VASCULAR RESPONSE OF CANINE RENAL ALLOGRAFTS TO VASOACTIVE DRUGS

MICROANGIOGRAPHIC STUDY

Abstract

I examined the response of intrarenal vasculature to vasoactive agents in acute rejection using adult mongrel dogs and attempted to elucidate the nature of vascular functional abnormalities which are thought to have some part in ischemic process of rejection.
The materials were 36 allografts, 13 autografts and 38 contralateral normal kidneys which were all removed 7 days after transplantation surgery. No immunosuppression was given. Renal perfusion was modified by adding one of the following drugs, norepinephrine, acetylcholine, isoproterenol or phenoxybenzamine each in high concentration to heparinized lactated Ringer's solution. Renal vascular resistance calculated from perfusion pressure and rate of venous effluent, microangiography performed on injection of 10% micropaque-saline solution, and glomerular intermittence obtained by counting the number of glomeruli filled with micropaque, served to estimate the grade of vascular abnormality of an allograft.
The effect of norepinephrine on isolated normal kidneys was demonstrated by patchy filling of the cortex in contrast to rich filling of the medulla on microangiography. The glomerular intermittence of this group of kidneys averaged 40±4.4% and the renal vascular resistance 9.4±1.5mmHg/ml/min, which was the highest value obtained in the present experiment. The cortex of the normal kidneys treated with acetylcholine was amply supplied with wide arteries. Their luminal diameters at the origins were estimated 102±20.5 microns on microangiograms and were significantly larger as compared with those of control kidneys (68±7.2 microns, P<0.01). Glomerular perfusion was nearly complete and the renal resistance was as low as 1.5±0.3mmHg/ml/min. In the normal kidneys infused with isoproterenol or phenoxybenzamine the entire cortex and medulla were well filled with contrast medium, while the calibers of interlobular arteries were normal. Excessive capillary filling was distinctive and in the outer medulla it presented a frizzled appearance. Almost all the glomeruli were filled with micropaque and the renal vascular resistances were low. Nearly the same findings were obtained on infusion of these vasoactive drugs into the renal autografts. Summarizing these informations about the three vasodepressive drugs, it can be said that they assure suitable renal perfusion in isolated kidneys and are useful to get microangiograms of good quality. This method of microangiography has never been reported previously and I would name it pharmacomicroangiography.
The renal allografts which underwent mononuclear cell infiltration over less than three fourths of the cortex were grouped as under moderate cellular rejection. On microangiography cortical perfusion was not uniform, the interlobular arteries were varying in calibre, most of the afferent arterioles were tortuous or spiralling, and the filling of the postglomerular vessels was poor while that of the outer medullary ones was fairly good. The renal vascular resistance was modestly high. Injection of norepinephrine affected cortical perfusion to a further extent. On the contrary, any of the currently used vasodepressive drugs improved it. The microangiograms obtained after infusion of acetylcholine revealed equally and evenly well filled cortical arteries and no tortuous or coiled arterioles. The renal resistance was significantly lowered. The intrarenal vasculature of the allografts with moderate acute rejection reacted to isoproterenol or phenoxybenzamine in the similar fashion as with acetylcholine. The allografts having massive cellular rejection over more than three fourths of the cortex seemed to be deprived of responsiveness to the vasoactive drugs. The norepinephrine or acetylcholine-treated allografts presented indistinguishable appearances on microangiography. The interlobular arteies were variably dilated and cut off at periphery throughout the cortex and, instead of spiralling, numerous