PubMed Health⌕ Search

Biomedical subjects

M Tago

Publications and source records attributed to M Tago.

At least 55 records · Page 3Linked to original sources

Core-cooling, heart-perfusion, lung-immersion technique provides successful cardiopulmonary preservation for heart-lung transplantation.

Mongrel dogs underwent heterotopic heart-orthotopic left lung transplantation. In Group I (N = 6), donor organs procured following core cooling to 15 degrees C on cardiopulmonary bypass (CPB) with cardioplegic arrest were immediately transplanted. In Group II (N = 6), following cardioplegic arrest without CPB core-cooling, the pulmonary artery was flushed with modified Collins' solution. Heart-lung blocks were immersed in extracellular solution for 6 hours and then transplanted. In Groups III and IV (N = 6 each), following CPB core-cooling to 15 degrees C and cardioplegic arrest, the organ blocks were immersed in extracellular solution (Group III) and the heart was perfused with oxygenated extracellular solution (Group IV). Evaluation of lung function using differences in arterial oxygen tension between the left and right atria demonstrated no differences between groups. However, extravascular lung water and pulmonary vascular resistance were significantly elevated in Group II. Cardiac function assessed by the ratio of end-systolic pressure to end-systolic dimension was significantly better in Group IV than in Groups II and III. Thus, adequate 6-hour hypothermic cardiopulmonary preservation with core cooling plus heart perfusion can be achieved for heart-lung transplantation.

Animals↗

Oxygenated perfluorocarbon, recombinant human superoxide dismutase, and catalase ameliorate free radical induced myocardial injury during heart preservation and transplantation.

The effect of free radical scavengers on free radical-induced myocardial injury during heart preservation and transplantation was examined. Four groups of nine hearts each were harvested from mongrel dogs (12.5 to 16.5 kg) and orthotopically transplanted to size-matched recipients. All hearts received a continuous perfusion of oxygenated modified Collins' solution (group A). In addition, groups B, C, and D received Fluosol DA and albumin. Preservation perfusion was performed for 18 hours, at 4 degrees C, pH = 7.4, and 20 mm Hg. In group C, recombinant human superoxide dismutase (4,080 U/mg, 20 mg/kg) and bovine catalase (46,200 U/mg, 20 mg/kg) were administered only during preservation perfusion. In group D, these scavengers were administered just before and during reperfusion for 1 hour. Hemodynamic studies were performed before excision of the donor hearts and 1 hour after the termination of cardiopulmonary bypass. Creatinine kinase MB isoenzyme and thiobarbituric acid reactive substance levels in the coronary effluent were determined during preservation perfusion and reperfusion. Only group A showed a significant heart weight gain (p less than 0.05) and a decline in passive compliance (p less than 0.05) during preservation. Lactate release was higher in group A than in the groups receiving Fluosol DA. In contrast, pyruvate levels in group A were lower than in other groups. The generation of free radicals stayed at a low level during preservation, but significantly increased during reperfusion and was associated with a corresponding increase in creatinine kinase MB isoenzyme. Perfusion with a perfluorochemical solution (group B) inhibited the sharp rise in levels of thiobarbituric acid reactive substances and of creatinine kinase MB isoenzyme and improved cardiac function during reperfusion (versus group A). Exogeneous free radical scavengers administered just before and during reperfusion (group D) significantly ameliorated thiobarbituric acid reactive substances and creatinine kinase MB isoenzyme levels and also induced a significant hemodynamic improvement during reperfusion. However, administration of scavengers during preservation did not. This study demonstrates that the generation of free radicals is primarily significant during reperfusion and reoxygenation after ischemia. Thus the best time for administration of scavengers is just before and just after the onset of reperfusion. Furthermore, perfusion with perfluorochemicals effectively maintains aerobic metabolism and ameliorates free radical damage during this period.

Animals↗

Prevention of free radical-induced myocardial injury by allopurinol. Experimental study in cardiac preservation and transplantation.

To determine the role of free radical-induced injury during heart preservation and transplantation, we harvested hearts from 28 mongrel dogs (12.5 to 16.5 kg), divided them into four groups, and orthotopically transplanted them. A group of seven hearts were orthotopically transplanted immediately after excision (group A). A second group of seven animals received allopurinol pretreatment (50 mg/kg/day) for 72 hours, and the hearts were orthotopically transplanted immediately after excision (group B). A third group of seven hearts were transplanted after continuous perfusion with oxygenated modified Collins solutions at 4 degrees C, pH 7.4, and a pressure of 20 mm Hg for 18 hours (group C). A fourth group of seven animals received allopurinol pretreatment (50 mg/kg/day) for 72 hours, and the hearts were orthotopically transplanted after perfusion with modified Collins solutions in the same manner as group C hearts (group D). The generation of free radicals, estimated by measurement of thiobarbituric acid reactive substances (malondialdehyde) in the coronary effluent, stayed at low levels during perfusion in groups C and D and also remained at low levels during operational ischemia in group A and B. During reperfusion, their levels abruptly and significantly increased and were associated with a corresponding increase in creatinine kinase MB isoenzyme (malondialdehyde levels at 30 minutes' reperfusion: A, 2.25 +/- 0.43; B, 1.55 +/- 0.25 nmol/ml/100 gm wet weight [p less than 0.05 versus group A]; C, 2.67 +/- 0.28; D, 1.77 +/- 0.27 nmol/ml/100 gm wet weight [p less than 0.05 versus group C]). In the allopurinol pretreatment groups, allopurinol significantly slowed the appearance of malondialdehyde and the release of creatinine kinase MB isoenzyme during reperfusion. Furthermore, cardiac functions during reperfusion, expressed as percent of control (mean +/- standard deviation), were significantly better in the allopurinol pretreatment groups than in the untreated groups: maximum first derivative of left ventricular pressure: A, 76.4 +/- 9.5; B, 99.7 +/- 14.3 [p less than 0.05 versus group A]; C, 25.2 +/- 2.6; D, 42.7 +/- 7.9 [p less than 0.05 versus group C]). These results indicate that (1) the generation of oxygen free radical is not significant during perfusion with modified Collins solutions nor during operational ischemia, but only during reperfusion, and (2) allopurinol reduces free radical-induced injury during reperfusion. Allopurinol has potential application in the prevention of reperfusion injury during heart transplantation.

