Continuous arteriovenous hemodialysis for acute renal failure after cardiac operations.
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Biomedical subjects
Publications and source records attributed to A Piwnica.
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Iron catalysis is involved in the generation of the highly cytotoxic hydroxyl radical and in the chain reactions of subsequent lipid peroxidation that lead to irreversible membrane damage. Assuming that ischemically stored heart transplants may incur free radical injury at the time of reoxygenation, we assessed the effects of the iron chelator deferoxamine in 70 isolated isovolumic buffer-perfused rat hearts subjected to the following protocol: cardioplegic arrest; cold (2 degrees C) storage for 5 hours; global ischemia at 15 degrees C for 1 hour, intended to simulate the implantation procedure; and normothermic reperfusion for 1 additional hour. During poststorage ischemic arrest, the following techniques of myocardial protection were evaluated: hypothermia alone; high-pressure (60 cm H2O) cardioplegia given at 0, 30, and 55 minutes of arrest; low-pressure (30 cm H2O) cardioplegia given at 0 and 55 minutes of arrest; and low-pressure (30 cm H2O) cardioplegia only given at 55 minutes of arrest. Treated hearts had deferoxamine (6 mumol) added to the cardioplegic solution used throughout the experimental time course. Further, in the treated group subjected to the protocol of single cardioplegic delivery at end ischemia, deferoxamine was given both in the cardioplegic reperfusate and in the Krebs buffer over the 15 initial minutes of reflow. Based on comparisons of postreperfusion ventricular pressure development, maximal rate of rise of ventricular pressure, left ventricular compliance, and coronary flow, the best myocardial protection was afforded by deferoxamine given as an additive to single-dose cardioplegic solution at the end of arrest and to the reperfusate during the initial phase of reoxygenation. As the drug has no inotropic effect, its protective action is most likely related to a decrease in catalytic iron available for free radical production and lipid peroxidation. These results support the hypothesis that oxidative damage may contribute to donor heart failure and demonstrate that this form of damage can be efficiently acted upon by iron chelation. The clinical relevance of these data stems from the fact that deferoxamine is available for human use and might become an effective means of improving donor heart preservation in the setting of clinical heart transplantation.
Oxygen-derived free radicals are now considered important contributors to tissue injury associated with ischemia and reperfusion. Transition metals, primarily iron, greatly enhance the generation of these active species, which can destroy a large variety of biomolecules, in particular the lipid components of cell membranes. This review tries to demonstrate why cardiopulmonary bypass and aortic cross-clamping are situations that predispose to oxygen free radical production, and how "anti-free radical" agents such as enzymatic scavengers, antioxidants, and iron chelators may prove to be useful therapeutic adjuncts in the clinical setting of open heart surgery.
A long-term experimental morphological study was carried out in 22 adult sheep to evaluate a new pericardial valve prosthesis (Pericarbon), which had been implanted in the tricuspid or mitral position. This prosthetic device differs substantially from others in that its construction design consists of two sheets of glutaraldehyde-fixed bovine pericardium and a low-profile flexible plastic stent (Delrin) covered by a pyrolytic carbon coated dacron fabric; one pericardium sheet forms the three cusp valve and is sutured to the second, which lines the inner surface of the plastic stent. Twenty animals were sacrificed at fixed intervals, while 2 are still living at about 3 years post-surgery. Tricuspid explants (mean duration, 295 days) showed significant fibrous sheathing and a mean calcium X-ray score of 1.75. Mitral medium-term explants (mean duration, 325 days) had fairly well preserved pliability and a mean calcium X-ray score of 2.5. Long-term explants (mean duration, 467 days) were all stiffened by calcification (mean score, 3.75). None of the explants had tears or perforations. Medium or long-term mechanical failure was not observed. A significant host tissue reaction took place in the tricuspid but not in the mitral position. Calcification mainly involved the collagen fibres and increased progressively with time. Ultrastructural studies invariably disclosed fair preservation of graft tissue structures, surface reendothelization and initial nuclei of calcification within the collagen fibres. These morphological findings confirm the potential advantages of this new prosthetic device and warrant long-term clinical trials to test its actual durability.
