Myocardial fibrosis

Deletion of the Cav3.1 channel in thalamocortical relay neurons prevents absence epilepsy. Block of the neuronal LVA channels alleviates certain forms of epilepsy. Deletion of Cav3.2 leads to coronary artery constriction and focal myocardial fibrosis. 

Angiotensin II is a neurohormone produced primarily in the kidney. It is a potent vasoconstrictor and stimulates the production of aldosterone. Together, angiotensin II and aldosterone increase blood pressure and sodium and water retention (increasing ventricular wall tension), cause endothelial dysfunction, promote blood clot formation, and cause myocardial fibrosis. 

To reduce mortality, administration of an aldosterone antagonist, either eplerenone or spironolactone, should be considered within the first 2 weeks following MI in all patients who are already receiving an ACE inhibitor (or ARB) and have an EF of equal to or less than 40% and either heart failure symptoms or diagnosis of diabetes mellitus.3 Aldosterone plays an important role in heart failure and in MI because it promotes vascular and myocardial fibrosis, endothelial dysfunction, hypertension, left ventricular hypertrophy, sodium retention, potassium and magnesium loss, and arrhythmias. Aldosterone antagonists have been shown in experimental and human studies to attenuate these adverse effects.70 Spironolactone decreases all-cause mortality in patients with stable, severe heart failure.71... 

ACE inhibitors (Table 8-2) decrease angiotensin II and aldosterone, attenuating many of their deleterious effects, including reducing ventricular remodeling, myocardial fibrosis, myocyte apoptosis, cardiac hypertrophy, norepinephrine release, vasoconstriction, and sodium and water retention. 

Serum immunoglobulin type (mg/ml) Endo- myocardial fibrosis Bheumatic heart disease Hypertensive heart failure The rest... 

The term, arrhythmogenic substrate, became a matter of interest to many researchers. The arrhythmogenic substrate means the pathologic and anatomic preconditions for the initiation of tachyarrhythmias such as myocardial fibrosis, aneurysm, the border zone between normal and ischemic or infarcted tissue, scars, diffuse myocardial injury in cardiomyopathy or the chronic alterations induced by myocarditis, and furthermore, accessory pathways or variations in the specific cardiac conduction system. These anatomic or pathologic altera-... 

Pathophysiology In HF patients, the levels of aldosterone are elevated, even in the presence of ACE inhibitors or angiotensin-receptor blockers (34,35). Aldosterone has detrimental effects in HE such as causing potassium and magnesium loss, sodium retention, baroreceptor dysfunction, and myocardial fibrosis it also decreases the neuronal uptake... 

Brooks, W.W., and Conrad, C.H. 2000. Myocardial fibrosis in transforming growth factor beta(l)heterozygous mice. J Mol. Cell. Cardiol. 32 187-195. 

Sun, Y. 1997. Local angiotensin II and myocardial fibrosis. In Hypertension and the Heart, A. Zanchetti (ed.). Plenum Press, New York, 55-61. 

Sun, Y., Qeutjens, J.R, Diaz-Arias, A.A., and Weber, K.T. 1994. Cardiac angiotensin converting enzyme and myocardial fibrosis in the heart. Cardiovasc. Res. 28 1423-1432... 

Rat 15 Inhalation 660 90 d, continuous 13 of 15 animals died. Histopathologic examination revealed focal or diffuse interstitial pneumonitis, calcification of renal tubules, calcification of bronchial epithelial, renal tubular epithelial proliferation, myocardial fibrosis fatty changes of the liver in several animals. Changes were also found in control animals, but were of lesser seventy. LOAEL 660 Goon et al. 1970... 

Brilla CG, Matsubara L, Weber KT. Advanced hypertensive heart disease in spontaneously hypertensive rats. Lisinopril-mediated regression of myocardial fibrosis. Hypertension 1996 28(2) 269-75. 

Brilla CG, Funck RC, Rupp H. Lisinopril-mediated regression of myocardial fibrosis in patients with hypertensive heart disease. Circulation 2000 102(12) 1388-93. 

Figure 3.37 Low QRS complex and T-wave voltage in all the ECG leads. This pattern, especially if it is accompanied by bradycardia, must lead one to suspect myxedema. Generalised low-voltage patterns can be seen in many other processes, in which there is a border factor that decreases the voltage secondary to cardiac causes (e.g. myocardial fibrosis in myxedema, as in this case, or pericarditis) or extracardiac causes (emphysema, pleural effusion, ascites, etc.).

Endothelial dysfunction is associated with the progression of myocardial diastolic dysfunction in patients with CAD. Both in the acute manifestation of myocardial ischemia and within the chronic consequences of myocardial fibrosis, epicardial CAD is frequently the underlying pathologic cause of DHE Myocardial ischemia caused either by an acute decrease in supply or an increase in demand (exercise and tachycardia) results in impaired relaxation and an acute increase in myocardial stiffness. Chronic coronary occlusions may result in myocardial fibrosis, remodeling, and DHF It is clear that the same basic mechanisms causing diastolic dysfunction in the presence of pressure-overload hypertrophy also underlie changes produced by CAD. 

A small, prospective, double-blind, randomized trial compared lisinopril with hydrochlorothiazide in 35 patients with primary hypertension, LVH, and LV diastolic dysfunction. After 6 months of therapy, lisinopril caused regression of myocardial fibrosis and improved LV diastolic function, although LVH was unchanged. 

Abnormalities in filling are also associated with changes in chamber stiffness that occur in HCM. This stiffness may be the result of myocardial fibrosis, cellular disorganization, or increased myocardial mass. The decreased distensibility leads to an abnormally steep slope of the diastolic pressure-volume curve such that an increase in LV volume results in a disproportionate increase in diastolic pressure. 

Cardiac arrhythmia is known as a complication of catecholamine excess (Lermann et al., 1999), and chronic exposure to high levels of catecholamines can induce a type of myocardial fibrosis that favors arrhythmias, but a linkage with ephedrine and its isomers has never been shown. The literature contains one case report (Weesner et al., 1982). The report described arrhythmias occur-... 

Ogata, T., Miyauchi, T., Sakai, S., Takanashi, M., Irukayama-Tomobe, Y. and Yamaguchi, I. (2004) Myocardial fibrosis... 

Silver MA, Pick R, Brilla CG, Jalil JE, Janicki JS, Weber KT. Reactive and reparative fibrillar collagen remodelling in the hypertrophied rat left ventricle two experimental models of myocardial fibrosis. Cardiovasc Res 1990 24 741—7. 

T. Akatsu, J. Iwasaka et al. (2002). Aldosterone synthase (CYP11B2) expression and myocardial fibrosis in the failing human heart. Clin. Sci. (London) 102, 381-386. 

Myocardial fibrosis, fibroblast proliferation Alterations in Na channel expression... 

Drug-related epidemics have occurred, mercifully relatively infrequently. However, with each unfortunate episode, there is inevitably a variety of regulatory and clinical fallout. Indeed, the illnesses associated with ingestion of glycol-tainted linctus led to the Food, Drugs and Cosmetics ( ) Act in the USA, and the disastrous association of phocomelia with thalidomide propelled reforms of drug regulations worldwide. Other famous examples include, of course, practolol-induced ocu-lomucocutaneous syndrome, and, more recently, fenfluramine-induced myocardial fibrosis, and isotretinoin-associated birth defects. 

---