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.

SourceResearch connectionFrom yearThrough year

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

At least 577 records · Page 32Linked to original sources

PubMed2002

Clinical effects of different protamine doses after cardiopulmonary bypass.

The optimal dose of protamine needed to reverse the anticoagulant effect of heparin after cardiopulmonary bypass is still not known. In this retrospective cohort study, we investigated 3 different dose regimes in 300 patients undergoing coronary artery bypass grafting. Group A patients (n = 100) were given protamine in the ratio of 1.3 mg to 1 mg heparin, group B patients (n = 100) were given 0.75 mg protamine to 1 mg heparin, and group C patients (n = 100) were given protamine in fractionated doses of 1 mg + 0.15 mg + 0.15 mg to 1 mg heparin. The groups were comparable in all major clinical and operative variables. The heparin dose was almost identical in the groups. The rate of red cell transfusion was significantly higher in group B than in the other groups. A similar but nonsignificant trend was observed in the incidence of resternotomy for postoperative bleeding, mediastinal drainage, and postoperative hemoglobin loss. The study demonstrates that a single bolus dose of 1.3 mg protamine to 1 mg heparin is safe and efficient for neutralizing heparin after cardiopulmonary bypass.

Aged↗

PubMed1997

The effect of protamine on the epicardial microflow and the graft flow in open-heart surgery.

To evaluate the effect of coronary revascularization on myocardial perfusion and surgical outcome regarding graft flow, we used laser Doppler flowmetry to assess the epicardial microcirculation in patients undergoing coronary artery bypass grafting (CABG) or valve replacement (VR) and electromagnetic flowmetry to measure graft flow in the CABG group. In the CABG group, the preoperative mean laser Doppler flow rate (LDF) in the epicardium of the left ventricle significantly increased at the end of cardiopulmonary bypass (CPB) (22 +/- 7 arbitrary units (AU) to 60 +/- 13 AU, p < 0.001). This value further increased 10 min after protamine infusion (66 +/- 14 AU, p < 0.01), but was significantly reduced 30 min later (51 +/- 14 AU, p < 0.002). Compared to the post-CPB value (34 +/- 10 ml/min) before protamine infusion, the mean graft flow (ml/min) to this area significantly increased 10 min after protamine infusion (41.3 +/- 10 ml/min, p < 0.001) but significantly decreased 30 min later (29 +/- 9 ml/min, p < 0.001). The preoperative mean LDF in the VR group was significantly higher than in the CABG group (p < 0.01). In the CABG group, there was a positive correlation between the LDF and graft flow at the end of CPB (r = 0.788) and 10 (r = 0.767) and 30 (r = 0.784) min after protamine infusion. This study shows that coronary bypass grafting increases the myocardial microcirculation which, together with graft flow, could give an early indication of the effect of surgery on myocardial microcirculation. Furthermore, protamine was found to be one of the factors contributing to graft flow reduction postoperatively and, therefore, newer methods of heparin reversal may be desirable.

Aged↗

PubMed1996

Prophylactic administration of histamine 1 and/or histamine 2 receptor blockers in the prevention of heparin- and protamine-related haemodynamic effects.

The efficacy of prophylactic administration of H1 and H2 receptor blockers to prevent adverse haemodynamic responses to heparin and protamine was studied. The control group (n = 10) received no histamine receptor blocker, group H1 (n = 10) received oral terfenadine 60 mg, group H2 (n = 10) received oral ranitidine 300 mg, and group H1+H2 (n = 10) received both terfenadine and ranitidine on the night before the operation and on call to the operating room. Heparin sulphate 300 U/kg was injected directly into the right atrium, and protamine hydrochloride was administered at the conclusion of bypass over at least three minutes through a peripheral route. Following the injection of heparin, plasma histamine-like activity (H-LA) was increased significantly in all four groups. While systolic, diastolic, mean arterial and central venous pressures were decreased significantly in the control group, no significant changes were observed in the H1 and H2 groups. Protamine infusion did not lead to an increase in H-LA. Prophylactic administration of histamine receptor blockers (H1 or H2) attenuated the heparin-induced adverse haemodynamic response but did not change the protamine-related haemodynamic effects. Factors other than histamine may play a major role in protamine induced cardiovascular changes.

