Effects of Trypanosoma cruzi infection on myocardial morphology, single cardiomyocyte contractile function and exercise tolerance in rats

Abstract

The aim of this study was to investigate the effects of Trypanosoma cruzi (T. cruzi) infection on myocardial morphology, single cardiomyocyte contractile function and exercise tolerance in rats. Adult Wistar rats were randomized into control (n = 14) and infected (n = 14) groups. Infected animals were inoculated with T. cruzi Y strain (300,000 trypomastigotes/50 g body weight). After 9 weeks, the animals were subjected to a treadmill running protocol. Then, the right atrium (RA) and left ventricle (LV) were removed for morphological and cell contractile evaluation. The infected animals exhibited a significant reduction in distance travelled, total time to fatigue and workload. In addition, these animals had hypertrophy, increased myocardial cellularity, and an increase in the proportion of collagen and blood vessels. RA and LV myocytes from infected animals showed marked contractile dysfunction under basal conditions and a reduced contractile response to β-adrenergic stimulation. The workload of infected animals was correlated closely with the amplitude of cell shortening of RA and LV myocytes. T. cruzi infection influenced the myocardial morphology and the mechanical properties of RA and LV single myocytes negatively and reduced exercise tolerance. Single cardiomyocyte contractile dysfunction could constitute an additional mechanism of cardiac impairment and reduced exercise tolerance in this infection.

Basal and �-Adrenergic Cardiomyocytes Contractility Dysfunction Induced by Dietary Protein Restriction is Associated with Downregulation of SERCA2a Expression and Disturbance of Endoplasmic Reticulum Ca2+Regulation in Rats

“…After euthanasia, the hearts from other 10 animals were quickly removed and LV cardiomyocytes were isolated as described by Novaes et al [11]. Briefly, each heart was cannulated through the aorta in a Langendorff system and perfused with isolation solution (composition [mM]: 130 Na + , 5.4 K + , 1.4 Mg 2+ , 140 Cl - , 0.75 Ca 2+ , 5 Hepes, 10 glucose, 20 taurine and 10 creatine, pH = 7.3 at room temperature).…”

“…Cardiomyocyte contractile function was measured using an edge motion detection system (Ionoptix, Milton, MA, USA) mounted on an inverted microscope (Nikon Eclipse TS100®, Tokyo, Japan), as previously described [11]. Briefly, myocytes were placed in an experimental chamber with the base glass and bathed in buffer with the following composition (in mM): 136.9 NaCl; 5.4 KCl; 0.37 NaH2PO4; 0.57 MgCl2; 5 Hepes; 5.6 glucose; and 1.8 CaCl2 (pH = 7.4 at room temperature).…”

“…After recording the baseline cell shortening, ISO was infused in the experimental chamber through an automatic pipette. The cells were electrically stimulated after 5 min of infusion when cell shortening was recorded [11]. This procedure was repeated for each ISO concentration in different myocytes.…”

“…The slides were visualized and the images captured using a light microscope (Olympus BX-60®, Tokyo, Japan) connected to a digital camera (Olympus QColor-3®, Tokyo, Japan). Sixty fields from H&E (objective ×40) were randomly chosen and a total of 4.37×10 6 μm 2 myocardium area was analyzed [11]. Histopathological parameters of cardiomyocytes hypotrophy, inflammatory infiltrate, pyknosis, cardiomyocytes and extracellular matrix distribution and organization were observed.…”

The Absence of Myocardial Calcium-Independent Phospholipase A 2 γ Results in Impaired Prostaglandin E 2 Production and Decreased Survival in Mice with Acute Trypanosoma cruzi Infection

“…This cycle of infection and multiplication of the parasites, resulting in host cell lysis, directly causes tissue injury in the myocardium. Myocytes also contribute indirectly to disease progression via cytokine, chemokine, and reactive oxygen species (ROS) production, accompanied by changes in myocyte morphology (8,10,11).…”