Protamine cardiotoxicity and nitric oxide

Citation
D. Pevni et al., Protamine cardiotoxicity and nitric oxide, EUR J CAR-T, 20(1), 2001, pp. 147-152
Citations number
25
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Respiratory Systems
Journal title
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY
ISSN journal
1010-7940 → ACNP
Volume
20
Issue
1
Year of publication
2001
Pages
147 - 152
Database
ISI
SICI code
1010-7940(200107)20:1<147:PCANO>2.0.ZU;2-H
Abstract
Objectives: The purpose of this study is to assess the role of the nitric o xide (NO) pathway in protamine-induced cardiotoxicity and to formulate a po ssible explanation far this adverse effect. Methods: Isolated rat hearts we re perfused by Krebs-Henseleit (KH) solution using a modified Langendorff m odel. They were randomized into three groups: A, 40 min perfusion with KH s olution; B, 20 min perfusion with KH solution and 20 min with protamine; C, as B but Ng-monomethyl-L-arginine (L-NMMA), a non-selective inhibitor of t he NO pathway, was added during 40 min of the perfusion period. Left ventri cular (LV) function was measured every 10 min. NO and tumor necrosis factor -alpha (TNF) were detected in the effluent from the coronary sinus (CS) and in the supernatant of the cardiac myocytes culture. Nitric oxide synthases (NOS) mRNA levels were determined in groups A and B from LV samples at bas eline and after 40 min of perfusion. Results: We found that protamine at a dose of 12 mug/ml causes significant depression of LV function (decreased p eak systolic pressure to 22.5 +/- 3.2% and dP/dt max to 22.9 +/- 3.1%). L-N MMA did not prevent protamine cardiotoxicity. NOS mRNA was not detected fro m LV samples in any group. The NO in the effluent from the CS and from the supernatant of the cardiomyocytes culture was below detectable levels. Howe ver, a significant amount of TNF was measured in the effluent from the CS ( 108 +/- 17 pg/min for group B and 117 +/- 13 pg/min for group C) and in the supernatant of the cardiomyocytes culture (65 +/- 21 pg/ml). Conclusions: This study suggests that direct protamine-induced cardiotoxicity does not d epend on the NO pathway. Our finding that protamine induced TNF release by cardiomyocytes can shed new light on the understanding of protamine cardiot oxicity. (C) 2001 Elsevier Science B.V. All nights reserved.