Hjc. Swan, LEFT-VENTRICULAR DYSFUNCTION IN ISCHEMIC-HEART-DISEASE - FUNDAMENTAL IMPORTANCE OF THE FIBROUS MATRIX, Cardiovascular drugs and therapy, 8, 1994, pp. 305-312
Citations number
45
Categorie Soggetti
Pharmacology & Pharmacy","Cardiac & Cardiovascular System
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.