Radionuclide Analysis of Drug-Induced Blood-Pool Changes in Liver and Other Organs

Although it is possible to repopulate the animal liver with transplanted hepatocytes, the success of such transplants depends, in part, on the number of transplanted cells that enter the hepatic sinusoids. Pharmacologic alteration of hepatic vascular tone, and hence blood volume, can increase the number of cells that are successfully transplanted. Although analysis of changes in vascular beds is helpful for developing strategies for cell transplantation, convenient methods to analyze such changes are lacking. The objective of this study was to determine whether 99mTc-labeled red blood cells could be used to reveal pharmacologically induced blood pool changes in various organs. F344 rats were injected with syngeneic labeled red blood cells and subjected to blood pool analysis with gamma camera imaging. Animals were treated with phenylephrine, phentolamine, labetalol, and nitroglycerine. To correlate hepatic blood pool changes with structural alterations at the vascular level, microspheres were injected into the portal circulation of these animals. Phenylephrine significantly increased cardiac and pulmonary blood pools, findings in agreement with its alpha-adrenergic effects. Phentolamine increased the hepatic, splenic, and pulmonary blood pools, whereas labetalol increased only the pulmonary blood pool. Nitroglycerine increased both hepatic and splenic blood pools. Prior administration of phentolamine, labetalol, and nitroglycerine prevented the phenylephrine-induced changes. When microspheres were injected into the portal circulation after nitroglycerine administration, they penetrated more distal locations in the liver lobule. These data indicate that it is possible, using radionuclide methods, to noninvasively show pharmacologically induced hemodynamic changes. This finding is potentially useful for studying hepatic physiology and may also have applications for cell therapy.