Rationale Fatty acid oxidation is transcriptionally regulated by peroxisome proliferator-activated receptor (PPAR)α and under normal conditions accounts for 70% of cardiac ATP content. Reduced Ppara expression during sepsis and heart failure leads to reduced fatty acid oxidation and myocardial energy deficiency. Many of the transcriptional regulators of Ppara are unknown. Objective To determine the role of Krüppel-like factor 5 (KLF5) in transcriptional regulation of Ppara. Methods and Results We discovered that KLF5 activates Ppara gene expression via direct promoter binding. This is blocked in hearts of septic mice by c-Jun, which binds an overlapping site on the Ppara promoter and reduces transcription. We generated cardiac myocyte-specific Klf5 knockout mice that showed reduced expression of cardiac Ppara and its downstream fatty acid metabolism-related targets. These changes were associated with reduced cardiac fatty acid oxidation, ATP levels, increased triglyceride accumulation and cardiac dysfunction. Diabetic mice showed parallel changes in cardiac Klf5 and Ppara expression levels. Conclusions Cardiac myocyte KLF5 is a transcriptional regulator of Ppara and cardiac energetics.

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The pathophysiology of hypertension in patients on renal replacement therapy is not yet clear, and the role of extracellular fluid overload is still a matter of debate. The main problem is the lack of techniques to determine the fluid state. Recently new noninvasive techniques have become available which make it possible to accurately determine the hydration state in these patients. We have studied the influence of the hydration state on interdialytic blood pressure in 45 patients: 21 (46.6%) using antihypertensive medication and 24 (53.4%) without antihypertensive medication. Total body water (TBW) was determined by bioelectrical impedance analysis performed just before a hemodialysis session. The TBW was then related to the fat-free mass calculated by the anthropometric method (aFFM) of Durnin. The hydration state was defined using the following formula: TBW/aFFM·100. Furthermore, for each patient the ideal TBW was calculated according to the Watson formula. The difference between TBW and ideal TBW was considered a further index of the hydration state. Ambulatory blood pressure monitoring was performed by using a Takeda 2420 recorder according to the Korotkoff method during the 24 h before the midweek hemodialysis session. Blood pressure monitoring showed a significant correlation with the hydration state of these patients. In conclusion, the hydration state seems to play a major role in interdialytic blood pressure control.

The antiarrhythmic potential of postconditioning in in vivo models remains poorly defined. We compared the effects of pre- and postconditioning on ventricular arrhythmogenesis against controls with and without reperfusion. Wistar rats (n = 40, 269 ± 3 g) subjected to ischemia (30 minutes)--reperfusion (24 hours) were assigned to the following groups: (1) preconditioning (2 cycles), (2) postconditioning (6 cycles), or (3) no intervention and were compared with (4) nonreperfused infarcts and (5) sham-operated animals. Infarct size was measured, and arrhythmogenesis was evaluated with continuous telemetric electrocardiographic recording, heart rate variability indices, and monophasic action potentials (MAPs). During a 24-hour observation period, no differences in mortality were observed. Reperfusion decreased infarct size and ameliorated sympathetic activation during the late reperfusion phase. Preconditioning decreased infarct size by a further 35% (P = .0017), but only a marginal decrease (by 18%, P = .075) was noted after postconditioning. Preconditioning decreased arrhythmias during ischemia and early reperfusion, whereas postconditioning almost abolished them during the entire reperfusion period. No differences were noted in MAPs or in the magnitude of sympathetic activation between the 2 interventions. Compared to postconditioning, preconditioning affords more powerful cytoprotection, but both interventions exert antiarrhythmic actions. In the latter, these are mainly evident during the ischemic phase and continue during early reperfusion. Postconditioning markedly decreases reperfusion arrhythmias during a prolonged observation period. The mechanisms underlying the antiarrhythmic effects of pre- and postconditioning are likely different but remain elusive.

The persistence of a left superior vena cava is the result of a lack of an embryological involution of the left anterior cardinal vein. This anomaly is very rare: about 0.3% of the general population. Its incidence increases remarkably from 3-10% in those patients affected with congenital heart disease. Described herein is a case of persistent left superior vena cava, discovered by chance, following the placement of a central venous catheter for hemodialysis. A chest X-ray in projection back-forward showed the central venous catheter along the left sternal margin simulating a placement in the aorta artery. This clinical picture, as described in the literature, is often accompanied by other anatomical anomalies, in our case, by the congenital agenesis of a solitary pelvic kidney. In agreement with the literature and in contrast with what has been reported recently, we sustain that a central venous catheter placed, for any reason, in the persistent left superior vena cava must be removed immediately because it can induce hyperkinetic arrhythmia and cardiac arrest as in our case. Our case report should be a warning that lack of awareness of the anomalies of the big central veins can cause a rise in morbidity.