarily from blocking acid groups on the erythrocyte surface and not from chemical modification of IgG antibodies. In this system protamine sulphate leads to the formation of agglutinates but it does not represent an obligate constituent of the formed agglutinate.

ABO Blood-Group System↗
PubMed1993

Effect of a thromboxane synthetase inhibitor on protamine-induced circulatory changes in sheep.

BACKGROUND: Rapid intravenous administration of protamine after procedures requiring cardiopulmonary bypass is occasionally associated with severe pulmonary hypertension, systemic hypotension, cardiac dysfunction, and lung edema. We hypothesized that the mechanism for these hemodynamic changes after protamine administration is the release of thromboxane. We therefore examined the effect of a thromboxane synthetase inhibitor (OKY-046) on these hemodynamic changes in a sheep model. METHODS: Ten female sheep were prepared with lung lymph fistulas and balloon-tipped pulmonary artery, left atrial, arterial, and venous catheters. After a 5-day recovery period, 2 mg/kg protamine was infused 10 minutes after 200 units/kg heparin, with (n = 5; OKY-046 group) and without (n = 5; heparin/protamine group) OKY-046 (10 mg/kg). RESULTS: In the heparin/protamine group, pulmonary arterial pressure and lung lymphatic flow were significantly increased soon after administration of protamine, from 19 +/- 1 to 51 +/- 2 mm Hg and 5 +/- 1 to 8 +/- 1 ml/hr, respectively. The circulating leukocyte count was significantly reduced, from 3304 +/- 318 to 903 +/- 898 mm3. Cardiac output was also reduced, from 5.8 +/- 0.3 to 3.4 +/- 0.7 L/min/m2. These changes were completely blocked in the OKY-046 group, except for the neutrophil depletion and the increase in lung lymphatic flow. CONCLUSIONS: We conclude that thromboxane plays a significant role in protamine-induced hemodynamic deterioration and pulmonary permeability changes.

Animals↗
PubMed1996

Randomized trial of recombinant platelet factor 4 versus protamine for the reversal of heparin anticoagulation in humans.

BACKGROUND: Protamine reverses heparin anticoagulation, but it can have important side effects. We compared the safety and effectiveness of intravenous recombinant platelet factor 4 (rPF4) as an alternative to protamine in a randomized blinded trial. METHODS AND RESULTS: In 81 patients having diagnostic cardiac catheterization, baseline hemodynamics were measured after a 5000-U bolus of heparin. Repeat measurements were obtained at the end of the procedure, and the anticoagulation status was determined by an activated coagulation time (ACT) and activated partial thromboplastin time (aPTT). Patients then received either protamine (50 mg IV over 10 minutes) or rPF4 (1.0 mg/kg IV over 2 minutes) in a blinded fashion. Serial measurements of hemodynamic and clotting functions were performed 5, 10, 20, and 30 minutes after drug administration. Follow-up measurements and clinical assessments were made at 1, 4, 6, and 24 hours later and after 7 days. Before drug administration, ACTs, aPTTs, and hemodynamics were similar among the groups. After drug infusion, there was no difference in ACT between the protamine and rPF4 patients. At 20 and 30 minutes after drug infusion, ACT and aPTT were slightly higher in those receiving rPF4, but these changes were small and of no clinical significance. There were no clinically meaningful differences in any of the hemodynamic variables between the groups, and there were no serious side effects in any patient. CONCLUSIONS: At the dose used in this study, rPF4 was well tolerated and reversed the anticoagulant effect of heparin. These data support its continued evaluation as an alternative to protamine after cardiac surgery.

Adult↗
PubMed1977

Reiteration frequency of the protamine genes in rainbow trout (Salmo gairdnerii).

Protamine mRNA was isolated in a very pure form from trout testis and used as a template for the synthesis of a complementary DNA of high specific activity. The cDNA represented a full copy of the mRNA template and was used in hybridization reactions with purified trout DNA to determine the number of genes for protamines in trout testis. Our results indicate that there are less than four genes for each protamine polypeptide per the content of DNA in the male gamete and that the control of protamine synthesis in trout testis cells does not involve specific amplification of the protamine genes.

Animals↗