Donor treatment with the lazeroid U74389G reduces ischemia-reperfusion injury in a rat lung transplant model

BACKGROUND: Antioxidant treatment with lazeroids has proven beneficial for the amelioration of reperfusion injury in experimental lung transplantation. This study compares the effect of donor versus recipient treatment on immediate postoperative graft function. METHODS: A model of acute double-lung transplantation in rats was used to assess graft function. Transplanted controls after 2 (group I) and 16 hours of ischemia (group II) were compared to a recipient (group III; 16-hour ischemia) and a donor treatment group (group IV; 16-hour ischemia) using the lazeroid U74389G (6 mg/kg). Serial assessment of alveolar-arterial oxygen difference, dynamic lung compliance, airway and pulmonary vascular resistance was obtained during a 2-hour reperfusion period. Final analysis included survival, weight gain, and histologic examination. RESULTS: Graft function was significantly better after 2 hours of ischemia than in any of the three 16-hour ischemia groups (II, III, IV). After 16 hours of ischemia, donor treatment provided superior graft function with respect to dynamic lung compliance, airway resistance, and alveolar-arterial oxygen difference when compared with groups II and III. The pulmonary vascular resistance was significantly higher in group III when compared with groups II and IV. Graft weight increase reflecting edema was highest in groups III (104%) and II (98%). CONCLUSIONS: After prolonged ischemia only donor treatment with the lazeroid U74389G was able to significantly reduce ischemia-reperfusion-related graft dysfunction.     

Early markers of major adverse events in children after cardiac operations

OBJECTIVES: The purpose of this study was to determine the physiologic variables that predict major adverse events in children in the intensive care unit after cardiac operations. METHODS: A cohort observational study was conducted. At the time of admission to the intensive care unit and 4, 8, 12, and 24 hours later the following variables were recorded: mean arterial pressure, heart rate, cardiac index, oxygen delivery, mixed venous oxygen saturation, base deficit, blood lactate, gastric intramucosal pH, carbon dioxide difference (the difference between arterial carbon dioxide tension and gastric intraluminal carbon dioxide tension), and toe-core temperature gradient. Major adverse events were prospectively identified as cardiac arrest, need for emergency chest opening, development of multiple organ failure, and death. RESULTS: Ninety children were included in the study; 12 had major adverse events and there were 4 deaths. Blood lactate level, mean arterial pressure, and duration of cardiopulmonary bypass were the only significant, independent predictors of major adverse events when measured at the time of admission to the intensive care unit. The odds ratio (95% confidence intervals) for major adverse events if a lactate level was greater than 4.5 mmol/L was 5.1 (1.2 to 21.1), for admission hypotension 2.3 (0.5 to 9.8), and for a cardiopulmonary bypass time greater than 150 minutes 13.7 (3.3 to 57.2). Four hours after admission lactate and carbon dioxide difference, and 8 hours after admission lactate and base deficit, were independently significant predictors. The odds ratios for major adverse events if the blood lactate level was greater than 4 mmol/L at 4 and 8 hours were 8.3 (1.8 to 38.4) and 9.3 (1.9 to 44.3), respectively. At no time in the first 24 hours were cardiac output, oxygen delivery, mixed venous oxygen saturation, toe-core temperature gradient, or heart rate significant predictors of major adverse events. CONCLUSIONS: In the context of our current treatment strategies, the duration of cardiopulmonary bypass and blood lactate level, measured in the early postoperative period, were the best predictors of impending major adverse events.     

Biphasic graft preservation for lung transplantation

The standard, most widely applied way of preserving a lung for transplantation is infusion through the pulmonary artery (PA) of a pulmonaryplegic solution. In this prospective study, we analyzed the initial function of the pulmonary and cardiac graft after biphasic infusion of a solution introduced retrograde through the left auricle and antegrade through the PA. Twenty-six heart and lung grafts (9 unilateral and 17 bilateral) were preserved by cardioplegia and pulmonaryplegia (biphasic) between January 1996 and March 1997. Indicators of graft viability recorded were the ratio of arterial oxygen pressure (PaO2) to inspired fraction (FiO2), mean systemic pressure (MSP), mean pulmonary artery pressure (MPAP) cardiac output, pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR). The variables were recorded upon arrival of the grafts in the intensive care unit and in the first 24 h. Morbidity and mortality after heart transplants were recorded throughout a follow-up period of one month. After transplantation, most patients had a oxygenation coefficient (PaO2/FiO2) greater than 252 mmHg in the first 48 h. Hemodynamic parameters were also kept within normal ranges immediately after surgery and 24 h later. Mean ischemic time was 245 min for unilateral transplants, 215 for the first lung in double lung transplants, and 300 min for the second lung. In the early postoperative period, 3 patients suffered lung graft dysfunction, which was treated satisfactorily with nitric oxide (NO). No heart transplant patient suffered primary heart failure or left ventricular dilatation. We conclude that biphasic pulmonary preservation achieves satisfactory initial functional viability of the graft. Heart grafts removed simultaneously functioned successfully in the transplanted patient without additional pharmacological or mechanical support.     