Administration, Oral↗

PubMed1992

A nationwide investigation of a possible protamine drug-product defect.

OBJECTIVE: To follow-up a report submitted to FDA Spontaneous Reporting System, we investigated the hypothesis that there was not a striking increase in unexpected deaths within four hours after elective coronary artery bypass surgery associated with protamine sulfate use. DESIGN: Surveys were mailed to clinical pharmacists at 521 hospitals participating in the Drug Surveillance Network. Questionnaires were to be completed with the assistance of cardiac surgeons and anesthesiologists. Hospitals responding with a suspected problem with protamine were contacted via telephone. RESULTS: Surveys were received from clinical pharmacists at 380 hospitals (73 percent response rate) and 29 hospitals reported the occurrence of potential problems associated with protamine during coronary artery bypass graft surgery. Telephone interviews of the positive responders yielded six cases of possible myocardial decomposition potentially associated with protamine. There was no association with a specific distributor, however, and none of the hospitals reported a dramatic increase in serious adverse events around the time of index cases. CONCLUSIONS: There was no evidence of a widespread public health problem with protamine and a product recall was not necessary. The high response rate and the ability to follow-up with telephone interviews suggests that the Drug Surveillance Network is an effective mechanism for investigating possible outbreaks of serious adverse events in the hospital setting.

Adverse Drug Reaction Reporting Systems↗

PubMed1988

Rat sperm protamine. Isolation and sequence analysis.

Rat protamine was extracted from S-(pyridylethylated) epididymal sperm cell nuclei with dilute hydrochloric acid. The final purification was achieved by reversed-phase high-performance liquid chromatography. The primary structure was determined by N-terminal sequencing of the total S-(pyridylethylated) protein, and of endoproteinase Lys-C- and thermolysin-derived fragments. Rat protamine consists of 50 amino-acid residues. It is a typical type 1 protamine and differs in two and ten positions from the corresponding mouse and rabbit protamine, respectively. Only 26 positions are invariant in all type 1 mammalian protamines.

Amino Acid Sequence↗

PubMed1978

Post-vasectomy autoimmunity to protamines in relation to the formation of granulomas and sperm agglutinating antibodies.

The development of antibodies reacting with nuclear antigens was studied in sera from vasectomized men and monkeys (obtained at intervals of up to 2 and 4 years, respectively, after the operation), by means of a comparative fluorescence study on swollen nuclei of somatic cells, human and salmon spermatozoa. About 30% of forty-seven vasectomized men developed antibodies to protamines. Also four out of fifteen monkeys, vasectomized with or without ligation, developed antibodies reacting with protamines. In general, when antibodies to the homologous protamines reached higher levels, cross-reactions with salmon protamine could be demonstrated as well. No significant reactions could be detected with somatic nuclear antigens in the sera. Comparison between the results obtained with the immunofluorescence test, the agglutination tests and the clinical findings confirmed the association between the development of immune responses to various sperm-antigens and revealed a coherence of anti-protamine activity and granuloma formation at the site of the operation.

Animals↗

PubMed2003

[Successful management after cardiopulmonary bypass without administration of protamine in a patient with severe food allergy--beneficial result with the use of heparin-coated bypass circuit].

We experienced the anesthetic management for cardiac surgery without the administration of protamine in a patient with severe food allergy. The patient, a 15-year-old boy, who had been avoiding many kinds of food including fish due to severe food allergy, received a correction of ventricular septal defect under cardiopulmonary bypass (CPB). To detect intraoperative drugs, including protamine, which might induce allergic reaction, we performed intradermal tests and prick tests. We used heparin-coated bypass circuit to minimize the amount of heparin necessary for anticoagulation during CPB. After CPB, hemostasis was achieved without the administration of protamine, and the patient received neither transfusion nor blood product throughout the perioperative period. Avoidance of protamine is advisable if the patient is allergic to food especially fish. The use of heparin-coated bypass circuit should be considered to establish hemostasis without protamine after CPB and to reduce blood products.

Adolescent↗

PubMed2005

[Analysis of protamine content in patients with asthenozoospermia].

