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PubMed1978

Platelet aggregation following heparin and protamine administration.

The effects of heparin, protamine, and the heparin-protamine complex on the abilities of platelets to aggregate in vitro in response to adenosine diphosphate (ADP) and epinephrine were determined. Citrated blood was obtained from normal volunteers and portions were treated with heparin, protamine, and three different ratios of heparin and protamine. The threshold concentrations of ADP and epinephrine required to produce complete platelet aggregation were then determined. Compared with control citrated plasma, the geometric mean of the threshold concentration for ADP in the heparinized sample was decreased twofold, from 1.88 to 0.94 micrometer; and that for epinephrine more than threefold, from 0.5 to 0.14 micrometer. In contrast, the threshold concentration for ADP was increased to 3.68 micrometer in the neutralized and to 2.78 micrometer in the overneutralized samples and that for epinephrine to 1.62 micrometer in the neutralized and 1.82 micrometer in the overneutralized samples. These data indicate that heparin increases the sensitivity of platelets to ADP and epinephrine as determined by platelet aggregation, and protamine added to heparinized blood not only reverses this effect, but decreases platelet sensitivity when it is added in concentration that neutralize heparin. Additional protamine has no further effect, and protamine alone has no effect on platelet aggregation.

Adenosine Diphosphate↗

PubMed1991

Inhaled nitric oxide. A selective pulmonary vasodilator of heparin-protamine vasoconstriction in sheep.

Nitric oxide (NO) has recently been discovered to be an important endothelium-derived relaxing factor and produces profound relaxation of vascular smooth muscle. To learn if NO could be a potent and selective pulmonary vasodilator, NO was inhaled by 16 awake lambs in an attempt to reduce the increase in pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) induced by either the infusion of an exogenous pulmonary vasoconstrictor (the thromboxane analog U46619) or the endogenous release of thromboxane that occurs during the neutralization of heparin anticoagulation by protamine sulfate. Inhaling greater than or equal to 40 ppm of NO during a continuous U46619 infusion returned the PAP to a normal value, without affecting systemic blood pressure or vascular resistance. Pretreatment with the cyclooxygenase inhibitor indomethacin before infusing U46619 did not reduce the pulmonary vasodilatory effect of inhaled NO, and we conclude that the dilatory effect of NO on the lung's circulation is independent of cyclooxygenase products such as prostacyclin. Continuously inhaling NO at 180 ppm did not significantly reduce the mean peak thromboxane B2 concentration at 1 min after protamine injection; however, the mean values of pulmonary hypertension and vasoconstriction at 1 min were markedly reduced below the levels in untreated heparin-protamine reactions. Breathing NO at lower concentrations (40-80 ppm) did not decrease the mean peak PAP and PVR at 1 min after protamine but decreased the PAP and PVR values at 2, 3, and 5 min below those of control heparin-protamine reactions. Intravenous infusion of nitroprusside completely prevented the transient increase of PAP and PVR during the heparin-protamine reaction; however, marked concomitant systemic vasodilation occurred. Inhaled NO is a selective pulmonary vasodilator that can prevent thromboxane-induced pulmonary hypertension during the heparin-protamine reaction in lambs and can do so without causing systemic vasodilation.

Animals↗

PubMed2001

Interaction of protamine with alpha- and beta-adrenoceptor stimulations in rat myocardium.

BACKGROUND: Protamine alters the inotropic responses to beta-adrenoceptor stimulation, but its mechanism of action is not well-understood. Moreover, its interaction with alpha-adrenoceptor stimulation and the lusitropic (relaxation) response to beta-adrenoceptor stimulation remain unknown. METHODS: The effects of protamine (10 or 100 microg/ml) on the responses induced by phenylephrine and isoproterenol were studied in rat left ventricular papillary muscles. Inotropic and lusitropic effects were studied under low and high loads. The authors also studied the interaction of protamine with forskolin (50 microm) and dibutyryl 3',5'-cAMP (0.5 mm). Data are mean percentage of baseline active force +/- SD. RESULTS: In control groups, phenylephrine (135 +/- 17%, P < 0.05) and isoproterenol (185 +/- 44%, P < 0.05) induced a positive inotropic effect. Isoproterenol induced positive lusitropic effects under low and high loads. Protamine abolished the inotropic responses to alpha- (102 +/- 23%, not significant) and beta-adrenoceptor stimulations (99 +/- 17%, not significant) but did not modify the lusitropic responses to isoproterenol. Protamine abolished the inotropic responses to forskolin (89 +/- 6 vs. 154 +/- 20%, P < 0.05) and markedly decreased that of dibutyryl 3',5'-cAMP (132 +/- 31 vs. 167 +/- 30%, P < 0.05) but did not modify their lusitropic responses. CONCLUSIONS: Protamine abolished the inotropic responses to alpha- and beta-adrenoceptor stimulations but preserved the lusitropic responses to beta-adrenoceptor stimulation. Although protamine may act at several sites on the adrenoceptor stimulation cascade, one of its main sites of action is situated downstream from cAMP-mediated phosphorylation.

