Abstract 11489: Autoimplantation of Astrocytes into the Cardiovascular Center of Brainstem Causes Sympathoinhibition and Decreases the Mortality Rate in Myocardial Infarction-Induced Heart Failure
Backgrounds: Long considered merely a mechanical support to neurons, astrocytes have been shown to protect and mediate neural function. In hypertensive rats with sympathoexcitation, we previously demonstrated that apoptosis was occurred in astrocytes in the rostral ventrolateral medulla (RVLM, known as a cardiovascular center), and that autoimplantation of astrocytes into the RVLM induced sympathoinhibition and decreased the mortality rate. In heart failure (HF), sympathoexcitation causes the left ventricular (LV) remodeling and worsens the survival rate. The aim of the present study was to determine whether the autoimplantation of astrocytes into the RVLM in rats with HF causes sympathoinhibition and decreases the mortality rate.
Methods and Results: We ligated the left coronary artery to induce myocardial infarction (MI) and subsequent HF. We isolated neural stem cells from the tissue of lateral ventricles by cell sphere method. Neural stem cells cocultured with the leukocyte inhibitory factor and bone morphogenetic protein receptor 2 differentiated into astrocytes. After coronary ligation, we microinjected astrocytes into bilateral RVLMs. At 2 days after coronary ligation, the number of astrocytes in RVLM was significantly lower in the HF-vehicle group than in the sham group. At 7 days after autoimplantation, astrocyte implantation lowered urinary norepinephrine excretion (uNE, a parameter of sympathoexcitation, 1.0±0.2μ g vs. 2.2±0.4μ g, n=5 for each, p<0.01) and kept uNE low for 8 weeks. At 4 weeks after autoimplantation, astrocyte implantation decreased the LV systolic dimension and lowered LV end diastolic pressure (7±2 vs. 13±3mmHg, n=5 for each, p<0.01). Astrocyte implantation markedly improved the survival rate (12% vs. 78%, at 4 weeks after the autoimplantation).
Conclusion: Autoimplantation of astrocyte into the RVLM causes sympathoinhibition, prevents the LV remodeling, and decreases the mortality rate in MI-induced HF in rats. These results suggest that apoptosis of astrocyte in the RVLM causes abnormal sympathoexcitation, LV remodeling, and worsens the prognosis of heart failure.
- © 2011 by American Heart Association, Inc.