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 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.

• Authors: Kristofer F Nilsson, Waldemar Gozdzik, Stanislaw Zielinski, Kornel Ratajczak, Sofie P Göranson, Sylwia Rodziewicz, Piotr Harbut, Barbara Barteczko-Grajek, Johanna Albert, Claes Frostell
• Journal: Shock (Augusta, Ga.) (Shock) Vol. 54 Issue 1 Pg. 119-127 (07 2020) ISSN: 1540-0514 [Electronic] United States
• PMID: 31425404 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nitrites
• Propylene Glycols
• Propylene Glycol
• Nitroglycerin

Topics

• Animals
• Disease Models, Animal
• Female
• Hypertension, Pulmonary (drug therapy, physiopathology)
• Infusions, Intravenous
• Male
• Nitrites (administration & dosage, pharmacology)
• Nitroglycerin (administration & dosage, pharmacology)
• Propylene Glycol (administration & dosage, pharmacology)
• Propylene Glycols (administration & dosage, pharmacology)
• Pulmonary Artery (drug effects)
• Swine
• Vasodilation (drug effects)