Inhaled Nitric Oxide Reduces Lung Injury During Cardiac Surgery With One-Lung Ventilation in an Experimental Pig Model

Abstract

Objective:

Minimally invasive cardiac surgery (MICS) may require one-lung ventilation (OLV) during minithoracotomy. One of the problems associated with MICS is postoperative unilateral pulmonary edema of the collapsed lung, which may be fatal. Several reports have demonstrated the effects of inhaled nitric oxide (NO) on lung ischemia-reperfusion injury. In this study, we created an in vivo pig model using cardiopulmonary bypass (CPB) and OLV, enabling us to compare bilateral lung injury at the same time point in the same individual. The aim of this study is to examine the effects of inhaled NO in a model that approximates MICS.

Methods:

Ten pigs were subjected to 3 h of CPB and OLV with clamping of the main pulmonary artery. The bilateral lungs of the pigs were categorized into 4 groups according to their ventilation status and the presence or absence of NO inhalation (n = 5 per group). Lungs were collected after the experiment, and inflammatory cytokine measurements and pathological evaluations were performed.

Results:

In the OLV group (group 1 vs 2), the levels of interleukin-6, interleukin-8, and myeloperoxidase in collapsed lung tissue increased, along with an increase in the number of apoptotic cells and exacerbation of pulmonary edema. In the collapsed lungs (group 2 vs 4), NO inhalation reduced the levels of interleukin-6 and myeloperoxidase, the number of apoptotic cells, and pulmonary edema.

Conclusions:

In an animal model using a combination of CPB and OLV, inhaled NO suppressed pulmonary edema and improved the exacerbated lung injury of collapsed lungs.

Visual abstract

Keywords

inhaled nitric oxide lung ischemia-reperfusion injury one-lung ventilation cardiopulmonary bypass minimally invasive cardiac surgery

Get full access to this article

View all access options for this article.

References

Tutschka

Bainbridge

Chu

, et al. Unilateral postoperative pulmonary edema after minimally invasive cardiac surgical procedures: a case-control study. Ann Thorac Surg 2015; 99: 115–122.

Shires

Green

Owen

, et al. Case 4–2009. Severe reexpansion pulmonary edema after minimally invasive aortic valve replacement: management using extracorporeal membrane oxygenation. J Cardiothorac Vasc Anesth 2009; 23: 549–554.

Ignarro

Harbison

Wood

, et al. Activation of purified soluble guanylate cyclase by endothelium-derived relaxing factor from intrapulmonary artery and vein: stimulation by acetylcholine, bradykinin and arachidonic acid. J Pharmacol Exp Ther 1986; 237: 893–900.

Fattouch

Sbraga

Sampognaro

, et al. Treatment of pulmonary hypertension in patients undergoing cardiac surgery with cardiopulmonary bypass: a randomized, prospective, double-blind study. J Cardiovasc Med 2006; 7: 119–123.

Potapov

Meyer

Swaminathan

, et al. Inhaled nitric oxide after left ventricular assist device implantation: a prospective, randomized, double-blind, multicenter, placebo-controlled trial. J Heart Lung Transplant 2011; 30: 870–878.

De Caterina

Libby

Peng

, et al. Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. J Clin Invest 1995; 96: 60–68.

Walley

McDonald

Higashimoto

, et al. Modulation of proinflammatory cytokines by nitric oxide in murine acute lung injury. Am J Respir Crit Care Med 1999; 160: 698–704.

Kagawa

Morita

Nagahori

, et al. Prevention of ischemia/reperfusion-induced pulmonary dysfunction after cardiopulmonary bypass with terminal leukocyte-depleted lung reperfusion. J Thorac Cardiovasc Surg 2010; 139: 174–180.

Luna-Flores

Olmos-Zuñiga

Jasso-Victoria

, et al. Expression of Claudin-4 in lung ischemia-reperfusion injury in experimental lung transplantation. J Invest Surg 2022; 35: 191–200.

10.

Levy

and Tanaka

KA.

Inflammatory response to cardiopulmonary bypass. Ann Thorac Surg 2003; 75: S715–S720.

11.

Allison

Kyle

Adkins

, et al. Effect of ischemia reperfusion or hypoxia reoxygenation on lung vascular permeability and resistance. J Appl Physiol 1990; 69: 597–603.

12.

den Hengst

Gielis

Lin

, et al. Lung ischemia-reperfusion injury: a molecular and clinical view on a complex pathophysiological process. Am J Physiol Heart Circ Physiol 2010; 299: H1283–H1299.

13.

Yamashita

Akamine

Sumida

, et al. Inhaled nitric oxide attenuates apoptosis in ischemia-reperfusion injury of the rabbit lung. Ann Thorac Surg 2004; 78: 292–297.

14.

Moncada

and Higgs

EA.

The discovery of nitric oxide and its role in vascular biology. Br J Pharmacol 2006; 147: S193–S201.

15.

Miller

McMullin

, et al. A phase I clinical study of inhaled nitric oxide in healthy adults. J Cyst Fibros 2012; 11: 324–331.

16.

Janssens

Bogaert

Zalewski

, et al. Nitric oxide for inhalation in ST-elevation myocardial infarction (NOMI): a multicentre, double-blind, randomized controlled trial. Eur Heart J 2018; 39: 2717–2725.

17.

Mitchell

Grocott

Phillips-Bute

, et al. Cytokine secretion after cardiac surgery and its relationship to postoperative fever. Cytokine 2007; 38: 37–42.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.05 MB

0.02 MB