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J H Wolfe

Publications and source records attributed to J H Wolfe.

At least 19 recordsLinked to original sources
PubMed2001

Recent progress in lysosomal alpha-mannosidase and its deficiency.

Lysosomal alpha-mannosidase (EC 3.2.1.24) is a major exoglycosidase in the glycoprotein degradation pathway. A deficiency of this enzyme causes the lysosomal storage disease, alpha-mannosidosis, which has been described in humans, cattle, domestic cats and guinea pigs. Recently, great progress has been made in studying the enzyme and its deficiency. This includes cloning of the gene encoding the enzyme, characterization of mutations related to the disease, establishment of valuable animal models, and encouraging results from bone marrow transplantation experiments.

Animals↗
PubMed2001

In utero transplantation of fetal liver cells in the mucopolysaccharidosis type VII mouse results in low-level chimerism, but overexpression of beta-glucuronidase can delay onset of clinical signs.

Mice with the lysosomal storage disease mucopolysaccharidosis (MPS) VII, caused by a deficiency of beta-glucuronidase (GUSB), have signs of disease present at birth. Bone marrow transplantation (BMT) or retroviral vector-mediated gene transfer into hematopoietic stem cells can partially correct the disease in adult mice, and BMT performed at birth results in a better clinical outcome. Thus, treatment in utero may result in further improvement. However, this must be done without cyto-ablation, and the donor cells do not have a competitive repopulating advantage over host cells. Transplantation in utero of either syngeneic fetal liver hematopoietic stem cells marked with a retroviral vector, or allogeneic donor cells that constitutively express high levels of human GUSB from a transgene, resulted in only about 0.1% engraftment in the adult. Immuno-affinity enrichment of stem and progenitor cells of 5- to 10-fold resulted in significantly higher GUSB activities at 2 months of age, but by 6 months engraftment was about 0.1%. Attempts to further increase the number of stem and progenitor cells were deleterious to the recipients. Nevertheless, GUSB expressed during the first 2 months of life in MPS VII fetuses could delay the onset of overt signs of disease. This suggests that the expression of some normal enzyme activity beginning in fetal life may offer the possibility of slowing the progression of the disease until more definitive postnatal transplantation or gene transfer to stem cells could be accomplished.

Animals↗
PubMed2001

Accumulation of abnormal amounts of glycosaminoglycans in murine mucopolysaccharidosis type VII neural progenitor cells does not alter the growth rate or efficiency of differentiation into neurons.

Mucopolysaccharidosis type VII (MPS VII) results from deficiencies in the gene encoding the lysosomal enzyme beta-glucuronidase (GUSB). To study how the genetic and biochemical defects of MPS disease affect neural cell populations, neural progenitor cells (NPCs) were isolated from MPS VII mice and normal littermates. After growth in culture, approximately 90% of cells from both genotypes were nestin positive, a marker for NPCs, and lacked markers associated with lineage commitment. The mutant NPCs contained elevated levels of undegraded glycosaminoglycans (GAGs), the substrate for GUSB. Transduction with a retrovirus-vector expressing normal GUSB resulted in correction of the biochemical defects. Because of the demonstrated roles that GAGs and proteoglycans have in NPC biology and neural development, we tested whether the alterations in GAG metabolism affected MPS VII NPC properties regulated by GAG-containing molecules. MPS VII NPC cultures had growth rates in response to FGF-2 that were similar to normal cultures and the efficiency of differentiation into neurons was the same as with normal cells. Thus, even though isolated NPCs accumulate abnormally high levels of GAGs, these two key developmental properties were not altered when the cells were examined outside the milieu of the diseased brain.

Animals↗
PubMed2001

Sympathetic autoregulation in peripheral vascular disease.

