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High rate right ventricular pacing causes global impairment of myocardial blood flow in an experimental model of heart failure

Session Poster session 1 Saturday 08:30 -17:30

Speaker Danilo Neglia

Event : Heart Failure 2015

  • Topic : basic science
  • Sub-topic : Basic Science
  • Session type : Poster Session

Authors : C Vecoli (Pisa,IT), M Marinelli (Pisa,IT), A Pippa (Pisa,IT), S Burchielli (Pisa,IT), L Panchetti (Pisa,IT), S Pardini (Pisa,IT), F Bernini (Pisa,IT), M Piacenti (Pisa,IT), MA Morales (Pisa,IT), D Neglia (Pisa,IT)

Authors:
C Vecoli1 , M Marinelli1 , A Pippa2 , S Burchielli3 , L Panchetti3 , S Pardini1 , F Bernini2 , M Piacenti3 , MA Morales1 , D Neglia3 , 1CNR-Istituto Fisiologia Clinica - Pisa - Italy , 2High School Sant'Anna - Pisa - Italy , 3Fondazione G. Monasterio CNR - Regione Toscana - Pisa - Italy ,

Citation:
European Journal of Heart Failure Abstracts Supplement ( 2015 ) 17 ( Supplement 1 ), 119

Purpose: Prolonged right ventricular (RV) pacing at high heart rate (HR) induces dyssynchronous contraction and progressive left ventricle (LV) dysfunction in the experimental animal. The possible effects of pacing on regional or global myocardial blood flow (MBF) and on nitric oxide syntethases (NOS) gene expression are unknown. Aim of the study was to measure MBF and cardiac NOS expression in a group of minipigs undergoing prolonged high rate pacing.

Methods: Seven adult minipigs underwent RV apical pacing (220 beats/min) for 4 weeks. Positron emission tomography and 2D-echocardiography (ECHO) were performed at baseline (PRE) and soon after interruption of 4 weeks high rate pacing (POST). Regional myocardial blood flow (MBF) ([13N]ammonia as a flow tracer) was quantified in 17 LV segments from PET data. LV fractional shortening (FS) was computed from ECHO. To evaluate the possible effects of dyssynchrony due to RV stimulation, all PRE and POST measurements were performed either during spontaneous rhythm and during PM induced rhythm (20 bpm over spontaneous HR to ensure capture). After the completion of the protocol, the hearts were excised for measurements of eNOS and stress induced iNOS gene expression in six myocardial regions corresponding to the mid LV segments in the PET 17 segments model.

Results: From PRE to POST, FS significantly decreased from 32.6 ± 3.4% to 15.8 ± 1.6% (p < 0.001) and MBF at spontaneous rhythm significantly decreased in all LV segments from 1.08 ± 0.25 to 0.88 ± 0.28 ml/min/g (p < 0.001). RV stimulated rhythm in  normal hearts, induced an increase of MBF in the regions adjacent to the pacing site (septum and inferior walls) as compared with the opposite regions (1.39 ± 0.43 vs 1.15 ± 0.26 P < 0.001) but did not affect regional MBF distribution in the failing hearts (1,19 ± 0,46 vs 1,17 ± 0,40, ns). Regional eNOS expression was not significantly affected by prolonged RV pacing while the myocardial regions adjacent to the site of chronic stimulation had a higher expression of iNOS gene as compared to the opposite regions (1.50 ± 0.39 vs 0.78 ± 0.22, P< 0.001).

Conclusions: Prolonged high rate pacing in minipigs causes global reduction in LV function and a global decrease of MBF as observed in clinical dilated cardiomyopathy. LV dyssynchrony, caused by RV stimulation, is no more able to affect regional MBF distribution in the failing hearts despite increased myocardial stress in regions adjacent to stimulation. These results may have clinical implications for the timing of biventricular stimulation in patients with early or advanced LV dysfunction.

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