Factors related to the donor organ are major determinants of renal allograft function and survival

In this study, we analyzed the relative impact of donor and recipient variables on cadaveric renal allograft function and survival. The unique feature of the study population is that each pair of recipients received their allografts from a single donor. The study includes 378 adult patients. In 129 pairs both recipients were Caucasian, and in 60 pairs one recipient was Caucasian and the other was African-American. All transplants were done in one center, thus minimizing differences in preservation time and providing uniform posttransplant management. The initial analysis showed a relationship between the function of the allograft 6 months after transplantation (serum creatinine [SCr]6 mo) and donor variables (P = 0.0004, analysis of variance). Furthermore, it was calculated that 64% of the variability in the SCr 6mo among patients was due to donor factors and 36% was due to recipient factors. An elevated SCr 6 mo was significantly associated with older donors, male recipients, and patients with acute rejection episodes. Furthermore, other unidentified donor factors may have an impact on allograft function. Reflecting the importance of donor factors, there was a significant relationship between SCr 6mo in paired recipients (P < 0.0008 by Spearman). Analysis of racially dissimilar pairs showed that the SCr 6mo and graft survival 6 months after transplantation were not significantly different between Caucasians and African-Americans. However, beyond 6 months, graft survival was worse in African-Americans (P < 0.0001 by Cox). Compared with Caucasians, graft survival was significantly worse in African-Americans with poorly controlled blood pressure (mean arterial pressure > 105 mmHg) (P = 0.002, Cox), but not in those patients with mean arterial pressure < 105 mmHg. In conclusion, donor factors are major determinants of renal allograft function. However, those factors may not be easily identifiable or quantifiable. Donor factors do not contribute to racial differences in allograft survival. However, poorly controlled hypertension correlates with poor renal graft survival in African-Americans.     

Controlled reperfusion and pentoxifylline modulate reperfusion injury after single lung transplantation

OBJECTIVE: Rodent models have suggested that initial low-pressure reperfusion of transplanted lungs reduces injury after ischemia. We investigated this phenomenon and the use of pentoxifylline in a porcine model of left single lung transplantation. METHODS: Donor lungs were preserved with Euro-Collins solution for a mean ischemic time of 18.4 hours. Neutrophil trapping in the graft, pulmonary artery pressure, and gas exchange were assessed over a 12-hour period. Partial occlusion of the contralateral pulmonary artery allowed manipulation of the pulmonary artery pressure in the transplanted lung. Group A (n = 5) was perfused at a mean pulmonary artery pressure of 20 mm Hg, group B was reperfused at a mean pulmonary artery pressure of 45 mm Hg for 10 minutes before reducing the pressure to the same as group A, and group C was reperfused at a mean pressure of 20 mm Hg for 10 minutes, then increased to a mean of 45 mm Hg for the remainder of the experiment. Group D was reperfused as in group A with the addition of intravenous pentoxifylline. RESULTS: Leukocyte sequestration was observed in the first 10 minutes after reperfusion in groups A, B, and C, with maximal sequestration at 2 minutes. Significantly more sequestration was observed in the first 6 minutes in group B than in groups A and C, which were similar. Pentoxifylline significantly reduced leukocyte sequestration. Pulmonary venous oxygen tension in the allograft lung was worst in group B. Groups A and C were similar, but group D was superior to all other groups (p < 0.001). CONCLUSIONS: Low-pressure reperfusion, even when limited to the first 10 minutes, modulates reperfusion injury possibly through a leukocyte-dependent mechanism. The addition of pentoxifylline in the recipient confers significant additional benefit.     

