Ultrasound Renal Denervation Attenuates Early Cardiac Remodeling After Acute Myocardial Infarction in a Swine Model of Hypertensions and Dyslipidemia: A Pilot Study

Abstract

Acute myocardial infarction (AMI) patients typically present with a constellation of one or more risk factors including hypertension, dyslipidemia, obesity, or diabetes. Neurohormonal modulation has been a mainstay pharmacotherapy in patients; however, patient compliance is a major obstacle towards clinical efficacy due to side effects and lifelong drug regimens. FDA approval of ultrasound renal denervation (uRDN) for the treatment of resistant hypertension raises the possibility of uRDN therapy for additional disease states involving sympathetic overactivity. In the current pilot study, we sought to explore if prior uRDN has cardioprotective effects against AMI in a comorbid-laden minipig model. Göttingen minipigs (female) were subject to mineralocorticoid excess and a Western high-fat, high-salt diet to induce hypertension, obesity, and hyperlipidemia. Minipigs were randomized to bilateral uRDN (n = 5) treatment or sham-RDN (n = 5) after 4 weeks. After 6 weeks of hypertension and Western high-fat, high-salt diet, animals were subjected to a 75-min left anterior descending coronary artery occlusion followed by 2 weeks of reperfusion. Markers of renal nerve viability, ischemic injury, and cardiac structure and function were assessed. In the uRDN treatment group, there was reduced renal norepinephrine content, improved survival, and reduced myocardial infarct area and calcification compared to sham-RDN treatment. Preservation of the myocardial performance Tei index indicated preserved systolic and diastolic function 2 weeks post AMI. The beneficial effects of uRDN were independent of any reductions in blood pressure. Our pilot study provides new preliminary evidence regarding the efficacy of uRDN in a preclinical large animal model of AMI that features clinically relevant comorbidities.

FIGURE 1

(A) Experimental protocol. (B) Ambulatory systolic and diastolic blood pressure. (C) Total circulating cholesterol. (D) Representative 20× photomicrographs with magnified representative images of tyrosine hydroxylase staining. Scale bars are 200 μM and 50 μM, respectively. (E) Quantification of tyrosine hydroxylase stain intensity. (F) Renal cortex norepinephrine content. (G) Cardiac Troponin I (cTnI) levels. (H) Probability of survival. Numbers in parentheses denote the number of animals left in each group across the remainder of the study. (I) Left ventricular ejection fraction (LVEF). (J) Myocardial performance (Tei) index. (K) Representative photomicrographs of hematoxylin and eosin staining of transmural section of the infarct zone (IZ). Quantification of infarct area as a percentage of total tissue area. (L) Representative photomicrographs of myocardial dystrophic calcification. Quantification of calcification as a percentage of total tissue area. Scale bars = 200 μM. Data are expressed as the mean ± SEM. Data analysis was performed using Prism 10. Nonparametric data was analyzed using the Mann–Whitney test, while parametric data underwent Student's t‐test. All p values of < 0.05 were considered statistically significant. BP, blood pressure; DOCA, deoxycorticosterone acetate; HFHS, high fat high salt diet; HTN, hypertension; NS, not significant. “N” or Numbers in circle represent the animals per group (i.e., biological replicates).