Table 4.
Mapping cardiac innervation in animal models of cardiac sympathetic neurodegeneration
| Reference | Specie | Animal Model (dose) | Number of subjects | Time of evaluation after model induction | Homogenous cardiac perfusion (Y/N) | Method of radiotracer analysis (In vivo/ex vivo) | % of LV global uptake reduction | LV regions/ ROI analyzed | Region of maximal reduction (% of loss) | Significant loss of plasma catechol-amines (Y/N) | |
|---|---|---|---|---|---|---|---|---|---|---|---|
|
|
|||||||||||
| Exp | Control | ||||||||||
| 123/125 I-MIBG | |||||||||||
| Kiyono et al., 2001 | Rat | STZ (55 mg/kg iv) | 7 | 7 | 4 weeks | Y ([99mTc]MIBI) | ex vivo | No global results provided | Anterior and inferior walls | Inferior (13.1%b; 25.3%b compared to anterior wall in STZ) | - |
| Kiyono et al., 2005 | Rat | STZ (55 mg/kg iv) | 5 | 5 | 4 weeks | - | ex vivo | No global results provided | Anterior, inferior, lateral, and septal walls | Inferior (no values provided) | - |
| Kusmic et al., 2008 | Mouse | STZ (35 mg/kg x 5 ip) | 7 | 7 | 7 months | - | in vivo | No global loss (similar value to controls) | - | - | - |
| Goethals et al., 2009 | Rat | STZ (60 mg/kg iv) | 12 | 12 | 8 weeks | - | in vivo | 3.6-8.4%b | Anterior, anterolateral, inferolateral, inferior, inferoseptal and anteroseptal | Anteroseptal (9-10%c compared to inferoseptal and inferolateral in STZ) | - |
| Matsuki et al., 2010 | Rat | STZ (65 mg/kg ip) | 7 | 7 | 5 weeks | - | ex vivo | 26-33%c | Anterior, inferior, lateral, and septal walls | No differences found between regions | - |
| Takatsu et al., 2000 | Mouse | MPTP (5 mg/kg x 1 sc) | 7 | 7 | 1 week | - | ex vivo | 40%c | - | - | - |
| MPTP (5 mg/kg x 2 sc) | 6 | 66%c | |||||||||
| MPTP (50 mg/kg x 2 sc) | 10 | 73%c | |||||||||
| Takatsu et al., 2002 | Mouse | MPTP (50 mg/kg x 2 sc) | 10 | 10 | 1 week | - | ex vivo | 70%c | - | - | - |
| Fukumitsu et al., 2006 | Mouse | MPTP (10 mg/kg x 1 ip) | 10 | 10 | 1 week | - | ex vivo | 49.6%b | - | - | - |
| MPTP (10 mg/kg x 4 ip) | 10 | 61.1%b | |||||||||
| Fukumitsu et al., 2009 | Mouse | MPTP (40 mg/kg x 4 ip) | 14 | 14 | 1 day | - | ex vivo | 71.7%b | - | - | Y (NE) |
| MPTP (40 mg/kg x 4 ip) | 14 | 4 days | 57.6%b | N | |||||||
| MPTP (40 mg/kg x 4 ip) | 14 | 7 days | 49.5%b | N | |||||||
| MPTP (40 mg/kg x 4 ip) | 14 | 21 days | 47.3%b | N | |||||||
| MPTP (40 mg/kg at 7, 14, and 21 days ip) | 14 | 21 days | 60.3%b | N | |||||||
| Sisson et al., 1987 | Rat | 6-OHDA (100 mg/kg ip) | 11 | 9 | 5 days | - | ex vivo | 31%a | - | - | - |
| Nomura et al., 2006 | Rabbit | Reserpine (2 mg/kg ip) | 4 | 4 | 14 days | Y ([13N]NH3) | ex vivo | 18%b | - | - | - |
| 6-OHDA (100 mg/kg iv) | 4 | 90%a | |||||||||
| 18 F-FDA | |||||||||||
| Goldstein et al., 1990 | Dog | Reserpine (3 mg/kg po) | 3 | Same animals after 2 weeks | 24 hours | - | in vivo | No global results provided | Free wall and septal wall | No differences found between regions | Y(NE, DHPG) |
| Goldstein et al., 1991 | Dog | 6-OHDA (50 mg/kg iv) | 3 | 0 | 3 days | - | in vivo | >95%a | - | - | Y (DHPG, DOPAC) |
| Goldstein et al., 2003 | Monkey | MPTP (4 doses, dose not clear) | 1 | 2 | 2 weeks | - | in vivo | no loss, 70% increaseb | - | - | Y (NE, EPI, DHPG, DOPAC) |
| MPTP (4 doses x 2 separated by 2 weeks, dose not clear) | 1 | 6 weeks | 27.5%b | Y (NE, EPI, DHPG, DOPAC) | |||||||
| MPTP (4 doses x 2 separated by 2 weeks, dose not clear) | 1 | 2 years | no loss, 21.9% increaseb | N (only slightly decreased) | |||||||
| 6-OHDA (50 mg/kg iv) | 3 | 1 week | 60%b | Y (NE, EPI, DHPG, DOPAC) | |||||||
| 11 C-MHED | |||||||||||
| Schmid et al., 1999 | Rat | STZ (50 mg/kg ip) | 18 | 15 | 6 months | - | ex vivo | No global results provided | Proximal and distal segments | Distal (33%a) | - |
| STZ (50 mg/kg ip) | 11 | 11 | 9 months | Proximal (44%a) | |||||||
| Thackeray et al., 2011 | Rat | STZ (45 mg/kg ip) | 4 | 6 | 2 weeks | - | ex vivo | No change | Free wall and septal wall | No change | N |
| STZ (45 mg/kg ip) | 14 | 8 | 8 weeks | 13%a | Free wall and septal evenly decreased (13%a) | N (increased 2.5x) | |||||
| Nomura et al., 2006 | Rabbit | Reserpine (2 mg/kg ip) | 4 | 4 | 14 days | Y ([13N]NH3) | in vivo | 50.3%b | - | - | - |
| 6-OHDA (100 mg/kg iv) | 4 | 90%a | |||||||||
| Raffel et al., 2006 | Rat | 6-OHDA (7 mg/kg ip) | 5 | 5 | 24 hours | - | ex vivo | 28.2%b | - | - | - |
| 6-OHDA (11 mg/kg ip) | 5 | 60.1%b | |||||||||
| 6-OHDA (15 mg/kg ip) | 5 | 53.8%b | |||||||||
| 6-OHDA (22 mg/kg ip) | 5 | 72.5%b | |||||||||
| 6-OHDA (100 mg/kg ip) | 5 | 91.9%b | |||||||||
| Joers et al., 2013 | Monkey | 6-OHDA (50 mg/kg iv) | 5 | Same animals at baseline | 1, 4, 10, 14 weeks | - | in vivo | 51.1%a | Anterior, inferior, lateral, and septal walls | Inferior (49.5%b) | Y (NE, DOPAC) |
Listed percentages describe loss compared to controls (unless otherwise noted) and reported originally in the reference (a) or calculated based on data (b numbers or c graph) from the publication. 123/125I-MIBG, [123/125I]-Meta-iodobenzylguanidine; 6-OHDA, 6-hydroxydopamine; DHPG, Dihydroxyphenylglycine; DOPAC, dihydroxyphenylacetic acid; EPI, epinephrine; LDOPA, L-3,4-dihydroxyphenylalanine; LRRK2, leucine rich repeat kinase 2; LV, left ventricle; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; NE, norepinephrine; NH3, ammonia; PD, Parkinson’s disease; STZ, streptozotocine.