Nuclear factor (NF)-kappaB and activation protein (AP)-1 transcription factors play an important role in the signal transduction of delayed ischaemic preconditioning (PC) leading to myocardial cytoprotection. Because the exact mechanism of the activation of these factors is still not clear, we aimed to monitor the time fluctuation of NF-kappaB and AP-1 induction in an in vivo animal model. Furthermore, we measured the induction rate of these factors using repeated cycles of PC. Following median thoracotomy, anaesthetized animals (24 New Zealand White rabbits) were subjected to ischaemic PC by occlusion of the left anterior descending coronary artery for 5 min. After 10 and 30 min, and 1, 2, 3 and 4 h of reperfusion, tissue samples were taken from the ischaemic myocardium, and the DNA binding activity of the transcription factors was measured with electrophoretic mobility shift assay. A further 12 animals were subjected to 2 x, 3 x or 4 x 5-min ischaemic PC, and after a 30-min or 1-hour reperfusion period, we investigated the possible modulation of NF-kappaB and AP-1 induction. Our results show significant, biphasically increased NF-kappaB activity with peak levels at 30 min and 3 h of reperfusion in preconditioned myocardium. AP-1 increased monophasically, with the peak level at 1 h of reperfusion. Repeated PC stimuli enhanced the activity of both transcription factors analyzed, but there was no significant correlation between the number of cycles and the rate of activation. Our results show that the activation of NF-kappaB and AP-1 have a specific time curve, and the induction of these factors is only slightly influenced by the number of PC cycles.

Animals↗

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Expression of CD97 and adhesion molecules on circulating leukocytes in patients undergoing coronary artery bypass surgery.

OBJECTIVE: Leukocyte activation is thought to be responsible for the adverse effects and postoperative complications following cardiopulmonary bypass (CPB). A novel cell surface molecule, CD97, is a sensitive marker of leukocyte and primary lymphocyte activation. The present study aimed to determine the activation of different leukocyte subsets by comparing the expression of CD97 and adhesion molecules (CD11, CD18) in patients receiving coronary surgery with or without CPB. METHODS: 30 patients were enrolled and scheduled for coronary bypass surgery under CPB (20 patients, group A) and with off-pump (OP) operation (10 patients, group B). Blood samples were taken before and during surgery, and over the following first week. RESULTS: Here, we report an early decrease in CD97 expression of granulocytes (PMN) and monocytes (MC) followed by an intensive increase reaching the maximum on postoperative days 2 and 3 in patients operated with CPB. The rate of active CD97-positive lymphocytes showed a marked, gradual increase until postoperative day 3 and remained elevated up to day 7 after CPB. OP surgery resulted in moderate alteration in the presence of CD97 on PMN, MC and lymphocytes. The expression of adhesion molecules was similar to CD97 in all leukocyte subsets. CONCLUSION: The findings about CD97 expression suggest considerable leukocyte activation following coronary bypass with CPB compared to OP surgery. The collected data show that the lymphocytes are highly activated and involved in leukocyte sequestration after CPB. Moreover, the importance of CD97 in CPB-related inflammatory response can be stated.

Aged↗

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The physician as a health care proxy.

Many states prohibit patients from appointing their physicians as health care proxies, fearing paternalism and conflict of interest. But the potential for conflict is not unique to physicians, and patients may have compelling reasons to prefer that their doctor make decisions on their behalf. Managing potential conflicts serves patients better than denying them the right to choose who will make health care decisions for them when they are no longer competent.

Authoritarianism↗

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Is peripheral blood a reliable indicator of acute oxidative stress following heart ischemia and reperfusion?

BACKGROUND: Reactive oxygen species (ROS) play a crucial role in membrane damage in ischemic-reperfusion syndromes. The aim of our work was to determine whether blood samples taken from a peripheral vein are a reliable indicator to reflect the development of oxidative stress following acute heart ischemia and reperfusion. MATERIAL AND METHODS: In a dog model, the left descending coronary artery (LAD) was occluded for 60 min followed by 60 minutes of reperfusion. The lipid peroxidation marker malondialdehyde (MDA), endogenous antioxidants reduced glutathione (GSH), the activity of superoxide dismutase (SOD) enzyme and the stimulated radical production of isolated neutrophil granulocytes (PMN) were measured simultaneously from the peripheral vein and the coronary sinus before and at the end of the LAD occlusion, and again during reperfusion. RESULTS: MDA and SOD values increased during reperfusion. At the end of 1 hour the reperfusion changes in the coronary sinus were significant (p<0.05). GSH increased in the femoral vein, but decreased in the coronary sinus. The radical-producing capacity of PMNs decreased by the end of LAD occlusion, and a further significant decrease was measured during reperfusion in the coronary sinus (p<0.01). In the peripheral venous blood samples the decrease of PMN radical production became significant only at 30 minutes of reperfusion (p<0.02), and the earlier difference between the coronary sinus and the femoral vein tended to level out following 60 minutes of reperfusion. CONCLUSIONS: During early reperfusion following myocardial ischemia coronary sinus blood sampling gives an earlier indication of myocardial damage. At a later phase, peripheral blood samples may also be informative regarding the altered balance between ROS production and the antioxidant capacity.

Animals↗

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Effects of lidocaine on cerebral lipid peroxidation and neutrophil activation following complete compression ischemia.

The effect of lidocaine on brain lipid peroxidation, as reflected by jugular vein malondialdehyde concentrations, and of polymorphonuclear leukocyte activation in peripheral venous blood samples following transient global cerebral ischemia, were studied. In normothermic dogs subjected to a 10 min elevation of cerebrospinal fluid pressure and a subsequent 60 min reperfusion, the malondialdehyde concentration during the first 3 min of reperfusion increased significantly (p < 0.05) in the jugular vein. Lidocaine (10 mg/kg, i.v.), administered 10 min before ischemia, not only prevented the elevation of the malondialdehyde concentrations during ischemia, but also provoked a significant transient decrease 10 min after the start of reperfusion. A 10 min ischemia and a 60 min reperfusion caused no significant changes in the polymorphonuclear leukocyte radical production, neither following ischemia nor after addition of lidocaine. These results suggest that lidocaine exerts a scavenging action on free radical processes but that it has no direct effect on the polymorphonuclear leukocyte activation in the early phase of reperfusion following ischemia.

Animals↗

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The authority of the clinical ethicist.

Mediator? Moral Expert? Or both? "Discourse Ethics" suggests that consensus provides the foundation for defensible moral norms. Thus in building consensus on a moral problem, an ethicist is not just negotiating a compromise but is contributing to the construction of moral rules and principles that have a genuine claim on us. In this way, not only does expertise on a variety of moral positions facilitate mediation, but mediation opens the way to a kind of moral expertise.

Clinical Competence↗