Myocardial salvage is increased after sympathetic renal denervation in a pig model of acute infarction

Clin Res Cardiol. 2021 May;110(5):711-724. doi: 10.1007/s00392-020-01685-y. Epub 2020 Jun 8.

Abstract

Rationale: Despite advances in treatment of acute myocardial infarction (AMI), many patients suffer significant myocardial damage with cardiac dysfunction. Sympathetic renal denervation (RD) may reduce adrenergic activation following AMI.

Objective: To investigate the potential role of RD limiting myocardial damage and remodeling when performed immediately after AMI.

Methods and results: Sixteen farm pigs underwent 90 min left anterior descending artery balloon occlusion. Eight pigs underwent RD immediately after reperfusion. LV function, extent of myocardium at risk, and myocardial necrosis were quantified by cardiac magnetic resonance 5 and 30 days after AMI. 123I-MIBG scintigraphy was performed 31 days after AMI to image myocardial sympathetic innervation. Heart norepinephrine was quantified (from necrotic, border and remote zone). RD and control did not differ in myocardium at risk extent (59 ± 9 vs 55 ± 11% of LV mass) at 5 days. At 30 days CMR, RD pigs had smaller necrotic areas than control as assessed by gadolinium delay enhancement (18 ± 7 vs 30 ± 12% of LV mass, p = 0.021) resulting in improved myocardial salvage index (60 ± 11 vs 44 ± 27%, p < 0.001). RD pigs had higher cardiac output (3.7 ± 0.8 vs 2.66 ± 0.7 L/min, p < 0.001) and lower LV end diastolic volume (98 ± 16 vs 113 ± 31 ml, p = 0.041). 123I-MIBG defect extension was smaller in RD than control (60 ± 28 vs 78 ± 17%, p < 0.05) with significant reduction in the difference between innervation and perfusion defects (25 ± 12 vs 36 ± 30%, p = 0.013). NE content from necrotic area (238; IQR 464 vs 2546; IQR 1727 ng/g in RD and control, respectively, p < 0.001) and from border zone (295; IQR 264 vs 837; IQR 207 in RD and control, respectively, p = 0.031) was significantly lower in RD than control.

Conclusions: RD results in increased myocardial salvage and better cardiac function, when performed immediately after AMI. Reduction of sympathetic activation with preservation of cardiac sympathetic functionality warranted by RD may sustain these effects.

Keywords: Acute myocardial infarction; Cardiac remodeling; Renal denervation.

MeSH terms

  • 3-Iodobenzylguanidine / administration & dosage
  • Animals
  • Disease Models, Animal
  • Humans
  • Male
  • Myocardial Infarction / physiopathology
  • Myocardial Infarction / surgery*
  • Myocardial Reperfusion
  • Myocardium / pathology*
  • Norepinephrine / metabolism
  • Renal Artery / innervation
  • Renal Artery / surgery*
  • Swine
  • Sympathectomy / methods*
  • Ventricular Remodeling

Substances

  • 3-Iodobenzylguanidine
  • Norepinephrine