Potential role of sympathetic activity on the pathogenesis of massive pulmonary embolism with circulatory shock in rabbits

Abstract

Background: We recently showed that intravenous sodium nitroprusside treatment (SNP) could relieve the pulmonary vasospasm of pulmonary embolism (PE) and non-pulmonary embolism (non-PE) regions in a rabbit massive pulmonary embolism (MPE) model associated with shock. The present study explored the potential role of cardiopulmonary sympathetic activity on the pathogenesis and the impact of vasodilators on cardiopulmonary sympathetic activity in this model.

Methods: Rabbits were randomly divided into sham operation group (S group, n = 8), model group (M, equal volume of saline intravenously, n = 11), SNP group (3.5 μg/kg/min intravenously, n = 10) and diltiazem group (DLZ, 6.0 μg/kg/min intravenously, n = 10).

Results: MPE resulted in reduced mean arterial pressure and increased mean pulmonary arterial pressure as well as reduced PaO₂ in the M, SNP and DLZ groups. Tyrosine hydroxylase (TH), neuropeptide Y (NPY) and endothelin-1 (ET-1) expression levels were significantly increased, while nitric oxide (NO) levels were reduced in both PE and non-PE regions in the M group. Both SNP and DLZ decreased mean pulmonary arterial pressure, reversed shock status, downregulated the expression of TH, NPY and ET-1, and increased NO levels in PE and non-PE regions.

Conclusion: Present results indicate that upregulation of the sympathetic medium transmitters TH and NPY in whole lung tissues serves one of the pathological features of MPE. The vasodilators SNP and DLZ could relieve pulmonary vasospasm in both embolization and non-embolization regions and reverse circulatory shock, thereby indirectly downregulating the sympathetic activation of the whole lung tissues and breaking a vicious cycle related to sympathetic activation in this model.

Keywords: Acute pulmonary embolism combined with shock; Diltiazem; Pulmonary arterial hypertension; Sodium nitroprusside; Sympathetic activity.

Fig. 1

Kaplan-Meier survival curves (a), mean pulmonary artery pressure (MPAP) and mean arterial pressure (MAP) changes (b) and blood gas analysis (c) among various groups. * P < 0.05 versus S group, † P < 0.05 versus M group. ‡ P < 0.05 versus Baseline, § P < 0.05 versus PE. S, sham operation group; M, model group; SNP, sodium nitroprusside group, DLZ, diltiazem group. Baseline, before pulmonary embolism; PE, pulmonary embolism referring to the moment of shock status post bolus injection of autologous blood clots; PE-120 min, at 120 min after the initiation of treatment

Fig. 2

The gross anatomical morphology of the representative lungs. Histological features in the (a) S, (b) M, (c) SNP and (d) DLZ groups at the scheduled study end. Histological features of rabbits immediately after death before scheduled study end: b1 (M), c1 (SNP) and d1 (DLZ). S, sham operation group; M, model group; SNP, sodium nitroprusside group; DLZ, diltiazem group. Yellow arrows indicate the autologous thrombus clot

Fig. 3

The expression of TH (a) and NPY (b) in PE and non-PE areas. Data are expressed as mean ± SD by bar graphs. * P < 0.05 versus S group, † P < 0.05 versus M group. S, sham operation group; M, model group; SNP, sodium nitroprusside group; DLZ, diltiazem group. PE, pulmonary embolism tissue; non-PE, non-pulmonary embolism tissue. Scale bars =50 μm. Original magnification × 200

Fig. 4

Protein expressions of TH and NPY in PE and non-PE tissues detected by Western-blot. Data are expressed as mean ± SD by bar graphs. * P < 0.05 versus S group, † P < 0.05 versus M group. S, sham operation group; M, model group; SNP, sodium nitroprusside group; DLZ, diltiazem group. PE, pulmonary embolism tissue; non-PE, non-pulmonary embolism tissue

Fig. 5

Pathological changes of MPE and potential working effects of SNP and DLZ