Anna-Maja Åberg

Ischaemic pre-conditioning (IP) is a potent protective mechanism for limiting the myocardial damage due to ischaemia. It is not fully known as to how IP protects. The metabolism of adenosine may be an important mechanistic component. We study the role of adenosine turnover together with glycolytic flow in ischaemic myocardium subjected to IP. An acute myocardial ischaemia pig model was used, with microdialysis sampling of some metabolites (lactate, adenosine, glucose, glycerol, taurine) of ischaemic myocardium. An IP group was compared with a control group before and during a prolonged ischaemia. ¹⁴C-labelled adenosine and glucose were infused through microdialysis probes, and lactate, ¹⁴C-labelled lactate, glucose, taurine and glycerol were analysed in the effluent. The glycogen content in myocardial biopsies was determined. The ¹⁴C-adenosine metabolism was higher as there was a higher production of ¹⁴C-lactate in IP animals compared with the controls. The glycolytic flow, measured as myocardial lactate formation, was retarded during prolonged ischaemia in IP animals. Myocardial free glucose and glycogen content decreased during the prolonged ischaemia in both groups, with higher free glucose in the IP group. We confirmed the protective effects of IP with lower myocardial concentrations of markers for cellular damage (glycerol). This association between increased adenosine turnover and decreased glycolytic flow during prolonged ischaemia in response to IP can possibly be explained by the competitive effect for the metabolites from both glucose and adenosine metabolism for entering glycolysis. We conclude that this study provides support for an energy-metabolic explanation for the protective mechanisms of IP.

Purine nucleoside phosphorylase (PNP) in mammalian tissue is an enzyme responsible for formation of purine bases in DNA. It is also believed that PNP is crucial under energy-deprived conditions for the cell to metabolise adenosine during ATP degradation. This work describes a new method for determination of PNP activity in myocardial tissue using a commercially available substrate, 2-amino-6-mercapto-7-methylpurine riboside (MESG). The method involves the photometric assessment of the reaction between PNP (extracted from myocardial tissue) and MESG. Quantification as well as temperature- and pH-dependency for myocardial PNP activity is described. Also, the effect of some modulators has been studied. We have established the presence of PNP activity in pig myocardial tissue. Further, the results indicate a pH tolerance under slightly acid conditions and a calcium ion dependence of the enzyme.

BACKGROUND: Carbon monoxide (CO) is normally present in the human body due to endogenous production of CO. CO can also be inhaled by exposure to external sources such as cigarette smoke, car exhaust, and fire. The purpose of this study was to investigate CO concentrations in blood from 410 blood donors at the blood center in Umeå, Sweden. To further evaluate the effects of cigarette smoking on CO concentrations, the elimination time for CO was examined in six volunteer smokers after a smoked cigarette.STUDY DESIGN AND METHODS: Blood samples from whole blood donors were obtained during the blood center's routine operation. In connection with blood donations, demographic and behavioral data were collected from the donors. The CO concentration was determined using gas chromatography.RESULTS: The majority of blood donors had approximately the same CO concentration (mean, 84.5 µmol/L). In 6 percent of the samples, the concentrations were higher than 130 µmol per L. The highest CO concentration was 561 µmol per L. The main source for these high CO concentrations appeared to be cigarette smoking. In the volunteer smokers, the elimination time after a smoked cigarette varied significantly, with elimination half‐lives from 4.7 to 8.4 hours.CONCLUSION: These results show that blood bank red blood cell bags may have CO concentrations above the physiologic level. The time interval between cigarette smoking and blood donation seems to be a particularly important factor for elevated CO concentrations.

Carbon monoxide (CO) has recently been suggested to have anti-inflammatory properties, but data seem to be contradictory and species-specific. Thus, in studies on macrophages and mice, pretreatment with CO attenuated the inflammatory response after endotoxin exposure. On the other hand, human studies showed no effect of CO on the inflammatory response. Anti-inflammatory efficacy of CO has been shown at concentrations above 10% carboxyhaemoglobin. This study was undertaken to elucidate the possible anti-inflammatory effects of CO at lower CO concentrations.