Pulmonary Vasodilation by Intravenous Infusion of Organic Mononitrites Of 1,2-Propanediol in Acute Pulmonary Hypertension Induced by Aortic Cross Clamping and Reperfusion: A Comparison With Nitroglycerin in Anesthetized Pigs
Kristofer F. Nilsson , Waldemar Goździk , Stanislaw Zielinski , Kornel Ratajczak , Sofie P. Göranson , Sylwia Rodziewicz , Piotr Harbut , Barbara Barteczko-Grajek , Johanna Albert , Claes Frostell
AbstractIntroduction: Suprarenal aortic cross clamping (SRACC) and reperfusion may cause acute pulmonary hypertension and multiple organ failure. Hypothesis: The organic mononitrites of 1,2-propanediol (PDNO), an nitric oxide donor with a very short half-life, are a more efficient pulmonary vasodilator and attenuator of end-organ damage and inflammation without significant side effects compared with nitroglycerin and inorganic nitrite in a porcine SRACC model. Methods: Anesthetized and instrumented domestic pigs were randomized to either of four IV infusions until the end of the experiment (n = 10 per group): saline (control), PDNO (45 nmol kg min), nitroglycerin (44 nmol kg min), or inorganic nitrite (a dose corresponding to PDNO). Thereafter, all animals were subjected to 90 min of SRACC and 10 h of reperfusion and protocolized resuscitation. Hemodynamic and respiratory variables as well as blood samples were collected and analysed. Results: During reperfusion, mean pulmonary arterial pressure and pulmonary vascular resistance were significantly lower, and stroke volume was significantly higher in the PDNO group compared with the control, nitroglycerin, and inorganic nitrite groups. In parallel, mean arterial pressure, arterial oxygenation, and fraction of methaemoglobin were similar in all groups. The serum concentration of creatinine and tumor necrosis factor alpha were lower in the PDNO group compared with the control group during reperfusion. Conclusions: PDNO was an effective pulmonary vasodilator and appeared superior to nitroglycerin and inorganic nitrite, without causing significant systemic hypotension, impaired arterial oxygenation, or methaemoglobin formation in an animal model of SRACC and reperfusion. Also, PDNO may have kidney-protective effects and anti-inflammatory properties.
|Journal series||Shock, ISSN 1073-2322, e-ISSN 1540-0514, (N/A 100 pkt)|
|Publication size in sheets||0.5|
|Keywords in English||Abdominal, acute kidney injury, aorta, cytokines, ischemia, multiple organ failure, nitric oxide donors, REBOA, reperfusion injury, FiO2, inspired fraction of oxygen, GTN, nitroglycerin, HR, heart rate, IL, interleukin, MAP, mean systemic arterial pressure, MPAP, mean pulmonary arterial pressure, NO, nitric oxide, P50, partial pressure of oxygen where haemoglobin is 50% saturated, PCWP, pulmonary capillary wedge pressure, PCO2, partial pressure of carbon dioxide, PDNO, the organic mononitrites of 1,2-propanediol, PO2, partial pressure of oxygen, PVRI, pulmonary vascular resistance index, SEM, standard error of the mean, SVI, stroke volume index systemic and pulmonary resistance indices (SVRI and PVRI, SVRI, systemic vascular resistance index, SRACC, suprarenal aortic cross clamp, TNF, tumor necrosis factor|
|Score||= 100.0, 15-09-2020, ArticleFromJournal|
|Publication indicators||: 2016 = 1.005; : 2019 = 2.96 (2) - 2019=3.275 (5)|
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