BACKGROUND: Lower limb venous pressure increases on dependency, stimulating a local sympathetic axon reflex which triggers precapillary and arteriolar vasoconstriction. The resulting decrease in arterial calf inflow, known as the venoarteriolar response (VAR), is impaired in critical leg ischaemia. The aim of the study was to evaluate the VAR in symptomatic non-critical leg ischaemia and after restoration of leg perfusion following successful revascularization. METHODS: The study included 30 normal subjects, 30 patients with stable intermittent claudication and 30 patients with severe ischaemia who had undergone successful infrainguinal revascularization. In all patients the foot skin blood flow (flux) in the horizontal (HBF) and sitting (SBF) positions was measured using laser Doppler fluxmetry. The VAR was calculated as (HBF - SBF)/HBF x 100 per cent. The pressure that elicited the reflex (pVAR) was evaluated in the horizontal position. RESULTS: The median VAR was significantly lower in patients with stable claudication than in normal subjects or patients following successful revascularization (29.1 versus 59.5 and 63.9 per cent respectively; P < 0.0001). Similar results were obtained for the pVAR (22 versus 45 and 40 mmHg respectively; P < 0.001). There was no difference, however, in either the VAR or pVAR between normal individuals and patients following a successful bypass. CONCLUSION: Patients with claudication had a significant impairment of orthostatic sympathetic autoregulation. After successful revascularization, and in spite of the extensive disease in the receiving circulation, this autoregulation returned to normal. Presented previously to the Vascular Surgical Society in London, November 1997 and published in abstract form as Br J Surg 1998; 85: 557

Aged↗
PubMed2001

Cardiac investigation and intervention prior to thoraco-abdominal aneurysm repair: coronary angiography in 35 patients.

OBJECTIVE: retrospective studies indicate a high risk of cardiac events in patients undergoing thoraco-abdominal aneurysm repair. We aimed to determine the prevalence of coronary disease in these patients, define the role of non-invasive cardiac testing and assess the short-term outcome of coronary re-vascularisation. DESIGN: a prospective cohort study of consecutive patients referred to a single surgeon. MATERIALS AND METHODS: forty patients recruited over 16 months (Type I, 6; II, 11; III, 8; IV, 15). Dobutamine stress echocardiography, coronary angiography and coronary re-vascularisation (PTCA or CABG) were performed according to a pragmatic protocol. Main outcome measures were the prevalence of coronary artery disease, sensitivity and specificity of clinical assessment and non-invasive cardiac testing, and adverse events associated with coronary investigation and intervention. RESULTS: seven patients (17.5%) were stratified as having high perioperative cardiac risk. The majority of patients (23, 57.5%) had no cardiac risk factor other than the operation type. Five patients (12.5%) had inducible ischaemia on non-invasive testing. Fourteen patients (40%) had haemodynamically significant coronary artery stenoses, of whom 12 (34%) underwent coronary revascularisation. Dobutamine stress echocardiography demonstrated 100% specificity and 71% sensitivity for the detection of significant coronary artery lesions. Coronary re-vascularisation by three-vessel bypass grafting was complicated by non-fatal stroke in one patient. Thirty-five patients (87.5%) proceeded to aneurysm repair. No patient who had been adequately investigated suffered a cardiac complication. CONCLUSIONS: the 40% prevalence of coronary artery disease in these patients is comparable to that of other patients undergoing arterial surgery. Non-invasive testing proved beneficial, both in screening low-risk patients and planning intervention in patients at higher risk. An aggressive approach to intervention was associated with an acceptable complication rate and favourable short-term outcome.

Adult↗
PubMed2001

Patency following successful thrombolysis of occluded vascular grafts.

AIM: to determine patency after successful lysis of occluded bypass grafts. METHODS: data were collected from four centres with a wide experience of thrombolysis. Outcome following successful lysis was determined from prospectively collected data or case notes. Data from 75 patients, 53 men, were analysed. RESULTS: median age at time of lysis was 68 years (range 33-88). Median age of graft was 12 months (range 1-120). Patency at 12 months was 33% (95% conf. interval: 21-44%). There were no differences in patency depending on whether the graft was above or below the inguinal ligament or whether an additional procedure eg. percutaneous or vein patch angioplasty was carried out. However in those 48 cases when lysis was deemed complete, i.e. there was restoration of graft patency and at least one vessel run off patency at 12 months was 39% compared with 17% if lysis was incomplete (p=0.04). CONCLUSIONS: at the present time it is difficult to justify routine thrombolysis of occluded grafts when patency, based on intention to treat, is approximately 20% at one year. Following successful graft lysis the role of anticoagulation and careful graft surveillance require further investigation.

Adult↗
PubMed2001

Peripheral sympathetic autoregulation in arterial calf inflow enhancement with intermittent pneumatic compression.

