Bicarbon valve -- European multicenter clinical evaluation.

OBJECTIVE: Fifteen collaborating centers in eight countries present their pooled experience with the new Bicarbon bileaflet valve. METHODS: Between 4/90 and 4/96, 1351 patients, 806 males and 545 females, aged 10 to 83, mean 58.4 +/- 12.4, underwent valve implantation. OPERATIONS: aortic valve replacement (AVR), 726; mitral valve replacement (MVR), 475; double valve replacement (DVR), 150. Additional procedures: CABG, 211; TV repair, 64; other, 152. RESULTS: Mortality: 67 early (seven valve related) and 56 late (40 valve related). Valve thrombosis: six obstructive, three non-obstructive; embolism: nine major cerebral, 37 other. Major bleeding: 29. Hemolysis: two clinically significant. Non-structural dysfunction: 24 paravalvular leaks, one leaflet interference. No structural failure! Endocarditis: 24. Reoperation 48: 22 non-structural dysfunctions, 14 endocarditis, seven thrombosis and embolism, five other. Estimated 5-year freedom from valve-related deaths is 97.2% for AVR and 92.4% for MVR; 4-year freedom from valve related deaths for DVR is 90.5%. Mean calculated NYHA improvement is 1.24. CONCLUSIONS: The Bicarbon mechanical prosthesis is well designed, durable, has good hemodynamic features and an acceptably low incidence of complications.

Patterns of changes in neutrophil adhesion molecules during normothermic cardiopulmonary bypass. A clinical study.

The adhesion of activated neutrophils to endothelial cells is a key feature of the inflammatory response to cardiopulmonary bypass (CPB) because it "unlocks" a cascade of cytotoxic events. This adhesion is made possibly by the sequential involvement of two sets of neutrophil cell surface receptors: L-selection and beta 2 integrins (CD 11 a/CD 18; CD 11 b/CD 18; CD 11 c/CD 18). We have assessed the changes in the expression of these adhesion molecules in ten patients who underwent various open-heart procedures with the use of "warm" (33.4 degrees-37 degrees C) CPB. Arterial blood samples were obtained before, during and after bypass and processed for immunofluorescent flow cytometric analysis. CD 11 a expression remained unchanged throughout the study period. Conversely, CD 11 b drastically increased early after the onset of bypass (at 15 min on bypass: 172 +/- 17 [mean fluorescence (arbitrary units), mean +/- SEM] versus 63 +/- 13 before bypass. P < 0.02) and was still markedly elevated 30 min after the end of bypass (160 +/- 38, P < 0.05 versus the pre-by-pass value). CD 11 c expression underwent a similar upregulation (at 15 min of bypass: 54 +/- 5 versus 34 +/- 5 at baseline, P < 0.01). L-selectin expression did not change significantly during the period of observation. Put together, these results suggest that CPB is associated with an increased adhesive potential of neutrophils, which enhances their binding to the vascular endothelium and thereby initiates tissue damage through the release of cytotoxic mediators from adherent cells. Manipulation of integrin expression could therefore represent an effective means of alleviating the component of bypass-induced inflammatory tissue damage which is more specifically neutrophil-mediated.

Preconditioning with potassium channel openers. A new concept for enhancing cardioplegic protection?

