Related Experiment Videos
Role of adenosine in coronary blood flow regulation after reductions in perfusion pressure
Insights
Endogenous adenosine does not appear essential for coronary autoregulation or vasodilation. Adenosine deaminase administration attenuated reactive hyperemia but did not affect autoregulation during reduced coronary pressure.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
Background:
- Endogenous adenosine is implicated in regulating coronary blood flow.
- Its role in coronary autoregulation and vasodilation under reduced pressure is not fully understood.
Purpose of the Study:
- To investigate the role of endogenous adenosine in coronary blood flow regulation following acute reductions in coronary artery pressure.
- To determine if adenosine is essential for coronary autoregulation or vasodilation when autoregulatory reserve is depleted.
Main Methods:
- Intracoronary infusion of adenosine deaminase in anesthetized dogs to block endogenous adenosine.
- Measurement of coronary blood flow during controlled reductions in perfusion pressure.
- Assessment of myocardial reactive hyperemia and coronary autoregulation.
Main Results:
- Adenosine deaminase effectively blocked adenosine's vasodilator effects and attenuated reactive hyperemia by 30%.
- The enzyme did not alter the time course or steady-state of coronary autoregulation between 125 and 75 mm Hg.
- Adenosine deaminase did not affect steady-state coronary flow when pressure dropped below the autoregulatory range (60-40 mm Hg).
Conclusions:
- Endogenous adenosine is not essential for coronary autoregulation.
- Adenosine does not play a critical role in maintaining coronary vasodilation when autoregulatory vasodilator reserve is exhausted.
Abstract:
We employed intracoronary infusion of adenosine deaminase to test the hypothesis that endogenous adenosine contributes to regulation of coronary blood flow following acute reductions in coronary artery pressure. In 16 closed-chest anesthetized dogs, we perfused the left circumflex coronary artery from a pressurized arterial reservoir and measured coronary blood flow following changes in perfusion pressure before and 10 minutes after the start of intracoronary adenosine deaminase, 5 U/min per kg body weight. Parallel studies showed that this dose of enzyme resulted in cardiac lymph adenosine deaminase concentrations of 3.2 +/- 0.4 U/ml. Adenosine deaminase abolished the vasodilator response to intracoronary adenosine, 4 and 8 micrograms, but had no effect on the vasodilator response to intracoronary papaverine, 200 and 300 micrograms, demonstrating enzyme efficacy and specificity. Additional experiments demonstrated that adenosine deaminase reversibly attenuated myocardial reactive hyperemia following 5- and 10-second coronary occlusions by 30% (P less than 0.05), evidence that the infused enzyme effectively degraded endogenous adenosine. However, adenosine deaminase did not alter the time course for coronary autoregulation or the steady state autoregulatory flow response over the pressure range between 125 and 75 mm Hg. Further, adenosine deaminase did not alter steady state coronary flow when perfusion pressure was reduced below the range for effective autoregulation (60-40 mm Hg). Such results show that adenosine is not essential for either coronary autoregulation or for the maintenance of coronary vasodilation when autoregulatory vasodilator reserve is expended.