Hemodynamic follow-up of cardiac allografts from poisoned donors

BACKGROUND: The current shortage of donor organs, combined with an increasing demand for cardiac allografts, means that extended donor criteria are becoming more and more accepted. The use of cardiac allografts for transplantation from donors after acute poisoning is still under discussion; few data are currently available in the medical literature. We describe our experience with 19 orthotopic heart transplant recipients of organs from donors after acute intoxication with different agents. METHODS: Between March 1989 and December 1997, 883 orthotopic heart transplantations were performed at our transplant unit. Within this group, we accepted donor hearts after ethanol intoxication (n=1), benzodiazepine (n=1), alkylphosphate (E 605) in combination with beta-blocker intoxication (n=1), carbon monoxide poisoning (n=5), digitalis (n=1), digitalis/glibenclamide (n=1), chlormethiazole (n=1), propoxyphene (n=1), alkylphosphate (E 605) (n=1), insulin (n=2), neprobamate/ thiocyacide/flurazepam (n=1), paracetamol (n=1), carbamazepine (n=1), and cyanide (n=1) intoxication. At the time of organ explantation, hemodynamic data were available from all patients. RESULTS: Early mortality in this group was 11%; cumulative survival after 5 years was 74%. CONCLUSIONS: Based on our limited experience, cardiac allografts from donors exposed to different kinds of poisons can be transplanted in selected cases. If the donor organ is not hemodynamically compromised, showing regular filling pressures on low or mild inotropic support just before explantation, and if there are no electrocardiographic changes in combination with elevation of the transaminases, cardiac allograft transplantation seems to be a safe and life-saving procedure.     

Use of liver allografts from carbon monoxide poisoned cadaveric donors

Carbon monoxide (CO) inhalation leads to cerebral, cardiac, and, more rarely, liver damage. The use of liver allografts from CO poisoned donors with evidence of liver damage has not previously been reported. In this report we describe two recipients, both in fulminant hepatic failure, who received liver grafts from such donors. One donor had markedly abnormal liver function tests (LFTS), and in the other LFTS were mildly abnormal. In both, the liver appeared normal at procurement. There was satisfactory early function of both allografts, although marked patchy necrosis was seen on the postreperfusion biopsy (case 1), and on a 10 day postoperative biopsy (case 2). In both cases the changes were considered to be related to damage sustained from CO inhalation. Both allografts soon achieved normal function and both recipients are well. We conclude that CO poisoning can cause liver damage that can recover completely following liver transplantation.     

Donor lung procurement: assessment and operative technique

Given the relative scarcity of suitable donors and the widespread application of cardiac and pulmonary transplantation, it is imperative that a heart and two lungs be extracted from each donor. From increasing clinical experience and laboratory investigation in lung preservation, more flexible criteria for the assessment of potential lung donors are emerging. In this communication, we present our current criteria of donor lung suitability, and a simple and reliable technique of combined cardiopulmonary extraction that has provided suitable heart and lung grafts with excellent preservation, used in our last 150 donor organ procurements.     

Infectivity of hepatic allografts with antibodies to hepatitis B virus

BACKGROUND: Since suitable recipients for hepatic allografts from donors with antibodies to hepatitis B virus (HBV) have not been determined, a review of our 7-year experience with donors positive for hepatitis B surface antibody (anti-HBs), hepatitis B core antibody (anti-HBc), or both was undertaken. METHODS: Recipients of hepatic allografts from donors with antibodies to HBV were identified by a retrospective review of procurement records and screened for HBV infection. RESULTS: From January 1, 1990, to January 1, 1997, 2578 liver transplants were performed and 140 (5.4%) recipients received an allograft from a donor with antibodies to HBV. Twenty-five of 48 recipients of a hepatic allograft from a donor positive only for anti-HBs were screened and none developed HBV infection. Twenty-five of 41 naive recipients of a hepatic allograft from an anti-HBc positive donor were screened and 18/25 (72%) developed HBV infection. Four of these 18 naive recipients with HBV infection received an allograft from a donor positive for both anti-HBc and anti-HBs. Seven of 13 anti-HBs-positive recipients of an allograft from an anti-HBc-positive donor were screened and none developed HBV infection. Fifteen of 16 recipients positive only for anti-HBc who received a hepatic allograft from an anti-HBc-positive donor were screened and 2/15 (13%) developed HBV infection. CONCLUSIONS: Hepatic allografts from donors positive only for anti-HBs do not transmit HBV infection. Hepatic allografts from anti-HBc-positive donors frequently transmit HBV infection to naive recipients regardless of the donor anti-HBs status, and antiviral prophylaxis may be indicated. Anti-HBs-positive recipients appear resistant to HBV infection after orthotopic liver transplantation with an allograft from an anti-HBc-positive donor. Recipients positive only for anti-HBc infrequently develop HBV infection when transplanted with an allograft from an anti-HBc-positive donor; however, HBV prophylaxis may be justified.     

