Table 1.
Summary of all the animal studies in to the pathogenesis of PAVMs from 2000 to 2013.
| Study | Animal model | SVC blood | IVC blood | Analysis | Candidate molecule | Results | Mechanism of PAVM |
|---|---|---|---|---|---|---|---|
| Malhotra 2001 | Lamb N=24 |
RPA | RA-RV-LPA | Tissue mRNA expression Blood from RPA |
ACE Angiotensin II |
Reversible decreased ACE activity in lung | Enzyme involved in angiogenesis inhibition |
| Malhotra 2002 | Sheep | Tissue | Angiotensin receptors | Increased type 1, 2 angiotensin receptors | Pathological vascular remodeling | ||
| Malhotra 2002 | Lamb N=6 |
HIF | Upregulation of HO1, GLUT1 | Oxidative stress | |||
| Starnes 2002 | Rat N=8 |
Tissue microscopy Immunohistochemistry |
Nil | Time dependent increase in micro-vessel density in the shunted lung | Angiogenesis | ||
| Ikai 2004 | Lamb N=6 |
RA-RV-LPA LPA band |
Tissue-lung Western blot, Immunostaining |
HGF Cmet Bcl2 |
C-met expression increased in lung | Growth factor in angiogenesis anti-apoptotic |
|
| Ikai 2004 | Rabbit | RA-RV-LPA | Tissue | HIF1α | Lack of hypoxic pulmonary vasoconstriction | Oxidative stress | |
| Mumtaz 2004 | Rat N-=3 |
RA-RV-LPA | Tissue mRNA expression | VEGF | Progressive increase in VEGF mRNA | Final pathway VEGF | |
| Ikai 2005 | Rabbit | RPA/ PA band | RA-RV-LPA | Tissue | Nil | Even partial maintenance of right lung blood supply (from hepatic vein) maintains hypoxic pulmonary vasoconstriction | Oxidative stress |
| McMullan 2008 | Lamb N=23 |
RPA | RA-RV-LPA | Tissue morphology | Nil | Morphology of PAVMs | |
| Kavarana 2013 | Porcine N=5 |
RPA | RA-RV-LPA | Tissue gene expression | Angiopoietin1 TIE2 (Angiopoietin receptor) Angiostatin |
Conversion of PAEC to a proangiogenic phenotype Increased proliferation and tubule formation |
Angiogenesis HIF Gene expression not different |
| Henaine 2013 | Porcine N=10 |
RPA/PA band | RA-RV-LPA | Tissue | Pulsatile flow | PAVMs, Increased PAP, PVR in non-pulsatile > micro-pulsatile > pulsatile | Antegrade pulsatile flow prevents PAVMs |
Note. 11 studies using Rabbit, Lamb, pigs and rats. SVC blood connected to RPA and IVC blood from IVC to RA to LPA after banding or disconnecting the RPA. Looked for blood or tissue for ACE, Angiotensin, HGF, HIF, VEGF, Angiopoietin, angiopoietin receptor or angiostatin or to define the pulsatility of pulmonary blood flow. There is evidence of angiogenesis in the lungs, ACE is involved in inhibition of angiogenesis, and the final pathway for PAVMs is through VEGF evidenced by progressive increase in VEGF mRNA [19-30].