Ischemic cardiomyopathy leads to inflammation and left ventricular (LV) dysfunction. Animal studies provided evidence for cardioprotective effects of the endocannabinoid system, including cardiomyocyte adaptation, inflammation, and remodeling. Cannabinoid type-2 receptor (CB2) deficiency led to increased apoptosis and infarctions with worsened LV function in ischemic cardiomyopathy. The aim of our study was to investigate a possible cardioprotective effect of endocannabinoid anandamide (AEA) after ischemia and reperfusion (I/R). Therefore, fatty acid amide hydrolase deficient (FAAH)^−/− mice were subjected to repetitive, daily, 15 min, left anterior descending artery (LAD) occlusion over 3 and 7 consecutive days. Interestingly, FAAH^−/− mice showed stigmata such as enhanced inflammation, cardiomyocyte loss, stronger remodeling, and persistent scar with deteriorated LV function compared to wild-type (WT) littermates. As endocannabinoids also activate PPAR-α (peroxisome proliferator-activated receptor), PPAR-α mediated effects of AEA were eliminated with PPAR-α antagonist GW6471 i.v. in FAAH^−/− mice. LV function was assessed using M-mode echocardiography. Immunohistochemical analysis revealed apoptosis, macrophage accumulation, collagen deposition, and remodeling. Hypertrophy was determined by cardiomyocyte area and heart weight/tibia length. Molecular analyses involved Taqman^® RT-qPCR and immune cells were analyzed with fluorescence-activated cell sorting (FACS). Most importantly, collagen deposition was reduced to WT levels when FAAH^−/− mice were treated with GW6471. Chemokine ligand-2 (CCL2) expression was significantly higher in FAAH^−/− mice compared to WT, followed by higher macrophage infiltration in infarcted areas, both being reversed by GW6471 treatment. Besides restoring antioxidative properties and contractile elements, PPAR-α antagonism also reversed hypertrophy and remodeling in FAAH^−/− mice. Finally, FAAH^−/−-mice showed more substantial downregulation of PPAR-α compared to WT, suggesting a compensatory mechanism as endocannabinoids are also ligands for PPAR-α, and its activation causes lipotoxicity leading to cardiomyocyte apoptosis. Our study gives novel insights into the role of endocannabinoids acting via PPAR-α. We hypothesize that the increase in endocannabinoids may have partially detrimental effects on cardiomyocyte survival due to PPAR-α activation.

Background: In patients with medication-related osteonecrosis of the jaw (MRONJ), the use of nasogastric tubes (NGTs) after surgery is recommended to allow adequate nutrition without food interfering with oral wound healing. However, NGT therapy is often perceived as irritating and rejected by some patients. This study evaluates the effect of NGT feeding on oral wound healing and patients' oral health-related quality of life (OHRQoL) after surgical treatment of MRONJ. Methods: We assessed early wound healing in 68 patients after Surgery for MRONJ. Postoperative comparison was made between patients with NGT feeding and a matched control group receiving an oral clear liquid diet. At 14 days postoperatively, the healing of the surgical site was morphologically classified as “complete” or “incomplete”. The Early Healing Score (EHS) and the Inflammatory Proliferative Remodeling (IPR) Scale were examined on Days 1, 5 and 14 after surgery. The German version of the Oral Health Impact Profile-14 (OHIP-G 14) was used to assess OHRQoL. Results: No significant difference was observed in the rate of complete wound healing in patients receiving NGT feeding (61.1%) compared to patients receiving an oral clear liquid diet (62.5%) at 14 days postoperatively. The mean total EHS and the IPR Scale were not significantly different between patients on NGT feeding (EHS: 18.08 ± 5.35, IPR Scale: 14.36 ± 3.08) and patients on an oral clear liquid diet (EHS: 18.03 ± 5.26, IPR Scale: 14.66 ± 3.24). Furthermore, there was no significant difference in the mean OHIP-G 14 total score regardless of NGT therapy or consumption of an oral clear liquid diet. Conclusions: The results indicate that postoperative NGT feeding has no beneficial effect on wound healing after surgical treatment of MRONJ. It can be assumed that NGT feeding can be replaced by an oral clear liquid diet after surgery for MRONJ without compromising oral wound healing. Additionally, our data suggest that there is no difference in OHRQoL between patients treated with an NGT and those treated with an oral clear liquid diet. Therefore, patients' negative perceptions of NGTs do not appear to affect OHRQoL. Trial registration. The trial was retrospectively registered with the German Clinical Trials Register on February 26, 2024 (DRKS00033706).