Matrix metalloproteinases in the pathology of natural and bioprosthetic cardiac valves.

Degenerative dysfunction of cardiac valves may be accounted for by uncontrolled extracellular matrix degradation processes in which matrix metalloproteinases could play a major role. In this study, 24 pathologic human valves and 26 pericardial-derived bioprostheses were analysed for metalloproteinases by gelatin zymography. Compared to controls, human stenotic valves and bioprostheses explanted because of either calcifying or noncalcifying degeneration revealed three notable biochemical aspects: (1) an amplification in the levels of metalloproteinase 9 (gelatinase B), suggestive of its active role in valvular pathology; (2) minimal modifications in the gelatinolytic levels of metalloproteinase 2 (gelatinase A), indicative of a constitutive secretion; and (3) activation products derived from both gelatinase A and B. All gelatinolytic activities identified in pathologic specimens were inhibited in vitro by zinc and calcium chelators (captopril, doxycycline, dithiothreitol, and ethylenediaminotetraacetic acid), suggesting potential therapeutic approaches. High levels of beta-glucuronidase (a lysosomal marker enzyme for phagocytic cells) were found in human calcified stenotic valves and in ruptured and calcified pericardial-derived bioprostheses. Mononuclear recruitment was minimal to moderate in pathologic human valves, and in noncalcified ruptured bioprostheses infiltrating mononuclear cells were concentrated in large numbers at the cuspal free edge. These findings suggest the involvement of infiltrating phagocytic cells and putative common mechanisms in the degeneration of both the natural and the bioprosthetic valvular extracellular matrix (ECM).

New evolution in mitral physiology and surgery: mitral stentless pericardial valve.

The human adult mitral valve, with a mean diastolic area of up to 7.6 cm2, excess leaflet surface area for coaptation in systole, mitral annulus-papillary muscle continuity, and systolic constriction of the posterior left ventricular wall around the mitral annulus functions in concert with other components of the left side of the heart. Mitral valve replacement with an artificial valve that interferes with the normal physiology could account for less than adequate late results. A stentless biologic mitral valve substitute has been designed, constructed, and tested. The size of the valve is selected according to the circumference of the excised valve within certain limits. The valve is manufactured of two square or trapezoidal pieces of selected stabilized human autologous or bovine pericardium. The pericardial pieces are sutured together by their lateral margins, thus creating a frusto-conical valvular body. The upper circumference of the valvular body is sutured at the mitral annulus and the lower margin with the new chordae is attached by suture at each papillary muscle. In vitro testing of six stentless bovine pericardial valves in a Rowan-Ash fatigue tester at 1,200 cycles/min revealed a durability of more than 320 million cycles. Clinical use of described technique initiated in 1989 was performed in 18 patients by one surgeon (30 patients in the same institution). The mean valve size was 29 mm circularized diameter. There was no mortality in this group of patients up to 70 months of follow-up. Valve competence was obtained in every case by adequate sizing of the valve.(ABSTRACT TRUNCATED AT 250 WORDS)

Large animal model of ischemic mitral regurgitation.

A large animal model of ischemic mitral regurgitation (MR) that resembles the multiple presentations of the human disease was developed in sheep. In 76 sheep hearts, the anatomy of the coronary arterial circulation was determined by observation and polymer casts. Two variations, types A and B, which differed by the vessel that supplied the left ventricular apex, were found. In all hearts, the circumflex coronary artery has three marginal branches and terminates in the posterior descending coronary artery. The amount and location of left ventricular (LV) mass supplied by each marginal circumflex branch was determined by dye injection and planimetry. In type A hearts, ligation of the first and second marginal branches infarcts 23% +/- 3.0% of the LV mass, does not infarct either papillary muscle, significantly (p < 0.001) increases LV cavity size 48% at the high papillary muscle level by 8 weeks, and does not cause MR. Ligation of the second and third marginal branches infarcts 21.4% +/- 4.0% of the LV mass, includes the posterior papillary muscle, significantly increases (p < 0.001) LV cavity size 75%, and causes severe MR by 8 weeks. Ligation of the second and third marginal branches and the posterior descending coronary artery infarcts 35% to 40% of the LV mass, increases LV cavity size 39% within 1 hour, and causes massive MR. After moderate (21% to 23%) LV infarction, development of ischemic MR requires both LV dilatation and posterior papillary muscle infarction; neither condition alone produces MR. Large posterior wall infarctions (35% to 40%) that include the posterior papillary muscle produce immediate, severe MR.(ABSTRACT TRUNCATED AT 250 WORDS)