Abstract
The sympathetic nervous system plays a critical role in the pathogenesis of acute myocardial infarction (AMI) and heart failure. This study tested whether pre‐conditioning with radiofrequency renal artery ablation (RF‐ABL) protects the heart against myocardial ischemia/reperfusion (MI/R) in the setting of hypertension. Spontaneously hypertensive rats (SHR) received either bilateral RF‐ABL (n=14) or Sham‐ABL (n=14) (Biosense Webster Stockert 70 RF generator). Four weeks following treatment, hypertensive SHR were subjected to 30 minutes of left coronary artery occlusion. After 24 hours reperfusion, the myocardial infarct size/area‐at‐risk (AAR) were determined. In addition, the left ventricle (LV) was collected for measurement of nitric oxide (NO) metabolites, nitrite (NO2−) and S‐nitrosothiol (RSNO), and oxidative stress. RF‐ABL produced a significant decrease in myocardial infarct size per AAR compared to Sham‐ABL (26.8 vs. 43.9%) and lower plasma cardiac troponin‐I (6.8 vs. 10.3 ng/ml). Cardiac NO2− levels increased from 2.6 to 3.2 nmol/mg and RSNO levels increased from 0.5 to 1.1 nmol/mg following RF‐ABL. Myocardial oxidative stress was markedly attenuated as measured by 8‐Isoprostane, carbonyl content, and MDA levels. Greater transcription (RT‐PCR) of antioxidants, SOD1 and GPX‐1 were also observed following RF‐ABL. These findings translated to a significant increase in 24‐hr survival of RF‐ABL (13 of 14) as compared to Sham‐ABL (8 of 14) SHR to MI/R. Together, these findings demonstrate that in hypertensive SHR, RF‐ABL produced a sustained increase in myocardial NO bioavailability and attenuation of oxidative stress, both of which can contribute to preconditioning the myocardium against subsequent MI/R injury. These findings provide new insights into the remote cardioprotective effects of RF‐ABL in the setting of AMI.Support or Funding InformationBiosense Webster IIS‐175 to DRK & FS; P30 GM103514 to DRK. 1R01 HL092141, 1R01 HL093579, 1U24 HL 094373, & 1P20 HL113452 to DJL.
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