OBJECTIVE: To study the significance of the change of protamine content in the management of male infertility. METHODS: Sperm nuclear proteins extracted from 199 infertile patients were analyzed by polyacrylamide gel-electrophoresis and scanning microdensitometry. RESULTS: Forty-two (21%) cases of the total number had normal sperm nuclear proteins and 157 (79%) had aberrant ones, which mainly presented the interruption of HPRR and abnormality of P2 protamine. Thirty patients were selected at random from 157 abnormal cases for clinical treatment. After the treatment, the sperm nuclear proteins were extracted and analyzed and the results demonstrated that 11 cases (36.6%) improved markedly, 5 (16.6%) restored to normal and the other 16 (46.6%) remained unchanged. CONCLUSION: There is a reduced level or selective absence or even complete selective absence of protamines in infertile patients. Protamines may act as a parameter for evaluating the treatment effect of infertile males and protamine content can be influenced by a certain or several factors.

Adult↗

PubMed2005

[A case of severe coronary artery spasm associated with anaphylactic reaction caused by protamine administration].

A 65-year-old man with mitral regurgitation and atrial fibrillation underwent mitral valve plasty and Maze's operation. Cardiopulmonary bypass (CPB) was finished uneventfully. But after protamine administration, severe systemic hypotension occurred suddenly with electrocardiographic ST-segment elevation and wide QRS intervals. We thought that this reaction had been caused by coronary spasm and not by anaphylactic reaction because he was without typical anaphylactic manifestations such as general rash and bronchospasm. We administered epinephrine, methylprednisolone, heparin for restarting CPB, and used IABP support to assist systemic circulation. We again tried to administer protamine to neutralize the anticoagulative effect of heparin when his vital sign had recovered, but the same reaction occurred immediately with small amounts of protamine. The second CPB was necessary for some time. This case suggests that coronary artery spasm associated with anaphylactic reaction was induced by administration of protamine. It is known that intravenous protamine administration sometimes causes adverse events. As in this case, we should consider the possibility of severe coronary spasm associated with anaphylactoid reaction even if other symptoms of anaphylactic reactions such as cutaneous manifestation and bronchospasm are not present.

Aged↗

PubMedDate not supplied

An anaphylactic reaction to protamine sulfate.

Presented is a case in which protamine sulfate administration caused an immediate allergic-like reaction. The patient, a 50-year-old woman, had received protamine previously to reverse the anticoagulant effect of heparin after open heart surgery. In a similar operation 7 years later, protamine was used again for the same reason. Immediately following intravenous infusion of 3 mg/kg protamine sulfate, a sudden drop of the mean arterial blood pressure to 40 mm Hg occurred, and the heart rate increased from 100 to 130 beats/min. Severe angioneurotic edema of the face and trunk also developed. The reaction was successfully treated with vasopressors, steroids, and volume expansion. Subsequent skin testing revealed a positive reaction to protamine sulfate.

Anaphylaxis↗

PubMed1991

Sagaxine, the protamine from Sardinops sagax. Characterization, sequence and secondary structure prediction.

This paper describes the isolation, purification and full characterization of the protamine from Sardinops sagax. The protein was purified by both gel filtration and ion exchange chromatography and its amino acid composition, electrophoretic behaviour and sequence were determined. We postulate that the protamine exhibits microheterogeneity with a major and a minor component. The molecular weight for the major component is 4377, as calculated from the sequence. The N-terminal amino acid is proline and the C-terminal is arginine. The amino acid composition is: Thr-Ser-Glx-(Pro)2-Gly-(Ala)3-(Val)2-(Lys)2-(Arg)20 The secondary structure for the protamines was also predicted and a revision of our previously published results in this area is discussed. We have called this protamine Sagaxine and an overall comparison with the hitherto described fish protamines is also made.

Amino Acid Sequence↗

PubMed1991

[The effects of thromboxane receptor antagonist on hemodynamic responses after neutralization of heparin by protamine].

