Experimental Inhibition of Protamine Cardiotoxicity by Prostacyclin

Abstract

Twelve animals (26+/-5 kg) were subjected to the study. In this experimental study, the authors used prostacyclin to inhibit the toxic metabolite release during protamine administration. Animals were divided into two equal groups. Six animals received prostacyclin (the prostacyclin group), and the other six animals did not receive any additional treatment (the control group). All cardiac output and biochemical measurements were evaluated at baseline; before cardiopulmonary bypass; and at 5, 30, and 60 minutes after protamine administration. The measured cardiac index showed that the hearts treated with prostacyclin had satisfactory preservation of left ventricular function. Metabolic and biochemical data showed that the tumor necrosis factor level was raised significantly in the control group (20.75+/-2.2 in the control group and 13.75+/-2.5 pg/mL in the prostacyclin group). Also, E and P selectin levels were elevated in the control group, but this change was less marked in the prostacyclin group. In addition, the intracellular adhesion molecule-1 (ICAM-1) level was significantly higher in the control group than in the prostacyclin group (9.26+/-2.13 in the control group and 5.13+/-1.66 ng/mL in the prostacyclin group). The authors observed that prostacyclin inhibited the toxic mediator release during heparin reversal with protamine. This inhibition is one way of protecting the myocardium reserves from protamine cardiotoxicity.

Cyclic AMP elevating agents and nitric oxide modulate angiotensin II‐induced leukocyte‐endothelial cell interactions in vivo

“…Moreover, other studies have also shown that cyclic AMP elevating agents or NO donors can reduce P‐selectin expression and release in stimulated platelets ( Konstantopoulos et al ., 1998 ; Salas et al ., 1994 ). Furthermore, as witnessed in platelets, prostacyclin treatment in animals subjected to protamine administration provokes a decrease in E and P‐selectin levels and a more marked preservation of left ventricular function ( Katircioglu et al ., 1999 ). Similarly, treatment with NO donors has been found to attenuate homocysteine‐induced P‐selectin expression in rat mesenteric venules ( Pruefer et al ., 1999 ).…”

Ulinastatin attenuates protamine-induced cardiotoxicity in rats by inhibiting tumor necrosis factor alpha

“…However, protamine administration is occasionally associated with serious side effects, including myocardial dysfunction (Oguchi et al 2001). Reversal of the effects of heparin with protamine results in elevation of plasma TNF-α concentration in the animal cardiopulmonary bypass model (Katircioglu et al 1999). Pevni et al also demonstrated that TNF-α plays an important role in protamine-induced cardiac depression (Pevni et al 2001).…”

Heparin Reversal in Off-Pump Coronary Artery Bypass Surgery: Complete, Partial, or no Reversal?

“…From clinical and experimental observations, it is known that heparin reversal with protamine causes dose~dependent. decreases in cardiac contractility a~d In myocardial oxygen extraction and consumpnon [15][16][17][18]. Furthermore, low-dose administration of protamine spares platelet function [19][20][21].…”