BACKGROUND: Peroperative mortality, graft failure and balloon angioplasty limitations mitigate against active intervention for claudication. With the exception of exercise programmes, conservative treatments yield limited results. Intermittent pneumatic compression of the foot (IPC(foot)) used daily for over 3 months enhances significantly the walking ability and pressure indices of stable claudicants; this is attributable to the significant calf inflow enhancement with IPC(foot); however, the physiologic mechanisms involved are only partially understood. Aims by comparing the effects of IPC(foot)and postural alteration on calf inflow haemodynamics, this study examines the role of peripheral sympathetic autoregulation, which controls homeostasis in lower limb vessels when posture changes, in the enhancement of calf inflow with IPC(foot)in healthy subjects and claudicants. MATERIAL AND METHODS: forty-one limbs of healthy subjects (n =34; Group I) and 48 limbs of stable claudicants (Fontaine II) (n =42; Group II) were studied. The volume flow (Q), pulsatility index (PI), mean (mV), peak systolic (PSV) and end diastolic (EDV) velocities were measured in the popliteal artery using duplex ultrasound in: the horizontal position, and on sitting with or without IPC(foot). RESULTS: in Group II: median Q, mV, PSV and EDV increased by 61%, 53%, 29% and 51% respectively, and PI decreased by 20% as posture changed from sitting to horizontal; with IPC(foot)median Q, mV, PSV and EDV increased by 70%, 58%, 22% and 75% respectively, and PI decreased by 26% (all p < 0.001). In Group I: median Q, mV, PSV and EDV increased by 125%, 115%, 51% and 38% respectively and PI decreased by 30% as posture changed from sitting to horizontal; with IPC(foot)median Q, mV, PSV and EDV increased by 119%, 153%, 23% and 46%, respectively, and PI decreased by 50% (all p < 0.001). The effects of IPC(foot)and postural alteration (from sitting to horizontal) did not differ haemodynamically (p > 0.1) in both groups. Q on lying was similar in Groups I and II. On sitting Q was higher in Group II [p =0.027 (95% CI 1.7, 27 ml/min)]. CONCLUSIONS: the striking similarity in the haemodynamic effects of IPC(foot)and postural alteration in the popliteal artery strongly suggests that the leg inflow enhancement with IPC(foot)is mediated by a transient suspension of peripheral sympathetic autoregulation. In addition to their role as clinical markers of PVD severity, the autoregulatory reflexes of peripheral circulation appear to have functions with significant clinical implications in the management of patients with leg inflow impairment.

Adult↗
PubMed2001

In situ hemodynamics of perforating veins in chronic venous insufficiency.

PURPOSE: The prevalence of incompetent perforators increases linearly with the clinical severity of chronic venous insufficiency (CVI) and the presence of deep vein incompetence. Putative transmission of deep vein pressure to skin may cause dermal hypoxia and ulceration. Despite extensive prospective interest in the contribution of perforators toward CVI, their hemodynamic role remains controversial. The aim of this prospective study was to determine the in situ hemodynamic performance of incompetent perforating veins across the clinical spectrum of CVI, by means of duplex ultrasonography. METHODS: A total of 265 perforating veins of 90 legs that had clinical signs and symptoms consistent with CVI in 67 patients referred consecutively to the blood flow laboratory were studied. The clinical distribution of the examined limbs was CEAP(0), 10 limbs; CEAP(1-2), 39 limbs; CEAP(3-4), 21 limbs; and CEAP(5-6), 20 limbs. With the use of gated-Doppler ultrasonography on real-time B-mode imaging, the flow velocity waveforms were obtained from the lumen of perforators on release of manual distal leg compression in the sitting position and analyzed for peak and mean velocities, time to peak velocity, volume flow, venous volume displaced outward, and flow pulsatility. The diameter and duration of outward flow (abnormal reflux > 0.5 seconds) were also measured. RESULTS: Incompetent perforators had bigger diameters, higher peak and mean velocities and volume flow, longer time to peak velocity, and bigger venous volume displaced outward (VV(outward)) than competent perforators (all, P <.0001). The diameter of incompetent perforators did not change significantly with CEAP class (all, P >.1). Incompetent thigh and lower-third calf perforators had a significantly bigger diameter than perforators in the upper and middle calf combined (both, P <.05), in incompetent perforators: reflux duration was unaffected by CEAP class or site (P >.3); peak velocity was higher in those in CEAP(3-4) than those in CEAP(1-2) (P =.024); mean velocity in those in CEAP(3-6) during the first second of reflux was twice that of those in CEAP(1-2) (P <.0001); both higher volume flow and VV(outward) were found in the thigh perforators than those in the upper and middle calf thirds (P <.03); CEAP(3-6) volume flow and VV(outward), both in the first second, were twice that in those in CEAP(1-2) (P <.002); flow pulsatility in those in CEAP(5-6) was lower than in those in CEAP(1-2) (P =.014); in deep vein incompetence, higher peak velocity, volume flow, VV(outward), and diameter occurred than in its absence (P <.01). CEAP designation correlated significantly with mean velocity and flow pulsatility, both in the first second (r = 0.3, P <.01). The flow direction pattern in perforator incompetence was uniform across the CVI spectrum: inward on distal manual limb compression, and outward on its release; competent perforators had a smaller percentage of outward flow on limb compression (P <.01). CONCLUSION: In addition to an increase in diameter, perforator incompetence is characterized by significantly higher mean and peak flow velocities, volume flow, and venous volume displaced outward, and a lower flow pulsatility. Differences in early reflux enable a better hemodynamic stratification of incompetent perforators in CVI classes. In the presence of deep reflux, incompetent perforators sustain further hemodynamic impairment. In situ hemodynamics enable quantification of the function of perforators and can be used in the identification of the clinically relevant perforators and the impact of surgery.