In a double blind test, the effects of ONO 3708, thromboxane A2 (TXA2) receptor antagonist, on hemodynamic responses after neutralization of heparin by protamine, were evaluated in 19 patients undergoing coronary artery bypass graft. Severe circulatory disturbances were not observed in all patients after intravenous administration of protamine (3 mg.kg-1) over 5 minutes, and in particular ONO 3708 (2.5 micrograms.kg-1.min-1 given with continuous infusion) group (n = 10) showed no deleterious hemodynamic responses to protamine. On the other hand, in placebo group (n = 9) the mean pulmonary artery pressure (mPAP) and the mean pulmonary/systemic artery pressure ratio (Pp/Ps) increased significantly, immediately following protamine administration, compared with the baseline values and ONO 3708 group. The results suggest that pulmonary hypertension after protamine is associated with TXA2 release and that ONO 3708 is useful to avoid this reaction.

Aged↗

PubMed1990

Protamine-induced pulmonary hypertension in heparinized monkeys and pigs is inhibited by the thromboxane receptor antagonist SQ 30,741.

When protamine reverses heparin anticoagulation a small fraction of patients develops pulmonary hypertension. This response is variably expressed in other species and thromboxane may be one of its mediators. We have compared the pulmonary vascular responses of pigs and monkeys to protamine (3 mg/kg, i.v.) administered 15 min after heparin (300 U/kg, i.v.). The role of thromboxane A2/prostaglandin H2 (TxA2/PGH2)-receptor activation in this response was investigated with the selective TxA2/PGH2-receptor antagonist, SQ 30,741, at a dose (1 mg/kg, i.v.) shown to inhibit U-46,619-induced pulmonary vasoconstriction by greater than or equal to 99%. SQ 30,741 or vehicle (1.5 ml saline) was given 2 min before protamine in Yucatan minipigs (n = 6-7) and African green monkeys (n = 8-9). In saline-treated monkeys and pigs, protamine increased pulmonary vascular resistance (131 +/- 46 and 478 +/- 18%, respectively) primarily by increasing pulmonary artery pressures (54 +/- 19 and 166 +/- 42%, respectively). In pigs only, pulmonary artery flow was also reduced by 33 +/- 9%. These responses peaked within 1 to 3 min and returned to baseline in approximately 5 (monkey) and approximately 15 (pig) min. In monkeys and pigs pretreated with SQ 30,741 the increases in pulmonary vascular resistance (17 +/- 4 and 16 +/- 9%, respectively, p less than 0.05) and pulmonary artery pressure (10 +/- 3 and 16 +/- 9%, respectively, p less than 0.05) were significantly inhibited. SQ 30,741 also accelerated reversal of established hypertension in pigs when given 1 min after protamine. However, transient reductions in circulating monkey leukocytes (approximately 70%) and platelets (approximately 16%) were unaffected by SQ 30,741.(ABSTRACT TRUNCATED AT 250 WORDS)

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

PubMed1989

The pharmacological profile of the low molecular weight heparin 21-23 in man: anticoagulant, lipolytic and protamine reversible effects.

The anticoagulant, lipolytic and protamine reversible effects of high doses of low molecular weight (LMW) heparin 21-23 and unfractionated heparin were compared in man. 7,500 units of each heparin were applied, which corresponds to 90 mg LMW heparin and 48 mg unfractionated heparin. The anticoagulant properties of the LMW heparin are characterized by a doubled half life of factor Xa activity, smaller influence on aPTT and thrombin after intravenous (i.v.) and subcutaneous (s.c.) injection, and higher bioavailability of factor Xa activity after s.c. administration (90% versus 15%). Protamine chloride completely neutralizes the effect on aPTT and thrombin and reduces the anti factor Xa activity by 60%. The bleeding time is prolonged by both normal and LMW heparin by 20%. This effect is normalized by protamine chloride, too. Thrombelastography with recalcified whole blood demonstrates that protamine chloride shortens but not completely normalizes the coagulation time in presence of either unfractionated or LMW heparin. The half life of lipoprotein lipase (LPL) activity is 60 min after i.v. administration of unfractionated heparin and 120 min with LMW heparin. Although the release of lipases (LPL and HTGL) is higher after i.v. and s.c. administration of the LMW heparin they do not induce higher releases of free fatty acids. This indicates that the lipolytic activity of this LMW heparin and unfractionated heparin is similar. The results show an improved anticoagulant pharmacological profile of this LMW heparin as compared to unfractionated heparin. Protamine normalizes the anticoagulant effects of LMW heparin with exception of a residual anti factor Xa activity and normalizes the changes of bleeding time and thrombelastography.

