Low bioavailability of the amino acid arginine may contribute to cardiopulmonary dysfunction in patients with β-thalassemia, according to researchers.
Via previous work, the team found that arginine deficiency is a major factor in acute pain episodes in sickle cell disease.
With the current study, they discovered that arginase activity and concentration correlate with echocardiographic and cardiac-MRI measurements of cardiopulmonary function.
Claudia R. Morris, MD, of Emory University School of Medicine in Atlanta, Georgia, and her colleagues described this research in the British Journal of Haematology.
“We are finding that arginine dysregulation is an important hematologic mechanism beyond sickle cell disease,” Dr Morris said. “This new study shows that it plays a role in thalassemia patients as well and may contribute to cardiopulmonary dysfunction. Interventions aimed at restoring arginine bioavailability could be a promising area of focus for new therapeutics.”
Dr Morris and her colleagues noted that pulmonary hypertension (PH) is a common problem in patients with thalassemia. An elevated tricuspid-regurgitant jet-velocity (TRV) of 2.5 m/s or greater on Doppler echocardiography can identify patients with an increased risk of PH. But a right heart catheterization is required to confirm the condition.
The researchers wanted to provide a comprehensive description of the cardiopulmonary and biological profile of thalassemia patients at risk of developing PH. So they analyzed 27 patients with β-thalassemia.
Fourteen patients had an elevated TRV (≥ 2.5 m/s). According to echocardiography, these patients had a significantly larger right atrial size (P=0.03), left atrial size (P=0.002), left ventricular (LV) mass (P=0.03), and left septal-wall thickness (P=0.03) than patients with a TRV below 2.5 m/s.
According to MRI, patients with elevated TRV had significantly higher left atrial volume than patients with a TRV < 2.5 m/s (P=0.008).
Patients with an elevated TRV also had elevated lactate dehydrogenase (LDH) levels (P=0.03) and biomarkers of abnormal coagulation, including thrombin-antithrombin complex (P=0.04) and monoclonal prothrombin fragment 1.2 (P=0.02).
Patients with a TRV ≥ 2.5 m/s had significantly lower plasma arginine concentration (P<0.001) and biomarkers of global arginine bioavailability, including plasma arginine/ornithine ratio (P=0.01) and mean plasma global arginine bioavailability ratio (arginine/ornithine + citrulline ratio, P=0.04).
These patients also had significantly higher arginase concentration and activity than patients with TRV below 2.5 m/s (P=0.02).
These findings prompted the researchers to evaluate the relationship between arginase activity/concentration and clinical and laboratory markers of disease severity.
They found that arginase concentration was significantly correlated with several parameters of cardiovascular function, including left atrial volume (echo and MRI), right atrial volume (MRI), LV end systolic volume (echo and MRI), LV end diastolic volume (echo and MRI), LV mass (echo and MRI), and cardiac index (echo).
Arginase concentration was also significantly correlated with white blood cell count (P=0.03), plasma arginine (P=0.0002), arginine/ornithine (P=0.01) and arginine/ornithine + citrulline ratios (P=0.05), and hemoglobin (P=0.02), bilirubin (P=0.02), and LDH levels (P=0.001).
In multiple regression analysis, only cardiac index, bilirubin, and plasma arginine/ornithine ratio remained significantly associated with arginase concentration (P<0.05 for all).
Arginase activity was significantly correlated with several biomarkers of coagulation, including monoclonal prothrombin fragment 1.2 (P=0.04), thrombin-antithrombin complex (P=0.04), and tissue factor concentration (P=0.02).
Considering these results together, the researchers said it seems low arginine bioavailability contributes to cardiopulmonary dysfunction in patients with β-thalassemia.
