LEFT-VENTRICULAR DYSFUNCTION IN ISCHEMIC-HEART-DISEASE - FUNDAMENTAL IMPORTANCE OF THE FIBROUS MATRIX

The contractile function of the myocardium is coordinated by a fibrous matrix of exquisite organization and complexity. In the normal heart, and apparently in physiological hypertrophy, this matrix is submicros copic. In pathological states changes are frequent, and usually progre ssive. Thickening of the many elements of the fine structure is due to an increased synthesis of Type I collagen, This change, which affects the myocardium in a global manner, can be observed by light microscop y using special techniques. Perivascular fibrosis, with an increase in vascular smooth muscle, is accompanied by development of fibrous sept a, with a decrease in diastolic compliance. These structural changes a re believed to be due to increased activation of the renin-angiotensin -aldosterone system, and to be independent of the processes of myocyte hypertrophy. Reparative or replacement fibrosis is a separate process by means of which small and large areas of necrosis heal, with the de velopment of coarse collagen structures, which lack a specific organiz ational pattern. Regarding ischemic heart disease, an increase in tiss ue collagenase is found in experimental myocardial ''stunning'' and in the very early phase of acute infarction. Absence of elements of the fibrous matrix allow for myocyte slippage, and-if the affected area is large-cardiac dilatation. If, subsequently, the necrosis becomes tran smural, there is further disturbance of collagen due to both mechanica l strain and continued autolysis, During healing collagen synthesis in creases greatly to allow for reparative scarring in the available tiss ue matrix. In cases of infarction with moderate or severe initial dila tation, pathological hypertrophy of the spared myocardium is progressi ve, accounting for late heart failure and poor survival. Experimental studies on hypertension indicate that proliferation of the fibrous mat rix can be modified by ACE inhibition. Also, there are reports that th rombolysis may prevent cardiac enlargement. Appreciation of the role o f the fine fibrous matrix of the ventricle and its various collagens i n ischemic heart disease is fundamental to the pharmacological managem ent of the various acute coronary syndromes and their short- and long- term clinical consequences.