Percutaneous Carbon Dioxide Treatment Using a Gas Mist Generator Attenuates the Development of Right Ventricular Dysfunction in Monocrotaline-induced Pulmonary Hypertensive Rats

Osaka City Med J. 2015 Jun;61(1):31-41.

Abstract

Background: Highly concentrated carbon dioxide (GO2) is useful for treating ischemic diseases. Therefore, we investigated whether treatment with a few micrometers of CO2 molecules, atomized by two fluid nozzles (CO2 mist), could attenuate the development of right ventricular (RV) dysfunction in pulmonary hypertensive rats.

Methods: Six-week-old male Wistar rats were divided into three groups: one that received injected saline; a second that received subcutaneous monocrotaline (MCT; 60 mg/kg) without treatment (PH-UT) group; and a third that received MCT with CO2 mist treatment (PH-CM) after MCT administration. The lower body of each rat was encased in a polyethylene bag, filled with the designated gaseous agent via a gas mist generator, for 30 minutes daily. Hemodynamics and cardiac function were measured at 28 days after beginning MCT administration. Protein levels were measured by western blotting.

Results: Rats that received MCT without treatment began to die within 3-4 weeks of the initial administration. However, treatment with CO2 mist extended the survival period of rats in that group. At 28 days after MCT administration, the hemodynamic status, such as the blood pressure and heart rate, involved with left ventricular function, of rats in the PH-UT group were similar to those of rats in the PH-CM group. However, MCT-induced RV weight and RV dysfunction were significantly attenuated by treatment with CO2 mist. Both RV phosphorylated endothelial nitric oxide synthase and heat shock protein 72 levels increased significantly in the PH-CM group, compared to the PH-UT group.

Conclusions: Percutaneous CO2 mist therapy may alleviate RV dysfunction in patients with pulmonary hypertension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aerosols
  • Animals
  • Carbon Dioxide / administration & dosage*
  • Cardiovascular Agents / administration & dosage*
  • Disease Models, Animal
  • HSP72 Heat-Shock Proteins / metabolism
  • Hemodynamics / drug effects*
  • Hypertension, Pulmonary / chemically induced
  • Hypertension, Pulmonary / diagnosis
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / metabolism
  • Hypertension, Pulmonary / physiopathology
  • Male
  • Monocrotaline*
  • Myocardium / metabolism
  • Nebulizers and Vaporizers
  • Nitric Oxide Synthase Type III / metabolism
  • Phosphorylation
  • Rats, Wistar
  • Time Factors
  • Ventricular Dysfunction, Right / diagnosis
  • Ventricular Dysfunction, Right / metabolism
  • Ventricular Dysfunction, Right / physiopathology
  • Ventricular Dysfunction, Right / prevention & control*
  • Ventricular Function, Right / drug effects*

Substances

  • Aerosols
  • Cardiovascular Agents
  • HSP72 Heat-Shock Proteins
  • Carbon Dioxide
  • Monocrotaline
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat