Temporal relation of changes in regional coronary flow and myocardial lactate and nucleoside metabolism during pacing-induced ischemia

The temporal relation between myocardial lactate and hypoxanthine metabolism and regional changes in krypton-81m perfusion during pacing-induced ischemia was studied in 17 patients with coronary artery disease (CAD). During incremental atrial pacing, lactate production and hypoxanthine release occurred early and simultaneously, accompanied by ST-segment changes, but before angina and only few minutes after a significant (17%) reduction in krypton-81m perfusion in areas with more than 90% luminal diameter reduction. During maximal pacing heart rates, krypton-81m distribution decreased to 68 ± 7% of control in areas with more than 90% diameter reduction and to 80 ± 4% in 70 to 90% reduction (both p < 0.05 vs control). Maximal lactate production occurred 15 seconds after pacing (extraction −15 ± 7% vs 16 ± 2% during control, p < 0.05) and peak hypoxanthine release 1 minute after pacing (Δ arteriovenous −2.64 ± 0.8 μM vs 0.08 ± 0.21 μM during control, p < 0.05). Krypton-81m perfusion decreased in 20 of the 21 CAD areas. Angina, ST-segment changes, hemodynamic alterations and lactate production occurred in 15, 14, 9 and 15 patients, respectively. In contrast, hypoxanthine release was found in all cases. After pacing, lactate production and all general indexes of ischemia persisted for only 2 to 3 minutes. In contrast, krypton-81m perfusion was still significantly reduced 5 minutes after pacing and was only accompanied by hypoxanthine release (Δ arteriovenous −1.41 ± 0.6 μM, p < 0.05 vs control). Therefore, although lactate production and hypoxanthine release occur early and simultaneously during pacing-induced ischemia, closely following coronary flow changes in high-stenotic areas, hypoxanthine appears to be more sensitive and consistent as indicator of ischemia. Persistant reductions in krypton-81m perfusion and hypoxanthine release strongly suggest prolonged ischemia after cessation of pacing.