Effect Of Spinal Cord Stimulation On Pressure Overload-induced HFpEF Pig Model

Background: Heart failure with preserved ejection fraction(HFpEF)is a knotty disease with a high morbidity and mortality rate,lacking effective treatments.Spinal cord stimulation(SCS)is a widely used clinical technique to treat ischemia in peripheral,cardiac and cerebral vascular diseases.SCS at thoracic spinal segments(between T1-T5 areas)has been reported to significantly improve cardiac contractile function in Heart failure with reduced ejection fraction(HFr EF).However,its effect on HFpEF remains unknown.Here we reported the effects of Spinal cord stimulation(SCS)on a pressure overload-induced HFpEF pig model.Methods: HFpEF pigs were established by using a combination of deoxycorticosterone acetate(DOCA)and angiotensin II(Ang II)infusion,with western diet(WD)feeding for 18 weeks.In the 9th week,some HFpEF pigs received SCS treatment for another 9 weeks.Blood pressure,echocardiography and cardial hemodynamics,as well as crucial hormone levels in plasma and tissues were measured.After sacrifice,cardiac fibrosis,distribution of tyrosine hydroxylase(TH)and NO-c GMP-PKG pathway activity in aorta were also determined.Results: Blood pressure was raised in HFpEF pigs and significantly decreased by SCS treatment.By echocardiographic and hemodynamic assessment,SCS obviously attenuated heart concentric remodeling in HFpEF group,but not impaired diastolic function and compliance of left ventricular(LV).Sympathetic tone of LV and aorta was determined by TH immunostaning.We found that SCS strongly mitigated TH expression in aorta compared with that in HFpEF group.Moreover,inflammatory cytokines such as IL-6 and TNF-? in aorta tissue were markedly elevated in HFpEF pigs and inhibited by SCS treatment.Further,reduced expression of e NOS and PKG-1 protein and c GMP content in aorta of HFpEF pigs was significantly restored with SCS treatment.Conclusion: Our results indicate that SCS therapy may improve hypertension and partly reverse LV concentric remodeling in HFpEF pigs through restraining sympathetic tone in aorta,leading to inhibition of inflammatory response and NO-c GMP-PKG pathway activation.