Structural and morphological changes in rat ventricular myocardium induced by chronic systemic hypoxi.
OBJECTIVE
to explore the effects of chronic systemic hypoxia on myocardial structure and morphology. In addition, the goal of present study is to develop a hypoxia-induced heart failure model in rats.


METHODS
Sprague-Dawley male rats, weighing 220-250 g at the time of recruitment were randomly allocated into 7 groups (n = 4 per group), the control normoxia group was exposed to room air, while the hypoxia groups were caged in a plexiglas hypoxic chamber (8% O2 and 92% N2) for 28 days. Structural and morphological changes of ventricular myocardium were determined at day 28, while blood gas parameters were measured at day 1, 3, 7, 14, 21, and 28.


RESULTS
histopathologic and morphologic evaluation showed massive hypertrophy accompanied by damage of the intercalated disk (ID) structure, angiogenesis, necrosis, fibrosis, and apoptosis as a hallmark of ventricular remodeling. At the end of treatment, there were increases of LV (2.79 vs 3.71) and RV (1.72 vs 2.54) wall thicknesses, and also in hypertrophy index (from 3.19 to 5.74). Blood gas analysis revealed metabolic acidosis compensated by respiratory alkalosis. There was an observed decrease of blood gas parameters in hypoxia group compared to control group: PO2 (24.7 vs 96.4 mm Hg), PCO2 (18.2 vs 40.4 mm Hg), O2 saturation (25.5 vs 94.1 %), and HCO3 (10.1 vs 23.4 mmol/L). On the other hand an increase in hemoglobin level (221.5 vs 120.3 g/L), haematocrit level (68.6 vs 45.2 %), and red blood cell count (10.4 vs 6.9 μL/1000) could be observed.


CONCLUSIONS
our data clearly show that chronic systemic hypoxia causes massive ventricular hypertrophy accompanied by severe structural and morphological impairment of ventricular myocardium, which eventually results in cardiac failure.
Department of Biochemistry and Molecular Biology, Faculty of Medicine, Tarumanagara University, Jl.Letjen S. Parman no.1, Jakarta 11440, Indonesia. frafrdl@tarumanagara.ac.id
Frans
F
Ferdinal
Franciscus D
FD
Suyatna
Septelia I
SI
Wanandi
Mohammad
M
Sadikin
D000818:Animals; D017209:Apoptosis; D002908:Chronic Disease; D004195:Disease Models, Animal; D018450:Disease Progression; D005500:Follow-Up Studies; D006352:Heart Ventricles / Q000473:pathology*; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000473:pathology*; D000860:Hypoxia / Q000150:complications*; D008297:Male; D009206:Myocardium / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley