The contemporary role of antioxidant therapy in attenuating liver ischemia-reperfusion injury: a review.

Oxidative stress is an important factor in many pathological conditions such as inflammation, cancer, ageing and organ response to ischemia-reperfusion. Humans have developed a complex antioxidant system to eliminate or attenuate oxidative stress. Liver ischemia-reperfusion injury occurs in a number of clinical settings, including liver surgery, transplantation, and hemorrhagic shock with subsequent fluid resuscitation, leading to significant morbidity and mortality. It is characterized by significant oxidative stress but accompanied with depletion of endogenous antioxidants. This review has 2 aims: firstly, to highlight the clinical significance of liver ischemia-reperfusion injury, the underlying mechanisms and the main pathways by which the antioxidants function, and secondly, to describe the new developments that are ongoing in antioxidant therapy and to present the experimental and clinical evidence about the role of antioxidants in modulating hepatic ischemia-reperfusion injury.     

Hydroxyethyl starch does not improve pancreas preservation with HTK

The effect of hydroxyethyl starch on pancreas preservation with cardioplegic histidine-tryptophan-ketoglutarate solution (HTK) was investigated. The study was performed using an in vitro reperfusion system of the porcine pancreas. During organ preservation pancreatic weight, arterial pressure, volume flow, and washout of amylase and lactate were quantified. Addition of hydroxyethyl starch did not affect arteriovenous volume flow or washout of amylase and lactate during protective perfusion after pancreas preparation. However, hydroxyethyl starch in HTK prevented an increase in pancreatic weight at the end of the protective perfusion (102.2 ± 4.55% vs 127.8 ± 4.62% in controls; p < 0.005) and after 24 h cold ischemia (72.9 ± 3.91 % vs. 83.5 ± 3.49 % in controls; p < 0.05). Hydroxyethyl starch did not affect postischemic organ quality assessed during reperfusion in a perfusion chamber by pancreatic vascular resistance, amylase and lactate release, insulin secretion, and oxygen consumption. We conclude that hydroxyethyl starch does not bring about any further improvement in immediate postischemic organ quality assessed in an in vitro reperfusion system.

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Hydroxyäthylstärke bringt keine verbesserung der pankreaskonservierung mit HTK-Lösung

Zusammenfassung Der Effekt von Hydroxyäthylstärke auf die Pankreaskonservierung mit der kardioplegischen Histidin-Tryptophan-Ketoglutarat-Lösung (HTK) wurde untersucht. Die Studie wurde an einem Reperfusionssystem des in vitro perfundierten Pankreas vom Schwein durchgeführt. Während der Organprotektion wurden das Pankreasgewicht, der arterielle Perfusionsdruck, die Volumenstromstärke sowie Amylase und Laktat im Perfusat bestimmt. Der Zusatz von Hydroxyäthylstärke bewirkte keine Änderung der Volumenstromstärke oder der Amylase- und Laktatauswaschung aus dem Organ während der Protektion. Allerdings konnte eine Zunahme des Organgewichts am Ende der protektiven Perfusion (102,2 ± 4,55% vs. 127,8 ± 4,62%in Kontrollen; p < 0,005) und nach 24 h kalter Ischamie (72,9 ± 3,91 vs. 83,5 ± 3,49% in Kontrollen; p < 0,05) durch Hydroxyathylstärke in der HTK-Lösung verhindert werden. Hydroxyäthylstärke hatte keinen Einfluß auf die postischämische Organqualität, die während der Reperfusion in einer Perfusionskammer anhand von Gefäßwiderstand, Amylase- und Laktatfreisetzung, Insulinsekretion und Sauerstoffverbrauch abgeschätzt wurde. Wir schließen daraus, daß Hydroxyäthylstärke die sofort nach einer Ischämie in einem In-vitro-Reperfusionssystem bestimmte Pankreasfunktion nicht weiter verbessert.

     

In vitro stability of a novel compliant poly(carbonate-urea)urethane to oxidative and hydrolytic stress.

Poly(ester)urethane and poly(ether)urethane vascular grafts fail in vivo because of hydrolytic and oxidative degradative mechanisms. Studies have shown that poly(carbonate)urethanes have enhanced resistance. There is still a need for a viable, nonrigid, small-diameter, synthetic vascular graft. In this study, we sought to confirm this by exposing a novel formulation of compliant poly(carbonate-urea)urethane (CPU) manufactured by an innovative process, resulting in a stress-free. Small-diameter prosthesis, and a conventional poly(ether)urethane Pulse-Tec graft known to readily undergo oxidation in a variety of degradative solutions, and we assessed them for the development of oxidative and hydrolytic degradation, changes in elastic properties, and chemical stability. To simulate the in vivo environment, we used buffered solutions of phospholipase A(2) and cholesterol esterase; solutions of H(2)O(2)/CoCl(2), t-butyl peroxide/CoCl(2) (t-but/CoCl(2)), and glutathione/t-butyl peroxide/CoCl(2) (Glut/t-but/CoCl(2)); and plasma fractions I-IV, which were derived from fresh human plasma centrifuged in poly(ethylene glycol). To act as a negative control, both graft types were incubated in distilled water. Samples of both graft types (100 mm with a 5.0-mm inner diameter) were incubated in these solutions at 37 degrees C for 70 days before environmental scanning electron microscopy, radial tensile strength and quality control, gel permeation chromatography, and in vitro compliance assessments were performed. Oxidative degradation was ascertained from significant changes in molecular weight with respect to a control on all Pulse-Tec grafts treated with t-but/CoCl(2), Glut/t-but/CoCl(2), and plasma fractions I-III. Pulse-Tec grafts exposed to the H(2)O(2)/CoCl(2) mixture had significantly greater compliance than controls incubated in distilled water (p < 0.001 at 50 mmHg). No changes in molecular weight with respect to the control were observed for the CPU samples; only those immersed in t-but/CoCl(2) and Glut/t-but/CoCl(2) showed an 11% increase in molecular weight to 108,000. Only CPU grafts treated with the Glut/t-but/CoCl(2) mixture exhibited significantly greater compliance (p < 0.05 at 50 mmHg). Overall, results from this study indicate that CPU presents a far greater chemical stability than poly(ether)-urethane grafts do.     

Effect of amiodarone on signal-averaged and long-term ECG]

This prospective study examined the influence of long-term amiodarone therapy on the parameters of the signal-averaged ECG and their relation to simultaneously derived Holter monitoring data. For this purpose, 23 patients with angiographically confirmed dilated cardiomyopathy or coronary heart disease and high-grade ventricular arrhythmias, in whom an average of four class I antiarrhythmic drugs had proven ineffective, were stabilized on amiodarone. Before the beginning of therapy, as well as after 2 months and, subsequently, every 3 months, a resting ECG, a signal-averaged ECG by Simson's method, and Holter monitoring were performed. Compared to the initial measurement, we found a significant increase in the duration of the total filtered QRS complex from an average of 114 +/- 24 ms to 127 +/- 35 ms, while the change in voltage did not reach the significance level. The incidence of late potentials remained largely constant under amiodarone; 10 patients showed a constant late potential, 12 patients had no late potential, and one patient with coronary heart disease developed a new late potential. In the long-term follow-up, we ascertained a relatively high responder rate under amiodarone between 41% and 81%. No relation could be detected between the results of the signal-averaged ECG and those of 24-h Holter monitoring.     

Age-specific cerebral perfusion in 4- to 15-year-old children: a high-resolution brain SPET study using 99mTc-ECD

This study addresses the question of whether the normal range for distribution of local cerebral blood flow (lCBF) in adults can be transferred to the 4- to 15-year-old age group. Twenty-three children (age: 4–15 years; mean 11±3 years, group I) and 10 adults (age: 27–56 years; mean 45±10 years, group II) without evidence of cerebrovascular disease or other brain diseases underwent technetium-99m ethyl cysteinate dimer single-photon emission tomography. Counts in cortical and subcortical regions of interest (ROIs) were related to those in cerebellar ROIs (= 100%). Relative cortical activity in group I exceeded that in group II, particularly in left parietal (107.6%±9.8% vs 84.1%±12.4%), left frontal (97.7%±6.7% vs 79.4%±8.9%) and left temporal areas (99.7%±7.4% vs 84.9%±10.1%) and in the cingulate cortex (112.1%±9.1% vs 95.9%±10.1%, P<0.05). Cerebral activity uptake per injected dose was inversely correlated with age in 19 children of group I (r = –0.77, P<0.001). In group I, there was also an inverse correlation between age and the relative local count density in the parietal (r = –0.42 to –0.57), frontal (r = –0.48), temporal (r = –0.42 to –0.58) and occipital cortex (r = –0.44). In these cortical regions relative counts differed when subgroups of children aged 4–10 and 11–15 years were analysed. It is concluded that there are systematic differences between 4- to 15-year-old children and adults with regard to normal lCBF. Diagnostic use of perfusion agents has to consider age-adjusted normal flow maps; normal ranges should be determined separately for the age groups 4–10 and 11–15 years. Received 23 March and in revised form 11 July 1997     

Quantification of flow through an interatrial communication. Application to the partial Fontan procedure.