Intraoperative epicardial mapping data obtained in 73 consecutive patients operated upon for the Wolff-Parkinson-White syndrome were reviewed. Fifty-six patients had single and 17 patients had multiple accessory pathways. Except for right free wall pathways, all bypass tracts were divided using an endocardial approach. There were 2 operative deaths, 1 of which occurred after a concomitant mitral valve replacement. A total of 78 of the 87 pathways present in the 71 survivors were successfully ablated (90%). All failures occurred in patients with left posterior septal pathways. Epicardial mapping performed prior to bypass was found helpful in identifying multiple distinct accessory pathways which had been missed preoperatively. This occurred in 6 patients and led to appropriate combinations of classic operative approaches which resulted in all of these pathways being successfully divided. Further, by demonstrating that Kent bundles often presented as multiple closely-spaced or arborized accessory pathways, intraoperative mapping led to widening of the margins of surgical dissection, and in particular to an additional left atriotomy in all cases of left posterior septal accessory pathways which resulted in a substantial improvement in our rate of success.
Thirty patients have been operated on since July 1986. The mean age was 55 years (range 32-68). Twenty-three simple and 7 double bypasses were performed. The internal mammary artery and 1 prosthetic conduit were used for the 29 left anterior descending (LAD) anastomoses and saphenous vein for the others [5 right coronary artery (RCA), 3 diagonal]. The use of an implantable Doppler probe for continuous monitoring during the 1st postoperative week confirmed patency and gave an estimated flow (mean: 79.23 ml/min, range 43.4). There were no deaths and no cases of infarction or ischaemia, but stress test performance improved. The main advantage of this rapid and safe technique was avoidance of morbidity of extracorporeal circulation (ECC) and limited operative myocardial ischaemia. Criteria of selection were unstable, permanent angina (14); unsuccessful PTCA (8) PTCA and failure (5 emergency cases), redo surgery (4); poor LV function (EF less than 20%) (3); fibrinolytic treatment or severe coagulopathy (2). The ideal patient has severe stenosis with or without retrograde filling of LAD with either RCA or circumflex (which require a lateral thoracotomy).
Pericarbon, a new generation pericardial valve, is characterized by a single, three cuspal shaped pericardium sheet, which is sutured to a second sheet lining the inner surface of the plastic, low profile stent. A coating of hemocompatible carbon film covers all the exposed, nonbiological surfaces. Optimal preservation of collagen and graft cells is achieved by fresh tissue glutaraldehyde fixation and cusp shaping without mold. Accelerated fatigue testing showed a duration of over 150 million cycles, a figure much higher than that observed when current pericardial and porcine valves were tested with the same apparatus. Results of long-term (greater than 7 months, average 10.5) implantation in 20 sheep (13 mitral, 7 tricuspid) disclosed no case of mechanical failure, mild to moderate primary calcification in older explants, and significant fibrous tissue overgrowth only in the tricuspid position. Transmission electron microscopy studies revealed collagen and elastic fiber integrity, no significant plasma protein insudation, and well-preserved graft cells. Re-endothelialization by host cells was a regular finding on scanning electronic microscopy. Early ultrastructural nuclei of calcification were seen mostly on collagen fibers. Pericarbon presents basic changes in pericardial valve design, and optimal morphological preservation is obtained after industrial processing. Accelerated fatigue tests in vitro show long duration. At medium long-term animal experimental follow-up, mechanical failure was not observed; significant host tissue reaction occurred in the tricuspid but not in the mitral position; primary calcification increased progressively with time and involved mainly collagen fibers.
