Altered distribution and density of myocardial beta-adrenoceptors during acute rejection in rats.
BACKGROUND
A better understanding of altered expression of myocardial beta-adrenoceptors can facilitate the diagnosis of early and late acute rejection of heart transplants.


METHODS
We submitted rats to heterotopic heart transplantation (iso- and allografts) of which one of each were treated with or without cyclosporin A for 4, 7, and 14 days (n=5, respectively). The cardiac sections were incubated in vitro with [3H]CGP 12177, or the hearts were labeled in vivo by intravenous injection of [3H]CGP 12177. Autoradiographic images of both were analyzed digitally and compared with histologic findings.


RESULTS
Beta-adrenoceptor distribution in native hearts and isografts was homogeneous, but highly differential distribution and density in allografts were observed in the left and right ventricular walls and in the interventricular septum despite treatment with cyclosporin A. High-density areas in the progressive course of acute rejection are commonly associated with up-regulation of beta-adrenoceptors in apparently viable myocytes, although histologic findings confirmed many infiltrating mononuclear cells. Low-density areas, which were identified in the right and left ventricular walls as early as 4 days after transplantation, correlated with derangement of myocytes, which was suggestive of early acute rejection. The images obtained by in vivo technique were comparable to in vitro images.


CONCLUSIONS
The alteration of beta-adrenoceptor expression in allografts showed a close relationship with the severity of acute rejection, and the techniques employed in this model were useful in our study of the rejection process and in detecting early and late acute rejection in the rat.
Tofukuji
M
M
Department of Thoracic and Cardiovascular Surgery, Tohoku University School of Medicine, Sendai, Japan.
Nakame
T
T
Murata
S
S
Yanai
K
K
Ohmi
M
M
Tabayashi
K
K
D000208:Acute Disease; D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics; D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use; D006084:Graft Rejection / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016027:Heart Transplantation; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D011412:Propanolamines / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012016:Reference Values; D013997:Time Factors; D014018:Tissue Distribution; D016042:Transplantation, Heterotopic; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
D000319:Adrenergic beta-Antagonists; D007166:Immunosuppressive Agents; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D016572:Cyclosporine; C033394:CGP 12177