Ischemic preconditioning defines an adaptive endogenous mechanism in which a brief episode of reversible ischemia renders the heart more resistant to a subsequent period of sustained ischemia. Because the cardioprotective effects of ischemic preconditioning might be mediated by an activation of adenosine triphosphate-sensitive potassium channels, this study was designed to assess whether these effects could be duplicated by the preischemic administration of a potassium channel opener. Fifty isolated isovolumic buffer-perfused rat hearts underwent 45 minutes of normothermic potassium arrest followed by 1 hour of reperfusion. They were divided into five equal groups that differed with regard to the preconditioning regimen: Group 1 hearts were left untreated and served a controls; in group 2, preconditioning was achieved with 5 minutes of total global ischemia followed by 5 minutes of buffer reperfusion before cardioplegic arrest; in group 3, the preconditioning stimulus consisted of a 5-minute infusion of the potassium channel opener nicorandil (10 mumol/L) followed by 5 minutes of drug-free buffer perfusion before arrest; group 4 hearts underwent a similar protocol except that the infusion of nicorandil was preceded by that of the potassium channel blocker glibenclamide (10 mumol/L); group 5 hearts were ischemically preconditioned like those of group 2 except that the no-flow preconditioning period was also preceded by a 5-minute infusion of glibenclamide (50 mumol/L). The results demonstrate that ischemic preconditioning significantly improved contractility and reduced contracture during reperfusion, as compared with results in control hearts. These protective effects were duplicated by pretreatment with nicorandil but were abolished when the drug was antagonized by a prior infusion of glibenclamide. Likewise, the glibenclamide-induced blockade of potassium channels largely blunted the beneficial effects of ischemic preconditioning. These data suggest that opening of adenosine triphosphate-sensitive potassium channels substantially contributes to preconditioning-induced cardiac protection in a surgically relevant model of global ischemia and, consequently, that the use of potassium channel openers like nicorandil could be an effective means of enhancing cardioplegic protection.

Influence of temperature on neutrophil trafficking during clinical cardiopulmonary bypass.

BACKGROUND: The adhesion of neutrophils to endothelial cells and their subsequent transendothelial migration play a major role in inflammatory damage elicited by cardiopulmonary bypass (CPB) because these events are linked to the release of cytotoxic proteases and oxidants. However, the patterns of neutrophil trafficking in relation to systemic temperature during clinical CPB have not yet been characterized. METHODS AND RESULTS: Twenty case-matched patients undergoing warm (31.8 +/- 0.4 degrees C) or cold (26.3 +/- 0.5 degrees C, P < .0001 versus warm) bypass were studied. Blood samples were simultaneously collected from the right and left atria before, at the end of, and 30 minutes after CPB. Plasma levels of C3a, P- and E-selectins, elastase, and interleukin-8 were determined by immunoassays. The results demonstrate: (1) a rise in C3a, reflecting complement activation, (2) a fall in soluble E-selectin consistent with an increased adhesiveness of activated neutrophils, (3) a rise in soluble P-selectin expected to enhance endothelial adhesion of these neutrophils, (4) a rise in elastase, suggesting an adhesion-triggered neutrophil degranulation, and finally (5) a rise in interleukin-8 that is likely to promote transendothelial migration of adherent neutrophils. All of these changes occurred in the two groups of patients and were significant compared with prebypass values. However, in none of the groups was there a significant difference between right and left atrial values for any of the markers. The single difference between cold and warm bypass patients was a significant reduction of elastase release in the cold group (P < .001 versus the warm group). CONCLUSIONS: Clinical CPB is associated with biological changes suggesting the occurrence of neutrophil trafficking. Hypothermia provides only partial protection through a reduced release of elastase. Overall, these results reinforce the rationale for the development of therapeutic strategies targeted at blunting the neutrophil-mediated component of bypass-induced inflammatory damage.

Hypothermia during cardiopulmonary bypass delays but does not prevent neutrophil-endothelial cell adhesion. A clinical study.

BACKGROUND: An accurate evaluation of warm heart surgery cannot be limited to the assessment of the myocardial effects of warm blood cardioplegia but should also address the effects of systemic normothermia on the inflammatory response to cardiopulmonary bypass. A major component of this response is the endothelial adhesion of neutrophils, because it is linked to the release of cytotoxic compounds. This study was designed (1) to characterize the bypass-induced changes in the expression of neutrophil adhesion molecules (L-selectin and beta 2-integrins) and (2) to assess the influence of bypass temperature on these changes. METHODS AND RESULTS: Twenty case-matched patients undergoing open-heart procedures were divided into two equal groups according to the core temperature during cardiopulmonary bypass: warm (33.4 +/- 0.3 degrees C) or cold (27.1 +/- 0.4 degrees C, P < .0001 versus warm). Arterial blood samples were collected before, during, and 30 minutes after bypass and processed for the expression of L-selectin and beta 2-integrins (CD11a, CD11b, and CD11c) with flow cytometry. Warm bypass was associated with an early and sustained upregulation of CD11b. In contrast, hypothermia resulted in a strikingly less pronounced CD11b upregulation during bypass. However, CD11b expression sharply increased thereafter so that 30 minutes after bypass, it was no longer significantly different between the two groups. Changes in CD11c expression grossly paralleled those described for CD11b. Neither CD11a nor L-selectin changed significantly from baseline values in either group. CONCLUSIONS: Clinical cardiopulmonary bypass is associated with a marked upregulation of the neutrophil CD11b and CD11c integrins. Hypothermia delays but does not prevent the increased expression of these adhesion molecules, which could consequently represent logical targets for interventions designed to blunt the neutrophil-mediated component of bypass-induced inflammatory tissue damage.

