Trimethylamine-N-oxide acutely increases cardiac muscle contractility.

Cardiovascular disease is a major cause of morbidity and mortality among patients with chronic kidney disease (CKD). Trimethylamine-N-oxide (TMAO), a uremic metabolite that is elevated in the setting of CKD, has been implicated as a nontraditional risk factor for cardiovascular disease. While association studies have linked elevated plasma levels of TMAO to adverse cardiovascular outcomes, its direct effect on cardiac and smooth muscle function remains to be fully elucidated. We hypothesized that pathological concentrations of TMAO would acutely increase cardiac and smooth muscle contractility. These effects may ultimately contribute to cardiac dysfunction during CKD. High levels of TMAO significantly increased paced, ex vivo human cardiac muscle biopsy contractility (P < 0.05). Similarly, TMAO augmented contractility in isolated mouse hearts (P < 0.05). Reverse perfusion of TMAO through the coronary arteries via a Langendorff apparatus also enhanced cardiac contractility (P < 0.05). In contrast, the precursor molecule, trimethylamine (TMA), did not alter contractility (P > 0.05). Multiphoton microscopy, used to capture changes in intracellular calcium in paced, adult mouse hearts ex vivo, showed that TMAO significantly increased intracellular calcium fluorescence (P < 0.05). Interestingly, acute administration of TMAO did not have a statistically significant influence on isolated aortic ring contractility (P > 0.05). We conclude that TMAO directly increases the force of cardiac contractility, which corresponds with TMAO-induced increases in intracellular calcium but does not acutely affect vascular smooth muscle or endothelial function of the aorta. It remains to be determined if this acute inotropic action on cardiac muscle is ultimately beneficial or harmful in the setting of CKD.NEW & NOTEWORTHY We demonstrate for the first time that elevated concentrations of TMAO acutely augment myocardial contractile force ex vivo in both murine and human cardiac tissue. To gain mechanistic insight into the processes that led to this potentiation in cardiac contraction, we used two-photon microscopy to evaluate intracellular calcium in ex vivo whole hearts loaded with the calcium indicator dye Fluo-4. Acute treatment with TMAO resulted in increased Fluo-4 fluorescence, indicating that augmented cytosolic calcium plays a role in the effects of TMAO on force production. Lastly, TMAO did not show an effect on aortic smooth muscle contraction or relaxation properties. Our results demonstrate novel, acute, and direct actions of TMAO on cardiac function and help lay the groundwork for future translational studies investigating the complex multiorgan interplay involved in cardiovascular pathogenesis during CKD.

Repair of left atrial-esophageal fistula following percutaneous radiofrequency ablation for atrial fibrillation.

Atrial-esophageal fistula is a rare but often fatal complication of percutaneous radiofrequency ablation for atrial fibrillation. We present a patient who was diagnosed with this complication in a delayed fashion and successfully treated with primary repair via left thoracotomy. The details of the surgical approach are discussed.

The efficacy of supplemental magnesium in reducing atrial fibrillation after coronary artery bypass grafting.

BACKGROUND: Atrial fibrillation after coronary artery bypass is reported from 17% to 53%. Hypomagnesemia after this surgery is considered a contributing factor. METHODS: Two hundred-two coronary bypass patients were randomized to magnesium (n = 105) or placebo (n = 97). The experimental group received 80-mg magnesium sulfate per kilogram ideal weight in 100 mL dextrose 5% water 30 minutes preoperatively. Postoperatively, patients received 8-mg magnesium sulfate per kilogram ideal weight intravenous per hour more than 48 hours. The control group received dextrose 5% water at these intervals. RESULTS: After the first bolus serum magnesium was experimental 4.75 mg/dL versus control 1.91 mg/dL, p less than 0.001, and remained different until postoperative day 4 (experimental 2.33 mg/dL vs control 2.26 mg/dL, p = 0.24). Atrial appendage and strap muscle were analyzed after the first bolus and after revascularization. There were no differences between groups in tissue magnesium or calcium. Urinary magnesium was elevated in the experimental (experimental 324.5 mg/24 hours, vs control 45.1 mg/24 hours, p = 0.01). Calcium excretion was higher (experimental 370 mg/24 hours vs control 186 mg/24 hours, p < 0.001) and was associated with lower serum calcium. Serum calcium was higher in the control through the fourth postoperative day. The incidence of atrial fibrillation was experimental 32 of 105 (30.5%) versus control 41 of 97 (42.3%) p = 0.08. Atrial fibrillation was different on the first postoperative day (experimental 3/105, 2.9% vs control 9/97, 9.3%), p = 0.05. CONCLUSIONS: Overall prophylactic magnesium supplementation does not significantly reduce atrial and ventricular arrhythmias. The only significant benefit of magnesium supplementation was on the first postoperative day.