Effects of Cyproheptadine on Mitral Valve Remodeling and Regurgitation After Myocardial Infarction.

BACKGROUND: Ischemic mitral regurgitation (MR) is primarily caused by left ventricle deformation, but leaflet thickening with fibrotic changes are also observed in the valve. Increased levels of 5-hydroxytryptamine (5-HT; ie, serotonin) are described after myocardial infarction (MI); 5-HT can induce valve fibrosis through the 5-HT type 2B receptor (5-HT2BR). OBJECTIVES: This study aims to test the hypothesis that post-MI treatment with cyproheptadine (5-HT2BR antagonist) can prevent ischemic MR by reducing the effect of serotonin on mitral biology. METHODS: Thirty-six sheep were divided into 2 groups: inferior MI and inferior MI treated with cyproheptadine (0.5 mg/kg/d). Animals were followed for 90 days. Blood 5-HT, infarct size, left ventricular volume and function, MR fraction and mitral leaflet size were assessed. In a complementary in vitro study, valvular interstitial cells were exposed to pre-MI and post-MI serum collected from the experimental animals. RESULTS: Increased 5-HT levels were observed after MI in nontreated animals, but not in the group treated with cyproheptadine. Infarct size was similar in both groups (11 ± 3 g vs 9 ± 5 g; P = 0.414). At 90 days, MR fraction was 16% ± 7% in the MI group vs 2% ± 6% in the cyproheptadine group (P = 0.0001). The increase in leaflet size following MI was larger in the cyproheptadine group (+40% ± 9% vs +22% ± 12%; P = 0.001). Mitral interstitial cells overexpressed extracellular matrix genes when treated with post-MI serum, but not when exposed to post-MI serum collected from treated animals. CONCLUSIONS: Cyproheptadine given after inferior MI reduces post-MI 5-HT levels, prevents valvular fibrotic remodeling, is associated with larger increase in mitral valve size and less MR.

Effect of bariatric surgery on blood pressure response to exercise in a severely obese population.

BACKGROUND: Exaggerated blood pressure response to exercise is a cardiovascular risk factor associated to higher morbidity and mortality. Severely obese patients have an increased risk of exercise-induced hypertension (EIH). We aimed to assess the blood pressure response to exercise in patients with severe obesity who underwent bariatric surgery as well as the main determinants of this response. METHODS: We used data from the ACTIVE clinical trial, in which 60 severely obese patients who underwent bariatric surgery were enrolled. Anthropometric measurements, abdominal and mid-thigh computed tomography scans and maximal exercise testing were performed before bariatric surgery, as well as 3 and 6 months post-surgery. EIH was defined as a maximal SBP ≥210 mmHg for men and ≥190 mmHg for women. RESULTS: At baseline, 62% of patients had EIH. At 6 months, we observed an EIH resolution rate of 39%. The main determinant of EIH resolution was sex. Actually, patients with EIH resolution were mostly women without resting hypertension and a lower amount of visceral adipose tissue. CONCLUSION: These results suggest that bariatric surgery is efficient to resolve EIH, particularly in women with initially a better anthropometric profile.