Whether retrograde coronary sinus cardioplegia adequately preserves right ventricular (RV) function is still a point of concern. Using technetium Tc 99m-labeled red blood cells, we assessed global and segmental RV function by first-pass and gated blood-pool radionuclide angiocardiography before and within 24 hours after aortic valve replacement in 14 consecutive patients (age, 58 +/- 5 years; mean +/- SEM). Coronary sinus cardioplegia was given in a multidose fashion at a flow rate of 50-70 ml/min through a balloon-tipped catheter, with the inflated balloon kept seated around the intra-atrial rim of the coronary sinus orifice. Additional myocardial protection was provided by systemic (25 degrees C) and topical hypothermia. Postoperatively, none of the patients had clinical or hemodynamic patterns suggestive of RV dysfunction. The postoperative global RV ejection fraction (0.49 +/- 0.03) was similar to the preoperative value (0.49 +/- 0.01). Analysis of segmental wall motion did not reveal postoperative abnormalities of new onset in any of the three anatomically defined RV regions (free wall, apex, and septum). Similarly, RV end-diastolic and end-systolic volume indexes (ml/m2) were not significantly affected by coronary sinus cardioplegia, being 71.6 +/- 5.8 and 36.1 +/- 3.5 before, and 67.4 +/- 3.8 and 34.5 +/- 2.3 after aortic valve replacement, respectively. We conclude that retrograde coronary sinus cardioplegia does not cause a detectable impairment of RV function if the balloon catheter does not obstruct the terminal tributaries of the coronary sinus and, hence, does not impede delivery of cardioplegia to right-sided cardiac structures.
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Between october, 1982 and december, 1986, 17 patients were implanted with an automatic defibrillator. The thoracic route was used in 6 patients with installation of an epicardial patch and an endocavitary electrode. The subcostal route was used in the remaining 11 patients, with 2 epicardial patches. The device, badly tolerated by 2 of the first 6 patients, created no problem in the 11 patients of the second group. One patient died of pulmonary embolism on the 6th post-operative day. At follow-up, there was no inappropriate triggering of the AID-B: 8 patients had neither arrhythmia nor shock, and 8 received from 2 to 55 shocks with documented arrhythmia. Two patients died suddenly: one after end of life of the device, the other after 3 years, while the device was still working. The implantable defibrillator technique has improved and local complications are now seldom observed. The device is reliable and constitutes an effective weapon against sudden death caused by ventricular arrhythmia.
The morphologic, biochemical, and mechanical abnormalities of connective tissue fibrous proteins in Marfan's syndrome have been well studied, and their role in cardiovascular complications is well accepted. Less is known, however, about the state of the amorphous components of the aortic connective tissue. In the course of a study of transmural transport in blood vessels, we have had the opportunity to study dystrophic aorta from two young men who survived elective surgery; both with aortic insufficiency (AI) histologically compatible with Marfan's syndrome. One had recurrent chronic dissecting aneurysm (RCDA) as well. The aorta of the first (but not the second) was histologically compatible with Marfan's syndrome. Fresh specimens of intact ascending aorta were incubated in Krebs solution, pH 7.4, containing 125I-labelled bovine serum albumin for 2 h at 37 degrees C. The samples were then frozen, and serially sectioned in the plane of the lumenal surface. The radioactivity of the 20-micron thick sections was then determined, and expressed as a tissue/labelled solution concentration ratio. Transmural profiles of these ratios revealed no difference between the aorta of the RCDA patient with non-specific aortic dystrophy, and that of a 70-year-old man undergoing aortocoronary bypass. However, in the patient with aortic histology compatible with Marfan's syndrome, the average media concentration ratio was 5-fold less (4% vs. 20%).
Of 2171 patients who underwent open heart surgery between 1981 and 1986, 41 (1.8%) developed postoperative mediastinitis and were treated by closed irrigation drainage or open chest therapy. Six patients, (mean age 59 years) developed rupture of the right ventricular free wall. The primary procedures were: resection of akinetic fibrous plaque (2), mitral valve replacement (1), coronary bypass grafting (1), removal of a left atrial myxoma (1) and repair of post-infarction rupture of the left ventricle (1). In 2 patients, rupture occurred in the operating theatre during revision of the irrigation drainage. Both patients died after repair. In 4 patients, rupture occurred during coughing. One died before surgery. In the 3 other cases, the defects were repaired either by direct suture (2 patients) or with a pericardial patch (1 patient) with the aid of normothermic extracorporeal circulation. Three days later, a muscular flap (pectoral or dorso-lumbar) was mobilized to protect the mediastinal viscera. All 3 patients are alive and well. When bleeding occurs during treatment of mediastinitis, an immediate exploration with extracorporeal circulation to close the defect should be considered.