Adrenergic alpha-Agonists↗

PubMed1996

The antibacterial action of protamine: evidence for disruption of cytoplasmic membrane energization in Salmonella typhimurium.

Protamine is a polycationic peptide found in the nuclei of sperm of different animal species. While it has long been known to have antimicrobial properties, its mode of action has remained elusive. We have investigated the mechanism of action of protamine and established that this peptide exerts its antibacterial effect without causing cell lysis or permeabilization of the cytoplasmic membrane. Respiring cells were more susceptible than nonrespiring cells, and loss of viability could be prevented by incubation at low pH or the addition of respiratory poisons. This indicates that protamine activity is influenced by the electrical membrane potential (delta psi): increased killing occurs at higher delta psi values. Protamine caused inhibition of proline uptake, rapid efflux of proline from preloaded cells, and a reduction in the cellular ATP content. Furthermore, protamine-treated cells first lost the ability to accumulate leucine and then could not carry out protein synthesis. Cumulatively, our data indicate that protamine disrupts energy transduction and nutrient uptake functions, and suggest that the cytoplasmic membrane is the target of protamine action.

Adenosine Triphosphate↗

PubMed1992

Variations in blood platelet-activating-factor levels after protamine reversal of heparin in humans.

The potent inflammatory mediator PAF-acether (PAF = platelet-activating factor) can produce the same hemodynamic and hematological effects as protamine infusion. In 10 patients, blood PAF and precursor levels were measured in the left atrium, the pulmonary and the radial artery before and after protamine reversal of heparin during coronary artery bypass graft. Blood PAF level in the left atrium increased 6-fold (17 +/- 12 pg.ml-1 vs 98 +/- 46 pg.ml-1, P = 0.03) after protamine infusion. By contrast, a 4-fold decrease was observed in the pulmonary artery blood (130 +/- 48 pg.ml-1 vs 31 +/- 23 pg.ml-1, P = 0.03) and a 9-fold decrease was noted in the radial artery blood (285 +/- 104 pg.ml-1 vs 31 +/- 15 pg.ml-1, P = 0.01). No cardiovascular impairment was observed but all patients exhibited thrombocytopenia. After protamine, PAF in the left atrium reached lower levels than those observed in the pulmonary and radial artery before protamine infusion. Moreover, no significant correlation was observed between platelet counts and PAF levels. Thus PAF seems not to mediate the platelet drop induced by heparin-protamine complexes. A positive correlation was obtained between leukocyte counts in the pulmonary artery and PAF levels in the left atrium (r = 0.78, P = 0.02). Protamine infusion may stimulate PAF biosynthesis by leukocytes in the lung, on the one hand, and accelerate the disappearance of PAF in the arterial bed, on the other hand.

Coronary Artery Bypass↗

PubMed1985

Size changes of protamine 1 mRNA provide a molecular marker to monitor spermatogenesis in wild-type and mutant mice.

We utilized a cDNA encoding the cysteine-rich, tyrosine-containing mouse protamine, mouse protamine 1 (MP1), to detect the presence of several classes of differentiating germ cells in testicular extracts from wild-type and male sterile mutant mice. This assay is based on the changes in the poly (A) length of MP1-mRNA during spermatogenesis. Testicular extracts of sexually mature CD-1 mice contain a heterogeneous population of protamine-1 mRNA ranging in length from 450 to 580 nucleotides. When the protamine-1 probe was hybridized to testicular RNA preparations from 16- to 20-day-old animals, no MP1-mRNA was detected. Twenty-four-day-old mice contain only the 580-nucleotide form of MP1-mRNA. This size class of protamine mRNA is also present in purified populations of round spermatids, whereas elongating spermatids and residual bodies contain mRNAs ranging from 450 to 580 nucleotides in length, which are identical in size to those present in the testes of sexually mature animals. When the protamine cDNA probe was used to examine the progression of spermiogenesis in three male sterile mouse mutants, blind sterile (bs), quaking (qk) and testicular feminization (Tfm), the results demonstrated that each mutant is pathologically distinct. Analysis of the bs mutant revealed a diminution in the amount of both size classes of MP1-mRNA, in agreement with the cytological reports of reduced numbers of haploid spermatogenic cells in these animals. The presence of both size classes of protamine mRNA in the qk mutant indicates that germ-cell differentiation has proceeded at least to the step-12 spermatid in these animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgen-Insensitivity Syndrome↗

