Platelet Anti-aggregating and Hemodynamic Effects of Adenosine and Prostaglandin E1

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Abstract
The efficacy of using adenosine (ADEN) or Prostaglandin E1 (PGE1) to prevent platelet loss during cardiopulmonary bypass (CPB) was tested in experiments conducted with a simulated CPB circuit with cardiotomy suction. The hemodynamic effects of the compounds were tested in a canine model to ascertain hemodynamic tolerance of platelet-salvaging concentrations. Platelet concentrations were determined with a Coulter Counter Model S-Plus in 3 separate groups each composed of 10 experiments in which ADEN (1 mM) and PGE1 (0.5 and 1.0 μM) were added to the bypass circuit to determine platelet protection. It was found that PGE1 at both concentrations was effective in salvaging platelets (0.5 μM-70% and 1.0 μM-95%) and ADEN at 1 mM salvaged approximately 45 %. Hemodynamic effects of PGE1 and ADEN were studied in heparinized (3 mg/kg) mongrel dogs weighing between 20 and 27 kg which were artificially ventilated and catheters placed to measure left ventricular and arterial pressures and dP/dT. Via a left thoracotomy, a 15 mm Statham Blood Flowmeter Probe placed around the ascending aorta measured cardiac output (CO). ADEN, in 7 increasing doses (range: 0.45 to 3.40 mg/kg/min), was infused for 2 minutes with 5 minutes between doses. In 2 groups of 10 dogs each, PGE1 was infused with 2 dose ranges: 0.40 to 3.00 and 2.0 to 15.0 μg/kg/min. Prostaglandin E1 was infused in 7 increasing doses in each range and hemodynamic changes recorded during 3 minutes of infusion. Hemodynamically, ADEN reduced heart rate and systemic resistance progressively as the dose increased. The unchanging CO accompanied by reduced dP/dT and LV pressure suggests the myocardium is not directly affected. On the other hand, PGE1 continually reduced CO and dP/dT with increasing doses but, with the smallest dose, reduced arterial pressure 20% which then remained unchanged with increasing doses. Prostaglandin E1 therefore appears to directly depress the myocardium with maximal peripheral resistance changes occurring with the smallest doses. Although the platelet salvaging ability of ADEN is not as great as PGE1, its hemodynamic effects are more favorable for use during CPB.

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