THE EFFECT OF PERFUSION PRESSURE ON PAPAVERINE VASODILATATION IN RABBIT HEARTS

¹ The Research Laboratories, Parke, Davis and Company, Detroit 32, Michigan

In a statistically designed experiment on saline-perfused rabbit hearts, coronary flow and contraction heights were measured at various perfusion pressures between 29 and 43 cm. of solution, both before, and at the time of maximal flow during administration of 1/200,000 papaverine HCl.

Smallness of pressure influences on flow without drug, and on contraction heights with or without drug, suggested good vascular balance with the working tissue metabolism. There was a suggestion that this balance was surpassed at pressures of 39-43 cm. solution.

In the presence of papaverine, flow increased with pressure more than in proportion to pressure.

Without drug, local opposition to change in flow resulted in an increase in resistance (P/F) with pressure. In spite of this, in the presence of papaverine there was a decrease in resistance with rising pressure, indicating pressure-distension of small vessels and/or opening of additional ones.

There was a significant correlation between random variations in pre- and during-drug resistances. This enabled conservative statistical control of the influence on during-drug resistances by the local factors indicated in pre-drug resistances. The correlation took the form of an approximately first power regression of during- on pre-drug resistance. This rendered the logarithm of the ratio of during-drug to pre-drug resistance an efficient measure of vascular action at a given pressure. Sharp, inverse variations of the resistance ratio with pressure (0.6 to 0.4) demonstrated the need for experimental or statistical control of pressure in the use of resistance as a measure of vascular tonus. Manifest sensitivity to the vasodilator increased with pressure.

Statistical control of contraction height throughout revealed no evidence that flows or resistances were influenced thereby. Control of average differences among hearts and among stages within hearts, in a Latin square design, increased the efficiency of the experiment several-fold.