The carbon monoxide poisoning of two Byzantine emperors

CASE REPORT: In this paper, two possible cases of acute carbon monoxide poisoning previously not identified in the medical and historical literature are discussed. The first concerns the famous Byzantine Emperor Julian the Apostate, who may have suffered mild carbon monoxide poisoning from which he quickly and completely recovered. The second case involves his successor, Jovian, who may have succumbed to severe carbon monoxide poisoning. Both cases were in all likelihood due to the burning of coal in braziers, a usual method of indoor heating during that epoch.     

Extended surgery for gastric cancer: an historical commentary

Seizures are generally regarded as a manifestation of extreme, generally near-fatal carbon monoxide poisoning. A case is described in which a seizure attributable to carbon monoxide poisoning occurred in a small child at a level not thought to be associated with serious neurologic toxicity. A literature review of the occurrence of seizures in carbon monoxide poisoning found that no particular degree of carboxyhemoglobin was correlated with the presence of seizures. A seizure with no other apparent cause occurring in circumstances in which carbon monoxide toxicity would be suspected can be attributed to carbon monoxide poisoning.     

Acute intracranial complications of temporal bone trauma

BACKGROUND: A total of 110 patients, in whom kidneys from 95 living related and 15 cadaver donor, had experienced renal transplantation between February 1985 and October 1996 in our clinic. This study was conducted to evaluate the influence of the various pre-operative factors to the graft survivals and clinical course of patients in living related renal transplantation. METHODS: In 95 recipients, 17 adult patients had long term graft survivals over 5 years including 6 recurrent or denovo nephritis without chronic allografts nephropathy. Eight failed to graft loss attributed to chronic allografts nephropathy diagnosed within 5 years. Retrospective analysis were performed to elucidate the differences of these recipients. RESULTS: Donors of long graft survival recipients were younger (49.1 +/- 12.1 v.s. 58.9 +/- 10. 2) and had a better renal function evaluated by preoperative creatinine clearance in living related donors (115.5 +/- 37.0 v.s. 79.7 +/- 22.0 1/day). Graft long survival recipients had experienced less frequencies of acute rejection within 6 months (0.53 +/- 0.62: 8 patients, 9 times) compared with chronic allografts nephropathy recipients (1.00 +/- 0.53: 7 patients, 8 times). Long graft survival recipients had better responses to the antirejection therapy. Additionally acute rejection over 6 months were experienced only in chronic allografts nephropathy recipients. Higher serum creatinine level was revealed in recipients with chronic allografts nephropathy at 1 year after transplantation (1.27 +/- 0.27 v.s. 1.88 +/- 0.42 mg/dl). CONCLUSIONS: We concluded that donor age and renal function are related to the graft long survival as background factors. Long graft survival recipients had less frequency of acute rejection and good response to the antirejection therapy. In recipients with of acute rejection and good response to the antirejection therapy. In recipients with chronic allografts nephropathy, serum cretine level had already increased gradually within 1 year.     

