The systemic vasodilatory action of protamine: is it inhibited or mediated by heparin?

Ordoñez, Antonio; Domínguez, José Miguel; Tejero, P. Garcia; Bernal, José Pérez; Hinojosa, R.; López-Hidalgo, Javier

doi:10.1007/s004330050082

Cited by 7 publications

(2 citation statements)

References 18 publications

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“…PS has many well-known side effects, such as hypotension, pulmonary vasoconstriction, and anaphylaxis (32,40,50). While PS can induce dose-dependent proteinuria (35,52,55), high doses of PS can also cause oliguria (35).…”

Section: Discussionmentioning

confidence: 99%

Dynamic, size-selective effects of protamine sulfate and hyaluronidase on the rat glomerular filtration barrier in vivo

Sverrisson

Axelsson

Rippe

et al. 2014

American Journal of Physiology-Renal Physiology

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The proteinuric actions of protamine sulfate (PS) have classically been, at least partly, attributed to alterations of the negatively charged glomerular endothelial glycocalyx. To investigate whether the charge-selective properties of the glomerular filtration barrier (GFB) would be altered by PS, we assessed the glomerular sieving of conventional, uncharged, polydispersed Ficoll (n-Ficoll) compared with charge modified, conformationally intact, anionic (carboxymethylated) Ficoll (a-Ficoll) before and after systemic infusions of PS in rats. For comparison, we also investigated the impact of hyaluronidase (hyase), which partially degrades the glycocalyx, on GFB permeability. In anaesthetized Wistar rats, blood access was achieved, and the left ureter was cannulated for urine collection. Rats were infused with either n-Ficoll or a-Ficoll before and during systemic infusions with either PS or hyase. Plasma and urine samples were taken repeatedly and analyzed by high-performance size exclusion chromatography to assess glomerular sieving coefficients (θ) for Ficoll (radius 10-80 Å). The GFB showed a significant glomerular charge selectivity for Ficoll molecules of radius 20-35 Å. PS and hyase infusions reversibly increased θ for large Ficoll molecules (Ficoll molecules of radius 50-80 Å). Thus, for PS, θ for a-Ficoll molecules of radius 70 Å increased from 2.47 × 10(-5) ± 1.1(-5) to 7.25 × 10(-5) ± 1.1(-5) (P < 0.05) at 15 min. For hyase, changes in a-Ficoll molecules of radius 50-80 Å were, however, not statistically significant. Neither PS nor hyase had any effect on θ for n-Ficoll molecules of radius 20-45 Å or a-Ficoll molecules of radius 20-45 Å. It is concluded that systemically administered PS and hyase in moderate doses dynamically decreased the size selectivity of the rat GFB without affecting its charge selective properties.

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Section: Discussionmentioning

confidence: 99%

Dynamic, size-selective effects of protamine sulfate and hyaluronidase on the rat glomerular filtration barrier in vivo

Sverrisson

Axelsson

Rippe

et al. 2014

American Journal of Physiology-Renal Physiology

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“…Another reason could be that the protamine induced vasodilation. 23 If the vessels in muscle are dilated, more contrast medium could be delivered into muscle.…”

Section: Discussionmentioning

confidence: 99%

Assessment of protamine‐induced thrombosis of tumor vessels for cancer therapy using dynamic contrast‐enhanced MRI

Samoszuk

Wang

et al. 2002

NMR in Biomedicine

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Since the role of angiogenesis in cancer development has been recognized, the study of anti-angiogenic or anti-vascular therapeutic agents has become increasingly important for cancer treatment. Selective thrombosis is one approach towards this goal. Since many types of carcinoma accumulate large numbers of degranulating mast cells which will release heparin, intravenously injected protamine may bind to heparin, neutralize its anti-coagulant effect and induce thrombosis. In this work we studied the formation of thrombosis by using dynamic contrast enhanced MRI. The enhancement kinetics of the contrast medium measured before and after protamine treatment were compared to assess the thrombotic effect. The underlying concept was that if the vessels became clotted, the subsequently injected contrast medium could not be delivered into the tissue to cause enhancement. In addition to the tissue-specific changes, protamine may also induce systemic effect in the host. The therapy-induced changes measured in tumors were compared to changes in normal tissues: liver, kidney, and especially the muscle adjacent to tumor. The results showed that protamine induced pronounced changes in the tumor. However, the degree of change measured by MRI was not associated with the results of semiquantitative assessment of thrombosis assessed by histology, perhaps due to the heterogeneous nature of the tumor and the difficulty in sampling sufficient regions histologically. The protamine-induced temporal effects were also studied. We demonstrated that protamine could induce selective thrombosis in tumors, and that the effect could last for several hours. Dynamic contrast-enhanced MRI can serve as a suitable means to investigate the mechanism of this novel approach to induce selective thrombosis for anti-vascular cancer therapy.

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Protamine

Pugsley

2007

xPharm: The Comprehensive Pharmacology Reference

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The systemic vasodilatory action of protamine: is it inhibited or mediated by heparin?

Cited by 7 publications

References 18 publications

Dynamic, size-selective effects of protamine sulfate and hyaluronidase on the rat glomerular filtration barrier in vivo

Dynamic, size-selective effects of protamine sulfate and hyaluronidase on the rat glomerular filtration barrier in vivo

Assessment of protamine‐induced thrombosis of tumor vessels for cancer therapy using dynamic contrast‐enhanced MRI

Protamine

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