Effects of intravenous theophylline on exercise-induced myocardial ischemia: II. A concentration-dependent phenomenon

AbstractObjectives. The effects of varying concentrations of theophylline on exercise-induced myocardial ischemia were evaluated in patients with stable coronary artery disease.Background. Theophylline is a competitive antagonist of adenosine and may have potential as an anti-ischemic medication. It is not known whether these effects on myocardial ischemia are concentration dependent.Methods. In a double-blind, randomized, crossover manner, 11 patients received, at 1-week intervals, placebo and each of three theophylline doses by intravenous infusion for 45 min. Graded exercise testing was performed before randomization and immediately after each infusion. Concurrent anti-ischemic medications were withheld for 24 h before each exercise test. Serum theophylline concentrations achieved were 3.9 ± 1.0 mg/liter (low), 8.2 ± 1.8 mg/liter (medium) and 13.2 ± 2.3 mg/liter (high).Results. Compared with placebo, none of the three theophylline infusions produced a significant alteration in rest heart rate, blood pressure, mean frequency or severity of ventricular ectopic activity or noncardiac symptoms. The time to onset of ischemia was progressively increased, with medium and high concentrations achieving statistical significance. Similar patterns were observed for oxygen uptake and the heart rate-systolic blood pressure product at the onset of ischemia. Total exercise duration was significantly prolonged with the medium and high concentrations.Conclusions. It is concluded that administration of varying doses of theophylline before exercise produces a clinically significant and concentration-dependent improvement in the indicators of myocardial ischemia in patients with chronic stable coronary artery disease

A set of BAC clones spanning the human genome

Using the human bacterial artificial chromosome (BAC) fingerprint-based physical map, genome sequence assembly and BAC end sequences, we have generated a fingerprint-validated set of 32 855 BAC clones spanning the human genome. The clone set provides coverage for at least 98% of the human fingerprint map, 99% of the current assembled sequence and has an effective resolving power of 79 kb. We have made the clone set publicly available, anticipating that it will generally facilitate FISH or array-CGH-based identification and characterization of chromosomal alterations relevant to disease