Urban angina in the mountains: effects of carbon monoxide and mild hypoxemia on subjects with chronic stable angina

Seventeen men with stable angina pectoris who resided at or near sea level performed cardiopulmonary exercise stress tests after they were exposed to either carbon monoxide (3.9%), carboxyhemoglobin, or clean air. Investigators conducted the tests at sea level, and they simulated 2.1-km altitudes (i.e., reduced arterial oxygen saturation by approximately 4%) in a randomized double-blind experiment in which each subject acted as his or her own control. The duration of symptom-limited exercise, heart rate, indicators of cardiac ischemia and arrhythmia, blood pressure, and respiratory gas exchange were measured. Analyses of variance showed that both independent variables-altitude and carbon monoxide-significantly (p < or = .01) reduced total duration of exercise for the group as a whole (n=17) and reduced the time to onset of angina for a subset of 13 subjects who experienced angina during all four test conditions (p < .05). Time to onset of angina was reduced either after exposure to sea-level carbon monoxide (9%) or to simulated high-altitude clean-air exposures (11%), compared with clean air at sea level. Joint exposure to carbon monoxide at a simulated high altitude reduced the time to onset of angina, relative to clean air, by 18% (p < .05). Other cardiological, hemodynamic, and respiratory physiological parameters were also affected adversely by altitude and carbon monoxide exposures. None of the parameters measured were associated significantly with either altitude or carbon monoxide, indicating that the effects of carbon-monoxide-induced and high-altitude-induced hypoxia were additive. The results of this study suggest that high-altitude conditions exacerbate the effects of carbon monoxide exposures in unacclimatized individuals who have coronary artery disease.     

Neuropsychological impairment from acute low-level exposure to carbon monoxide

OBJECTIVE: To investigate the effects of acute low-level exposure to carbon monoxide on higher cognitive functions in healthy humans. DESIGN: An empirical study of the effects of low-level exposure to carbon monoxide on higher cognitive functions in young healthy volunteers and a matched nonexposed control group. SETTING: A dormitory at the Hebrew University campus in Jerusalem, Israel. PARTICIPANTS: Forty-five student volunteers who were exposed to carbon monoxide from residential kerosene stoves for 1.5 to 2.5 hours (air carbon monoxide concentrations of 17-100 ppm; mean +/- SD, 61 +/- 24 ppm) served as the experimental group and 47 nonexposed students served as the control group. MAIN OUTCOME MEASURES: A battery of neuropsychological tests was administered to each participant including digit span, the revised Wechsler Memory Scale for verbal and figural memory, Trail-Making Test parts A and B, digit symbol, block design, and the Rey Auditory Verbal Learning Test. RESULTS: Venous blood carboxyhemoglobin (Hbco) levels in participants of the study group ranged from 0.01 to 0.11 (mean +/- SD, 0.04 +/- 0.03) and correlated with air carbon monoxide concentrations (r = 0.39; P = .01). The experimental group scored significantly lower than controls on the following tests: digit span forward (P = .02), short-term (P = .008) and long-term semantic memory (P = .008), digit symbol (P = .004), block design (P = .009), recall of figural memory (P = .02), and Trail-Making part A (P = .04). No significant differences were found between the experimental and control groups in other tests. CONCLUSIONS: The lower scores on neuropsychological tests indicate dysfunctions in memory, new learning ability, attention and concentration, tracking skills, visuomotor skills, abstract thinking, and visuospatial planing and processing. These dysfunctions correspond with previous reports of carbon monoxide neurotoxic effects in patients with moderate carbon monoxide poisoning. Low-level exposure to carbon monoxide results in impairment of higher cognitive functions. Neuropsychological testing appears to be sensitive in the detection of subtle neurologic dysfunctions resulting from carbon monoxide poisoning.     

Pretransplant injection of allograft recipients with donor blood or lymphocytes permits allograft tolerance without the presence of persistent donor microchimerism

