Matrix metalloproteinase inhibition attenuates right ventricular dysfunction and improves responses to dobutamine during acute pulmonary thromboembolism.

Activated matrix metalloproteinases (MMPs) cause cardiomyocyte injury during acute pulmonary thromboembolism (APT). However, the functional consequences of this alteration are not known. We examined whether doxycycline (a MMP inhibitor) improves right ventricle function and the cardiac responses to dobutamine during APT. APT was induced with autologous blood clots (350 mg/kg) in anaesthetized male lambs pre-treated with doxycycline (Doxy, 10 mg/kg/day, intravenously) or saline. Non-embolized control lambs received doxycycline pre-treatment or saline. The responses to intravenous dobutamine (Dob, 1, 5, 10 µg/kg/min.) or saline infusions at 30 and 120 min. after APT induction were evaluated by echocardiography. APT increased mean pulmonary artery pressure and pulmonary vascular resistance index by ~185%. Doxycycline partially prevented APT-induced pulmonary hypertension (P < 0.05). RV diameter increased in the APT group (from 10.7 ± 0.8 to 18.3 ± 1.6 mm, P < 0.05), but not in the Doxy+APT group (from 13.3 ± 0.9 to 14.4 ± 1.0 mm, P > 0.05). RV dysfunction on stress echocardiography was observed in embolized lambs (APT+Dob group) but not in embolized animals pre-treated with doxycycline (Doxy+APT+Dob). APT increased MMP-9 activity, oxidative stress and gelatinolytic activity in the RV. Although doxycycline had no effects on RV MMP-9 activity, it prevented the increases in RV oxidative stress and gelatinolytic activity (P < 0.05). APT increased serum cardiac troponin I concentrations (P < 0.05), doxycycline partially prevented this alteration (P < 0.05). We found evidence to support that doxycycline prevents RV dysfunction and improves the cardiac responses to dobutamine during APT.

Right Ventricular Systolic Dysfunction in Chagas Disease Defined by Speckle-Tracking Echocardiography: A Comparative Study with Cardiac Magnetic Resonance Imaging.

BACKGROUND: Chagas disease leads to biventricular heart failure, usually with prominent systemic congestion. Although echocardiography is widely used in clinical routine, the utility of echocardiographic parameters to detect right ventricular (RV) systolic dysfunction in patients with Chagas disease is unknown. We sought to study the diagnostic value of echocardiography, including speckle-tracking parameters, to distinguish individuals with RV systolic dysfunction from those with normal RV systolic function in Chagas disease using cardiac magnetic resonance (CMR) as the reference method. METHODS: In this cross-sectional study, 63 individuals with Chagas disease underwent echocardiography and CMR evaluations. Conventional echocardiographic parameters for RV functional evaluation were tricuspid annular plane systolic excursion, RV systolic excursion velocity, fractional area change, and RV index of myocardial performance. Strain and strain rate were obtained by two-dimensional speckle-tracking echocardiography and defined as "RV free wall," when based only in segments from RV free wall, or "RV free wall and septum," when segments from both free RV wall and interventricular septum were included. RV systolic dysfunction was defined as RV ejection fraction (RVEF) < 50% by CMR. RESULTS: Mean age was 56 ± 14 years, and 58.7% of the patients were men. RV systolic dysfunction was detected by CMR in 18 (28.6%) individuals. RV free wall strain showed the highest correlation with RVEF by CMR (r = -0.62, P < .001), followed by fractional area change (r = 0.56, P < .001), RV free wall and septum strain (r = -0.54, P < .001), RV free wall and septum strain rate (r = -0.47, P < .001), RV free wall strain rate (r = -0.45, P < .001), and RV systolic excursion velocity (r = 0.30, P = .016). The RV index of myocardial performance and tricuspid annular plane systolic excursion showed a small and not significant correlation with RVEF (r = -0.20, P = .320; r = 0.14; P = .289, respectively). Using predefined cutoffs for RV systolic dysfunction, RV free wall strain (>-22.5% for men and >-23.3% for women) exhibited the highest area under the receiver operating characteristic curve (area under the curve = 0.829) to differentiate the presence from the absence of RV systolic dysfunction in Chagas disease, with a sensitivity and specificity of 67% and 83%, respectively. CONCLUSIONS: RV free wall strain is an appropriate and superior echocardiographic variable for evaluating RV systolic function in Chagas disease, and it should be the method of choice for this purpose.