Myocardial protection during surgically-induced cardiac ischemic arrest can be improved by promoting aerobic metabolism throughout the ischemic episode. Because of the problems encountered with both blood cardioplegia and oxygenated crystalloid cardioplegia, we assessed the effects of a recently developed lecithin-based perfluoroadamantane in an isolated isovolumic buffer-perfused rat heart model of cardioplegic arrest. Forty hearts divided into 4 equal groups underwent 90 min of global ischemia at 30.C followed by 45 min of normothermic reperfusion. During arrest, hearts were infused at 30 min intervals with either standard crystalloid cardioplegic solution, lecithin-enriched cardioplegic solution or cardioplegic solution mixed with a lecithin-based perfluorocarbon emulsion (F-dimethyladamantane in one group, and F-methyladamantane in the other). All perfusates were fully oxygenated prior to use. Although fluorocarbon-treated hearts had reduced postischemic coronary flows, they yielded a significantly better recovery of systolic indexes (developed pressure and left ventricular dP/dt) than the controls. Postischemic diastolic pressures were not different among the 4 groups. We conclude that, under severe conditions of ischemia, the Adamantech fluorocarbon emulsion significantly improves cardioplegic protection. The clinical relevance of these data is supported by the fact that, unlike previously developed pluronic-based fluorocarbon emulsions, the present solution has no complement-activating properties.
We assessed the effects of the iron chelator deferoxamine in 24 adult patients (12 controls, 12 treated) undergoing cardiopulmonary bypass for various cardiac operations. Deferoxamine was given both intravenously (30 mg/kg of body weight, starting 30 minutes before and ending 30 minutes after bypass) and as an additive to the cardioplegic solution (250 mg/L). Right atrial blood samples were taken before, during, and after bypass, and isolated polymorphonuclear neutrophils were evaluated for their capacity to generate superoxide radicals after stimulation with N-formyl-methionyl-leucyl-phenylalanine (FLMP, 10(-7) mol) and phorbol myristate acetate (100 ng/ml). At the same sampling times, measurement of the plasma levels of 6-keto-prostaglandin F1 alpha, the stable derivative of prostacyclin, was used as an index of membrane phospholipid breakdown. The two groups were not significantly different with regard to age, duration of bypass, and quantitative changes in polymorphonuclear neutrophil counts during the operation. Before bypass, the superoxide production of FMLP-stimulated polymorphonuclear neutrophils was comparable in the two groups. Conversely, after bypass, polymorphonuclear neutrophils harvested from deferoxamine-treated patients produced significantly fewer superoxide radicals than those of control patients (1.9 +/- 0.3 versus 3.7 +/- 0.2 nmol/10(6) polymorphonuclear neutrophils per minute, p less than 0.05). Stimulation of polymorphonuclear neutrophils by phorbol myristate acetate yielded similar changes, as the postbypass superoxide production was 12.6 +/- 2.5 nmol/10(6)/min in control patients and 7.1 +/- 0.9 nmol/10(6)/min in those receiving deferoxamine (p less than 0.05). In contrast, plasma levels of 6-keto-prostaglandin F1 alpha were not significantly different between the two groups. We conclude that deferoxamine-exposed polymorphonuclear neutrophils have a decreased oxidative responsiveness, compatible with the fact that they may have been less "primed" by secretagogues released during bypass, as compared with cells of untreated patients. Our results are consistent with the hypothesis that deferoxamine, by inhibiting iron-catalyzed free radical production, may limit the free radical-mediated amplification of the inflammatory response to bypass and as such could be effective in reducing the harmful effects of extracorporeal circulation.