[Does temperature in extracorporeal circulation affect neutrophil-endothelium interactions?]. / La température de la circulation extracorporelle influence-t-elle les interactions neutrophiles-endothélium?

The increasing interest in "warm" aerobic cardioplegia requires a critical reevaluation of the systemic effects of the associated normothermic cardiopulmonary bypass (CPB). As activated neutrophils seem to be essential mediators of the inflammatory response to CPB via the cytotoxicity of the products that are released during their adhesion to endothelial cells, the authors undertook a study of the influence of temperature on the interaction between the neutrophils and the endothelium in 95 patients undergoing warm (31-33.5 degrees C, n = 49) and cold (26-27 degrees C, n = 46) CPB surgery. Blood sampling was performed before, during and after CPB. The following markers of neutrophil-endocardium interaction were analysed: complement activation (C3a), cytokine production (tumor necrosis factor alpha, interleukines 1, 6 and 8, and interleukin-1 receptor antagonist); endothelial expression of cytokine-dependent [intercellular adhesion molecule (ICAM)] and cytokine-independent (P-selectin) adhesion molecules (P-selectin); expression of cytokine molecules on the surface of polynuclear neutrophils (CD11a, CD11b, CD11c); and finally, endothelial adhesion and transendothelial migration of neutrophils (interleukin 8 and elastase). The results showed that, irrespective of temperature, CPB was associated with changes strongly suggestive of phenomena of transendothelial adhesion and migration. Moreover, normothermia increased the intensity of the inflammatory response as shown by increased cytokine production, earlier expression of neutrophil adhesion molecules and increased elastase production.

Does normothermia during cardiopulmonary bypass increase neutrophil-endothelium interactions?

BACKGROUND: The use of warm blood cardioplegia is usually associated with that of warm cardiopulmonary bypass (CPB). Little is known, however, about the effect of temperature during bypass on neutrophil-endothelium interactions, which are currently considered a key component of the inflammatory response to CPB. METHODS AND RESULTS: Twenty-five patients operated on under CPB were studied. Core temperature during bypass was kept normothermic (33.5 degrees C to 37 degrees C) in 14 and lowered to 28 degrees C to 30 degrees C in the 11 remaining patients. The two groups were otherwise comparable. Arterial blood samples were collected before CPB and 30 minutes, 4 hours, and 24 hours thereafter. Samples were assayed for interleukin-1 receptor antagonist (IL-1ra), soluble intercellular adhesion molecule 1 (sICAM-1), and elastase, which are markers of cytokine production, cytokine-upregulated endothelial ligands for neutrophil adhesion molecules, and degranulation secondary to adhesion of neutrophils to endothelial cells, respectively. IL-1ra levels (mean +/- SEM) peaked 4 hours after bypass and were significantly higher in the warm group (87,926 +/- 24,067 versus 18,090 +/- 5798 mg/L, P < .02). Peak values of sICAM-1, which occurred 24 hours after bypass, were correspondingly higher in warm patients (414 +/- 74 versus 298 +/- 23 micrograms/L in cold patients). In keeping with these data, warm patients released significantly more elastase at both the 30-minute (703 +/- 101 versus 349 +/- 55 micrograms/L, P < .01) and 4-hour (627 +/- 116 versus 324 +/- 31 micrograms/L, P < .03) post-CPB study points. CONCLUSIONS: Temperature profoundly affects neutrophil-endothelium interactions, which leads one to question the use of systemic normothermia in patients at higher risk of suffering from postbypass inflammation-mediated organ damage.