Isradipine lowers human arterial low density lipoprotein retention in vivo

An 84-year-old woman was admitted to our hospital because of left heart failure of acute onset. Transthoracic echocardiography showed diffuse hypertrophy of the normal sized hyperkinetic left ventricle and chordae-like fluttering echoes attached to the mitral valve with severe mitral regurgitation signals. Mosaic flow signals were seen at the left ventricular outflow tract, but the velocity could not be measured. Emergent transesophageal echocardiography detected no obvious mitral valve prolapse. Cardiac catheterization showed greater than 100 mmHg pressure gradient between the left ventricle and femoral artery. Pressures in the femoral artery and pulmonary capillary wedge changed reciprocally in the intensive care unit; a bisferient narrow pulse pressure of the femoral artery was associated with increased v wave of the pulmonary capillary wedge pressure, and a wide pulse pressure of the femoral artery with absent v wave of the pulmonary capillary wedge pressure. Pressure monitoring in the intensive care unit, catheterization laboratory and transesophageal echocardiography were useful to understand the pathophysiology of the patient.     

Expression of nerve-regulated genes in muscles of mouse mutants affected by spinal muscular atrophies and muscular dystrophies

OBJECTIVE: Mature lobar transplantation will increase the pediatric donor organ pool, but it remains unknown whether such grafts will grow in a developing recipient and provide adequate long-term support. We hypothesized that a mature pulmonary lobar allograft implanted in an immature recipient would grow. METHODS: We investigated our hypothesis in a porcine orthotopic left lung transplant model using animals matched by the major histocompatibility complex to minimize the effects of chronic rejection. Twenty-three immature animals (< 12 weeks of age and < 10 kg total body weight) received either sham left thoracotomy (SH control, n = 4), left upper lobectomy to study compensatory growth (UL control, n = 4), age-matched immature whole left lung transplants (IWL TXP, n = 6), mature (donor > 1 yr in age and > 40 kg in total body weight) left lower lobe transplants (MLL TXP, n = 5), or mature left upper lobe transplants (MUL TXP, n = 4). Twelve weeks after implantation, functional residual capacity of the left lung was measured and arterial blood gas samples were obtained after the native right lung had been excluded. The graft was excised and weighed, and samples for microscopy and wet/dry ratios were collected. RESULTS: Initial and final graft weights were as follows: IWL TXP group (34.6 +/- 1.5 and 107.8 +/- 5.9 gm, p < 0.0001), MLL TXP group (72.4 +/- 6.8 and 111.4 +/- 8.7, p < 0.001), and MUL TXP group (32.8 +/- 1.3 and 92.8 +/- 7.1 gm, respectively, p < 0.004). No significant differences between groups were demonstrated when functional residual capacity, wet/dry ratios, or oxygenation were compared. Immunohistochemical staining for the nuclear antigen Ki-67 demonstrated dividing pneumocytes. CONCLUSIONS: We conclude that a mature lobar graft implanted into an immature recipient grows by pneumocyte division in this model. Mature lobar transplants can be expected to grow and provide adequate long-term function in developing recipients.     

Impact of ultrafiltration on blood use for atrial septal defect closure in infants and children

BACKGROUND: Infants and children undergoing open cardiac operations have a high incidence of blood product transfusion. Ultrafiltration has been shown to reverse hemodilution and improve myocardial function and hemodynamics after cardiopulmonary bypass (CPB). METHODS: The effect of ultrafiltration on the amount of blood transfusion and hospital charge in 39 consecutive patients who underwent elective atrial septal defect repair was examined. Patients in group I (n=26) had a conventional cardiopulmonary circuit prime with blood, whereas 13 patients had bloodless prime (group II). Ultrafiltration was used immediately after weaning from CPB in group II. The patients in group I received blood products after discontinuation of CPB to achieve a hematocrit of 30%. The amount of blood product used, hematocrit immediately after CPB and on arrival in intensive care unit, postoperative hemodynamics and saturations, total operating room charge, blood charge, hospital stay, and hospital charge were compared. RESULTS: Mean body weight (15.8 kg in group I versus 17.5 kg in group II) and preoperative hematocrit values (35.6% in group I versus 34.2% in group II) were similar. Mean hematocrit immediately after CPB was 22% and 14% in group I and II, respectively (p < 0.0001). The mean hematocrit upon arrival to the intensive care unit was 34% in group I and 22% in group II (p < 0.0001). The amount of blood product transfusion was 32 mL/kg in group I and 3 mL/kg in group II patients (p < 0.0001). The patients in group II had significantly less blood bank charges; however, operating room charges and total hospital charges were similar between the two groups. CONCLUSIONS: Elective atrial septal defect repair was performed with no blood product transfusion without increased morbidity or hospital stay. Ultrafiltration can be used to reverse hemodilution resulting from a bloodless CPB prime without an increase in hospital charge.     

