Min Adenosine Research Articles

MEASUREMENT OF PULMONARY FLOW RESERVE IN HIGHER PRIMATES

1. There are currently limited diagnostic methods for assessing the integrity of the pulmonary microvasculature. We hypothesized that a novel, invasively determined physiological index of 'pulmonary flow reserve' (PFR = maximal hyperaemic pulmonary blood flow divided by basal pulmonary flow) may facilitate microvascular assessment in the lung. Therefore, we developed a baboon model in which to: (i) validate the use of Doppler flow velocity for PFR assessment; (ii) define the optimal drug and dose regimen for attainment of maximal pulmonary hyperaemia; and (iii) demonstrate the feasibility of measuring PFR in healthy higher primates. 2. Doppler sensor guidewires were placed in segmental pulmonary arteries of 11 ketamine-anaesthetized baboons. Vessel diameter, flow velocity and haemodynamics were recorded before and after direct intrapulmonary artery administration of saline, adenosine (50-500 microg/kg per min) and papaverine (3-60 mg), enabling calculation of PFR. 3. Saline (either bolus injection or infusion) did not alter vessel diameter or flow velocity (P > 0.1), validating local drug administration. Both adenosine and papaverine induced dose-dependent increases in flow velocity from baseline (from 22.5 +/- 2.3 to 32.7 +/- 4.8 cm/s for 400-500 microg/kg per min adenosine; and from 23.9 +/- 1.1 to 34.6 +/- 4.0 cm/s for 24 mg papaverine; both P < 0.0001), without affecting pulmonary artery pressure or vessel diameter (P > 0.3). Healthy primate PFR values were 1.35 +/- 0.10 and 1.39 +/- 0.10 using 200 microg/kg per min adenosine and 24 mg papaverine, respectively (P > 0.8). 4. In conclusion, pulmonary flow reserve in higher primates can be assessed using Doppler sensor guidewire and either adenosine or papaverine as microvascular hyperaemic agents. Measurements of PFR may facilitate pulmonary microvascular assessments.

Persistent coronary vasodilation during long-term, supramaximal doses of adenosine.

Active and reactive hyperemias have been observed in the skeletal muscle circulation tachyphylactic to exogenous adenosine following 3-h supramaximal doses of the vasodilator. These findings failed to support a need for adenosine in metabolic control of skeletal muscle blood flow. The present study was conducted to determine if the coronary circulation also develops tachyphylaxis to adenosine while remaining sensitive to other metabolically linked vasodilator mechanisms. Experiments were conducted in eight pentobarbital-anesthetized, open-chest dogs whose blood flow in the left anterior descending coronary artery (LAD) was measured electromagnetically during 3-h infusion of adenosine into the LAD. Measurements of regional myocardial blood flow (radioactive microspheres), myocardial O2 consumption (Fick principle), and percent segment shortening (ultrasonic crystals) were also obtained. Adenosine was infused into the LAD at a rate of 27.0-72.0 mumol/min, depending on blood flow rate. Calculated concentration of adenosine in LAD blood averaged 0.484 +/- 0.111 mumol/ml, which was well in excess of that required for maximal coronary vasodilation. LAD blood flow averaged 21.5 +/- 2.2 ml/min during the preadenosine control condition. LAD blood flow after 3 h adenosine (123.3 +/- 23.0 ml/min) was not significantly different from that after 1-3 min adenosine (105.8 +/- 17.9 ml/min). There was no significant transmural variation in LAD blood flow during adenosine infusion. Adenosine had no significant effect on myocardial O2 consumption or percent segment shortening. Our results demonstrate persistent transmural vasodilation in the canine coronary circulation during long-term, supramaximal doses of adenosine and are consistent with a role for endogenous adenosine in maintenance of coronary vasodilation during sustained elevations in myocardial energy demands.