Analysis of the Local Opioid System in Human Left Ventricular Myocardial Tissue from Failing Hearts

The increasing age of surgical patients is associated with a higher prevalence of chronic pain and cardiovascular comorbidities, including heart failure (HF). Recent studies suggest the existence of an intrinsic cardiac opioid system that may be dynamically regulated during HF. This study investigated left ventricular myocardial tissue from patients with end-stage dilated (DCM) and/or hypertrophic obstructive cardiomyopathy (HOCM) to assess whether the expression of opioid receptors and their endogenous ligand precursor peptides varies with cardiomyopathy type and severity. It was hypothesized that the cardiac opioid system is differentially regulated in DCM and HOCM, reflecting disease-specific remodeling.

Left ventricular myocardial tissue was obtained from a biobank. Samples had previously been collected from patients with DCM who had undergone heart transplantation or left ventricular assist device implantation, and from HOCM patients who had undergone surgical myectomy. Patients were grouped by cardiomyopathy type and left ventricular ejection fraction (LVEF): DCM with moderate (20%-35%) or severely reduced (<20%) LVEF, and HOCM with preserved LVEF (>55%). Gene and protein expression of the opioid receptors delta (DOR), kappa (KOR), and mu (MOR), as well as their endogenous ligand precursors proenkephalin (PENK), prodynorphin (PDYN), and proopiomelanocortin (POMC), were analyzed by real-time PCR and western blot, respectively. In addition, opioid receptor expression was assessed by immunohistochemistry in postmortem human hearts.

KOR, PENK, and POMC mRNA were detected by real-time PCR, while DOR, MOR, and PDYN mRNA were below detection in end-stage left ventricular cardiomyopathy. Western blot analysis confirmed protein expression of DOR, KOR, MOR, and PENK. When comparing DCM to HOCM samples, KOR gene expression showed the largest difference (effect size: 0.93), and MOR protein expression showed a moderate difference (effect size: 0.62). However, none of the differences reached statistical significance ( P > .05). Immunohistochemistry confirmed the presence of opioid receptors in postmortem human myocardial tissue of the left ventricle.

This study confirms the presence of opioid receptors and opioid peptides in human left ventricular myocardial tissue, supporting the existence of an intrinsic cardiac opioid system. However, no statistically significant differences in gene or protein expression were observed between cardiomyopathy subtypes. These neutral findings suggest a largely uniform expression pattern across cardiomyopathy subtypes or only subtle disease-related changes and warrant further investigation into the potential role of the cardiac opioid system in HF pathophysiology.