Metabolic and functional evidence that retrograde warm blood cardioplegia does not injure the right ventricle in human beings.

BACKGROUND: Retrograde warm blood cardioplegia is now recognized as an effective method of myocardial protection, but concerns persist about its ability to adequately preserve the right ventricle. METHODS AND RESULTS: A total of 75 patients in whom warm blood cardioplegia was continuously given through the coronary sinus were included in this three-part study. Part 1, which involved 30 patients undergoing coronary artery bypass grafting operations, was designed to assess whether the right ventricle incurred a greater degree of anaerobic metabolism than the left ventricle during warm arrest. Immediately before aortic unclamping, antegrade perfusion was resumed and, within 1 minute of washout, blood samples were simultaneously taken from the right ventricle and coronary sinus and assayed for lactate. There was no significant difference in lactate concentrations between the two sampling sites (right ventricle, 2.53 +/- 0.1 mmol/L; coronary sinus, 2.47 +/- 0.1 mmol/L). Part 2 focused on recovery of function. A complete set of postoperative hemodynamic measurements was obtained in 15 among the 30 patients enrolled in part 1 and compared with that obtained in 15 case-matched patients who received conventional cold antegrade crystalloid cardioplegia. Postoperative right ventricular stroke work index was not significantly different between the two groups (retrograde warm, 4.6 +/- 0.2 g.m-1.m-2; antegrade cold, 4.8 +/- 0.2 g.m-1.m-2). Part 3 was also targeted at functional end points but in 30 additional patients undergoing reoperative mitral valve replacement and consequently deemed to be at higher risk of right ventricular ischemia. Fifteen patients who received retrograde warm cardioplegia were compared with 15 case-matched control subjects in whom antegrade cold crystalloid cardioplegia was used. In keeping with data of part 3, postoperative right ventricular stroke work index was not significantly different between the two groups (retrograde warm, 6.9 +/- 0.4 g.m-1.m-2; antegrade cold, 7.7 +/- 0.5 g.m-1.m-2), nor was there a difference in clinical outcomes or biological recoveries of hepatic function. CONCLUSIONS: Inadequate protection of the right ventricle associated with the use of retrograde warm blood cardioplegia does not appear to be a clinically founded concern since this technique preserves right ventricular function to the same extent as conventional antegrade cold cardioplegia does.

Retrograde warm blood cardioplegia preserves hypertrophied myocardium: a clinical study.

The ability of retrograde warm blood cardioplegia to preserve hypertrophied myocardium remains controversial. This two-part study was undertaken to address this question in patients subjected to aortic valve replacement for calcified aortic valve stenosis complicated with echocardiographically defined left ventricular hypertrophy. Part 1 was designed to assess the intraoperative patterns of myocardial oxidative metabolism in 20 patients in whom the severity of left ventricular hypertrophy was reflected by a mean (+/- standard error of the mean) myocardial mass index of 213 +/- 15 g/m2. After antegrade arrest, warm blood cardioplegia was continuously given through the coronary sinus at a flow rate of 200 +/- 5 mL/min. The use of a low-dilution cardioplegia delivery technique enabled us to keep hematocrit at 25.6% +/- 0.9% and the core temperature was allowed to drift to 32.7 +/- 0.2 degrees C. At the end of the arrest period, blood samples were simultaneously taken from inflow (coronary sinus catheter) and outflow (left coronary ostium) cardioplegia and assayed for blood gases, oxygen content and saturation and lactate. Part II was designed to compare the clinical outcomes of these 20 warm patients with those of 20 case-matched patients in whom a conventional hypothermic myocardial protection technique was used. The results of part I show that after an average arrest period of 72 +/- 4 minutes, the residual oxygen demand was still high as reflected by a percent oxygen extraction of 34.8% +/- 4.1%. This demand, however, was adequately met by the supply, as demonstrated by (1) the absence of transmyocardial acid production, (2) a negligible release (outflow minus inflow) of lactate (0.28 +/- 0.1 mmol/L), and (3) a high residual oxygen saturation (65.7% +/- 3.8%) in outflow cardioplegia. The results of part II show that the clinical outcomes of warm patients were overall good and not different from those of the cold group. We conclude that retrograde warm blood cardioplegia can adequately preserve hypertrophied myocardium by keeping its metabolism predominantly aerobic during aortic cross-clamping provided that measures are taken to optimize the determinants of the oxygen demand/supply ratio throughout. These measures include avoidance of left ventricular distention, immediate ablation of any recurring activity during arrest, maintenance of high retrograde flow rates, limitation of hemodilution, and uninterrupted mode of cardioplegia delivery.

