Prophylactic Phosphate Supplementation for the Inpatient Treatment of Restrictive Eating Disorders.

PURPOSE: The medical stabilization of adolescent patients with restrictive eating disorders can be associated with refeeding syndrome, a potentially fatal complication preceded by refeeding hypophosphatemia (RH). Whether RH can be prevented by routine prophylactic phosphate supplementation has not been previously examined. This study sought to determine the safety and efficacy of a refeeding strategy that incorporates prophylactic phosphate supplementation to prevent RH. METHODS: Retrospective chart data were collected for patients aged younger than 18 years with restrictive eating disorders admitted to a tertiary pediatric inpatient ward between January 2011 and December 2014. All patients were refed with a standardized protocol that included prophylactic oral phosphate supplementation (1.0 ± .2 mmol/kg/day). RESULTS: During the 4-year study period, 75 admissions (70 patients) were included for analysis. The mean age and percent median body mass index of included patients were 15.3 years and 83.5%, respectively. Seven out of 75 (9%) had percent median body mass index of <70% and 26 out of 75 (35%) had percent body weight loss >20%. All patients were normophosphatemic at the time of admission (mean serum phosphate 1.24 ± .2 mmol/L). Serial laboratory evaluation revealed that all supplemented patients maintained serum phosphate levels >1.0 mmol/L during the initial 7 days of refeeding. Eleven patients became mildly hyperphosphatemic (range 1.81-2.17 mmol/L) with no associated clinical consequences. Additional analysis of 11 patients presenting with hypophosphatemia before refeeding revealed that with supplementation, phosphate values normalized by Day 1, and this group experienced no further RH episodes during initial refeeding. CONCLUSIONS: Prophylactic oral phosphate supplementation appears safe, and no episodes of RH occurred in patients with restrictive eating disorders undergoing inpatient refeeding.

Changes in connexin expression and the atrial fibrillation substrate in congestive heart failure.

RATIONALE: Although connexin changes are important for the ventricular arrhythmic substrate in congestive heart failure (CHF), connexin alterations during CHF-related atrial arrhythmogenic remodeling have received limited attention. OBJECTIVE: To analyze connexin changes and their potential contribution to the atrial fibrillation (AF) substrate during the development and reversal of CHF. METHODS AND RESULTS: Three groups of dogs were studied: CHF induced by 2-week ventricular tachypacing (240 bpm, n=15); CHF dogs allowed a 4-week nonpaced recovery interval after 2-week tachypacing (n=16); and nonpaced sham controls (n=19). Left ventricular (LV) end-diastolic pressure and atrial refractory periods increased with CHF and normalized on CHF recovery. CHF caused abnormalities in atrial conduction indexes and increased the duration of burst pacing-induced AF (DAF, from 22+/-7 seconds in control to 1100+/-171 seconds, P<0.001). CHF did not significantly alter overall atrial connexin (Cx)40 and Cx43 mRNA and protein expression levels, but produced Cx43 dephosphorylation, increased Cx40/Cx43 protein expression ratio and caused Cx43 redistribution toward transverse cell-boundaries. All of the connexin-alterations reversed on CHF recovery, but CHF-induced conduction abnormalities and increased DAF (884+/-220 seconds, P<0.001 versus control) remained. The atrial fibrous tissue content increased from 3.6+/-0.7% in control to 14.7+/-1.5% and 13.3+/-2.3% in CHF and CHF recovery, respectively (both P<0.01 versus control), with transversely running zones of fibrosis physically separating longitudinally directed muscle bundles. In an ionically based action potential/tissue model, fibrosis was able to account for conduction abnormalities associated with CHF and recovery. CONCLUSIONS: CHF causes atrial connexin changes, but these are not essential for CHF-related conduction disturbances and AF promotion, which are rather related primarily to fibrotic interruption of muscle bundle continuity.

Funny current downregulation and sinus node dysfunction associated with atrial tachyarrhythmia: a molecular basis for tachycardia-bradycardia syndrome.

BACKGROUND: Sinoatrial node (SAN) dysfunction is frequently associated with atrial tachyarrhythmias (ATs). Abnormalities in SAN pacemaker function after termination of ATs can cause syncope and require pacemaker implantation, but underlying mechanisms remain poorly understood. This study examined the hypothesis that ATs impair SAN function by altering ion channel expression. METHODS AND RESULTS: SAN tissues were obtained from 28 control dogs and 31 dogs with 7-day atrial tachypacing (400 bpm). Ionic currents were measured from single SAN cells with whole-cell patch-clamp techniques. Atrial tachypacing increased SAN recovery time in vivo by approximately 70% (P<0.01), a change which reflects impaired SAN function. In dogs that underwent atrial tachypacing, SAN mRNA expression (real-time reverse-transcription polymerase chain reaction) was reduced for hyperpolarization-activated cyclic nucleotide-gated subunits (HCN2 and HCN4) by >50% (P<0.01) and for the beta-subunit minK by approximately 42% (P<0.05). SAN transcript expression for the rapid delayed-rectifier (I(Kr)) alpha-subunit ERG, the slow delayed-rectifier (I(Ks)) alpha-subunit KvLQT1, the beta-subunit MiRP1, the L-type (I(CaL)) and T-type (I(CaT)) Ca2+-current subunits Cav1.2 and Cav3.1, and the gap-junction subunit connexin 43 (were unaffected by atrial tachypacing. Atrial tachypacing reduced densities of the HCN-related funny current (I(f)) and I(Ks) by approximately 48% (P<0.001) and approximately 34% (P<0.01), respectively, with no change in voltage dependence or kinetics. I(Kr), I(CaL), and I(CaT) were unaffected. SAN cells lacked Ba2+-sensitive inward-rectifier currents, irrespective of AT. SAN action potential simulations that incorporated AT-induced alterations in I(f) accounted for slowing of periodicity, with no additional contribution from changes in I(Ks). CONCLUSIONS: AT downregulates SAN HCN2/4 and minK subunit expression, along with the corresponding currents I(f) and I(Ks). Tachycardia-induced remodeling of SAN ion channel expression, particularly for the "pacemaker" subunit I(f), may contribute to the clinically significant association between SAN dysfunction and supraventricular tachyarrhythmias.