The partial Fontan procedure has become an accepted alternative for the high-risk candidate. Creation of a small right-to-left shunt will lower the systemic venous pressure and improve systemic cardiac output while maintaining an acceptable systemic arterial saturation. However, because of variations in patient size and postoperative transpulmonary gradient, proper sizing of the residual defect is difficult. We have therefore conducted a series of experiments on a model that simulates the blood flow across interatrial defects of varying sizes at several pressure gradients. We used porcine blood to develop guidelines for the sizing of the residual defect. Our results demonstrate a linear relationship between flow and pressure gradient across all hole sizes tested. In addition, there was a linear relationship between atrial septal defect size and flow at each pressure gradient. Our data show that the Gorlin formula predictions overestimated flow by 10% to 40%. It is evident from these data that relatively small changes in the size of the atrial septal defect or in the pressure gradient result in significant changes in flow. Therefore we advocate the use of an adjustable interatrial communication such as the snare-controlled adjustable atrial septal defect for patients undergoing partial Fontan procedures.     

Surgical therapy in patients with active infective endocarditis: seven-year single centre experience in a subgroup of 255 patients treated with the Shelhigh stentless bioprosthesis

OBJECTIVE: We investigated outcomes after surgical therapy in patients with active infective endocarditis (AIE) with regard to survival in relation to surgical urgency, valve position, number of valves implanted and abscess formation. We aimed to identify independent risk factors for early mortality. METHODS AND RESULTS: Two hundred and fifty-five patients received Shelhigh bioprostheses between February 2000 and March 2007. A total of 74.1% had native and 25.9% prosthetic AIE. Surgery was regarded as urgent in 57.3% and as an emergency procedure in 38.4%. There was a highly significant difference in survival rate between patients who were operated on urgently versus in an emergency (p<0.0001), between single and double valve replacement (p=0.0206) and between patients with and without abscess formation (p=0.0245). There were two cases of early reinfection (0.78%) and six of late reinfection (2.35%) leading to re-operation. CONCLUSIONS: The survival of patients differs significantly in dependence on their surgical urgency. Better outcome could have been achieved if patients had been referred earlier for surgery and operated upon before heart failure or septic shock developed. Long-term survival was better in patients without abscess formation. The low reinfection rate of Shelhigh bioprostheses in AIE is promising and the early and mid-term results achieved need to be verified in the long-term course.     

Coronary atherosclerosis of the donor heart--impact on early graft failure.

OBJECTIVE: Due to the shortage of donor hearts, the criteria for organ acceptability have been considerably extended and donor grafts with coronary atherosclerosis are among those offered. This study evaluated whether and to what degree pre-existing coronary atherosclerosis may be acceptable. METHODS: A total of 1253 consecutive HTx recipients were investigated retrospectively for donor-transmitted coronary atherosclerosis (DCAS). Donor-transmitted coronary atherosclerosis was defined as focal atherosclerosis with stenosis of at least 50%. Inclusion criteria were absence of pre-HTx angiogram but performance of angiogram or autopsy within 6 months after heart transplantation. Kaplan-Meier analysis and log-rank test were used. RESULTS: Eighty-five out of 1253 (6.8%) cases were excluded, since coronary evaluation was not performed within 6 months (n=45) or hearts had undergone pre-transplant angiography (n=40). In 1086 patients no donor-transmitted coronary atherosclerosis was found (NDCAS group) and in 82 patients (7%) donor-transmitted coronary atherosclerosis was diagnosed by angiography (n=49) or autopsy (n=33). Single-vessel donor-transmitted coronary atherosclerosis was found in 53/82 patients (DCAS1 group) and double- or triple-vessel donor-transmitted coronary atherosclerosis in 26/82 patients (DCAS2/3 group). Three of the 82 patients with donor-transmitted coronary atherosclerosis were excluded since the autopsy report was unclear regarding degree of atherosclerosis. Early after heart transplantation the 30-day mortality in the NDCAS and DCAS1 groups was 12.2% versus 13.2% whereas in the DCAS2/3 group it was 61.5%. Beyond the first year the annual decrease with and without donor-transmitted coronary atherosclerosis (single-vessel disease) is comparable. CONCLUSIONS: Donor screening without coronary angiogram overlooks significant atherosclerotic lesions in a considerable number of cases (7.0%). Therefore, angiographic donor screening should be performed. Donor grafts with single-vessel coronary atherosclerosis may be accepted as marginal hearts; however, in our opinion, revascularisation (CABG, PTCA) should be considered. Grafts with two- or even three-vessel coronary atherosclerosis seem to have a serious risk for early graft failure. Beyond the first year the outcome of healthy grafts and grafts with donor-transmitted coronary atherosclerosis seems to be comparable.     

Near fatal infection of a patient with a left ventricular assist device due to unrecognized fetal death.

We report on an unusual case of a young female patient who received an implantable LVAD after unsuccessful emergency coronary bypass surgery following acute myocardial infarction. After LVAD placement, it became evident that the patient had been pregnant. She had to undergo gynaecological surgery during mechanical support to remove the deceased fetus.