PubMed1991

Processing of the precursor of protamine P2 in mouse. Identification of intermediates by their insolubility in the presence of sodium dodecyl sulfate.

Two basic proteins, protamines P1 and P2, are present in chromatin of mouse spermatozoa. Protamine P1, the less abundant protein in mouse, has a homolog in most mammals, and its synthesis follows a conventional route. In contrast, protamine P2 has been found only in certain other mammals, including humans, and it is synthesized as a precursor nearly twice as long as the mature protein. Processing of this precursor is not yet understood, although it necessarily takes place in elongating spermatids and is likely to play a role in the chromatin condensation occurring in these haploid cells. We have fractionated basic proteins from mouse testis chromatin and have identified six proteins on electrophoretic gels which, like protamines, are insoluble in SDS. All six were also soluble at the same trichloroacetic acid concentration as protamine P2 and were present in chromatin of elongating spermatids. Radioactive labelling patterns acquired by these SDS-insoluble proteins during translation in vitro of testis RNA indicate that the largest represents the precursor of protamine P2, and suggest that the others represent intermediates generated by proteolytic cleavage of the precursor. Results from pulse 3H labelling in vivo were also consistent with the conclusion that a precursor/product relationship exists between these proteins and protamine P2. Conclusions concerning the kinetics of processing have, in addition, been drawn from this data. Hypotheses concerning possible functional roles played by the precursor are presented.

Amino Acid Sequence↗

PubMed1987

Protamine sulfate causes pulmonary hypertension and edema in isolated rat lungs.

The polycation protamine sulfate increases microvascular permeability in the kidney by reducing glomerular charge. We have exposed the pulmonary vasculature to protamine sulfate to determine whether electrical charges play a role in protein permeability in lung vascular beds. In anephric rats, protamine sulfate increased hematocrit approximately 25%. With protamine sulfate doses of 0.08 and 0.04 mg/g body wt, lung blood-free wet-to-dry weight ratios were increased (5.24 +/- 0.8 and 4.89 +/- 0.7) compared with control (3.85 +/- 0.3) (P less than 0.05). In isolated, ventilated, and perfused lungs 0.04 mg/g body wt protamine sulfate increased pulmonary arterial pressure from 5.2 +/- 1.4 to 16.3 +/- 3.9 mmHg (P less than 0.01). These lungs gained weight and lung wet-to-dry weight ratios were significantly increased (15.33 +/- 4.26 compared with 6.04 +/- 0.24 for control lungs). Poly-L-lysine, another polycation, also caused significant increases in pulmonary arterial pressure, lung weight, and lung wet-to-dry weight ratios. The addition of diphenhydramine to the perfusate 10 min before the addition of protamine sulfate did not prevent these changes. Heparin (90 U/mg protamine sulfate) reversed the abnormalities. Pulmonary arterial pressure (7.0 +/- 1.1 mmHg) was not significantly different from the control value, lung weight did not increase, and the lung wet-to-dry weight ratio was 6.24 +/- 0.23 (P greater than 0.05). We conclude that polycations have a significant effect on pulmonary vascular resistance and perhaps on permeability.

Animals↗

PubMed1992

Role of platelet-activating factor in the ovine heparin-protamine reaction.

Platelet-activating factor (PAF) infusion into sheep, as well as protamine reversal of heparin anticoagulation, causes thromboxane release into plasma, pulmonary hypertension, hypoxemia, and leukopenia. We investigated the possible role of PAF in the heparin-protamine reaction. Intravenous protamine was administered to neutralize heparin anticoagulation in five awake sheep and caused an increase of mean pulmonary arterial pressure from 16.6 +/- 1 (SE) mmHg at base-line to 47 +/- 9 mmHg at 1 min after protamine injection (P < 0.01) because of a 4.5-fold increase of pulmonary vascular resistance. This neutralization reaction induced a 25% reduction of circulating leukocyte count and arterial PO2. Undetectable blood levels of PAF were measured by bioassay and high-performance liquid chromatography during these heparin-protamine reactions. Infusion of BN 52021 (20 mg/kg), a PAF receptor antagonist, before rechallenging the same sheep with heparin and then protamine did not reduce the level of peak pulmonary hypertension or the degree of hypoxemia and leukopenia. We conclude that the leukopenia and thromboxane-mediated pulmonary vasoconstriction occurring after rapid intravascular formation of heparin-protamine complexes in sheep are not due to the release of PAF.