Donor-recipient microchimerism has recently been suggested to play a critical role in the induction and maintenance of allograft tolerance. In this study we sought evidence for this hypothesis using the LEW-to-ACI cardiac allograft as a model system. Donor-specific tolerance to cardiac allografts was induced by intravenous or intraportal injection of graft recipients with donor peripheral blood, T cells, or B cells 7 days before transplantation. All the graft recipients injected with donor antigens accepted donor heart grafts indefinitely when compared with control recipients that rejected donor allografts in 12 days. Long-term graft survivors rejected third-party BN heart allografts in 14 days without an adverse effect on the survival of the first LEW heart allografts, demonstrating the specificity of the tolerance. Tissue lysates prepared from heart, kidney, liver, bone marrow, thymus, lymph nodes, and spleen of tolerant (>120 days) graft recipients were analyzed for the presence of donor DNA using LEW T cell receptor C beta gene-specific primers for polymerase chain reaction that detects donor DNA at > or = 1:10,000 dilution. Donor DNA was detected in 77% of tolerant graft recipients. Chimeric recipients showed variations in the levels and presence of donor DNA in different tissues. The status of donor microchimerism, with respect to its presence and tissue distribution, was dependent upon the donor cell type and route of injection used for the induction of tolerance. Intraportal injection of the graft recipients with donor peripheral blood resulted in the highest degree of chimerism, whereas intravenous injection with donor B cells did not induce detectable microchimerism in this group of recipients. These data clearly demonstrate that the presence of microchimerism is common following administration of donor cells, but that its presence is not an absolute requirement for the long-term survival of allografts.     

急性一氧化碳中毒的急救

介绍一氧化碳中毒的机制、临床特点、诊断和诊治,以及日常生活和生产中的预防。重点介绍纳洛酮联合高压氧综合治疗急性CO中毒的疗效。     

Ultrasonographic imaging of canine mammary tumours

Two-hundred-and-fifteen embryos recovered from 76 donor ewes from flocks endemically infected with sheep pulmonary adenomatosis (SPA) and mated with uninfected rams were transferred to 131 uninfected recipients under strict sanitary conditions using International Embryo Transfer Society protocols. The recipients and their progeny were kept in a closed, isolated SPA-free flock. Thirty-eight of 51 progeny from SPA-positive donors and 55 of 74 progeny from donors in which no lesions of SPA were detected survived for at least five years after birth. In a similar study 11 embryos from four uninfected donors mated to an SPA-infected ram were transferred to seven recipients, and four of five progeny born to four recipients survived for at least five years. No evidence of SPA was found in the recipients or their progeny by embryo transfer in either study. On the basis of clinical and pathological criteria, it is concluded that embryo transfer can be used to provide an effective barrier against the transmission of SPA from donors from infected flocks, whether or not the parents show clinical signs of the disease.     

Chronic CO poisoning. Use of generator gas during the second world war and recent research

The consequences of long-lasting and low-grade exposure to carbon monoxide are a matter of debate. During the second world war, lack of petrol led to widespread use of wood as fuel (generator gas vehicles), especially in the Nordic countries. This caused many cases of "acute" or "chronic" carbon monoxide poisoning. Typical symptoms of "chronic poisoning" were headache, dizziness and tiredness. Usually the symptoms disappeared after some weeks or month, but in some patients probably became permanent. The experiences from the generator gas era are now almost forgotten, and chronic carbon monoxide poisoning is easily overlooked. The authors describe two cases of such poisoning. A crane driver at a smelting works developed permanent symptoms after twenty years of exposure. A faulty oil-fired central heating system caused long-lasting symptoms in four members of a family.     

Induction of donor-specific ACAID can prolong orthotopic corneal allograft survival in "high-risk" eyes

PURPOSE: To examine the effect of donor-specific anterior chamber-associated immune deviation (ACAID) induction on the survival of orthotopic corneal allografts in neovascularized graft beds. METHODS: To induce donor-specific ACAID in recipients, peritoneal exudate cells (PEC) from C57BL/6 mice were incubated overnight with transforming growth factor (TGF)-beta. Cultured PEC were injected intravenously (i.v.) into BALB/c mice, and, 1 week later, these animals received orthotopic corneal allografts from C57BL/6 donors into neovascularized graft beds. Control mice received i.v. injection of syngeneic (BALB/c) PEC, cultured overnight with TGF-beta, and then received orthotopic corneal allografts from C57BL/6 donors. RESULTS: All corneal allografts (15 out of 15) were rejected within 2 weeks after grafting in the neovascularized graft beds of control animals. However, only 6 out of 16 (37.5%) of corneal allografts were rejected in recipients in which donor-specific ACAID had been induced by injection of allogeneic PEC cultured with TGF-beta. CONCLUSION: Previous studies revealed that rejection of orthotopic corneal allografts in neovascularized graft beds in mice correlated with acquisition of donor-specific delayed hypersensitivity (DH). The results of this study suggest that induction of donor-specific ACAID, which selectively impairs DH responses to donor antigens, effectively prolongs corneal allograft survival in "high-risk" eyes.     

