Improvement of left ventricular remodeling after myocardial infarction with eight weeks L-thyroxine treatment in rats

Abstract

BackgroundLeft ventricular (LV) remodeling following large transmural myocardial infarction (MI) remains a pivotal clinical issue despite the advance of medical treatment over the past few decades. Identification of new medications to improve the remodeling process and prevent progression to heart failure after MI is critical. Thyroid hormones (THs) have been shown to improve LV function and remodeling in animals post-MI and in the human setting. However, changes in underlying cellular remodeling resulting from TH treatment are not clear.MethodsMI was produced in adult female Sprague–Dawley rats by ligation of the left descending coronary artery. L-thyroxine (T4) pellet (3.3 mg, 60 days sustained release) was used to treat MI rats for 8 weeks. Isolated myocyte shape, arterioles, and collagen deposition in the non-infarcted area were measured at terminal study.ResultsT4 treatment improved LV ±dp/dt, normalized TAU, and increased myocyte cross-sectional area without further increasing myocyte length in MI rats. T4 treatment increased the total LV tissue area by 34%, increased the non-infarcted tissue area by 41%, and increased the thickness of non-infarcted area by 36% in MI rats. However, myocyte volume accounted for only ~1/3 of the increase in myocyte mass in the non-infarct area, indicating the presence of more myocytes with treatment. T4 treatment tended to increase the total length of smaller arterioles (5 to 15 μm) proportional to LV weight increase and also decreased collagen deposition in the LV non-infarcted area. A tendency for increased metalloproteinase-2 (MMP-2) expression and tissue inhibitor of metalloproteinases (TIMPs) -1 to −4 expression was also observed in T4 treated MI rats.ConclusionsThese results suggest that long-term T4 treatment after MI has beneficial effects on myocyte, arteriolar, and collagen matrix remodeling in the non-infarcted area. Most importantly, results suggest improved survival of myocytes in the peri-infarct area.

Post-infarct treatment with [Pyr1]apelin-13 exerts anti-remodelling and anti-apoptotic effects in rats’ hearts

“…After myocyte injuries, the infarct size increases and causes wall thinning and ventricular dilatation [22,23]. Our results also showed that apelin-13 given 24 h after MI for five days could improve myocardial structure and remodelling parameters, as shown in Figure 1.…”

How to improve the overall quality of cardiac morphometric data

“…But, over time the spared segment lengthens. Lengthening with minimal change in wall thickness of the spared segment is clearly due to an increase in myocyte length only with no change in CSA (2,7,21). Remodeling of myocyte shape is consistent with anatomical findings.…”

Long-term physiological T3 supplementation in hypertensive heart disease in rats

“…Consequently, there is a possibility that exogenous T 4 may be inadequately converted to active T 3 in the heart and may also inhibit T 3 secretion from the thyroid gland. Nonetheless, it should be pointed out that we have also observed rather dramatic improvements with T 4 treatment of rat models of HF (2,22).…”

“…All images were captured using an Olympus BX53 and cellSens imaging software (Olympus, Tokyo, Japan). Myocardial fibrosis was examined morphometrically using Masson's trichrome staining as described previously (2).…”