Animals↗

PubMed1993

Heparin-protamine reactions in pigs: role of oxygen-derived free radicals.

We tested the hypothesis that pulmonary hypertension and thromboxane A2 release after heparin neutralization by protamine are mediated by oxygen free radicals. Forty-five pigs in five groups were studied during general anesthesia. Group I animals received 250 IU heparin followed by 100 mg protamine after 15 min. Group II and group III animals received dimethyl sulfoxide (DMSO) and dimethylthiourea (DMTU) 30 min before heparin infusion. Group IV animals were given superoxide dismutase (SOD) 5 min before protamine. Group V served for testing the pulmonary vascular reactivity in DMTU-treated animals to a thromboxane A2 analogue (U-46619). Generation of oxygen free radicals by polymorphonuclear granulocytes (PMNs) was measured in vitro by chemiluminescence. Severe pulmonary hypertension and thromboxane A2 release after protamine were not prevented by either DMSO or SOD. DMTU reduced pulmonary vasoconstriction to U-46619 and protamine but not to TxA2 release, indicating that DMTU had unspecific vascular effects in group III. Heparin-protamine released no oxygen free radicals from isolated PMNs. The results indicate that oxygen free radicals do not have a key role in mediating pulmonary vasoconstriction after protamine neutralization of heparin.

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

PubMed1990

Thromboxane receptor blockade prevents pulmonary hypertension induced by heparin-protamine reactions in awake sheep.

We used competitive thromboxane A2-prostaglandin endoperoxide receptor blockade (SQ 30,741) as a probe to evaluate the role of thromboxane in ovine pulmonary vasoconstriction associated with protamine reversal of heparin anticoagulation. Control heparin-protamine reactions induced rapid release of thromboxane into arterial plasma (more than 1 ng/ml plasma), a 2.5-fold increase of pulmonary artery pressure, a 20% decrease of PaO2, and a 30% reduction in arterial white blood cell concentration. After giving SQ 30,741 despite similar thromboxane release into arterial plasma after heparin-protamine challenge, acute pulmonary hypertension was significantly reduced when 94% of pulmonary vascular smooth muscle thromboxane receptors were occupied with SQ 30,741 (p less than 0.01 at 1 minute after protamine versus control heparin-protamine reaction) and was completely abolished by a 10 mg/kg i.v. bolus (p less than 0.0001 at 1 minute after protamine versus control). Peripheral leukopenia was not affected by SQ 30,741 prophylaxis, but hypoxemia was prevented. We conclude that thromboxane causes pulmonary vasoconstriction in ovine heparin-protamine-induced pulmonary hypertension. Pulmonary vasoconstriction and hypoxemia can be completely prevented by thromboxane receptor blockade.

Animals↗

PubMed2001

Low molecular weight protamine (LMWP) as nontoxic heparin/low molecular weight heparin antidote (I): preparation and characterization.

Low molecular weight protamine (LMWP) appears to be a promising solution for heparin neutralization without the protamine-associated catastrophic toxic effects. The feasibility of this hypothesis was proven previously by using a peptide mixture produced from proteolytic digestion of protamine. To further examine the utility of this compound as an ultimate nontoxic protamine substitute, detailed studies on the purification and characterization of LMWP including the precise amino acid sequence, structure-function relationship, and possible mechanism were conducted. A number of LWMP fragments, composed of highly cationic peptides with molecular weights ranging from 700 to 1900 d, were prepared by digestion of native protamine with the protease thermolysin. These fragments were fractionated using a heparin affinity chromatography, and their relative binding strengths toward heparin were elucidated. Five distinct fractions were eluted at NaCl concentration ranging from 0.4 to 1.0 M and were denoted as TDSP1 to TDSP5, in increasing order of eluting ionic strength. Among these 5 fractions, TDSP4 and TDSP5 contained 3 LMWP peptide fragments, and they were found to retain the complete heparin-neutralizing function of protamine. By using a peptide mass spectrometry (MS) fingerprint mapping technique, the amino acid sequences of the microheterogeneous LMWP fragments in all these 5 elution fractions were readily identified. A typical structural scaffold made by arginine clusters in the middle and nonarginine residues at the N-terminal of the peptide sequence was observed for all these LMWP fragments. By aligning the sequences with the potency in heparin neutralization of these LMWP fragments, it was found that retention of potency similar to that of protamine required the presence of at least 2 arginine clusters in the LMWP fragments; such as the sequence of VSRRRRRRGGRRRR seen in the most potent LMWP fraction-TDSP5. The above finding was further validated by using a synthetic LMWP analogue-CRRRRRRR-and it was found that its heparin-neutralizing ability was increased by changing from a monomeric to a dimeric structure of this analogue peptide. Based on these results, the structural requirement for a compound to function as an effective heparin antidote and the possible mechanism involved in heparin neutralization were established.

