Dopamine Alleviation of ROS Mediate Diaphragm Fatigue

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Name: Janet Pierce

Rank: CDR, USNR

Organization: University of Kansas Medical Center

Performance Site: University of Kansas Medical Center, Kansas City, KS

Year Published: 2002

Abstract Status: Final

Abstract

Purpose: In military hospitals, hundreds of patients require mechanical ventilation. Often, weaning from ventilators is difficult because of diaphragm fatigue. The objective of this research was to determine the mechanisms by which dopamine affects reactive oxygen species (ROS) formation and, therefore, diaphragm fatigue. Design: This study used a quasi-experimental design in Sprague-Dawley male adult rats to study the effects of dopamine on ROS-mediated diaphragm fatigue. ROS damage was measured directly by cellular DNA damage and apoptosis and indirectly by noninvasive measurement of exhaled H2O2.Methods: The rats were anesthetized, a tracheostomy was performed, and a two-way valve was attached. Either normal saline (control group) or low-dose dopamine at 2 ┬╡g/kg/minute (treatment group) was intravenously infused for 10 minutes. Following the infusion, inspiratory resistance loading (IRL) was applied for 45 minutes to maintain the intrathoracic pressure at'80 mm Hg. After the IRL, the diaphragm was removed to assess DNA damage and apoptosis.Analysis: Nonparametric statistics were used to compare diaphragm shortening (DS), DNA damage, exhaled H2O2, and apoptosis within and between groups. Findings: In rats receiving a normal saline infusion (control group), DS decreased by 45% following 45-minute IRL whereas rats infused with low-dose dopamine demonstrated a 40% increase in DS compared to sham controls. The dopamine group also had significantly less apoptotic and necrotic chromatin. Comet assays indicated that significantly less DNA damage occurred in the dopamine group. Administration of low-dose dopamine during IRL may prevent diaphragm fatigue in rats by decreasing ROS.Nursing Implications: These findings provided the data necessary for clinical trials to test dopamine as a means for improving diaphragm function. Furthermore, molecular and biochemical markers proved to be reliable methods for determining the effects of dopamine on diaphragm function. Pharmacological support to enhance diaphragm performance could be used alone or with other weaning protocols to re-establish respiratory function.