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

Abstract

Introduction: 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−1 min−1), nitroglycerin (44 nmol kg−1 min−1), 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.

NO-Donation Increases Visceral Circulation in a Porcine Model of Abdominal Hypertension

“…However, PDNO completely counteracted the increase in systemic vascular resistance, an effect that was not present in the Control group. The known IAH effect on MPAP was confirmed in the present study [ 7 ]. It was evident that PDNO significantly delayed the MPAP increase whereas placebo did not.…”

“…In contrast, organic nitrite NO-donors are associated with less tolerance development and have therefore been presented as an attractive alternative. Previously, we designed a novel NO-donor, comprising the organic mononitrites of 1,2-propanediol, nitrosooxypropanol (PDNO), and found that it was an effective vasodilator in some different models of acute pulmonary hypertension [7,[9][10][11], and that it ameliorated renal ischemia reperfusion injury [12]. A phase I study in humans is ongoing (Eura-daCT No.…”

“…As a cardiovascular signalling molecule, nitric oxide (NO) has been shown to positively affect both lung and kidney function after aortic cross clamping by having a mitigating effect on the systemic inflammatory response [ 7 , 8 ]. Organic nitrate NO-donors (e.g., nitroglycerin) have the drawback of tolerance development in both the systemic and the pulmonary circulation [ 9 ].…”

Effect Of Microvessels Stiffness on Hemodynamic; an FSI Analysis

“…In this work, the effect of changes in vascular stiffness in blood pressure and WSS was investigated numerically. While vasodilation is known as the most important way to control hypertension (Giles, Sander, Nossaman, & Kadowitz, 2012), its side effects are always controversial (Nilsson et al, 2020), (Okada et al, 2020). Therefore, finding the causes and roots of hypertension and its symptoms can be an effective step in determining the treatment strategy.…”