Anticoagulants↗

PubMed1992

Comparison of thromboxane synthetase inhibitor and methylprednisolone effects on protamine responses in dogs.

Neutralization of heparin anticoagulation by protamine produces catastrophic hemodynamic reactions in some patients. Using a canine model, we tested effects of thromboxane synthetase inhibition (CGS-13080) and glucocorticoid pretreatment on the cardiorespiratory effects of protamine. In control dogs, protamine decreased mean arterial pressure and cardiac output and increased mean pulmonary artery pressure, systemic and pulmonary vascular resistances (SVR, PVR), and airway pressure. Both CGS-13080 and methylprednisolone ameliorated some effects of protamine. CGS-13080 infusion decreased mean pulmonary artery pressure, SVR, and airway pressure after protamine injection relative to controls. Cardiac output and PVR were unaffected by the drug, whereas the decrease in mean arterial pressure was prolonged. Plasma thromboxane A2 metabolite (TXB2) concentrations were lower and prostacyclin metabolite (6-keto PGF1 alpha) concentrations were higher compared with that of controls. These experiments support a role for TXA2 in the response to protamine. Methylprednisolone pretreatment produced larger cardiac output and lower airway pressure after protamine injection compared with controls. Mean arterial pressure was improved, but not significantly. Mean pulmonary artery pressure, SVR, and PVR were not different from that of controls; TXB2 and 6-keto PGF1 alpha were unaffected. The effects of methylprednisolone appear unrelated to arachidonic acid metabolism, as TXB2 and 6-keto PGF1 alpha levels were unaffected.

6-Ketoprostaglandin F1 alpha↗

PubMed1993

Heparin prevents the vasodilating actions of protamine on human small mesenteric arteries.

Despite the wide clinical use of protamine, the precise mechanisms of its hypotensive effects during reversal of heparin anticoagulation have not been elucidated fully. We, therefore, investigated the effects of protamine on isolated human small mesenteric arteries, both in the absence and presence of heparin, employing the isometric tension recording method. Protamine exerted vasodilating actions in the absence of heparin: 1) protamine (> or = 50 or 150 micrograms/mL) inhibited (P < 0.05) both norepinephrine (1 microM)- and high K+ (40 mM)-induced contractions in the presence of extracellular Ca2+ both in endothelium-intact and -denuded tissues; and 2) protamine inhibited (P < 0.05) norepinephrine (1 microM)-induced, but not caffeine (10 mM)-induced, contractions in the absence of extracellular Ca2+. Such vasodilating actions were blocked almost completely in the presence of heparin. We conclude that only protamine, but not a heparin-protamine complex, has a vasodilating action on the human arteries.

Aged↗

PubMed2005

Protamine after heparin produces hypotension resulting from decreased sympathetic outflow secondary to increased nitric oxide in the central nervous system.

To elucidate whether there are linkages among protamine-induced hypotension, nitric oxide (NO), and sympathetic nerve activity, we administered 3 mg/kg protamine sulfate after 300 U/kg heparin after 20 mg/kg of N(G)-nitro-D-arginine methyl ester (D-NAME) or N(G)-nitro-L-arginine methyl ester (L-NAME) as a pretreatment to baroreceptor-denervated rabbits and compared changes in hemodynamic variables and renal sympathetic nerve activity (RSNA). In the D-NAME group, heart rate (HR), mean arterial blood pressure (MAP), and RSNA significantly decreased to 93.7% +/- 0.7%, 75.0% +/- 5.1% and 65.2% +/- 4.6% (mean +/- SE), respectively. In the L-NAME group, the pretreatment of L-NAME significantly inhibited the depressant effects of protamine on these variables. Because the animals were totally baroreceptor-denervated, decreased RSNA was attributable to the central depressant effect of protamine, and decreased sympathetic outflow could have contributed to the reduction of HR and MAP. The depressant effect of protamine on sympathetic outflow was inhibited by the pretreatment with L-NAME, a NO synthase inhibitor, suggesting that decreased sympathetic outflow secondary to a protamine-induced increase in NO concentration in the central nervous system may contribute to protamine-induced cardiovascular depression.