Dramatic effect on oxygenation in patients with severe acute lung insufficiency treated in the prone position

OBJECTIVE: To confirm the positive effect of prone positioning on oxygenation in patients with acute lung insufficiency. DESIGN: Clinical follow-up study. SETTING: The intensive care unit at a tertiary care academic hospital. PATIENTS: Thirteen patients suffering from severe acute lung insufficiency caused by trauma, septicemia, aspiration, and burn injury. Eleven of the patients had severe hypoxia (oxygenation indices [PaO2/FIO2] < or = 80 torr [< or = 10.7 kPa]). Patients > 70 yrs of age were excluded from the study. INTERVENTIONS: Treatment in the prone position without changing other ventilatory settings than FIO2 when saturation increased. MEASUREMENTS AND MAIN RESULTS: Twelve of the 13 patients responded to treatment in the prone position. The patient that did not respond improved her gas exchange when nitric oxide was instituted. She died, however, from a Gram-negative septicemia. No patient needed extracorporeal membrane oxygenation. Apart from the settings of FIO2 when saturation increased, the ventilatory settings were unchanged. In the prone position, the oxygenation index increased (p < .0002) and the alveolar-arterial oxygen gradient, P(A-a)O2, decreased dramatically (p < .0001). CONCLUSIONS: The prone position significantly improves impaired gas exchange due to severe acute lung insufficiency. It is suggested that this treatment is used before more complex modalities.     

Determinants of prolonged mechanical ventilation after coronary artery bypass grafting

BACKGROUND: Early extubation of cardiac surgical patients enhances ambulation, improves cardiopulmonary function, and can lead to savings in health care costs. METHODS: We retrospectively examined the role of 48 variables in determining the period of ventilatory support in 507 patients having coronary artery bypass grafting. RESULTS: Fifteen (< 3%) of 507 patients required ventilatory support in excess of 24 hours. Among the remaining patients, extubation was achieved early (< or = 8 hours) (mean time, 5.65 +/- 1.31 hours) in 53% and late (> 8 hours) (mean time, 13.7 +/- 3.4 hours) in 47%. Logistic and linear multivariate regression analyses implicated increased age, New York Heart Association functional class IV, intraoperative fluid retention, postoperative intraaortic balloon pump requirement, and bank blood transfusions as predictors of late extubation. Also, the linear regression linked lower body weight and number of anastomoses (or grafts) to increased mechanical ventilatory support. CONCLUSIONS: Analysis of the fluid balance and cardiopulmonary bypass data suggests that earlier extubation may be achieved by actively reducing fluid retention (eg, by hemoconcentration) and time on bypass (eg, normothermia). Finally, intensive care unit stay and postoperative length of stay were significantly lower in the early versus late extubation groups without an increase in pulmonary complications.     

Phenotypical heterogeneity of CD4+CD8+ double-positive chronic T lymphoid leukemia

BACKGROUND: One of the most controversial areas in patient selection and donor allocation is the high-risk patient. Risk factors for mortality and major infectious morbidity were prospectively analyzed in consecutive United States veterans undergoing liver transplantation under primary tacrolimus-based immunosuppression. METHODS: Twenty-eight pre-liver transplant, operative, and posttransplant risk factors were examined univariately and multivariately in 140 consecutive liver transplants in 130 veterans (98% male; mean age, 47.3 years). RESULTS: Eighty-two percent of the patients had postnecrotic cirrhosis due to viral hepatitis or ethanol (20% ethanol alone), and only 12% had cholestatic liver disease. Ninety-eight percent of the patients were hospitalized at the time of transplantation (66% United Network for Organ Sharing [UNOS] 2, 32% UNOS 1). Major bacterial infection, posttransplant dialysis, additional immunosuppression, readmission to intensive care unit (P=0.0001 for all), major fungal infection, posttransplant abdominal surgery, posttransplant intensive care unit stay length of stay (P<0.005 for all), donor age, pretransplant dialysis, and creatinine (P<0.05 for all) were significantly associated with mortality by univariate analysis. Underlying liver disease, cytomegalovirus infection and disease, portal vein thrombosis, UNOS status, Childs-Pugh score, patient age, pretransplant bilirubin, ischemia time, and operative blood loss were not significant predictors of mortality. Patients with hepatitis C (HCV) and recurrent HCV had a trend towards higher mortality (P=0.18). By multivariate analysis, donor age, any major infection, additional immunosuppression, posttransplant dialysis, and subsequent transplantation were significant independent predictors of mortality (P<0.05). Major infectious morbidity was associated with HCV recurrence (P=0.003), posttransplant dialysis (P=0.0001), pretransplant creatinine, donor age, median blood loss, intensive care unit length of stay, additional immunosuppression, and biopsy-proven rejection (P<0.05 for all). By multivariate analysis, intensive care unit length of stay and additional immunosuppression were significant independent predictors of infectious morbidity (P<0.03). HCV recurrence was of borderline significance (P=0.07). CONCLUSIONS: Biologic and physiologic parameters appear to be more powerful predictors of mortality and morbidity after liver transplantation. Both donor and recipient variables need to be considered for early and late outcome analysis and risk assessment modeling.     

