Effects of hyaluronidase and protamine on resistance and transport after coronary flow reduction in heparinized dogs.

We have measured the effects of hyaluronidase, protamine and a mixture of the two drugs on coronary flow resistance and transcapillary exchange in 20 heparinized, anesthetized dogs in which flow to the left anterior descending coronary artery was supplied through an extracorporeal shunt from the carotid artery. Multiple-tracer measurements were made by injecting a mixture of isotopes into the shunt and sampling from the coronary sinus. These were carried out under base-line conditions, after 1 hr of reduced flow to the left anterior descending coronary artery and after a 2nd hr during which the drug under study was infused into the ischemic zone. The results of multiple-tracer measurements were expressed as extravascular water volume (VT), extravascular sucrose volume (VS) and microvascular permeability surface area for sucrose. It was found that flow reduction significantly reduced VT, VS and permeability surface area. Resistance increased during the period of reduced flow after an initial decrease immediately upon flow reduction. In five dogs, a mixture of hyaluronidase and protamine significantly lowered coronary flow resistance and increased permeability surface are, VT, VS and VS/VT compared to preinfusion, reduced flow values. Infusion of hyaluronidase alone had significantly less effect in five other dogs, whereas infusion of protamine alone (N = 5) and saline (N = 5) did not affect resistance or transport. It is concluded that protamine enhances the effects of hyaluronidase when heparin is present, probably by preventing its blockade of hyaluronidase action.