Changes in cardiac contrability in an animal model of diabetes mellitus.

Author(s)

Gustavo Shimabukuro Marchini

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Escola Politécnica (EP/BC)
• Defense date: 2018-05-15

Examining board members

Idágene Aparecida Cestari; Marco Antonio Gutierrez; Oswaldo Horikawa; Vera Maria Cury Salemi; Antonio Carlos Shimano

• Advisor: Idágene Aparecida Cestari; Ismar Newton Cestari

Abstract

Diabetes mellitus (DM) is among the top 10 causes of global death and is considered a major risk factor for cardiovascular disease. Data from the International Diabetes Federation indicate that 425 million people have this disease and its treatment is considered one of the health priorities. In the heart, changes at the cellular level caused by DM lead to the appearance of structural and functional abnormalities that result in so-called diabetic cardiomyopathy. DM can be studied from experimental models in animals including induction by streptozotocin, a cytotoxic substance for pancreatic cells that produce insulin. Objectives: The objective of this study was to evaluate the existence of early cardiac changes in the contractility of isolated myocytes, in the morphology and cardiac function by high resolution echocardiogram and in the heart electrical activity . Method: Male Wistar rats were used for induction of DM with streptozotocin. Cardiomyocytes were isolated by enzymatic dissociation using the Langendorff preparation and the contractility studied by measuring cell and sarcomere length variation in electrically stimulated cardiomyocytes. The evaluation of cardiac morphology and function was performed by high resolution echocardiogram and eletrocardiogram was was obtained in anesthetized animals. Results: DM resulted in alteration of cardiomyocyte contractility with measurement of cell length variation and with sarcomere length variation. Compared to controls, diabetic animals presented an increase in the time intervals to reach the peak of contraction (0.049 vs 0.068 s and 0.043 vs 0.063 s, P<0.001) increase in relaxation (0.028 vs 0.038 s and 0.025 vs 0.035 s, P<0.03) and the intervals until the maximum shortening velocity (0.019 vs 0.024 s, P<0.001) and relaxation (0.021 vs 0.032 s and 0.020 vs 0.025 s, P<0.03) in relation to the control group measured by length and by sarcomere, respectively. The echocardiogram evidenced morphological changes with an increase in the diastolic (24.4 vs 28.0 mm/kg, P<0.01) and systolic diameter (11.0 vs 18.2 mm/kg, P<0.01) increase in left ventricle mass (1.9 vs 2.5 mg/g, P<0.02) and maintenance of the relative thickness of the posterior wall in relation to the control group, characterizing eccentric hypertrophy in DM. Functional changes were also observed, such as a significant reduction in ejection fraction (73.4 vs 62.1 %, P<0.01), of the fractional shortening (44.2 vs 34.7 %, P<0.01) and the S\' wave (46.9 vs 38.1 mm/s, P<0.01) evaluated by tissue Doppler, indicating an initial systolic dysfunction in this experimental model. With the electrocardiogram it was possible to verify an increase in P wave duration (9.15 vs 14.15 ms, P<0.005). Conclusion: The results obtained allowed to identify early changes in this model of DM. A correlation was observed between contractility changes observed directly at the cellular level by measuring cell and sarcomere variation with changes in cardiac morphology and function as a result of DM. (AU)

• FAPESP's process: 13/24543-3 - Contractility changes in isolated cardiomyocytes following pediatric VAD support
• Grantee: Gustavo Shimabukuro Marchini
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)