Superimposition of cardioplegic arrest on acute low-cardiac-output states, as may occur after failure of percutaneous transluminal coronary angioplasty requiring emergency surgery, is associated with an increased operative risk. This increased risk is possibly attributable to reperfusion, which, after sequential episodes of myocardial ischemia, exacerbates tissue injury mediated by oxygen free radicals. One of the most cytotoxic of these active oxygen species is the hydroxyl radical, which is formed from superoxide anion and hydrogen peroxide through an iron-catalyzed reaction. This study assesses the effects of peroxidase, a hydrogen-peroxide scavenger, and of deferoxamine, an iron chelator, in isolated working rat hearts subjected to 30 minutes of low-flow ischemia (75% reduction in coronary flow) followed by 2 hours of cardioplegic arrest at 15 degrees C and by 30 minutes of normothermic reperfusion. Three groups of hearts (n = 7) were studied. Two groups were pretreated with either peroxidase (10,000 units/l) or deferoxamine (0.03 mM) during the last 15 minutes of the low-flow ischemic period. The third group received no prearrest intervention and served as a control group. In addition to hemodynamic determination, high-energy phosphate content [adenosine 5'-triphosphate (ATP)] and intracellular pH were monitored serially by 31P nuclear magnetic resonance spectroscopy. The two pretreated groups had better recovery of ATP levels and aortic flow values than did the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
Hydroxyl is one of the most cytotoxic of all oxygen-derived free radicals produced during the myocardial ischaemia-reperfusion sequence. The purpose of the present study was to determine the effects of various interventions aimed at diminishing the production of hydroxyl radicals by reducing either one of their precursors (hydrogen peroxide) or the metal (ferric iron) which catalyzes the reaction generating these radicals. Sixty isolated and perfused rat hearts with isovolaemic contraction were studied. Except for non-ischaemic controls, these hearts were subjected to a 3-hour cardioplegic arrest in hypothermia (15-18 degrees C) followed by a 45-min reperfusion. The following interventions were performed: pretreatment with peroxidase, a hydrogen peroxide scavenger; pretreatment with peroxidase combined with deferoxamine, an ironchelating agent; pretreatment with peroxidase followed by addition of deferoxamine to the cardioplegic solution; addition of deferoxamine to the cardioplegic solution without pretreatment with the enzyme. Judging from the post-ischaemic values of developed pressure (maximum systolic pressure--diastolic pressure), left ventricular dP/dt and diastolic pressure and coronary flow rate, it appeared that the best myocardial protection was provided by deferoxamine-enriched cardioplegia. This study confirms that hydroxyl radicals most probably play a role in the genesis of the myocardial lesions associated with global ischaemia followed by reperfusion. Moreover, our results highlight the potential value of deferoxamine added to cardioplegic protection in heart surgery performed under extracorporeal circulation.
We present the fourth case report of an histiocytoid hemangioma of the heart, which was found incidentally, as in the other three reported cases, in a 50 year old man during surgery for congenital heart disease. A polypoid sessile reddish tumor with a smooth surface, which measured 2 cm in diameter, was found in the right atrium. No necrosis nor cystic areas were seen. Histologic evaluation revealed a proliferation of histiocytoid or epithelioid cells, whose arrangement varied a great deal within the infiltrate. Sometimes, the cells were isolated but in most places they were arranged in sheets or nests surrounded by connective tissue. Some of these nests were compact whereas in others a lumen formation, frequently occupied by erythrocytes, could be appreciated. A striking feature was the presence of vacuolated tumor cells sometimes assuming a signet-ring configuration. Some large vascular spaces were lined by histiocytoid or epithelioid endothelial cells, many of which protruded into the lumen. Multinucleated tumor cells were occasionally observed. Mitoses were rare (up to 1/10 HPF) and scattered inflammatory cells such as lymphocytes, macrophages, neutrophils and eosinophils were seen. Histologic appearance of our patient's tumor is identical to the histiocytoid hemangioma of Rosai et al., which is an ubiquitous endothelial benign neoplasm.
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