Allopurinol↗

Pulmonary artery connection in the Fontan procedure. Flexible polytetrafluoroethylene conduit for expansion.

From clinical experiences with the Fontan operation in six cases, a few practical contrivances and operative steps are described. We stress that meticulous care should be taken not to cause any stenotic complication in the outflow tract toward the pulmonary artery, particularly by traction of the right atrial appendage only to achieve a direct anastomosis. Conduit repair would be necessitated by cases in order to expand the indicative criteria vertically as well as horizontally. For conduit material, we used consecutively nonvalved polytetrafluoroethylene that was reinforced by handmade stainless steel wire ring (Gore-Tex, Inc) or by spirally built-in stent (IMPRA, Inc). The latter was eventually useful in obtaining natural curving of the conduit without kinking or compression. Some contrivances in anastomosing a conduit were also proposed to achieve an excellent result. We believe these practical contrivances will serve for expansion of the indicative criteria and promise improved operative outcome.

Adolescent↗

Cardiac function following prolonged preservation and orthotopic transplantation.

Donor dog hearts perfused with whole blood were preserved ex vivo, beating, for 12 hours before orthotopic implantation. Twenty-four to 48 hours following implantation, ventricular function was studied using sonomicrometric techniques and compared to that of acutely denervated and conventionally preserved transplanted hearts. Hearts preserved ex vivo for 12 hours and then implanted in an orthotopic position had ventricular function statistically equal to or better than acutely denervated or conventionally preserved transplanted hearts.

Animals↗

Platelet deposition on and calcification of bovine pericardial valve.

Platelet deposition on bovine pericardial mitral valves was quantified in healthy adult mongrel dogs at 1, 14 and 30 days post-implantation and 24 h after i.v. injection of 400-500 microCi of autologous 111In-platelets. In vitro quantitation of platelet deposition on components of the prosthesis indicated maximal activity at one day with a successive decrease in activity at 14 and 30 days. At one day, platelet-associated radioactivity on the sewing ring was 3-4 times as great as on the leaflets, but at 14 and 30 days this had dropped to approximately half of the value on the leaflets. Calves underwent mitral valve replacement with a bovine pericardial valve. Thirty days post-operatively, 111Indium labeled labeled platelets were administered i.v.; 24 h later, calves were sacrificed and sections of each valve leaflet were analyzed for platelet and calcium deposition. Platelet deposition per mm2 of surface was greatest at the free edge of the leaflet, followed by the central zone and flexion point. Calves treated with sodium hydroxyethylene diphosphonate (5 mg kg-1 day-1 s.c.) had reduced platelet deposition but no reduced calcium content on the valves after 30 days compared with untreated calves. In flow chamber studies, platelet deposition from the heparinized blood of normal calves was significantly less on the smooth (inner) than on the rough (outer) surface of fixed bovine pericardium.

Animals↗

Quantification of platelet retention in aortocoronary femoral vein bypass graft in dogs treated with dipyridamole and aspirin.

Autologous femoral vein segments were implanted as aortocoronary bypass grafts in 50 dogs, 25 of which were treated with dipyridamole and aspirin to inhibit platelet deposition and 25 that were not. Autologous platelets labeled with indium-111 were injected into some dogs 48 hr before they were killed on the first day after surgery; other dogs were injected 24 hr before they were killed (3, 7, 30, and 90 days after surgery). Radioactivity on the grafts and on control specimens of contralateral femoral veins was converted to quantification of platelets adhering to the vessel wall (platelets/cm2). The treated group had fewer graft platelets per square centimeter than the untreated group on postoperative days 3, 7 (p less than .01), and 30 (p less than .05). Graft and control vein platelets per square centimeter were nearly equal by day 90. Comparison of graft and control specimens by scanning electron microscopy nearly equal by day 90. Comparison of graft and control specimens by scanning electron microscopy revealed deendothelialization at 1 and 7 days after grafting and reendothelialization at 30 and 90 days. The data suggest that indefinite prolongation of therapy to inhibit platelet deposition after bypass grafting may be unnecessary (although other atherosclerotic vessels may benefit from therapy).

Animals↗