Heart transplant coronary artery disease detected by coronary angiography: a multiinstitutional study of preoperative donor and recipient risk factors. Cardiac Transplant Research Database

BACKGROUND: Controversy exists regarding donor and recipient factors that promote the development and progression of coronary artery disease after heart transplantation and the likelihood of coronary artery disease causing death or retransplantation. METHODS: To investigate this issue in a large cohort of patients, we analyzed 5963 postoperative angiograms performed in 2609 of the 3837 patients undergoing heart transplantation at 39 institutions between January 1990 and December 1994. Coronary artery disease was classified as mild, moderate, or severe on the basis of left main involvement, primary vessel stenoses, and branch stenoses. Coronary artery disease was considered severe if left main stenosis was > 70% or 2 or more primary vessels stenoses were > 70% or branch stenoses were > 70% in all 3 systems. RESULTS: By the end of 5 years after heart transplantation, coronary artery disease was present in 42% of the patients, mild in 27%, moderate in 8%, and severe in 7%. Coronary artery disease-related events (death or retransplantation) had an actuarial incidence of 7% at 5 years and occurred in 2 of 3 of the patients with development of angiographically severe coronary artery disease. By multivariable logistic analysis, risk factors for donor coronary artery disease included older donor age (P < .0001) and donor hypertension (P=.0002). By multivariable analysis in the hazard function domain, risk factors identified for the earlier onset of allograft coronary artery disease included older donor age (P < .0001 ), donor male sex (P=.0006), donor hypertension (P=.07), recipient male sex (P=.02), and recipient black race (P=.01). The actuarial incidence of severe coronary artery disease was 9% at 5 years. CONCLUSIONS: Angiographic coronary artery disease is very common after heart transplantation, occurring in approximately 42% of the patients by 5 years. Older donor age, donor hypertension, and male donor or recipient predict earlier onset of angiographic allograft coronary artery disease. Although severe angiographic allograft coronary artery disease occurs in only 7% of the patients at 5 years, its presence is highly predictive of subsequent coronary artery disease-related events or retransplantation.     

Beneficial effect of a stable PGI2 analogue (ONO-1301) on prostanoid release after reperfusion in canine left single lung allotransplantation model

Recently much interests have focused on the imbalance between the release of thromboxane A2 (TXA2) and prostaglandin I2 (PGI2), which may contribute to the development of pulmonary vascular injury. TXB2 has potents of platelet aggregation and vasoconstriction, while PGI2 has against in its activities. We investigated the effect of new PGI2 analogue (ONO-1301), which is a novel prostacyclin mimetic with inhibitory activity against thromboxane synthetase, on the early graft function in canine left single lung allotransplantation model. 19 donor dogs were divided into three groups. Seven dogs were comprised control group and received heparin administration (400 Unit/kg) before pulmonary arterial flushing with 50 ml/kg of 4 degrees C low potassium dextran glucose (LPDG) solution. Each six dogs were comprised I2-10 and I2-50 groups respectively, with receiving a 10-minute infusion of ONO-1301 (10 micrograms/kg/min) before flushing. The pulmonary cold preservation was performed with LPDG solution at 4 degrees C for 18 hours. After left single lung transplantation, in control group, saline solution was administered to the recipient for 10 minutes encompassing the reperfusion process (starting from 5 minutes prior to reperfusion). In I2-10 group, the ONO-1301 (10 micrograms/kg/min) was administered in the same manner. In I2-50 group, the ONO-1301 was administered from the same timing as I2-10 group, but for 50 minutes. The recipient dogs were observed for 6 hours after ligation of the right pulmonary artery and bronchus. We measured the transplanted lung function, including arterial blood gas and pulmonary hemodynamics, and plasma 6-keto-PGF1 alpha, TXB2 and lipid peroxide levels of left atrial blood. Pulmonary histological investigation was performed after preservation and sacrifice the recipient dog. All recipient dogs were survived for observation period. I2 groups provided significantly better gas exchange and pulmonary hemodynamics than control group. The 6-keto-PGF alpha levels in control group peaked after an early rise in TXB2 levels, and reached maximum at one hour after contra-lateral ligations. These prostanoid release levels rose again at 6 hours. While in I2 groups, the levels of them were significantly lower compared with control group. Histological examination of the transplanted lung after assessment, revealed disruption of alveoli forced by pulmonary edema in control group. In contrast, there was minimal fluid extravasation without alveolar disruption in both I2-10 and I2-50 groups. There were no significant differences between I2-10 and I2-50 groups. Although it dose not protect the implanted lung completely from developing edema, the ONO-1301 administration (10 micrograms/kg/min) to the donor and the recipient resulted in prevention of TXA2 and PGI2 release and improvement of the respiratory function and pulmonary hemodynamics after reperfusion. We conclude that it seems beneficial to administer the ONO-1301 to the donor and the recipient in order to regulate the prostanoid release and maintain the early graft function.     