Adolescent↗
PubMed2001

Infection and establishment of latency in the dog brain after direct inoculation of a nonpathogenic strain of herpes simplex virus-1.

A number of diseases affecting the CNS occur in the dog and can be used as models for gene therapy in a large brain. HSV-1 has several potential advantages as a vector to transfer genes into the CNS. However, the ability of HSV-1 to infect CNS cells varies among species and no information was available for the dog. When the nonpathogenic 1716 strain of HSV-1 was injected into the brains of normal dogs it established a latent infection without signs of pathology. Thus, it appears to be suitable as a vector for therapeutic, or marker genes, in this species.

Animals↗
PubMed2001

Histopathology, electrodiagnostic testing, and magnetic resonance imaging show significant peripheral and central nervous system myelin abnormalities in the cat model of alpha-mannosidosis.

Alpha-mannosidosis is a disease caused by the deficient activity of alpha-mannosidase, a lysosomal hydrolase involved in the degradation of glycoproteins. The disease is characterized by the accumulation of mannose-rich oligosaccharides within lysosomes. The purpose of this study was to characterize the peripheral nervous system (PNS) and central nervous system (CNS) myelin abnormalities in cats from a breeding colony with a uniform mutation in the gene encoding alpha-mannosidase. Three affected cats and 3 normal cats from 2 litters were examined weekly from 4 to 18 wk of age. Progressively worsening neurological signs developed in affected cats that included tremors, loss of balance, and nystagmus. In the PNS, affected cats showed slow motor nerve conduction velocity and increased F-wave latency. Single nerve fiber teasing revealed significant demyelination/remyelination in affected cats. Mean G-ratios of nerves showed a significant increase in affected cats compared to normal cats. Magnetic resonance imaging of the CNS revealed diffuse white matter signal abnormalities throughout the brain of affected cats. Quantitative magnetization transfer imaging showed a 8%-16% decrease in the magnetization transfer ratio in brain white matter of affected cats compared to normal cats, consistent with myelin abnormalities. Histology confirmed myelin loss throughout the cerebrum and cerebellum. Thus, histology, electrodiagnostic testing, and magnetic resonance imaging identified significant myelination abnormalities in both the PNS and CNS that have not been described previously in alpha-mannosidosis.

Animals↗
PubMed2001

Widespread gene delivery and structure-specific patterns of expression in the brain after intraventricular injections of neonatal mice with an adeno-associated virus vector.

Developing a system for widespread somatic gene transfer in the central nervous system (CNS) would be beneficial for understanding the global influence of exogenous genes on animal models. We injected an adeno-associated virus serotype 2 (AAV2) vector into the cerebral lateral ventricles at birth and mapped its distribution and transduction pattern from a promoter capable of expression in multiple targets. The injections resulted in structure-specific patterns of expression that were maintained for at least 1 year in most regions, with efficient targeting of some of the major principal neuron layers. The patterns of transduction were explained by circulation of the viral vector in the subarachnoid space via CSF flow, followed by transduction of underlying structures, rather than by progenitor cell infection and subsequent migration. This study demonstrates that gene transfer throughout the CNS can be achieved without germ line transmission and establishes an experimental strategy for introducing genes to somatic cells in a highly predictable manner.

Animals↗
PubMed2000

Characterization of an unusual variant mRNA of human lysosomal alpha-mannosidase.

