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Immunosuppressive properties of the benzothiazepine calcium antagonists diltiazem and clentiazem, with and without cyclosporine, in heterotopic rat heart transplantation
- Source :
- Transplantation. 56(1)
- Publication Year :
- 1993
-
Abstract
- In vitro studies have shown that calcium channel blockers (CCB) exert inhibitory effects on immunocompetent cells but conflicting results have been reported as to the translation of these effects into significant in vivo immunosuppression. In this study we evaluated the effects of the benzothiazepine-like calcium blockers diltiazem and clentiazem, given alone or associated with cyclosporine on survival improvement of heterotopic rat heart transplants. Inbred male rats of the Lewis strain were used as recipients and Wistar-Furth as donors. Following abdominal implantation of the graft, recipients were randomly divided into 9 groups (n = 5). Group 1 were control isografts (Lew-Lew); group 2 were control allografts (WFu-Lew), and group 3 were allografts treated with low-dose oral cyclosporine 2 mg/kg/day. Groups 4 and 5 were allografts treated with oral diltiazem 0.25 and 2.50 mg/kg/day. Groups 6 and 7 were treated with oral clentiazem, 0.25 and 2.50 mg/kg/day. Groups 8 and 9 consisted of allografts receiving low-dose cyclosporine with either diltiazem or clentiazem 2.50 mg/kg/day, all drugs were administered daily by gavage. Graft function was monitored by transabdominal palpation, and rejection was considered to be complete when no contraction of the graft could be detected. Mean survival time of untreated allografts was 6.4 +/- 0.5 days. Cyclosporine alone increased the mean survival time to 10.6 +/- 2.7 days (P < 0.05 vs. group 2). At all doses studied, diltiazem and clentiazem significantly increased mean survival time of allografts, clentiazem being slightly more potent than diltiazem. In addition, the observed beneficial effects of the benzothiazepine-like calcium channel blockers were dose-dependent. When combined with cyclosporine, diltiazem and clentiazem interacted synergistically (mean survival time increased to 16.8 +/- 3.4 days for diltiazem and 15.8 +/- 1.4 days for clentiazem). These results demonstrate that the benzothiazepine-like calcium channel blockers, as opposed to phenylalkylamines or dihydropyridines, afford significant immunosuppression when used alone. These observations, and the fact that they beneficially interact with cyclosporine, suggest that the benzothiazepine-like calcium antagonists should be considered the drugs of choice when CCBs are to be selected in transplanted patients.
- Subjects :
- Male
medicine.medical_specialty
Time Factors
Transplantation, Heterotopic
medicine.medical_treatment
chemistry.chemical_element
Rats, Inbred WF
Pharmacology
Calcium
Clentiazem
chemistry.chemical_compound
Diltiazem
In vivo
Internal medicine
medicine
Animals
Transplantation, Homologous
Transplantation
Chemotherapy
business.industry
Calcium channel
Graft Survival
Immunosuppression
Calcium Channel Blockers
Rats
Transplantation, Isogeneic
Endocrinology
chemistry
Rats, Inbred Lew
Cyclosporine
Heart Transplantation
Drug Therapy, Combination
business
Immunosuppressive Agents
medicine.drug
Subjects
Details
- ISSN :
- 00411337
- Volume :
- 56
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Transplantation
- Accession number :
- edsair.doi.dedup.....4144b09ce6cfc8332bbb4b3aa4b7a20f