Background: The rate of adaptation of coronary blood flow in response to stepwise changes in heart rate (HR) has been extensively studied in dogs and goats to improve our understanding of the dynamics of coronary regulation processes and their pathophysiology and to obtain time constants for mathematical modeling of the coronary regulation. However, little is known about the dynamic characteristics of coronary flow adaptation in humans. In patients undergoing coronary artery surgery, we investigated the rate of coronary adaptation in response to stepwise changes in HR, in the awake and anesthetized states. Methods: In 11 patients with stable coronary artery disease, arterial blood pressure, right atrial pressure, and coronary sinus blood flow, measured by continuous thermodilution, were calculated per beat. The ratio of beat-averaged arterial blood pressure minus right atrial pressure and coronary sinus blood flow was calculated to obtain an index of coronary resistance. The rate of change of coronary resistance index was quantified by t 50, defined as the time required to establish 50% of the total change in coronary resistance index. Responses of coronary resistance index after HR changes, before and after induction of anesthesia, were compared. The anesthesia technique consisted of 100 μg · kg -1 fentanyl and 0.1 mg · kg -1 pancuronium bromide in combination with oxygen in air ventilation (FI(O 2) = 0.5). Results: In the awake situation, t 50 values of the dilating and constricting responses, induced by an increase and a decrease in HR were 5.0 ± 2.1 (SD) s (range 2.6-9.0 s) and 5.7 ± 1.2 s (range 4.1-7.8 s), respectively. During fentanyl/pancuronium anesthesia, the rate of coronary flow adaptation was significantly slower, with t 50 values of 10.2 ± 2.1 s (range 7.7-13.1 s) after an HR step-up and 9.8 ± 2.1 s (range 6.6-13.2 s) after an HR step-down. Compared to the awake situation, arterial blood pressure was significantly reduced during anesthesia, but coronary vascular resistance remained unchanged. This implies that the steady-state static regulation of coronary blood flow had not changed. Conclusions: These preliminary data suggest that, in patients with coronary artery disease, the rate of change in coronary vascular resistance in response to pacing-induced changes in HR is mitigated by fentanyl/pancuronium anesthesia during positive pressure ventilation. A further qualification of our findings in a larger number of patients is warranted.@en