[Use of myoplasty after acute mediastinitis occurring after heart surgery. Apropos of 167 cases]. / Utilisation des myoplasties après mise à plat des médiastinites aiguës post-chirurgie cardiaque. A propos de 167 cas.

Infected median sternotomy often requires open wound management. A large thoracic defect usually results in subsequent exposure of heart, great vessels, aorto-coronary bypass grafting or vascular prosthesis. After thorough wound debridement, coverage with muscle transposition was carried out in a series of 167 cases observed over a period of 10 years. Transposition of both pectoralis major muscles on internal pedicles was performed in 75 cases. In 27 of these cases, internal mammary grafting did not preclude their use. Since 1986, intrathoracic transposition of the trapezius muscle has been our treatment of choice in 25 cases, most frequently combined with a double pectoralis major transposition. Rectus abdomini muscle flap was seldom used alone whereas latissimus dorsi was mainly used as a salvage flap. Muscle transposition provided effective heart and great vessel protection after acute hemorrhage in 18 cases. This series confirms that mortality and mean hospital stay have decreased dramatically since the routine use of muscle transposition.

Experimental evaluation of Celsior, a new heart preservation solution.

An original heart preservation solution (Celsior) has been developed, the formulation of which has been designed to fulfil two major objectives: (1) to combine the general principles of hypothermic organ preservation with those specific for the myocardium, and (2) to offer the possibility of being used not only as a storage medium but also as a perfusion fluid during initial donor heart arrest, poststorage graft reimplantation and early reperfusion. The major principles addressed by the Celsior formulation include (1) prevention of cell swelling (by mannitol and lactobionate), (2) prevention of by the Celsior formulation include (1) prevention of cell swelling (by mannitol and lactobionate), (2) prevention of oxygen-derived free radical injury (by reduced glutathione, histidine and mannitol), and (3) prevention of contracture by enhancement of energy production (glutamate) and limitation of calcium overload (high magnesium content, slight degree of acidosis). Two experimental preparations were used: The isolated isovolumic buffer-perfused rat heart model and the heterotopic rabbit heart transplantation model. In isolated heart experiments, hearts were arrested with and stored in Celsior for 5 h at 4 degrees C and subsequently reperfused for 1 h. A similar protocol was used in the transplantation experiments except that the total ischemic time was approximately 1 1/2 h longer (corresponding to 6 h of storage followed by the 25 additional minutes of cold ischemia required for graft implantation.(ABSTRACT TRUNCATED AT 250 WORDS)

A potential mechanism of vasodilation after warm heart surgery. The temperature-dependent release of cytokines.