Evidence that human cardiac allograft acceptance is associated with a decrease in donor-reactive helper T lymphocytes

We have reported that acute cardiac allograft rejection is associated with increased numbers of donor-reactive helper T lymphocytes (HTL) in the peripheral blood of patients. Further, increased frequencies of circulating donor-reactive HTL may predict allograft rejection episodes diagnosed by endomyocardial biopsy. The present study evaluates the relationship between donor-reactive HTL and allograft "acceptance" in cardiac transplant recipients bearing long-term allografts (> 1 year). Patients were categorized as either long-term acceptors or persistent rejecters based on the number of rejection episodes and the ability to withdraw steroid therapy. Limiting dilution analysis for IL-2-producing HTL was utilized, with cadaver donor splenocytes as a source of donor alloantigens. Donor-reactive HTL frequencies were determined from peripheral blood samples obtained before transplant, and at 1 month and 1 year after transplant. Individuals who accommodated their allografts and were withdrawn from steroid therapy had reduced numbers of donor-reactive HTL at 1 year after transplant as compared with earlier time points. Further, PBMC obtained from these individuals at 1 year after transplant responded weakly to donor alloantigens in a mixed lymphocyte response (MLR). This relationship between donor-reactive HTL and allograft accommodation was exemplified in a cardiac/liver transplant patient who was diagnosed with progressive multifocal leukoencephalopathy and removed from all immunosuppression. No subsequent rejection episodes were diagnosed. Donor-reactive HTL were not detectable and this individual failed to mount an MLR to donor alloantigens. However, a vigorous donor-reactive response was observed when MLR cultures were supplemented with exogenous IL-2. Therefore, nonresponsiveness to the allograft appeared to be due to a deficit in IL-2 production. In contrast, patients who experienced persistent rejection episodes and required continued steroid therapy maintained large numbers of donor-reactive HTL at 1 year after transplant. PBMC from these individuals responded vigorously to donor alloantigens in an MLR. Hence, monitoring donor-reactive HTL may identify individuals who have accommodated their graft and may tolerate a reduction in immunosuppression.     

The distinction between coronary and myocardial reperfusion after thrombolytic therapy by clinical markers of reperfusion

BACKGROUND: On the basis of a previous experience in a chronic sheep model in which partial mitral allografts remained viable and properly functioning 12 months after operation, we assessed the results obtained by replacing the tricuspid valve with fresh antibiotic-preserved mitral allografts. METHODS: Twenty 3-month-old sheep with a mean weight of 23.7 +/- 2.3 kg underwent cardiopulmonary bypass and had a fresh antibiotic-preserved mitral allograft implanted in the tricuspid position with the heart beating under normothermic conditions. The tricuspid valve apparatus was not excised. After a mean follow-up of 13.2 months, the allograft was evaluated by gross inspection and light and electron microscopy. RESULTS: Nine sheep died of technical causes within the first week after operation and 2 at 4 and 6 months of infective endocarditis of the allograft. The hemodynamic study before heart explantation revealed residual tricuspid incompetence in 3 of the 9 survivors. Macroscopic examination showed flexible valves with no signs of structural deterioration, calcification, or thrombosis. Under light and scanning electron microscopic examination, allografts were almost completely denuded of endothelial cells and showed loosely arranged connective tissue with scarce signs of inflammatory reaction. Despite these findings, allografts were free from major structural damage. CONCLUSIONS: The mitral homograft could be an alternative to replacement of the tricuspid valve with a bioprosthesis or a mechanical prosthesis.     

