Research ArticleCLINICAL INVESTIGATIONS

Effect of Diabetes Mellitus on Sympathetic Neuronal Regeneration Studied in the Model of Transplant Reinnervation

Frank M. Bengel, Peter Ueberfuhr, Dominik Schäfer, Stephan G. Nekolla, Bruno Reichart and Markus Schwaiger
Journal of Nuclear Medicine September 2006, 47 (9) 1413-1419;

Article Figures & Data

Figures

  • FIGURE 1. 
    FIGURE 1. 

    (A and B) Assessment of neuronal regeneration by PET. Shown are representative left ventricular short- and long-axis tomographic images (A) and polar maps (2-dimensional display of 3-dimensional tracer distribution throughout myocardium, with apex displayed at center, base at periphery, septum on left, lateral wall on right, anterior wall on top, and inferior wall on bottom) (B) of cardiac transplant recipient without evidence of diabetes mellitus (top) and another recipient with history of diabetes (bottom). Gray-scale images show homogeneous myocardial perfusion, determined by 13N-ammonia. Color-scale images show regional uptake of 11C-epinephrine, indicating reinnervation in basal anterior wall. Extent of reinnervation was 42% in nondiabetic recipient and 13% in diabetic recipient. (C) Group results (mean ± SE) for neuronal regeneration rate. EPI = 11C-epinephrine; HTx = heart transplantation; LA = left atrium; LV = left ventricle; RA = right atrium; RV = right ventricle. *P < 0.05.

  • FIGURE 2. 
    FIGURE 2. 

    Functional importance of neuronal regeneration. Regression plots show relationship between left ventricular maximal 11C-epinephrine retention index and inotropic (increase of heart rate, left) and chronotropic (increase of left ventricular ejection fraction, right) response to exercise. Regression lines are shown for subgroups of diabetic (dashed line) and nondiabetic (dotted line) transplant recipients and for all individuals (solid line). LVEF = left ventricular ejection fraction; max EPI = maximal 11C-epinephrine.

Tables

  • TABLE 1

    Patient Characteristics

    CharacteristicOverall (n = 22)No diabetes (n = 12)Diabetes (n = 10)
    Age (y)59 ± 758 ± 959 ± 5
    Body weight (kg)84 ± 1378 ± 1291 ± 11*
    Body mass index (kg/m2)27.3 ± 3.925.6 ± 3.529.3 ± 3.6*
    Age at transplantation (y)54 ± 656 ± 753 ± 4
    Age of donor (y)38 ± 1338 ± 1238 ± 15
    Time after surgery (y)4.0 ± 3.42.7 ± 2.75.5 ± 3.5†
    Exposure of heart to diabetes (mo)——49 ± 28

    • ↵* P < 0.05 vs. no diabetes.

    • ↵† P = 0.05 vs. no diabetes.

  • TABLE 2

    Left Ventricular Catecholamine Storage Capacity

    ParameterOverall (n = 22)No diabetes (n = 12)Diabetes (n = 10)
    Extent of restored innervation (% of left ventricle)12.6 ± 17.019.1 ± 20.64.7 ± 5.3*
    Restoration rate (% of left ventricle/y)4.7 ± 8.28.0 ± 10.10.8 ± 1.0*
    Global 11C-epinephrine retention index (%/min)6.8 ± 2.67.6 ± 3.35.8 ± 1.0
    11C-Epinephrine retention index, LAD territory (%/min)8.5 ± 4.29.7 ± 5.27.0 ± 1.9
    11C-Epinephrine retention index, LCX territory (%/min)5.6 ± 1.96.2 ± 2.44.9 ± 0.6
    11C-Epinephrine retention index, RCA territory (%/min)5.4 ± 1.55.8 ± 1.95.0 ± 0.7
    Maximal 11C-epinephrine retention index (%/min)13.7 ± 6.715.4 ± 8.211.7 ± 3.7
    Totally denervated patients8 (36%)4 (33%)4 (40%)

    • ↵* P = 0.04 vs. no diabetes.

    • LAD = left anterior descending coronary artery; LCX = left circumflex coronary artery; RCA = right coronary artery.

  • TABLE 3

    Hemodynamics and Exercise Performance

    ParameterOverall (n = 22)No diabetes (n = 12)Diabetes (n = 10)
    Rest
     Heart rate (min−1)91 ± 1191 ± 1391 ± 9
     Systolic blood pressure (mm Hg)142 ± 19138 ± 18148 ± 19
     Diastolic blood pressure (mm Hg)93 ± 1495 ± 1590 ± 12
     Rate–pressure product (mm Hg/min)12,991 ± 2,55112,530 ± 2,52113,544 ± 2,627
     Left ventricular ejection fraction (%)65 ± 1070 ± 758 ± 10*
    Exercise
     Maximal workload (W)114 ± 28121 ± 33106 ± 17
     Exercise duration (min)7.0 ± 2.27.2 ± 2.36.7 ± 2.2
     Peak heart rate (min−1)129 ± 19135 ± 23121 ± 10
     Heart rate increase (min−1)38 ± 2044 ± 2231 ± 12
     Peak systolic blood pressure (mm Hg)194 ± 26190 ± 29198 ± 23
     Peak diastolic blood pressure (mm Hg)97 ± 1498 ± 1695 ± 12
     Peak rate–pressure product (mm Hg/min)25,267 ± 6,12424,137 ± 3,74526,115 ± 7,495
     Peak left ventricular ejection fraction (%)70 ± 1278 ± 761 ± 12*
     Increase of ejection fraction (%)5 ± 77 ± 62 ± 7
    Recovery
     Heart rate (min−1)112 ± 15114 ± 15108 ± 15
     Systolic blood pressure (mm Hg)163 ± 27162 ± 28165 ± 27
     Diastolic blood pressure (mm Hg)91 ± 993 ± 1088 ± 8
     Rate–pressure product (mm Hg/min)18,409 ± 4,48418,697 ± 4,67018,024 ± 4,472
     Left ventricular ejection fraction (%)72 ± 1177 ± 663 ± 10*

    • ↵* P < 0.01 vs. no diabetes.

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