Lysosomal alpha-mannosidase (EC 3.2.1.24) is an exoglycosidase in the glycoprotein degradation pathway and is encoded by a 3.0 kb cDNA. A 2.3 kb cDNA from a minor species of HeLa cell mRNA was discovered by RT-PCR cloning. Southern blotting and PCR analysis of the HeLa cell genomic DNA showed that the 2.3 kb message was encoded by the lysosomal alpha-mannosidase gene. Sequence comparison of the cDNA with the corresponding genomic DNA indicated that the 2.3 kb message was generated by an unusual intra-exonic joining event.

Alternative Splicing↗
PubMed2000

Significantly increased expression of beta-glucuronidase in the central nervous system of mucopolysaccharidosis type VII mice from the latency-associated transcript promoter in a nonpathogenic herpes simplex virus type 1 vector.

Herpes simplex virus (HSV) has the ability to establish life-long latent infections in postmitotic neurons and to remain transcriptionally active, continuously expressing latency-associated transcripts (LAT) while producing minimal disease. These properties have made HSV an excellent candidate for neuronal gene transfer. Previously, we have shown that in mucopolysaccharidosis type VII mice (MPS VII, beta-glucuronidase deficiency) the LAT promoter is capable of expressing beta-glucuronidase (GUSB) in the trigeminal ganglion and the brainstem after latency is established. However, the number of neurons expressing GUSB is much lower than the number expressing 2-kb LAT following a wild-type virus infection. In this study, we have evaluated the effect of the position of the coding sequence relative to the LAT promoter on beta-glucuronidase gene expression in the central nervous system (CNS). Non-neurovirulent (ICP-34.5-deleted HSV-1) vectors were used, allowing direct intracranial injection. Significantly more GUSB activity was detected in brains of MPS VII mice inoculated with a recombinant virus (HSV-LAT-GUSB-JS) in which the GUSB cDNA was inserted near the LAT promoter, compared to viruses where it was inserted farther downstream in either the LAT exon 1 or overlapping exon 1 and the 2-kb LAT intron. This vector produced more than 100 times the number of positive cells than the other constructs. During acute infection, the distribution of viral replication differed from the distribution of GUSB enzyme expression. Viral antigen was predominately present in cells around the site of injection in the caudate putamen and in ependymal cells lining the ventricles. In contrast, GUSB expression was present mainly in cells of the thalamus and hypothalamus, which did not exhibit viral antigen, suggesting that GUSB enzyme activity was expressed from latently but not acutely infected neuronal cells. This vector design should be useful for high-level expression of various genes in the CNS.

Animals↗
PubMed2000

Gene transfer of low levels of beta-glucuronidase corrects hepatic lysosomal storage in a large animal model of mucopolysaccharidosis VII.

Gene therapy has been at least partially effective in several mouse disease models, but treatment of large mammals has been more difficult to achieve. One major limitation is that only low levels of expression of the corrective gene are often maintained in vivo. In a mouse model of the lysosomal storage disease mucopolysaccharidosis (MPS) type VII (Sly disease) with a null mutation in beta-glucuronidase, gene transfer experiments have shown that only 1-2% of normal beta-glucuronidase can correct the storage in some major organs. In contrast, MPS VII dogs, cats, and humans that have residual beta-glucuronidase activity levels in this range are affected. Thus, higher levels of transferred gene expression may be needed to achieve a therapeutic effect in large animals and humans. We tested this by examining liver pathology in MPS VII dogs after intraperitoneal transplantation of neo-organs containing retrovirus vector-corrected autologous fibroblasts that expressed low levels of beta-glucuronidase. The enzyme secreted from the neo-organs was taken up by the liver and significantly reduced the substrate content compared with untreated dogs. This suggests that small amounts of normal enzyme, when delivered to target tissues, may be therapeutically effective in human MPS VII patients.

Animals↗
PubMed2000

The surgical management of renovascular hypertension in children and young adults.

