RESUMO
BACKGROUND: Adverse cardiovascular effect of hypothyroidism has been identified in many studies. Early identification of patients with sub-clinical hypothyroidism may lead to early treatment and thereby favourable effect on cardiovascular morbidity and mortality. OBJECTIVES: To find out the association of sub clinical hypothyroidism and left ventricular dysfunction and also to find out relationship between systolic and diastolic dysfunction in these patients. MATERIAL AND METHODS: A total 30 cases of sub clinical hypothyroidism along with 15 age sex matched healthy control subjects were included in study. Serum TSH, T4, T3 hormone level was measured and those who were found to have sub-clinical hypothyroidism underwent for 2DEcho. RESULTS: Significant reduction in peak early filling velocity (PE) (p<0.001) and early filling time velocity integral (Ei) (p<0.001). Ratio of early and late peak velocities (PE/PA) (p<0.001), ratio of time velocity integral of early and atrial filling (Ei/Ai) (p<0.001) and ratio of the early peak to average velocity (PE/M) (p<0.001) were also reduced. Mean EF was 54.9± 5.55 as compared to 55.7 ± 3.46 of control subjects with a T.value of 0.48 ,however there was significant diastolic dysfunction in case of hypothyroid patients (mean Ei/Ai = 1.35 ± 0.53) as compared to control group subjects (mean Ei/AI = 2.11 ± 0.26) with a T value of 5.22. CONCLUSION: Sub-clinical hypothyroidism showed significant diastolic dysfunction in the absence of significant impairment of systolic function.
RESUMO
L-PGlu-(2-propyl)-L-His-L-ProNH2 (NP-647) is a CNS active thyrotropin-releasing hormone (TRH) analog with potential application in various CNS disorders including seizures. In the present study, mechanism of action for protective effect of NP-647 was explored by studying role of NP-647 on epileptiform activity and sodium channels by using patch-clamp methods. Epileptiform activity was induced in subicular pyramidal neurons of hippocampal slice of rat by perfusing 4-aminopyridine (4-AP) containing Mg⺲-free normal artificial cerebrospinal fluid (nACSF). Increase in mean firing frequency was observed after perfusion of 4-AP and zero Mg⺲ (2.10±0.47 Hz) as compared with nACSF (0.12±0.08 Hz). A significant decrease in mean firing frequency (0.61±0.22 Hz), mean frequency of epileptiform events (0.03±0.02 Hz vs. 0.22±0.05 Hz of 4-AP+0 Mg), and average number of action potentials in paroxysmal depolarization shift-burst (2.54±1.21 Hz vs. 8.16±0.88 Hz of 4-AP+0 Mg) was observed. A significant reduction in peak dV/dt (246±19 mV ms⻹ vs. 297±18 mV ms⻹ of 4-AP+0 Mg) and increase (1.332±0.018 ms vs. 1.292±0.019 ms of 4-AP+0 Mg) in time required to reach maximum depolarization were observed indicating role of sodium channels. Concentration-dependent depression of sodium current was observed after exposure to dorsal root ganglion neurons to NP-647. NP-647 at different concentrations (1, 3, and 10 µM) depressed sodium current (15±0.5%, 50±2.6%, and 75±0.7%, respectively). However, NP-647 did not show change in the peak sodium current in CNa18 cells. Results of present study demonstrated potential of NP-647 in the inhibition of epileptiform activity by inhibiting sodium channels indirectly.