| Abstract: | 心室中隔缺損為最常見的先天性心臟病，發生率約為每千名活產嬰中2至4位，主要表徵為充血性心臟衰竭，呈現肺臟及全身鬱血，心肌收縮功能，心臟負擔，供血狀況及身體內各種調適機制運作下，不同程度失調的結果。
心臟超音波可作為診斷心臟疾病及畸形，預估心臟功能及心臟負擔情形的技術，而體內神經內分泌的調節機制在心臟衰竭過程中亦扮演著重要角色，足以影響心臟功能的預後。類胰島素生長因子-I及II(IGF-I，II)在胚胎的發育及心肌細胞的分化過程中扮有重要角色，但有關心肌生長因子對心室中隔缺損的影響研究訊息則甚少。目前雖然心臟超音波是診斷及評估心室中隔缺損及心臟功能的主要工具，但仍無有效方法可作為心室中隔缺損合併心臟衰竭預後的預測方法，我們的研究主要是提出一個特別的診斷標準：「心室中隔缺損合併輕度心臟衰竭者，血清中類胰島素因子－Ｉ(IGF-I)及類胰島素因子結合蛋白3 (IGF-BP3）呈輕度減少，而心室中隔缺損合併嚴重性心臟衰竭者，類胰島素因子－I，II (IGF-I ,IGF-II)及類胰島素因子— I與類胰島素結合蛋白3 (IGF1/IGFBP3)比率明顯過低且血中生長激素同時呈現代償性遽增」可作為預測心室中隔缺損合併心臟衰竭的預後，以早期規劃手術治療。
本研究中收錄嬰兒年齡從3個月到一歲，出生體重及妊娠週數，檢查時體重並無明顯差異下，分成四組為控制組,心室中隔缺損合併輕度心臟衰竭（Mild-VSD）、心室中隔缺損合併嚴重性心臟衰竭（Severe-VSD）及經外科手術後（post-surgery）。我們也利用ELISA方法，首次訂出台灣嬰幼兒血中類胰島素因子－Ｉ(IGF-I) 的標準值112 23 (微克/毫升)及類胰島素因子－II（IGF-II）的標準值(549 45微克/毫升)，相較於正常嬰幼兒，心室中隔缺損合併輕度心臟衰竭組(Mild-VSD) 血中類胰島素因子－Ｉ( IGF-I)及攜帶蛋白(IGF-BP3)較低，分別下降約43%及32%。更特別的是，心室中隔缺損合併嚴重性心臟衰竭嬰幼兒中，不僅僅血中類胰島素因子－Ｉ(IGF-I) 下降79%，結合蛋白(IGF-BP3)下降57%，IGF-I / IGF-BP3 比值下降39%，且生長激素呈代償性遽增3.1倍，但類胰島素因子-II (IGF-II)則下降24%，IGF-BP3攜帶蛋白分解脢及Pro-MMP- 9下降40%。在嚴重組中，所有的血清變化，有可能導因於心室中隔缺損導致血液溶積負荷過重而發生過度代謝，產生血中乳酸堆積增加。但是，一當手術後六個月，大部分的變化均可復原。結論：血清中類胰島素因子I、II、結合蛋白(IGF-BP3)及生長激素的改變，可提供成為一特別的方法來訂出心臟衰竭的程度，而做為預後的指標及做為外科手術的依據，在釐清這些生長因子的作用機制後,將可成為新的治療方法。
Novel Serum Prognostic Factors for Infants with Ventrcicular Septal Defect
ABSTRACT:
Ventricular septal defect, the most common congenital heart disease with incidence around 2-4/1000 livebirth, represents the major manifestions of congestive heart failure of the admixture of components that may reflex pulmonary and systemic congestion, the contractile status of the myocardium, loading conditons, perfusion status, and the operation of various adaptive mechanisms. Cardiac ultrasonography provides the key data to define the specific disorder or malformation and the functional status of the myopericardium, particularly the nature of the loading conditon. The major neurohormonal mechanisms play a key role in the pathophysiologic process of congestive heart failure and influence the natural history of certain volume- and pressure-loading. Insulin-like growth factors (IGF-I,II) play a major role for embryonic development and cardiomyocytes differentiation. However, very little information is available regarding the cardiac growth factors involved in ventricular septal defect (VSD). Although cardiac echocardiography plays the major tool for diagnosis and evaluation of heart functions., but there are no efficient methods to predict the outcome of VSD with congestive heart failure of different severity and to determine the optional time for surgical treatment. Our study was to provide a novel diagnostic criteria, a slight reduction of IGF-I and IGFBP3 for VSD with mild symptoms of congestive heart failure and a high reduction of IGF-I, IGF-II, and IGF-I/IGFBP3 ratio resulting in a compensative elevation of growth hormone for VSD with severe heart failure, to predict the outcome of infants with VSD of variable severity of congestive heart failure. In present study, infants aged from 3 months to one year were divided into four groups as control, mild-VSD (Qp/Qs≦1.5), severe-VSD (Qp/Qs≧2.0, symptoms of intractable heart failure ), and post surgery. For the first report, we set up the standard value of IGF-I (112±23ng/ml) and IGF-II (549±45ng/ml) of normal infants in Taiwan by ELISA. Compared to normal infants, IGF-I and its carry protein IGFBP3 are lower in mild-VSD infants by 43% and 32%, respectively. Moreover, it was found that not only more significant reduction of IGF-I (79%), IGFBP3 (57%), and IGF-I/IGFBP3 ratio(39%), which resulted in the compensative elevation of growth hormone by 3.1-fold, but also IGF-II reduced 24% and the protease of IGFBP3, pro-MMP-9, decreased 40% were observed in severe-VSD infants. All these changes of severe-VSD group might result from the increase of serum lactate concentration leading to the reduction of pH due to hyperdynamics of flow overloading. Following surgery reversed most of the changes. In conclusion, these results supply a novel approach to define mild and severe VSD to prevent intactable heart failure and help to make the decision for surgery. Furthermore, the elucidation of the mechanism of the results could supply a new strategy for treatment of infants with VSD. |
