The effects of thromboxane inhibitors on the microvascular and tumor response to photodynamic therapy.

Vascular stasis and tissue ischemia are known to cause tumor cell death in several experimental models after photodynamic therapy (PDT); however, the mechanisms leading to this damage remain unclear. Because previous studies indicated that thromboxane release is implicated in vessel damage, we further examined the role of thromboxane in PDT. Rats bearing chondrosarcoma were injected with 25 mg/kg Photofrin (intravenously) 24 h before treatment. Light (135 J/cm2, 630 nm) was delivered to the tumor area after injection of one of the following inhibitors: (1) R68070: a thromboxane synthetase inhibitor; (2) SQ-29548: a thromboxane receptor antagonist; and (3) Flunarizine: an inhibitor of platelet shape change. Systemic thromboxane levels were determined. Vessel constriction and leakage were evaluated by intravital microscopy. Tumor response was assessed after treatment. Thromboxane levels were decreased more than 50% with SQ-29548 as compared to controls. Thromboxane levels in animals given R68070 and Flunarizine remained at baseline levels. SQ-29548 and R68070 reduced vessel constriction compared to controls, while Flunarizine totally prevented vessel constriction. R68070 and SQ-29548 inhibited vessel permeability compared to PDT controls; Flunarizine did not. Animals given these inhibitors showed markedly reduced tumor cure. These results indicate that the release of thromboxane is linked to the vascular response in PDT.

Changes in canine saliva ion concentration induced by increased intraluminal pressure.

Hydrostatic pressure was applied to a cannula inserted into Wharton's duct of adult dogs anesthetized with pentobarbital and the effect of pressure on saliva flow rate and ionic composition of saliva was measured. Increasing the back pressure on a secreting gland resulted in a decrease in flow rate. Over the range of 0-100 mmHg back pressure the decrease in flow was proportional to the applied back pressure. The potassium concentration of saliva collected in the absence of back pressure and at raised pressure was similar even though back pressure reduced flow. In contrast, sodium concentration decreased when back pressure caused salivary flow rate to be reduced. However, when examined at the same flow rates the concentration of sodium is increased when back pressure is applied to the gland as compared to absence of back pressure. Under conditions of constant stimulation the total output of sodium and potassium into saliva decreases as back pressure is increased; but when equal flow rates are compared total sodium output increases in the presence of applied back pressure, whereas potassium output remains constant.