Our understanding of the left atrium is growing, although there are many aspects that are still poorly understood. The left atrium size as an imaging biomarker has been consistently shown to be a powerful predictor of outcomes and of different cardiovascular disorders, such as, but not limited to, atrial fibrillation, congestive heart failure, mitral regurgitation and stroke. Left atrial function has been conventionally divided into three integrated phases: reservoir, conduit and booster-pump. The highly dynamic left atrium and its response to the stretch and secretion of atrial neuropeptides leaves the left atrium far from being a simple transport chamber. The aim of this review is to provide an understanding of the left atrial physiology and its relation to disorders within the heart.

Park HJ, Link MS, Noujaim SF, Galper JB. Increased inducibility of ventricular tachycardia and decreased heart rate variability in a mouse model for type 1 diabetes: effect of pravastatin. Am J Physiol Heart Circ Physiol 305: H1807-H1816, 2013. First published October 25, 2013; doi:10.1152/ajpheart.00979.2012.-Although a reduction in the high-frequency (HF) component of heart rate variability (HRV) is a major complication of diabetes and a risk factor for sudden death, its relationship to ventricular tachycardia (VT) is unknown. We developed a mouse model for the study of VT and its relationship to changes in HRV in the Akita type 1 diabetic mouse. Programmed ventricular stimulation of anesthetized mice demonstrated that Akita mice were more inducible for VT compared with wild-type mice: 78.6% versus 28.6% (P ϭ 0.007). Optical mapping of perfused hearts demonstrated multifocal breakthroughs that occasionally gave rise to short-lived rotors consistent with focal initiation and maintenance of VT. Treatment of Akita mice with pravastatin, which had been previously shown clinically to decrease ventricular ectopy and to increase HRV, decreased the inducibility of VT: 36.8% compared with 75.0% with placebo treatment (P ϭ 0.022). The HF fraction of HRV was reduced in Akita mice (48.6 Ϯ 5.2% vs. 70.9 Ϯ 4.8% in wild-type mice, P ϭ 0.005) and was increased compared with placebo treatment in pravastatin-treated mice. Pretreatment of Akita mice with the muscarinic agonist carbamylcholine or the ␤-adrenergic receptor blocker propranolol decreased the inducibility of VT (P ϭ 0.001). In conclusion, the increased inducibility of focally initiated VT and reduced HF fraction in Akita mice were partially reversed by both pravastatin treatment and pharmacologic reversal of parasympathetic dysfunction. In this new animal model for the study of the pathogenesis of VT in type 1 diabetes, pravastatin may play a role in the prevention of VT by attenuating parasympathetic dysfunction. type 1 diabetes; ventricular tachycardia; statins; secondary effects of diabetes ALTHOUGH DIABETES MELLITUS is associated with an increase in cardiovascular mortality and sudden death (11), its relationship to ventricular tachycardia (VT) is not known. Risk factors for sudden death include clinical manifestations of parasympathetic dysfunction, such as a decreased high-frequency (HF), predominantly parasympathetic, component of heart rate (HR) variability (HRV) and increased dispersion of QT intervals (25,27). Furthermore, analysis of HRV in a group of patients with a history of nonsustained VT demonstrated a reduction in parasympathetic activity in conjunction with an increase in sympathetic activity before the onset of nonsustained VT, further supporting the relationship between decreased parasympathetic tone and the development of arrhythmia (21). Patients with diabetes for 10 yr have an impaired response of the heart to parasympathetic stimulation characterized by a reduction in the HF component of HRV. The increase in the incidence of sudden death in d...

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Background The incidence of sudden arrhythmic death is markedly increased in diabetics. Objective Develop a mouse model for Post MI VT in the diabetic heart and determine the mechanism of an antiarrhythmic effect of statins. Methods EKG transmitters were implanted in wild type (WT), placebo and pravastatin treated Type I diabetic Akita mice, MIs induced by coronary ligation, Ca2+ transients studied by optical mapping, Ca2+ transients and sparks in left VM (VM) by the Ionoptix system and confocal microscopy. Results Burst pacing of Akita mouse hearts resulted in rate related QRS/T-Wave alternans, which was attenuated in pravastatin treated mice. Post MI Akita mice developed QRS/T-wave alternans and VT, 2,820 ± 879 beats/mouse which decreased to 343 ± 115 in pravastatin treated mice, (n=13, P<0.05). Optical mapping demonstrated pacing induced VT originating in the peri-infarction zone and Ca2+ alternans, both attenuated in hearts of statin treated mice. Akita VM displayed: Ca2+ alternans, triggered activity, increased; Ca2+ transient decay time (Tau), incidence of Ca2+ sparks and cytosolic Ca2+ and decreased SR Ca2+ stores which were in part reversed in cells from statin treated mice. Homogenates of Akita ventricles demonstrated decreased SERCA2a/PLB ratio and increased ratio of protein phosphatase (PP-1) to the PP-1 inhibitor PPI-1 reversed in homogenates of pravastatin treated Akita mice. Conclusions Pravastatin decreased the incidence of post MI VT and Ca2+ alternans in Akita mouse hearts in part via the reversal of abnormalities of Ca2+ handling via the PP-1/PPI-1 pathway.