Pre-conditioning activates adenosine utilization in a cost-effective way during myocardial ischaemia.

During pre-conditioning the interstitial concentration of adenosine, in contrast to lactate, presents a die-away curve-pattern for every successive episode of ischaemia. This die-away pattern might not necessarily be attributed to diminished adenosine production. The present study was undertaken to investigate whether pre-conditioning alters the metabolic turnover of adenosine as observed by the lactate production during ischaemia. Interstitial levels of metabolites in pre-conditioned (n=21) and non-preconditioned (n=21) porcine hearts were monitored with microdialysis probes inserted in both ischaemic and non-ischaemic tissue in an open chest heart model. Three subgroups perturbated with either plain microdialysis buffer (control), buffer containing adenosine (375 microM), or buffer containing deoxyadenosine (375 microM) were studied. All animals were subjected to 90 min of equilibrium microdialysis before 40 min of regional myocardial ischaemia and 120 min of reperfusion. Pre-conditioning consisted of four repetitive episodes of 10 min of ischaemia and 20 min of reperfusion. Significantly higher levels of inosine and lactate were found in the ischaemic tissue of the pre-conditioned subgroup receiving adenosine (P < 0.05) compared with the other two subgroups receiving deoxyadenosine and plain buffer, respectively. This difference was only valid for pre-conditioned ischaemic myocardium, and hence equal amounts of inosine and lactate were produced in the non-preconditioned ischaemic myocardium regardless of the presence of adenosine or deoxyadenosine. In the non-ischaemic myocardium baseline levels of metabolites were measured in all subgroups. Pre-conditioning favoured degradation of exogenous adenosine to inosine successively ending up in enhanced lactate production. This was probably because of the involvement of the hexose monophosphate pathway in the pre-conditioned ischaemic myocardium. This route may therefore be supplementary in energy metabolism as a metabolic flow can be started by adenosine ending up in lactate without initial adenosine 5'-triphosphate (ATP) investment. Utilization of adenosine in this way may also explain the successive die-away pattern of adenosine seen in consecutive pre-conditioning cycles.

Energy economy of human uterine muscle strips under different in vitro conditions and its dependence on tissue redox potential.

OBJECTIVE: To study the energy economy of human myometrium in vitro. STUDY DESIGN: Myometric biopsies were kept for 10 min or 4 h in a buffer solution at +4 degrees C before preparation into 'early' and 'late' strips, respectively. The strips were perifused at +37 degrees C for different periods of time. Adenylates, energy charge (EC), adenosine and NAD+ were determined in individual strips. RESULTS: Mean EC and ATP values were low, the 'late' strips displaying 5% and 20% lower values than the 'early' strips, respectively. During perifusion the EC increased slightly, ADP decreased significantly and the strips began to contract. A correlation fitting a multiplicative function was evident between EC and NAD+ (r = 0.89, P < 0.001). CONCLUSION: Human myometrium, being operative at an unusually low EC level, maintained its energy economizing and contractile functions in vitro for 4 h, displaying a tight relationship between EC and NAD+, suggestive of a compromised energy balance.

Energy economy in the pregnant human uterus at term: studies on arteriovenous differences in metabolites of carbohydrate, fat and nucleotides.

Metabolic regulation was studied in the pregnant human uterus by determining its uptake and release of various substrates, some of which are commonly used as a fuel and some are markers of disturbed energy status in cells. Ten healthy women with normal pregnancy were examined when undergoing elective Caesarean section at term, before onset of labour. Carbohydrate metabolites (glucose, lactate and pyruvate), fat metabolites (free fatty acids (FFA) and glycerol) and nucleotide metabolites (hypoxanthine, xanthine and urate) were determined in arterial (radial artery) and venous (plexus of the uterine and ovarian veins) blood. In addition the arteriovenous difference in each substance across the uterus was calculated. A distinct uptake of glucose was a typical finding in the pregnant uterus as reflected by a positive difference. On the other hand, glycerol and FFA were released from the pregnant uterus. Similarly, a degradation of adenine-containing nucleotides seemed to be continuously ongoing in the pregnant uterus, since oxypurines displayed a negative difference as well.