Predegenerated nerve allografts versus fresh nerve allografts in nerve repair

This study reevaluated the possibility of using predegenerated nerves as donor nerve allografts for nerve repair and compared the results of functional recovery to those obtained after standard, fresh nerve allograft repair. Twenty donor rats underwent a ligature/ section of the left sciatic nerve 4 weeks before nerve graft harvesting. Forty recipient rats underwent severing of the left sciatic nerve leaving a 15-mm gap between the nerve stumps. Graft repair was undertaken using either the predegenerated left sciatic nerve of the 20 donor rats (predegenerated group, 20 recipient rats) or the normal right sciatic nerve of the 20 donor rats (fresh group, 20 recipient rats). Recovery of function was assessed by gait analysis, electrophysiologic testing and histologic studies. Walking tracks measurements at 2 and 3 months, electromyography parameters at 2 and 3 months, peroperative nerve conduction velocity and nerve action potential amplitude measurements at 3 months, as well as assessments of myelinated nerve fiber density and surface of myelination showed that fresh and predegenerated nerve grafts induced a comparable return of function although there was some trend in higher electrophysiologic values in the predegenerated group. The only slight but significant difference was a larger mean nerve fiber diameter in the nerve segment distal to a predegenerated nerve graft compared to a fresh nerve graft. Although our study does not show a dramatic long-term advantage for predegenerated nerve grafts compared to fresh nerve grafts, their use as prosthetic material is encouraging.     

Partial hepatectomy or orthotopic liver transplantation for the treatment of resectable hepatocellular carcinoma? A cost-effectiveness perspective

BACKGROUND: Na+/H+ exchange plays an important role in the ionic changes observed during myocardial ischemia and reperfusion. We investigated the cardioprotective efficacy of a selective Na+/H+ exchange inhibitor, 4-isopropyl-3-methylsulfonyl-benzoylguanidin-methanesulfonate (HOE642), in a canine model of long-term heart preservation. METHODS: Canine donor hearts were stored for 24 hours in hyperkalemic crystalloid cardioplegic solution; in cardioplegic solution enriched with HOE642; in cardioplegic solution enriched with HOE642, with donor and recipient treated with HOE642; in standard cardioplegic solution, with donor and recipient treated with HOE642; or in standard cardioplegic solution, with only the recipient treated. After orthotopic transplantation, pressure-volume relationships were obtained and dogs were weaned from bypass. Morphology was studied. RESULTS: Myocardial compliance was well preserved when donor and recipient were treated. These groups had the lowest myocardial water content, and no morphologic signs of irreversible damage. In these groups, weaning from cardiopulmonary bypass was successful in 10 of 10 animals, with a cardiac index around 2 L x min(-1) x m(-2). Only 3 of 5 animals in each of the other three groups could be weaned, with significantly lower cardiac indices. CONCLUSIONS: Treatment with HOE642 in both donor and recipient improves myocardial compliance, postweaning cardiac index, and ultrastructure of donor hearts preserved for 24 hours and orthotopically transplanted.     

A prospective evaluation of children under the age of 5 years living in the same household as adults with recently diagnosed pulmonary tuberculosis

Lung injury is a well-documented adverse effect of cardiopulmonary bypass. The mechanism of injury is not fully understood, but pulmonary hypoxia may be a factor. Post-operative pulmonary epithelial permeability (PEP) in ventilated versus non-ventilated lungs was measured within 2 h of return to the intensive care unit using a 99Tcm-diethylenetriamine pentaacetate aerosol technique. A portable scintillation detector system was required. Sodium iodide detectors have been used previously with this technique but are cumbersome. This study used mini caesium iodide detectors (Oakfield Instruments, Oxon, UK), which can be attached directly to the patient and are more suited to the intensive care setting. The clearance half-time from lung to blood (T1/2LB) was measured in 31 patients (62 lungs). The mean (+/- S.E.M.) clearance half-times were 42.3 +/- 2.7 and 45.7 +/- 3.8 min for non-ventilated and ventilated lungs respectively, with a mean difference of 3.4 +/- 3.1 min (P > 0.05). We conclude that, using this technique, no significant difference in PEP is observed between ventilated and non-ventilated lungs in patients undergoing cardiopulmonary bypass.     