Peripheral vasodilation is a common feature of warm heart surgery and creates clinical concerns when pressor agents become necessary because of the potential for some of these drugs to adversely affect flow through newly engrafted arterial and venous bypass conduits. The possible role of a temperature-dependent production of cytokines in the pathogenesis of this vasodilation was investigated in a two-part study. In part I, lipopolysaccharide-activated peritoneal rabbit macrophages (5 x 10(6)/ml) were incubated at 30 degrees or 37 degrees C up to 9 hours and the concentration of tumor necrosis factor released in the supernatant was serially measured by a bioassay. Tumor necrosis factor production was found to increase over time for each of the two temperatures of incubation but was significantly higher throughout the observation period in normothermic experiments than in those done at 30 degrees C. Part II was a prospective clinical study involving 30 patients who underwent either cold (core temperature 28 degrees to 30 degrees C, n = 15) or warm (37 degrees C, n = 15) cardiopulmonary bypass and in whom serum levels of tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6 were measured by enzyme-linked immunosorbent assays at 2, 4, 10, and 24 hours after bypass. Cytokine levels were found to be consistently higher in patients having normothermic bypass. Differences between the two groups were significant 2 hours after bypass for tumor necrosis factor alpha and interleukin-6 (p < 0.02 and p = 0.0001, respectively) and 4 and 10 hours after bypass for interleukin-1 beta (p < 0.01 and p < 0.04, respectively). The incidence of vasodilation necessitating vasopressor support was twofold higher in the normothermic group (six patients versus three in the hypothermic group). Taken as a whole, patients supported by pressor agents had significantly higher cytokine levels after bypass than those who did not require pressor therapy. Our results suggest that vasodilation occurring with warm heart operation is, at least partly, mediated by a temperature-dependent release of cytokines. Vasodilation might therefore be mitigated by simply allowing the core temperature to drift during bypass. Our recent clinical experience suggests that this "tepid" heart surgery (32 degrees to 34 degrees C) effectively blunts most of the vasodilatory response to strictly normothermic bypass without compromising maintenance of myocardial aerobiosis during arrest.

Limitation of vasodilation associated with warm heart operation by a "mini-cardioplegia" delivery technique.

Peripheral vasodilation is commonly seen during and after warm heart operations and can become of clinical concern when it requires vasopressors because some of these drugs adversely affect coronary artery bypass graft flows. As hemodilution lowers systemic vascular resistance, we assessed whether peripheral vasodilation could be limited by a drastic reduction of the volume of infused cardioplegia. Fifty patients underwent isolated coronary artery bypass grafting procedures using normothermic (35 degrees to 37 degrees C) bypass and normothermic continuous retrograde blood cardioplegia. They were divided into two equal groups: in group 1, blood was diluted 4:1 with hyperkalemic crystalloid cardioplegia, whereas in group 2, the cardioplegic "solution" was limited to the sole arresting agents that were concentrated in a small volume (16 mEq potassium chloride and 3 mEq magnesium chloride in a 20-mL ampoule). This "mini-cardioplegia" was continuously added to arterial blood so as to keep the heart arrested. The average volume of cardioplegia per patient was 1,000 mL in group 1 and 58 mL in group 2 (p < 0.0001). The mini-cardioplegia technique resulted in a reduced incidence of perioperative systemic vasodilation: group 2 patients required significantly less vasopressors (p < 0.05) and less volume loading, as reflected by significantly lower right atrial and pulmonary capillary wedge pressures (p < 0.05 and p < 0.03 at 12 hours postoperatively, respectively), compared with group 1 patients who received traditional high-volume cardioplegia. There were no differences between the two groups with respect to myocardial recovery, as assessed by standard clinical and hemodynamic end points.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of lactobionate-enriched cardioplegic solution in preserving compliance of cold-stored heart transplants.

Cardioplegic solutions of the extracellular type are commonly used as storage media for heart transplants. Because this type of formulation was not originally designed for preventing hypothermically induced edema, we assessed the effects of supplementing a standard, extracellular-like cardioplegic solution with the high molecular weight impermeant lactobionate on water content and postischemic compliance of isolated rat hearts. In one series of experiments, hearts were immersed in either a standard cardioplegic solution of the extracellular type or in the same solution supplemented with lactobionate (80 mmol/L). Hearts were then processed for measurements of water content after 4 hours, 6 hours, and 8 hours of storage at 4 degrees C. In a second series of experiments, hearts were stored in the same solutions for 4 hours and 8 hours and subsequently reperfused for 1 hour on a Langendorff column, at which time left ventricular pressure-volume curves were constructed and compared with those obtained during the preischemic perfusion. Lactobionate-treated hearts gained significantly less water than controls after 4 hours and 6 hours of storage, but the difference was no longer significant at the 8-hour time point. In contrast, the treated group yielded a significantly better recovery of compliance after both 4 hours and 8 hours of storage, suggesting that lactobionate might exert protective effects in addition to those caused by its impermeant properties, possibly involving calcium chelation and subsequent limitation of calcium-dependent contracture. Extracellular-type cardioplegic solutions are attractive because a single solution can be used during all phases of the transplantation procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Triiodothyronine therapy in open-heart surgery: from hope to disappointment.

