Abstract
OBJECTIVE:To examine if methylene blue (MB) can counteract or prevent protamine (P) cardiovascular effects.METHODS:The protocol included five heparinized pig groups: Group Sham -without any drug; Group MB - MB 3 mg/kg infusion; Group P - protamine; Group P/MB - MB after protamine; Group MB/P - MB before protamine. Nitric oxide levels were obtained by the nitric oxide/ozone chemiluminescence method, performed using the Nitric Oxide Analizer 280i (Sievers, Boulder, CO, USA). Malondialdehyde plasma levels were estimated using the thiobarbiturate technique.RESULTS:1) Groups Sham and MB presented unchanged parameters; 2) Group P - a) Intravenous protamine infusion caused mean arterial pressure decrease and recovery trend after 25-30 minutes, b) Cardiac output decreased and remained stable until the end of protamine injection, and c) Sustained systemic vascular resistance increased until the end of protamine injection; 3) Methylene blue infusion after protamine (Group P/MB) - a) Marked mean arterial pressure decreased after protamine, but recovery after methylene blue injection, b) Cardiac output decreased after protamine infusion, recovering after methylene blue infusion, and c) Sustained systemic vascular resistance increased after protamine infusion and methylene blue injections; 4) Methylene blue infusion before protamine (Group MB/P) - a) Mean arterial pressure decrease was less severe with rapid recovery, b) After methylene blue, there was a progressive cardiac output increase up to protamine injection, when cardiac output decreased, and c) Sustained systemic vascular resistance decreased after protamine, followed by immediate Sustained systemic vascular resistance increase; 5) Plasma nitrite/nitrate and malondialdehyde values did not differ among the experimental groups.CONCLUSION:Reviewing these experimental results and our clinical experience, we suggest methylene blue safely prevents and treats hemodynamic protamine complications, from the endothelium function point of view.
Highlights
Clinical and experimental observations prove that heparinneutralizing doses of protamine increase pulmonary artery pressures and decrease systemic blood pressure
Reviewing these experimental results and our clinical experience, we suggest methylene blue safely prevents and treats hemodynamic protamine complications, from the endothelium function point of view
The third study, carried out in anesthetized dogs, reported the methylene blue (MB) and nitric oxide (NO) synthase blockers neutralization of the protamine vasodilatory effects[3] The fourth study proposed that protamine causes endothelium-dependent vasodilation in heart microvessels and conductance arteries by different mechanisms, including hyperpolarization[4]. Reviewing those experimental results and our clinical experience, we suggest MB as a novel approach to prevent and treat hemodynamic complications caused by the use of protamine after cardiopulmonary bypass[5]
Summary
Clinical and experimental observations prove that heparinneutralizing doses of protamine increase pulmonary artery pressures and decrease systemic blood pressure. Protamine increases myocardial oxygen consumption, cardiac output (CO), and heart rate, and decreases systemic vascular resistance. These cardiovascular effects have clinical consequences that have justified studies in this area. Protamine adverse reactions usually can be classified into three different categories, namely: systemic hypotension, anaphylactoid reactions, and catastrophic pulmonary vasoconstriction. The precise mechanism that explains protamine-mediated systemic hypotension is unknown. Four experimental protocols performed at Mayo Clinic (Rochester, MN, USA) studied the intrinsic mechanism of
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