Hippocampal damage induced by carbon monoxide poisoning and spreading depression is alleviated by chronic treatment with brain derived polypeptides

A model of acute carbon monoxide poisoning combined with spreading depression (SD) induced metabolic stress was used to examine the protective effects of cerebrolysin (CL) on the development of electrophysiological, behavioral and morphological signs of hypoxic damage. Capillary electrodes were implanted into the neocortex and hippocampus of anesthetized rats which were then exposed for 90 min to breathing of 0.8% to 0.5% CO, while 3 to 4 waves of cortical and hippocampal SD were elicited by microinjections of 5% KCl. Duration of SD-provoked depolarization of cerebral cortex and hippocampus was noted. Nine and 18 to 19 days later propagation of SD waves was recorded with the same electrodes and decrease of their amplitude was used as an index of brain damage which was significant in the hippocampus but not in the cortex. CL-treatment (2.5 ml/kg per day) started after CO administration and continued for 14 days significantly improved hippocampal recovery manifested by increased amplitude of SD waves. Behavioral tests performed 10 and 20 days after CO poisoning in the Morris water maze revealed better performance (escape latency 7 s) in the CL-treated than in untreated animals (14 s). Morphological analysis showed marked damage in the hippocampus consonant with electrophysiological and behavioral findings in the same animals. No apparent histological damage was found in rats exposed to CO inhalation alone without the additional SD-provoked depolarization. It is concluded that chronic CL-treatment enhances recovery of hippocampal tissue after hypoxic damage of intermediate severity.     

Pulse oximetry in severe carbon monoxide poisoning

STUDY OBJECTIVES: To evaluate the accuracy and quantitate the error of pulse oximetry measurements of arterial oxygenation in patients with severe carbon monoxide (CO) poisoning. DESIGN: Retrospective review of patient clinical records. SETTING: Regional referral center for hyperbaric oxygen therapy. PATIENTS: Thirty patients referred for treatment of acute severe CO poisoning who demonstrated carboxyhemoglobin (COHb) levels >25%, with simultaneous determinations of arterial hemoglobin oxygen saturation by pulse oximetry (SpO2) and arterial blood gas (ABG) techniques. MEASUREMENTS AND RESULTS: COHb levels and measurements of arterial oxygenation from pulse oximetry, ABG analysis, and laboratory CO oximetry were compared. SpO2 did not correlate with COHb levels. SpO2 consistently overestimated the fractional arterial oxygen saturation. The difference between arterial hemoglobin oxygen saturation (SaO2) calculated from ABG analysis and SpO2 increased with increasing COHb level. CONCLUSIONS: Presently available pulse oximeters overestimate arterial oxygenation in patients with severe CO poisoning. An elevated COHb level falsely elevates the SaO2 measurements from pulse oximetry, usually by an amount less than the COHb level, confirming a prior observation in an animal model. Accurate assessment of arterial oxygen content in patients with CO poisoning can currently be performed only by analysis of arterial blood with a laboratory CO-oximetry.     

Double renal allografts successfully increase utilization of kidneys from older donors within a single organ procurement organization

BACKGROUND: In 1994, a policy of double renal allografting (DUAL) was used at two centers within our local organ procurement organization to increase utilization of kidneys from older donors that would otherwise be discarded. Both kidneys from an older donor (age > 60 years) were selectively transplanted into a single adult recipient. METHODS: The relative impact of a DUAL policy on the utilization of older donor kidneys is examined for the period of April 1994 to April 1996. Actual utilization is compared with the hypothetical case in which a DUAL policy is not present. RESULTS: In the actual setting, a total of 75 kidneys from older donors (> 60 years) were accepted for transplantation. Thirty-six kidneys were transplanted as singlets, and 16 additional kidneys were transplanted as DUAL renal allografts. Thus, a 44% increase in transplantable kidneys, and a 22% increase in patients transplanted with kidneys from older donors, was realized. In the actual setting, 23 older kidneys were discarded; without the DUAL policy, 39 kidneys would have been deemed untransplantable. When compared with the actual (n = 52) and hypothetical number of kidneys transplanted without a policy of DUAL transplantation (n = 36), the DUAL policy significantly increased the utilization of older donor kidneys (P = 0.01). The actuarial 1-year graft survival rate of the dual kidneys was 100%, with a mean follow-up of 11.1 +/- 2.9 months. Mean 6-month and 1-year serum creatinine level were 1.76 +/- 0.4 and 1.63 +/- 0.6 mg/dl, respectively. CONCLUSIONS: A DUAL policy significantly increased the number of older donor kidneys transplanted in a single organ procurement organization and reduced the rate of discard of older donor kidneys over a 2-year period. Long-term follow-up is necessary to substantiate satisfactory graft function in DUAL from older donors.