Canine myocardial reperfusion injury: protection by a free radical scavenger, N-2-mercaptopropionyl glycine

Oxygen-derived free radicals and their metabolites may contribute to the extension of irreversible cellular injury, which occurs on reperfusion of the previously ischemic myocardium. Therefore, therapy directed against the toxic effects of reactive oxygen species may provide protection to the ischemic myocardium, which undergoes subsequent reperfusion. We evaluated the effectiveness of N-2-mercaptopropionyl glycine (MPG), a free radical scavenger, to limit the extent of irreversible injury resulting from 90 min of ischemia followed by 6 h of reperfusion in a canine model of myocardial infarction. In three groups of dogs, MPG (20 mg/kg) was administered as a constant infusion into the left atrium. Group I received MPG for 2 h, starting 15 min before occlusion of the left circumflex coronary artery and ending 15 min after reperfusion. Group II received MPG for 1 h, starting 15 min before reperfusion. Group III received MPG for 1 h beginning 45 min after reperfusion. Each group was compared with its respective saline control group. Infarct size was reduced by 35% in Group I (32.2 +/- 5.1% vs. 47.7 +/- 3.4% of the area at risk, p less than 0.05) and Group II (31.4 +/- 3.6% vs. 47.5 +/- 5.1% of the area at risk, p less than 0.025) in comparison with the saline treated control animals. In contrast, in Group III infarct size did not differ significantly from the saline-treated control group (45.9 +/- 3.3% vs. 47.7 +/- 3.5% of the area at risk). The percent of left ventricle at risk did not differ among the groups. The beneficial effects of MPG could not be explained on the basis of hemodynamic differences. In addition, MPG did not influence regional myocardial blood flow. In vitro studies indicated that MPG effectively scavanges O2- generated by the hypoxanthine-xanthine oxidase reaction, as well as by PMA-activated polymorphonuclear leukocytes. Based on these observations, we propose that MPG exerts its beneficial effects by protecting against free radical-mediated damage during the early phase of reperfusion.     

What methods do stakeholders prefer for feeding back performance data: a qualitative study in palliative care.

OBJECTIVE: To investigate the opinions of stakeholders (service commissioners and providers) on how performance data should be presented, in order to develop effective feedback methods to facilitate the use of these data in decision making. DESIGN: A qualitative analysis of semi-structured face-to-face and telephone interviews. League tables and fictional box plots were presented as an illustrative guide. The themes covered in the interviews were the effectiveness of these two feedback formats, their positive and negative characteristics, and ideas for new and improved feedback mechanisms. PARTICIPANTS: Thirty-six stakeholders representing a range of clinical and non-clinical roles within palliative care and the wider health care system across a variety of statutory and non-statutory organizations from London and the West Midlands. RESULTS: Box plots were received more positively than league tables, and qualitative information was considered more appropriate than pictorial feedback. Conventional methods such as league tables and box plots were judged to lack essential information on which important decisions could be based, such as additional contextual information and the methodological assumptions of the instrument. Both feedback methods were considered useful as an impetus to further discussion. There was a consensus that feedback should be constructive and able to be adapted to the organizational realities in which UK health services function. CONCLUSION: Qualitative research was viewed as the right evidence for gaining an understanding of the quality of end of life care. Stakeholders highlighted the importance of the lay perspective, which requires approaches that illuminate the subjective meanings of patient experience.     

Differential effects of exercise and housing condition on murine natural killer cell activity and tumor growth.

Acute exercise and exercise conditioning have been shown to affect the activity of natural killer (NK) cells as well as the growth of experimentally induced tumors in animals. Since psychosocial factors are also known to alter NK activity and tumor growth, isolation, a known psychosocial stressor of mice, was also investigated to see if housing condition could alter exercise-induced changes in NK cell activity and tumor growth. NK cell activity and concentration of asialo GM1 (ASGM1) positive splenocytes were measured in male C3H mice inoculated i.v. with CIRAS 3 tumor cells. Mice were housed individually or in groups of four and trained to run for eight weeks on a rodent treadmill; controls remained sedentary throughout the experimental period. At four weeks into the training protocol, mice were injected with the tumor cells and continued to run for four weeks after tumor exposure. There was a significant effect of physical activity (p less than 0.019) but not of housing on splenic NK cytotoxicity against tumor targets in vitro. When the data were analyzed by presence or absence of lung metastases, only those animals without visible lung tumors had significantly higher NK activity as a function of exercise relative to sedentary controls. There were no significant differences in the frequency of ASGM1+ splenocytes between trained and untrained animals, irrespective of presence or absence of lung tumor colonies. There was a significant effect of housing (p less than 0.02), but not of physical activity, in mice with successful tumor takes with greater numbers of group housed animals (29/59) with tumor relative to individually housed animals (13/60).(ABSTRACT TRUNCATED AT 250 WORDS)