Multipotent adult progenitor cells sustain function of ischemic limbs in mice.

Despite progress in cardiovascular research, a cure for peripheral vascular disease has not been found. We compared the vascularization and tissue regeneration potential of murine and human undifferentiated multipotent adult progenitor cells (mMAPC-U and hMAPC-U), murine MAPC-derived vascular progenitors (mMAPC-VP), and unselected murine BM cells (mBMCs) in mice with moderate limb ischemia, reminiscent of intermittent claudication in human patients. mMAPC-U durably restored blood flow and muscle function and stimulated muscle regeneration, by direct and trophic contribution to vascular and skeletal muscle growth. This was in contrast to mBMCs and mMAPC-VP, which did not affect muscle regeneration and provided only limited and transient improvement. Moreover, mBMCs participated in a sustained inflammatory response in the lower limb, associated with progressive deterioration in muscle function. Importantly, mMAPC-U and hMAPC-U also remedied vascular and muscular deficiency in severe limb ischemia, representative of critical limb ischemia in humans. Thus, unlike BMCs or vascular-committed progenitors, undifferentiated multipotent adult progenitor cells offer the potential to durably repair ischemic damage in peripheral vascular disease patients.

Do donor characteristics really matter? Short- and long-term impact of donor characteristics on recipient survival, 1995-1999.

We reviewed the impact of multiple donor characteristics on recipient mortality by univariate and multivariate analyses in a cohort of heart donors from 1995 to 1999. A sub-cohort of donors was also selected who met "marginal" criteria, and the early and late survival of these patients was then compared. Surrogates of donor size (donor weight, donor body mass index [BMI], BMI mismatch >20%), under-resuscitation (hematocrit, 24-hour fluid intake) and age >56 years were significantly associated with peri-operative mortality in the univariate analysis; in the multivariate analysis, only average donor heart rate at procurement (p =.001), donor hematocrit (p =.02) and donor weight (p =.05) were significantly associated. Few donor characteristics actually impact significantly on recipient outcome, and thus recipient characteristics may figure more prominently than those of the donor toward the risk of death after transplantation.

Ninety-day mortality and major complications are not affected by use of lung allocation score.

BACKGROUND: In May 2005 the Organ Procurement Transplant Network (OPTN) and United Network for Organ Sharing (UNOS) implemented the donor lung allocation score (LAS) system to prioritize organ allocation among prospective transplant recipients. The purpose of our study was to determine the impact of LAS implementation on 90-day survival, early complications and incidence of severe primary graft dysfunction (PGD) after the transplant procedure. METHODS: Early outcomes among 78 patients receiving transplants after the initiation of the scoring system were compared with those of the 78 previous patients. Survival rates at 90 days and 1 year were the primary end-points of the study. Arterial blood-gas measurements were collected for all patients at the time of ICU arrival and at 12, 24 and 48 hours after surgery to determine the distribution of International Society of Heart and Lung Transplant (ISHLT) PGD grade. Major complications within 30 days post-transplant were recorded. RESULTS: We found a small but significant 1-year survival advantage among post-LAS implementation patients, which was largely due to decreased early mortality in comparison to the control cohort. The incidence of ISHLT Grade 3 PGD measured within the first 24 hours after transplant did not differ between groups, nor was there an increase in the rate of major post-operative complications. CONCLUSIONS: Implementation of the LAS system has not been associated with an increase in early mortality, immediate PGD or major complications.

The real estate of myoblast cardiac transplantation: negative remodeling is associated with location.

BACKGROUND: Skeletal myoblast transplantation has been proposed as a therapy for ischemic cardiomyopathy owing to its possible role in myogenesis. The relative safety and efficacy based on location within scar is not known. We hypothesized that skeletal myoblasts transplanted into peripheral scar (compared with central scar) would more effectively attenuate negative left ventricular (LV) remodeling but at the risk of arrhythmia. METHODS: New Zealand White rabbits (n = 34) underwent mid-left anterior descending artery (LAD) ligation to produce a transmural LV infarction. One month after LAD ligation, skeletal myoblasts were injected either in the scar center (n = 13) or scar periphery (n = 10) and compared with saline injection (n = 11). Holter monitoring and magnetic resonance imaging (MRI) was performed pre-injection; Holter monitoring was continued until 2 weeks after injection, with follow-up MRI at 1 month. RESULTS: The centrally treated animals demonstrated increased LV end-systolic volume, end-diastolic volume, and mass that correlated with the number of injected cells. There was a trend toward attenuation of negative LV remodeling in peripherally treated animals compared with vehicle. Significant late ectopy was seen in several centrally injected animals, with no late ectopy seen in peripherally injected animals. CONCLUSIONS: We noted untoward effects with respect to negative LV remodeling after central injection, suggesting that transplanted cell location with respect to scar may be a key factor in the safety and efficacy of skeletal myoblast cardiac transplantation. Administration of skeletal myoblasts into peripheral scar appears safe, with a trend toward improved function in comparison with sham injection.

Carotid endarterectomy prior to ventricular assist device placement.

While there has been considerable debate regarding the timing of carotid endarterectomy (CEA) with respect to coronary artery bypass grafting, the ventricular assist device (VAD) patient population presents possible new concerns, given the implications of stroke while on mechanical support as a bridge to transplant. We present the first report in the literature of CEA in a patient with severe carotid disease prior to elective VAD placement.