RESUMEN
BACKGROUND: Heart failure with preserved ejection fraction is the most common cause of heart failure and is characterized by impaired diastolic relaxation. Bariatric surgery significantly improves diastolic relaxation, but a mechanism beyond weight loss remains unknown. OBJECTIVES: We tested the hypothesis that a sleeve gastrectomy (SG) will improve diastolic dysfunction independent of weight loss due to postoperative alterations in the enterocardiac axis. SETTING: University research laboratory. METHODS: Male Wistar rats were fed a high-fat diet (HFD) or low-fat diet (LFD) for 10 weeks and then divided into SG-HFD, pair-fed sham HFD, ad-lib sham HFD, or ad-lib sham LFD groups (n = 9-14 per group). At least 2 months postoperatively, cardiac function, meal tolerance, glucose tolerance, and cardiac gene expression were compared between groups. RESULTS: Only the SG cohort showed significant improvements in postoperative diastolic relaxation (isovolumetric relaxation time pre-SG: 14.7 ± 2.3 msec, post-SG: 11.2 ± 1.8 msec, P < .001). SG significantly increased active glucagon-like peptide-1 (P = .03). Compared to pair-fed sham HFD rats, SG-HFD rats had significantly altered mRNA cardiac gene expression, including sarco/endoplasmic reticulum Ca2+-ATPase 2 a (SERCA2 a) (P < .001). CONCLUSIONS: SG improves diastolic function independent of weight loss in a rat model of obesity with beneficial alterations in cardiac gene expression of multiple known targets related to cardiac failure, including SERCA2 a. These data support that a greater curve gastrectomy induces beneficial intracellular cardiac signaling for diastolic function mediated by the enterocardiac axis that is independent of weight loss. These findings could translate to offering metabolic surgery to patients with heart failure with preserved ejection fraction.
Asunto(s)
Cirugía Bariátrica/métodos , Presión Sanguínea/fisiología , Gastrectomía/métodos , Obesidad/cirugía , Pérdida de Peso/fisiología , Animales , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Corazón/fisiología , Insuficiencia Cardíaca , Masculino , Obesidad/fisiopatología , Ratas , Ratas WistarRESUMEN
BACKGROUND: Recent studies have suggested that potential aberrant alterations in the gastrointestinal microbiome contribute to the development of cardiovascular disease, specifically hypertension. Bariatric surgery produces significant sustained weight loss and hypertension resolution likely through multiple mechanisms which includes beneficial changes in the gut microbiome. We hypothesized that the type of prophylactic antibiotic given for bariatric surgery could impact the resolution rate of hypertension by altering the post-operative gastrointestinal microflora. METHODS: A retrospective analysis of adult bariatric patients who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) between 2012 and 2016 was conducted. The standard antibiotic prophylaxis was cefazolin, or clindamycin in patients with a penicillin allergy. Univariate analyses were performed comparing the differing peri-operative antibiotic treatments with resolution of hypertension at 2-week (± 1 week), 6-week (± 2 weeks), 3-month (± 2 weeks), 6-month (± 6 weeks), and 1-year (± 2 months) follow-up appointments. The criterion for resolution of hypertension was no longer requiring medication at time of follow-up. RESULTS: In total, 123 RYGB and 88 SG patients were included. No significant differences were found between cefazolin and clindamycin regarding hypertension resolution rates after SG. However, patients who underwent RYGB and received clindamycin had a significantly higher rate of hypertension resolution compared to cefazolin. This effect started at 2 weeks post-operatively (52.4% vs. 23.5% respectively, p = 0.008) and persisted up to the 1-year (57.9% vs. 44.0% respectively, p = 0.05). CONCLUSION: Prophylactic peri-operative, intravenous clindamycin was associated with significantly increased resolution of post-operative hypertension compared to cefazolin. This finding was not observed in SG patients. Future studies are needed to confirm the mechanism of action for this novel finding is due to the differing modifications of the gastrointestinal microflora after RYGB resulting from the specific peri-operative antibiotic administered.