A controversy persists as to whether cardiopulmonary bypass (CPB) decreases plasma levels of triiodothyronine (T3), thereby justifying peri-operative administration of T3 to improve haemodynamic recovery. To examine the effects of T3 therapy on post-CPB haemodynamics and to determine whether the potential inotropic effects of T3 are mediated by an increase in beta-adrenergic responsiveness, a prospective, randomized, double-blind, placebo-controlled study was performed in 20 patients undergoing cardiac surgery with CPB. T3 or placebo solution (10 patients in each group) was given intravenously at the time of aortic unclamping and 4, 8, 12 and 20 h thereafter. End points included (1) thyroid hormone levels measured by radioimmunoassay (2) standard haemodynamic parameters (3) the density of lymphocyte beta-adrenoceptors measured by a radioligand (125I-iodocyanopindolol) binding technique. Post-CPB values (cross clamp removal) of T3 (pg.ml-1) were not significantly decreased compared with pre-CPB values: 3.3 +/- 0.2 vs 3.1 +/- 0.2 in controls and 3.3 +/- 0.4 vs 3.7 +/- 0.6 in T3-treated patients, respectively. The haemodynamic parameters were no different between the two groups at any postoperative time point. Likewise, density and affinity of lymphocyte beta-adrenoceptors were not significantly different from pre-operative values in either group. Thus, there seems to be no sound justification for a routine use of T3 in patients undergoing open-heart procedures.

Improved recovery of heart transplants with a specific kit of preservation solutions.

In the course of cardiac transplantation, donor hearts undergo a four-step sequence of events (arrest, cold storage, global ischemia during implantation, and reperfusion) during which myocardial damage can occur. We tested the hypothesis that the functional recovery of these hearts could be improved by exposure to two interdependently formulated preservation solutions throughout this four-step sequence. Solution I was used as a perfusion and storage medium during the first three steps, and solution II served as a modified reperfusate. The two solutions share the following principles of formulation: prevention of cell swelling (high concentrations of mannitol, a myocardium-specific impermeant) calcium overload (ionic manipulations), and oxidative damage (reduced glutathione) and enhancement of anaerobic energy production (glutamate). The two solutions differ with respect to the calcium content and buffering capacity. One hundred rat hearts perfused with isolated isovolumic buffer were subjected to cardioplegic arrest; cold (2 degrees C) storage for 5 hours, global ischemia at 15 degrees C for 1 hour, and normothermic reperfusion for 1 additional hour. In a first series of experiments (70 hearts), our kit of solutions was compared with six clinical preservation regimens that involved cardiac arrest with St. Thomas' Hospital or University of Wisconsin solutions followed by storage of the hearts in saline, Euro-Collins, St. Thomas' Hospital, or University of Wisconsin solutions. In a second series of experiments (30 hearts), the effects of the kit were more specifically investigated in relation to two types of additive--oncotic agents (dextran) and thiol-based antioxidants (reduced glutathione and N-acetyl-L-cysteine). According to comparisons of maximal rate of ventricular pressure increase and left ventricular compliance after reperfusion, the best myocardial protection was afforded by our kit of solutions. The addition of dextran during storage did not provide additional protection. Conversely, the omission of reduced glutathione was clearly detrimental; the replacement of reduced glutathione with N-acetyl-L-cysteine failed to improve recovery beyond that provided by antioxidant-free solutions, thereby suggesting the importance, in this model, of an anti-free radical compound that, like reduced glutathione, is operative extracellularly. We conclude that the preservation of heart transplants can be improved with the sequential use of two closely interrelated solutions, the formulations of which integrate the basic principles of organ preservation with those of myocardium-specific metabolism.