Direct delivery of syngeneic and allogeneic large-scale expanded multipotent adult progenitor cells improves cardiac function after myocardial infarct.

BACKGROUND: Multipotent adult progenitor cells (MAPC) comprise interesting candidates for myocardial regeneration because of a broad differentiation ability and immune privilege. We aimed to compare the improvement of cardiac function by syngeneic and allogeneic MAPC produced on a large scale using a platform optimized from MAPC research protocols. METHODS: Myocardial infarction was induced in Lewis rats by direct left anterior descending ligation followed immediately by direct injection into the infarct border zone of either Sprague-Dawley or Lewis MAPC from large-scale expansions. Echocardiography was performed to evaluate improvement in cardiac function, and immunohistochemistry was performed to identify MAPC within the infarct zone. RESULTS: Significant increases were observed in functional performance in animals transplanted with expanded MAPC compared with saline controls, with no significant differences between the syngeneic and allogeneic groups. Immunostaining demonstrated significant engraftment of expanded MAPC at 1 day after acute myocardial infarction, with <10% of either syngeneic or allogeneic cells remaining at 6 weeks. At this point there was no evidence of myocardial regeneration. However, a significant increase in vascular density within the infarct zone in MAPC-transplanted animals was observed, and MAPC were found to produce high levels of VEGF in culture. DISCUSSION: These findings support a model in which delivery of expanded MAPC following acute myocardial infarction results in improvement in cardiac function because of paracrine effects resulting in vascular density increases, as well as potentially other trophic effects, supporting newly injured cardiac myocytes. Thus transplantation with MAPC may represent a promising therapeutic strategy with application in the stimulation of neovascularization in ischemic heart disease.

Pharmacokinetic study of cefuroxime in the elderly.

1 The pharmacokinetics of cefuroxime have been investigated in 18 patients at least 70 years old. The drug was given either by continuous infusion (7 cases) or by multiple injections (11 cases) for 3 to 11 days (mean duration: 7 days). 2 The unchanged drug was assayed in blood plasma and in the urine by high performance liquid chromatography (h.p.l.c). 3 Cefuroxime was cleared, unchanged, almost exclusively by the kidneys, even when kidney function was impaired. Creatinine clearance ranged from 1.02 to 4.08 1/h (17 to 68 ml/min) in this group of patients and plasma clearance of cefuroxime varied from 1.02 to 8.16 1/h (17 to 136 ml/min) (r = 0.7 P less than 0.001 for linear correlation), but the apparent rate constant for nonrenal elimination remained quite small (average: 0.04 h-1) and independent of creatinine clearance (r = 0.06, n = 17). 4 Since creatinine clearance decreases sharply with age, it might be suggested that cefuroxime dosage be related to creatinine clearance in the elderly, even when no renal impairment is suspected.