OBJECTIVES: To assess the outcome and durability of operative revascularisation in young patients with renovascular hypertension. DESIGN: Retrospective study. METHOD: The records of all young patients (under 25 years) operated on for renovascular hypertension at St Mary's Hospital 1988-1998 were reviewed. We assessed the aetiology of hypertension, operations performed, effect of treatment on blood pressure, renal function and requirement for antihypertensive medication during follow-up. RESULTS: Ten patients were identified who had been considered for surgery, of median age 16 years (22 months to 22 years). Fibromuscular dysplasia was present in five patients, mid-aortic syndrome (MAS) in four and neurofibromatosis in one. Operations performed were aortorenal bypass (three), aorto-aortic bypass+/-renal bypass (three), splenorenal bypass (one) and autotransplantation (one). Of the three patients treated by balloon angioplasty, only one had a successful result. One patient with MAS is currently awaiting surgery. Over a median follow-up of 24 months (8-144), seven patients are normotensive off all antihypertensive medication. Of two patients on reduced doses of medication, one (splenorenal bypass) required surgical repair of a late (9 years) coeliac stenosis. CONCLUSIONS: The surgical treatment of renovascular hypertension in carefully selected young patients gives durable results. Blood pressure is well controlled long-term, and the need for antihypertensive medication is removed altogether in the majority of patients.

Adolescent↗
PubMed2000

Optimum intermittent pneumatic compression stimulus for lower-limb venous emptying.

OBJECTIVE: intermittent pneumatic compression (IPC) of the foot (IPC(foot)), calf (IPC(calf)) or both (IPC(foot+calf)) augments calf inflow, and improves the walking ability and peripheral haemodynamics of claudicants (IPC(foot), IPC(foot+calf)), largely due to venous outflow enhancement. This cohort study, using direct pressure measurements in healthy limbs, determines the optimal combination of frequency (2-4 impulses/minute), applied pressure (60-140 mmHg), mode (IPC(foot)-IPC(calf)-IPC(foot+calf)) and delay time of calf-to-foot impulse (0 s-0.5 s-1 s) that enables IPC to generate an almost complete and sustained decrease in venous pressure. RESULTS: (a) IPC(foot)at 120 and 80 mmHg generated lower venous pressure than that with 100 and 60 mmHg (p=0.036) respectively, for 2-4 impulses/minute; venous pressure differences between applied pressures of 140 and 120 mmHg or between 80 and 100 mmHg were insignificant. (b) Venous pressure with IPC(calf)at 80 mmHg was lower than that with 60 mmHg (p=0.036) (2-4 cycles/minute); differences in venous pressure between applied pressures of 140 and 100 mmHg or between 120 and 80 mmHg were insignificant. (c) At applied pressures 60-140 mmHg, IPC(foot+calf)with one-second delay generated lower venous pressure than that with half-second delay (p=0.036), the latter being more efficient than zero delay; increasing applied pressures produced lower venous pressure, but differences were small. Venous pressure decreased with increasing IPC frequency (from 2 to 3-4/minute), at applied pressures 60-140 mmHg. CONCLUSIONS: IPC(foot+calf)at applied 120-140 mmHg, a frequency of 3-4 impulses/minute and one-second delay, provided the optimum intermittent pneumatic stimulus.

Adult↗
PubMed2000

Myocardial injury in major aortic surgery.

PURPOSE: The purpose of this study was to examine the effects of major aortic surgery and its associated oxidative stress and injury on the myocardium. METHODS: Plasma from 27 patients who underwent thoracoabdominal aortic aneurysm (TAAA) repair and 17 patients who underwent infrarenal aortic aneurysm (AAA) repair was collected at incision, aortic crossclamping, and reperfusion and 1, 8, and 24 hours thereafter. Samples were assayed for the myocardial specific protein troponin-T, total antioxidant status, and lipid hydroperoxides. RESULTS: Ten patients experienced cardiac dysfunction in the first 24 hours after surgery (eight patients in the TAAA group and two patients in the AAA group). Immediately after reperfusion, total antioxidant status levels dropped in all patients with TAAA and with AAA; this was more marked in patients with TAAA, leading to a significant difference between the two groups at this time point and for up to 1 hour thereafter (P <.01). Patients with TAAA showed a sharp rise in lipid hydroperoxide levels immediately after reperfusion, and levels were significantly higher than in patients with AAA (P =.0007). In patients with AAA, no significant change in troponin-T was observed throughout the study period; whereas in patients with TAAA, levels were significantly elevated at 8 and 24 hours after reperfusion (P <.01). Troponin-T levels significantly correlated with total antioxidant status (r = -0.5) and lipid hydroperoxides (r = 0.78) but not with systolic blood pressure. CONCLUSION: Supracoeliac aortic crossclamping is associated with a significant release of the myocardial injury marker troponin-T. This seems to correlate with the severity of oxidative rather than hemodynamic stresses. Ameliorating oxidative injury during TAAA surgery may therefore have a cardioprotective effect.

APACHE↗