Researchers in the Netherlands conducted a study, which revealed that people suffering from respiratory muscle weakness, which often accompanies chronic diseases, such as chronic obstructive pulmonary disease (COPD) might benefit from levosimendan, a calcium-sensitizing drug that could improve muscle function. Levosimendan is usually prescribed for patients with acute heart failure as it increases muscle tissue’s sensitivity to calcium and therefore enhances the muscle’s ability to contract. The findings were published online ahead of the print edition of the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.
Leo Heunks, M.D. PhD, who is a pulmonary and critical care physician at Radboud University Nijmegen Medical Centre in Nijmegen, the Netherlands, said:
“We found that the calcium sensitizer levosimendan improves the mechanical efficiency of the human diaphragm, suggesting a new, therapeutic approach to improve respiratory muscle function in patients with respiratory failure. Respiratory muscle weakness frequently occurs in patients with chronic diseases, and also in critically ill patients on the ventilator, making breathing more difficult and causing more severe illness and even death. To date, there is no specific drug treatment available to improve respiratory muscle function in patients with respiratory muscle failure.”
Calcium is a vital element for the contraction of muscles. By enhancing the muscle tissue sensitivity to Calcium, drugs like levosimendan improve the tissue’s ability to contract. In vitro studies have proven that calcium sensitizers improve respiratory muscle function, while findings of animal studies have demonstrated that calcium sensitivity is reduced in specific chronic illness settings. A recent in vitro study that took diaphragm muscle tissue from COPD patients confirmed levosimendan’s ability to enhance muscle tissue contraction.
Based on the results of those studies, Dr. Heunk and his team decided to examine whether levosimendan would improve the ability of the diaphragm muscle to contract in healthy volunteers. They conducted a study involving 30 healthy volunteers who were randomized to receive either levosimendan or placebo.
Both groups performed two identical breathing exercises, one prior to receiving levosimendan or placebo and one afterward.
To measure the nervous system’s stimulation of the respiratory muscles and the amount of force those muscles used in forced exhalation during each exercise the researchers used a specialized catheter. Heart rate, blood pressure, exhaled carbon dioxide and blood oxygen levels were continuously measured in all volunteers and diaphragm movements before and after the exercise period were assessed by magnetic nerve stimulation.
At the end of the study findings revealed that after the exercises, volunteers in the placebo group had a 9-percent loss of muscle contraction, while those in the levosimendan group showed no loss of contraction. Researchers also discovered that the diaphragm’s mechanical efficiency improved by 21 % in the levosimendan group during the exercises compared with the placebo group. This means that volunteers in the levosimendan group required less effort to achieve the same amount of muscle force in the diaphragm than those treated with placebo.
Dr. Heunks explained:
“On average, the breathing exercises in subjects receiving placebo resulted in significant reductions in diaphragm muscle contractions, while the group receiving levosimendan had no significant decrease in contractions. Essentially, levosimendan prevents the development of muscle fatigue of the respiratory muscles.”
He pointed out that to confirm these results and determine the optimal dose, larger studies are required even though these findings indicate calcium sensitizers like levosimendan may provide an effective therapeutic option for chronically ill patients with respiratory muscle weakness or those using mechanical ventilation.
In a concluding statement Heunks said:
“The dose of levosimendan used in this current study was derived from earlier studies in healthy subjects, demonstrating limited side effects. Future studies should evaluate the effects of lower doses of levosimendan on respiratory muscle function in humans, to ensure patients can be effectively treated with as little risk for side effects or complications as possible.”
Written by Petra Rattue