Tissue heart valve mineralization: Review of calcification mechanisms and strategies for prevention.

Attempts to replace diseased human valves with prostheses began more than 30 yrs ago. Heart valve prostheses can be broadly classified into mechanical prostheses (made out of non-biological materials) and bioprostheses made out of biological tissue. Biological valves are made from animal tissue bovine pericardium and porcine valves. The use of these tissues became commercially available after the introduction of the glutaraldehyde (GA) fixation technique. GA reacts with tissue proteins to form inter- and intramolecular crosslinks, resulting in improved durability. The advantage of bioprostheses compared with mechanical valves is the freedom from thromboembolism; and therefore, the avoidance of long-term anticoagulation therapy. These prostheses are preferable in elderly people and in patients who do not tolerate anticoagulants. However, tissular calcification and primary tissue failure (caused by the mechanical stress) are the main unresolved problems. The causes of calcification are numerous and, to date, a satisfactory solution to this question has not been found, although chemical treatments with metal cations, diphosphonates and treatments eliminating phospholipids have proved to mitigate calcification. In addition, alterna-tive approaches to GA chemical treatment fixation are being proposed to provide the tissue with greater resistance to this process. Studies are under way using polyepoxy compounds, derivates of amino oleic acid (AOA), agents such as diphenylphosphorylazide, carbodiimide, amino acids etc. Further improvements in fixation techniques, as well as in bioprosthesis design (stentless valves) are being made to improve the durability and functional characteristics of bioprosthetic heart valves. The development of a biomaterial capable of withstanding calcification and mechanical stress, while being as durable as mechanical prostheses, would convert the bioprostheses into the replacement of choice by eliminating the need for anticoagulation therapy.

[Liver damage due to normothermic ischemia and reperfusion in the rat. The effects of pentoxifylline pretreatment]. / Daño hepático por isquemia normotérmica y reperfusión en la rata. Efectos del pretratamiento con pentoxifilina.

The effect of pretreatment with pentoxifylline on normothermic liver ischemia was studied in rats. This drug, a dimethylxanthine and fosfodiesterase inhibitor, improves microcirculation, decreases neutrophil activity in experimental sepsis and hemorrhagic shock, and inhibits "in vitro" cytokine production by isolated Kupffer cells. Partial liver ischemia was induced by occlusion of afferent vessels to the median and left lateral lobes for 60', followed by resection of nonischemic lobes just before reperfusion. The rats were divided in 4 groups: I (n = 6) sham operation, II (n = 6) resection of right and caudate lobes, III (n = 42) normal saline pretreatment and 60' ischemia, IV (n = 42) pentoxyfilline pretreatment (50mg/K/i.p. 2 h before clamping) and 60' ischemia. 12 animals were sacrificed 1 h and 6 h after reperfusion respectively (gr III and IV), and 20 rats were observed for a maximum of 24 h after reperfusion. Serum transaminases, LDH, CK (isoenzymes), bilirubin, and total bile acids were determined in each animal. A sample of the left lobe was taken for histological examination. Extent of necrosis 24 h after reperfusion was assessed. Bile output was measured before ischemia and during the first hour of reperfusion. Pentoxifylline pretreatment was associated with a lower rise in serum transaminases and LDH after reperfusion, but it did not modify the changes in either serum CK activity (mainly CKBB), or total bile acid concentration. A reduction of bile output was not avoided by pentoxifylline pretreatment.(ABSTRACT TRUNCATED AT 250 WORDS)

[Morphopathological changes before and after biliodigestive derivation in experimental cirrhosis induced by biliary ligation in the rat]. / Cambios morfopatológicos pre y postderivación biliodigestiva en cirrosis experimental por ligadura de vía biliar en rata.

OBJECTIVE: Study of the hepatic morphological and biochemical changes in an experimental model of cirrhosis in rat by ligation of the common bile duct before and after bilioduodenal anastomosis. DESIGN: Ligation of the common bile duct in a group of 80 female Wistar rats during 30 days. Liver biopsy for histological studies and staining, blood samples for biochemical determination were taken, and a bilioduodenal anastomosis was constructed. 30 days later new liver specimens and blood samples were taken. A control group consisted of 10 rats. RESULTS: 30 days after biliary obstruction histological changes were characterized by occurrence of bile canalicular proliferation and portal fibrosis that rounded hepatic lobules. No well-defined nodules indicative of cirrhosis were seen. There was cholestasis with an increase in serum bilirubin, alkaline phosphatase and transaminase levels, and a decrease of albumin levels. Survival was 63.7%. Thirty days after biliary diversion (60 days after ligation) the normal lobular pattern was disorganized and regenerative nodules indicative of cirrhosis appeared, separated by narrow fibrous connective tissue septa, in 65% of rats. Bilirubin levels returned to normal values. Alkaline Phosphatase and transaminase levels remained high and albumin levels remained low. Overall survival was 25%. CONCLUSIONS: 30 days after biliary obstruction there are no regeneration nodules indicative of cirrhosis. There is a precirrhotic change, biliary fibrosis. Biliary diversion does not improve the histological changes and regeneration nodules and cirrhosis appear in 65% of animals.