Adult↗

PubMed1989

The effects of protamine on hemodynamics and oxygenation during cardiac surgery.

The cardiopulmonary effect of protamine for heparin reversal was investigated in 100 patients, undergoing cardiac surgery, using cardiopulmonary bypass (CPB) at Siriraj hospital. Protamine sulfate at approximately equal to the amount of heparin was intravenously administered over 3 minutes after termination of CPB, together with rapid blood transfusion to establish the optimal level of central venous pressure. Following protamine administration, the heart rate was measured at 5, 15 and 30 minutes, and was not significantly different from the preoperative and post CPB values. The blood pressure was significantly decreased in the initial post CPB (P less than 0.05) and remained unchanged 5 minutes following intravenous protamine, thereafter, significantly rose to preoperative values. The arterial oxygen tension post CPB revealed shunting effect, but showed no significant change following protamine administration. The occurrence of cardiopulmonary adverse effect was not demonstrated in this study.

Adolescent↗

PubMed1989

Comparison of the hemodynamic changes following left atrial and peripheral venous administration of protamine during cardiac surgery.

The hemodynamic effects of left atrial administration of protamine for heparin reversal were compared with the peripheral venous route. One hundred patients, undergoing cardiac surgery, using cardiopulmonary bypass (CPB) at Siriraj hospital were randomly allocated into two equal groups of fifty. The preoperative and operative characteristics of the two groups were comparable. After the termination of CPB, protamine sulfate was administered over 3 minutes via the left atrium in group I, and via the peripheral vein in group II. The hemodynamics were measured before and 5, 15 and 30 minutes after protamine administration. There were no statistically significant differences in heart rate (HR), arterial blood pressure (BP), and central venous pressure (CVP) between the groups. After administrating protamine and adequate maintaining the preload in both groups of patients within the normal range, the HR did not change from immediate post CBP control values. The arterial BP was not changed for 5 minutes, thereafter, significantly elevated toward the preoperative baseline values. This data indicates that the left atrial injection of protamine does not provide any hemodynamic advantages over the peripheral venous administration.

Adult↗

PubMed1986

The effect of protamine sulfate on the course of immune complex glomerulonephritis in the rat.

In vivo studies in rats demonstrated that the binding of a highly cationic antigen (cationized human IgG, pI greater than 9.5) to glomerular polyanion could be significantly reduced by prior application of a small polycation, protamine sulfate. The degree of inhibition was dose dependent and the highest dose used, 4 mg/100 g body weight, reduced antigen binding by approximately 70%. In further experiments the ability of protamine sulfate to enhance elimination of cationic antigen-antibody immune complexes from the glomerular capillary wall was examined. Daily treatment with protamine sulfate, starting after induction of nephritis, produced a significant but only moderate reduction in the persistence of the antigen, without having any effect on proteinuria. Proteinuria could only be prevented when protamine sulfate was given immediately before induction of nephritis. Protamine sulfate had little influence on the course of established renal disease in the model employed. These results do not substantiate the concept of charge competition as a potentially useful therapeutic strategy.

Animals↗

PubMed1988

Adverse reactions to protamine sulfate during cardiac surgery in diabetic and non-diabetic patients.

The incidence of adverse reactions to protamine sulfate range from 0.06% to 27% and vary from mild urticaria to anaphylactic shock and death. In a retrospective analysis of 2996 patients, only four subjects experienced an adverse reaction due to protamine. Two individuals were NPH-insulin-dependent diabetics and two patients had exposure to protamine only during cardiac catheterization. Skin test titrations to protamine were done in three of four patients. One patient had a positive reaction at a 100-micrograms/mL dilution whereas the other two patients had positive reactions at 1000 micrograms/mL. In a comparable number of normal subjects, the threshold for a positive immediate skin response was 1000 micrograms/mL. Since the observed incidence of adverse reactions was 2.9% in NPH-insulin-dependent diabetics and 0.07% in non-diabetics, this represents a nearly 40-fold increased risk for diabetic patients (P less than .005). Skin testing appears to have limited applicability in the assessment of protamine sensitivity.

Anaphylaxis↗