Histopathological changes of the heart after neonatal dexamethasone treatment: studies in 4-, 8-, and 50-week-old rats.

Dexamethasone (Dex), for prevention of chronic lung disease in preterm infants, showed potential negative long-term effects. Studies regarding long-term cardiovascular effects are lacking. We investigated possible histopathological myocardial changes after neonatal Dex in the young and adult rat heart. Rats were treated with Dex on d 1, 2, and 3 (0.5, 0.3, and 0.1 mg/kg) of life. Control-pups received saline. At 4, 8, and 50 wk after birth rats were killed and anatomic data collected. Heart tissue was stained with hematoxylin and eosin, Cadherin-periodic acid schiff, and sirius red for cardiomyocyte morphometry and collagen determination. Presence of macrophages and mast cells was analyzed. Cardiomyocyte length of the Dex-treated rats was increased in all three age groups, whereas ventricular weight was reduced. Cardiomyocyte volumes were increased at 50 wk indicating cellular hypertrophy. Collagen content gradually increased with age and was 62% higher in Dex rats at 50 wk. Macrophage focus score and mast cell count were also higher. Neonatal Dex affects normal heart growth resulting in cellular hypertrophy and increased collagen deposition in the adult rat heart. Because previous studies in rats showed premature death, suggesting cardiac failure, cardiovascular follow-up of preterm infants treated with glucocorticoids should be considered.

A Laser-Assisted Anastomotic Technique: Feasibility on Human Diseased Coronary Arteries.

OBJECTIVE: Atherosclerotic disease might hamper the efficacy of the Excimer laser-assisted Trinity Clip anastomotic connector in coronary arteries. Therefore, its efficacy was evaluated on human diseased coronary arteries (study 1). In addition, the acute laser effects onto the coronary wall were assessed (study 2). METHODS: Thirty-eight anastomoses were constructed on ex vivo human hearts. Atherosclerosis was histopathologically determined and subsequently related to the success of the technique (ie, connector positioning and laser punching; study 1). In addition, 20 anastomoses were constructed in an ex vivo (porcine, n = 8) and an in vivo [rabbit (n = 9) and porcine (n = 3)] model. Subsequently, the coronary was histologically studied on the presence of laser-induced damage (study 2). RESULTS: In 13 of 38 anastomoses (study 1), the connector was malpositioned, 3 because of a severely diseased coronary wall and 10 because of an inner diameter less than the intended target range. The laser-punch success rates on coronary arteries with an early and advanced lesion were 100% (16/16) and 89% (8/9; lesions were located in the inferolateral wall), respectively. In one case, an advanced lesion (ie, fibrocalcified plaque) was located in the superolateral wall and caused a laser-punch failure. No histological signs of laser-induced damage were observed, in case of correct use (study 2). CONCLUSIONS: This study demonstrates the feasibility of an anastomotic connector on human diseased coronary arteries and shows that lasering does not induce coronary wall damage. However, careful selection of the coronary, regarding the target inner diameter and disease status, will prevent construction failures. This connector could facilitate less invasive coronary artery bypass grafting.

Suppression of physiological cardiomyocyte proliferation in the rat pup after neonatal glucocorticosteroid treatment.

BACKGROUND: Glucocorticosteroids (mostly dexamethasone) are widely used to prevent chronic lung disease in premature infants. Neonatal rats treated with dexamethasone have been shown to have reduced cardiac mass and cardiomyocyte hypertrophy, suggesting a lower number of cardiomyocytes at adult age, and a severely reduced life expectancy. In the present study we tested the hypothesis that a lower number of cardiomyocytes in later life is caused by a reduced cardiomyocyte proliferation and/or by early cell death (apoptosis). METHODS AND RESULTS: Rat pups received dexamethasone or saline control on day 1, 2 and 3 and were sacrificed at day 0, 2, 4, 7 and 21. The cardiomyocytes of dexamethasone treated pups showed a reduced proliferation as indicated by a lower mitotic index and reduced number of Ki-67 positive cardiomyocytes on day 2 and 4 as compared to day 0 and day 7 and also as compared to the age-matched saline pups. On day 7 and day 21 the mitotic index was not different between groups. From day 2 onward up to day 21 dexamethasone treated pups showed a lower number of cardiomyocytes. The cardiomyocytes showed no signs (<<1%) of apoptosis (Caspase-3 and cleaved-PARP) in any group. CONCLUSION: The temporary suppression of cardiomyocyte hyperplasia found in dexamethasone treated pups eventually leads to a reduced number and hypertrophy of cardiomyocytes during adult life.