Animals↗

PubMed1976

Purification and properties of biologically active rainbow trout testis protamine mRNA.

At least two classes of protamine mRNA are present in both trout testis polysomal RNA and RNA from the postribosomal supernatant fraction of trout testis hormogenate both of which direct the synthesis of protamine in a Krebs II ascites S-30. One contains poly(A) tracts and the other is devoid of poly(A). Sucrose gradient analyses showed that the poly(A) containing protamine mRNA (poly(A) (+)) sedimented IN THE 6 S region with a shoulder in the 4 S region while the protamine mRNA devoid of poly(A) (poly(A) (-)) appeared to sediment at about 4 S and could not be resolved from tRNA. Analysis of the poly(A) (+) protamine mRNA by boundary sedimentation in an analytical ultracentrifuge showed a sedimentation coefficient of 5.7 S, a value which gives rise to an estimate of 165 to 170 nucleotides per molecule. The poly(A) (+) protamine mRNA migrated as a single species in formamide-containing polyacrylamide gels and its mobility in relation to markers of tRNA (4 S) and 5 S RNA was consistent with its sedimentation velocity of 6 S. The RNA present in the major band on an aqueous polyacrylamide gel was extracted and shown to code for protamine in a wheat germ cell-free system.

Animals↗

PubMedDate not supplied

Pretreatment with H2 blocker famotidine to ameliorate protamine-induced hypotension in open-heart surgery.

An antagonist to H1 histamine receptor and one to H2 histamine receptor were used to prevent protamine-induced hypotension in 126 Japanese patients undergoing open heart surgery. In a study comparing an H1 antagonist "diphenhydramine" and an H2 antagonist "famotidine", 103 patients were divided into four groups: 31 patients were given no drugs (Group 1), 25 patients were given 0.4 mg/kg of diphenhydramine (Group 2), 33 patients were given 0.4 mg/kg of famotidine (Group 3), and 14 patients were given both the drugs (Group 4) before protamine administration. Although the systolic arterial pressure decreased significantly after protamine administration in all groups, famotidine was found to be effective in reducing protamine-induced hypotension, whereas diphenhydramine was not effective. In order to further investigate the hemodynamic changes in a double-blinded fashion, 12 patients were given normal saline (Group 5), while 11 patients were given 0.4 mg/kg of famotidine (Group 6) before protamine administration. Again, the minimal systolic and mean arterial pressures after protamine injection were significantly higher in Group 6 than in Group 5, while left atrial pressure, central venous pressure, heart rate, and cardiac index were almost the same and remained constant in the two groups. These results strongly suggest that the H2 antagonist "famotidine" is beneficial in reducing protamine-induced hypotension after cardiopulmonary bypass, while the H1 antagonist "diphenhydramine" is not.

Adolescent↗

PubMed1992

[Pulmonary reaction after protamine reversal of heparin in goats and rabbits].

Protamine reversal of heparin is often associated with severe hemodynamic side-effects, including pulmonary hypertension in cardiovascular surgery. However, the precise mechanism of this transient pulmonary hypertension is not clear. Recently, it was reported that pulmonary intravascular macrophages (PIM) react avidly with and phagocytize various foreign particles (liposome, latex, red cells). Sheep, goat and pig have a large population of PIM, but rabbit, rat and human have few. To investigate whether the pulmonary reaction after protamine reversal is related to PIM, we compared the pulmonary reaction after protamine reversal between goats and rabbits. We also studied it in patients for cardiac surgery. Protamine sulphate (2 mg.kg-1) was injected in 2.5 min into femoral artery at five min after heparin sodium (200 IU.kg-1) injection in goats and rabbits. Mean pulmonary arterial and peak airway pressures increased significantly after protamine reversal in goat. On the other hand, in rabbit and human, mean pulmonary arterial and peak airway pressures showed no significant changes. Goat was far more sensitive to protamine reversal than rabbit and human. We conclude that PIM may be the main cause of the pulmonary reaction after protamine reversal.

Animals↗