Congenital nystagmus image motion: influence on visual acuity at different luminances

This research study was undertaken to examine the relationship between pulmonary artery blood temperature (regarded as the 'gold standard' measurement for core body temperature), axilla temperature using the Tempa.DOT Ax chemical thermometer and tympanic membrane temperature using the Diatek 9000 InstaTemp thermometer. Sixty adult intensive care patients had their temperatures monitored. A single set of five simultaneous temperatures, i.e. left and right axilla, left and right tympanic membrane (TM), and pulmonary artery (PA) blood were recorded. The mean difference between left and right TM temperatures was 0.58 degree C, and although both were moderately well correlated with PA temperature (r = 0.63 and 0.78, respectively) the mean differences between the two sites were clinically significant (0.85 degree C and 0.94 degree C, respectively). The range of differences between the sites was significant. Plotting limits of agreement showed that both left and right TM temperatures may be up to 1.2 degrees C above or 1.3 degrees C below PA blood temperature: a clinically unacceptable range. In particular, large temperature differences were recorded when patients were lying with one side of their head to a pillow. Fan therapy directed to the head was not found to affect these differences significantly. The mean difference between left and right axilla temperatures was 0.36 degree C, and although both were modestly correlated with PA temperature (r = 0.48 and 0.53, respectively) the mean differences between the two sites were clinically significant (0.47 degree C and 0.50 degree C, respectively). The range of differences between the sites was particularly significant. Plotting limits of agreement showed that both left and right axilla temperatures may be up to 1.2 degrees C above or 1.6 degrees C below PA blood temperature: a clinically unacceptable range. Because the range of temperature differences found between PA blood and the other sites was so great, it is concluded that neither the chemical axilla thermometer nor the tympanic membrane thermometer used in this study are clinically reliable tools for adult intensive care patients.     

Long-term survival after retransplantation of the liver

OBJECTIVE: The authors determined the long-term outcome of patients undergoing hepatic retransplantation at their institution. Donor, operative, and recipient factors impacting on outcome as well as parameters of patient resource utilization were examined. SUMMARY BACKGROUND DATA: Hepatic retransplantation provides the only available option for liver transplant recipients in whom an existing graft has failed. However, such patients are known to exhibit patient and graft survival after retransplantation that is inferior to that expected using the same organs in naiive recipients. The critical shortage of donor organs and resultant prolonged patient waiting periods before transplantation prompted the authors to evaluate the results of a liberal policy of retransplantation and to examine the factors contributing to the inferior outcome observed in retransplanted patients. METHODS: A total of 2053 liver transplants were performed at the UCLA Medical Center during a 13-year period from February 1, 1984, to October 1, 1996. A total of 356 retransplants were performed in 299 patients (retransplant rate = 17%). Multivariate regression analysis was performed to identify variables associated with survival. Additionally, a case-control comparison was performed between the last 150 retransplanted patients and 150 primarily transplanted patients who were matched for age and United Network of Organ Sharing (UNOS) status. Differences between these groups in donor, operative, and recipient variables were studied for their correlation with patient survival. Days of hospital and intensive care unit stay, and hospital charges incurred during the transplant admissions were compared for retransplanted patients and control patients. RESULTS: Survival of retransplanted patients at 1, 5, and 10 years was 62%, 47%, and 45%, respectively. This survival is significantly less than that seen in patients undergoing primary hepatic transplantation at the authors' center during the same period (83%, 74%, and 68%). A number of variables proved to have a significant impact on outcome including recipient age group, interval to retransplantation, total number of grafts, and recipient UNOS status. Recipient primary diagnosis, cause for retransplantation, and whether the patient was retransplanted before or after June 1, 1992, did not reach statistical significance as factors influencing survival. In the case-control comparison, the authors found that of the more than 25 variables studied, only preoperative ventilator status showed both a significant difference between control patients and retransplanted patients and also was a factor predictive of survival in retransplanted patients. Retransplant patients had significantly longer hospital and intensive care unit stays and accumulated total hospitalization charges more than 170% of those by control patients. CONCLUSIONS: Hepatic retransplantation, although life-saving in almost 50% of patients with a failing liver allograft, is costly and uses scarce donor organs inefficiently. The data presented define patient characteristics and preoperative variables that impact patient outcome and should assist in the rational application of retransplantation.     

