Enhanced interstitial fluid adenosine attenuates myocardial stunning.

Reversible myocardial dysfunction associated with transient ischemia has been termed the stunned myocardium. Because exogenous adenosine has been shown to protect the ischemic myocardium, we hypothesized that augmentation of endogenous adenosine levels would attenuate myocardial stunning. To induce stunning, anesthetized dogs were subjected to 15 minutes of ischemia (left anterior descending artery occlusion) followed by 60 minutes of reperfusion. Erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA; 5 mg/kg/hr), an adenosine deaminase inhibitor, was used to augment adenosine levels. The effect of EHNA on interstitial fluid (ISF) adenosine levels, coronary blood flow, and regional systolic wall thickening was compared with that of an untreated group (n = 8). EHNA increased preischemia ISF adenosine levels threefold and was associated with a corresponding increase in coronary blood flow. EHNA administration did not alter preischemia systolic wall thickening. Although ISF adenosine increased fourfold during ischemia in the untreated group, ISF adenosine increased nearly sixtyfold above preischemia values in the EHNA-treated group and remained elevated throughout reperfusion. Postischemic regional function was enhanced significantly in the group treated with EHNA. These data show that adenosine deaminase inhibition increased ISF adenosine levels and attenuated myocardial stunning. Metabolic manipulation of myocardial ISF nucleoside levels may be beneficial in limiting postischemic myocardial dysfunction.

Interstitial purine metabolites during regional myocardial ischemia.

The purpose of this study was to determine the changes in cardiac interstitial fluid (ISF) purine metabolites during 90 min of regional myocardial ischemia. To collect ISF metabolites and measure local coronary blood flow (CBF), cardiac microdialysis probes were implanted into the left anterior descending artery (LAD) and left circumflex artery (LC) perfused myocardium of chloralose-urethane anesthetized dogs (n = 7). Regional ventricular wall thickness was measured in the LAD and LC perfused regions with sonomicrometric crystals, using systolic wall thickening (SWT) as an index of regional ventricular function. Regional myocardial ischemia, produced by occlusion of the LAD, resulted in a decrease in CBF (hydrogen clearance) from 77.3 +/- 12.4 to 10.9 +/- 4.4 ml/min/100 g (P less than 0.05), and systolic wall thinning (control SWT = 15.5 +/- 2.2%; ischemic SWT = -6.8 +/- 1.7%). ISF adenosine was transiently elevated in the ischemic region, obtaining a maximum sixfold increase after 15 min of ischemia. Inosine, hypoxanthine, and to a lesser extent xanthine, composed the majority of metabolites which accumulated in the ISF of the ischemic region, accounting for greater than 95% of the total purine metabolites in the ISF after 20 min of ischemia. Despite the marked increase in ISF inosine, hypoxanthine, and xanthine levels, ISF uric acid levels did not increase in the ischemic region. Although CBF and SWT did not change in the nonischemic LC perfused area, there were small transient increases (two- to fourfold) in ISF adenosine, inosine, and hypoxanthine levels. In summary, these data demonstrate that purine metabolites accumulate rapidly in the ISF during myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Physiologic changes during a marathon, with special reference to magnesium.

In a single case study of a moderately trained, healthy man, physiologic changes during a marathon are reported. Blood was drawn prior to the race, at 1 hour and 2 hours into the race, at the end of the race, and after 1 hour of recovery. By 1 hour into the race, norepinephrine, epinephrine, and dopamine had increased nearly nine-fold, two-fold and five-fold, respectively. After 1 hour of recovery, epinephrine had returned to the pre-race value but norepinephrine and dopamine were still elevated. Cortisol increased gradually and was more than doubled by the end of the race. It was still elevated after 1 hour of recovery. White blood cells gradually increased, reaching their maximum value at the end of the race; a four-to-five-fold increase. Thromboxane B2, which had an inverse relationship to serum magnesium, was below the pre-race value for the first 2 hours but increased nine-fold by the end of the race. Serum magnesium increased from 1.44 meq/l to 1.68 meq/l at 2 hours into the marathon, dropped to 1.07 meq/l by the end of the race, and returned to its pre-race value by 1 hour of recovery. The decrease in serum magnesium at the end of the race may be associated with increased plasma free fatty acid levels.