Abstract. The inotropic response to muscarinic receptor stimulation of isolated chick ventricular myocardium was examined at various developmental stages, and the receptor subtype involved was pharmacologically characterized. In embryonic chick ventricles, carbachol (CCh) produced positive inotropy at micromolar concentrations. In hatched chick ventricles, CCh produced negative inotropy at nanomolar concentrations. Neither positive nor negative inotropy was observed in the 19 -21-day-old embryos. Both positive and negative inotropy were also observed with acetylcholine and oxotremoline-M. The CCh-induced positive inotropy in 7 -9-day-old embryonic ventricles and the negative inotropy in 1 -3-day-old hatched chick ventricles were antagonized by muscarinic receptor antagonists; pA 2 values for the positive and negative responses of pirenzepine were 7.5 and 7.2, those of AF-] benzodiazepine-6-one) were 6.8 and 6.9, those of 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) were 9.0 and 8.5, and those of himbacine were 7.0 and 8.0, respectively. CCh had no effect on action potential configuration. In conclusion, the positive inotropy is most likely mediated by muscarinic M 1 receptors and the negative inotropy is mostly likely mediated by muscarinic M 4 receptors.

We have evaluated the peripheral blood progenitors harvest. Nineteen patients started stem cell mobilization, one failed mobilization (5%) and 18 patients mobilized (95%). Nine out 18 patients did not reinfuse and 9 reinfused: 7 (24%), after a median follow up of 24 months, are alive and without evidence of disease, 1 was in partial remission and 1 progressed immediately after transplant. The overall survival and progression free survival are reported in Figures 1 and 2. Sixteen patients (89%) mobilized after 1 or 2 apheresis and the other two patients after three or four. The mean number of CD34+ cells mobilized was 5.8, the median number was 5.5 (IQR: 5 -6.75). The mean number of reinfused CD34+ cells in the 9 patients was 4.1, the median number was 4.1 (IQR: 3.5 -5). Summary/Conclusion: The association of Obinutuzumab and DHAP did not pass the interim analysis because a lower rate of CMR reported in comparison with the hypothesis. To note that seven patients (4 refractory and 3 relapsed) among the nine transplanted are alive and free from disease after a median follow-up of 24 months. Obinutuzuamb associated with a standard mobilizing chemotherapy (DHAP) did not compromise stem cell mobilization and engraftment after ASCT in this group of DLBCL patients.