Deleterious effects of cardiopulmonary bypass on early graft function after single lung allotransplantation: evaluation of a heparin-coated bypass circuit

Clinical lung transplantation may necessitate the use of cardiopulmonary bypass during the procedure, resulting in increased morbidity with more severe early graft dysfunction and increased blood loss. A heparin surface-coated cardiopulmonary bypass circuit is now available with improved biocompatibility and reduced systemic heparin requirements and may offer advantages compared with standard uncoated cardiopulmonary bypass circuits. This study investigates in a canine model of single-lung allotransplantation whether cardiopulmonary bypass adversely affects early graft function and whether a heparin-coated cardiopulmonary bypass circuit with reduced systemic heparin dosage improves results compared with standard uncoated cardiopulmonary bypass systems. Fifteen dogs underwent left single-lung allotransplantation with occlusion of the contralateral pulmonary artery and bronchus 1 hour after reperfusion. In one group, five animals underwent the procedure without cardiopulmonary bypass. In the group with uncoated circuits, five animals underwent the procedure with the use of standard uncoated cardiopulmonary bypass circuits with full systemic heparin dosage. In the group with heparin-coated circuits, five animals underwent the procedure with the use of heparin-coated cardiopulmonary bypass circuits and reduced systemic heparin dosage. Early graft function was evaluated by arterial oxygenation, pulmonary mechanics, lung water measurements, and histologic analysis. Hemodynamics and postoperative blood loss were also measured. Two hours after reperfusion, partial pressure of oxygen in arterial blood on an inspired oxygen fraction = 1.0 was significantly greater (p < 0.001) in the group without cardiopulmonary bypass (467 +/- 58 mm Hg) than in the group with uncoated circuits (114 +/- 90 mm Hg) and the group with heparin-coated circuits (193 +/- 105 mm Hg), with no significant difference between the groups undergoing bypass procedures. Lung compliance decreased and lung water increased in all transplanted lungs without significant differences between groups. Histologic analysis did not differentiate between the groups. After reperfusion, cardiac index and mean arterial pressure were significantly reduced in the groups with uncoated circuits and with heparin-coated circuits compared with the group that did not undergo cardiopulmonary bypass (p < 0.001). Postoperative blood loss was significantly less (p < 0.002) in the group that did not undergo cardiopulmonary bypass (90 ml +/- 38 ml) compared with both the group with uncoated circuits (750 +/- 15 ml) and the group with heparin-coated circuits (690 +/- 387 ml), with no significant difference between the groups that underwent bypass. The use of cardiopulmonary bypass with systemic heparinization is detrimental to early graft function in this canine model of left single-lung allotransplantation.(ABSTRACT TRUNCATED AT 400 WORDS)     

Dexamethasone decreases the incidence of shivering after cardiac surgery: a randomized, double-blind, placebo-controlled study

Shivering after cardiac surgery is common, and may be a result of intraoperative hypothermia. Another possible etiology is fever and chills secondary to activation of the inflammatory response and release of cytokines by cardiopulmonary bypass. Dexamethasone decreases the gradient between core and skin temperature and modifies the inflammatory response. The goal of this study was to determine whether dexamethasone can reduce the incidence of shivering. Two hundred thirty-six patients scheduled for elective coronary and/or valvular surgery were randomly assigned to receive either dexamethasone 0.6 mg/kg or placebo after the induction of anesthesia. All patients received standard monitoring and anesthetic management. After arrival in the intensive care unit (ICU), nurses unaware of the treatment groups recorded visible shivering, as well as skin and pulmonary artery temperatures. Analysis of shivering rates was performed by using chi2 tests and logistic regression analysis. Compared with placebo, dexamethasone decreased the incidence of shivering (33.0% vs 13.1%; P = 0.001). It was an independent predictor of reduced incidence of shivering and was also associated with a higher skin temperature on ICU admission and a lower central temperature in the early postoperative period. IMPLICATIONS: Dexamethasone is effective in decreasing the incidence of shivering. The effectiveness of dexamethasone is independent of temperature and duration of cardiopulmonary bypass. Shivering after cardiac surgery may be part of the febrile response that occurs after release of cytokines during cardiopulmonary bypass.