Safety of Daptomycin in Patients Receiving Hemodialysis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90386/1/phco.31.7.665.pd

Complete atrial-specific knockout of sodium-calcium exchange eliminates sinoatrial node pacemaker activity.

The origin of sinoatrial node (SAN) pacemaker activity in the heart is controversial. The leading candidates are diastolic depolarization by "funny" current (If) through HCN4 channels (the "Membrane Clock" hypothesis), depolarization by cardiac Na-Ca exchange (NCX1) in response to intracellular Ca cycling (the "Calcium Clock" hypothesis), and a combination of the two ("Coupled Clock"). To address this controversy, we used Cre/loxP technology to generate atrial-specific NCX1 KO mice. NCX1 protein was undetectable in KO atrial tissue, including the SAN. Surface ECG and intracardiac electrograms showed no atrial depolarization and a slow junctional escape rhythm in KO that responded appropriately to β-adrenergic and muscarinic stimulation. Although KO atria were quiescent they could be stimulated by external pacing suggesting that electrical coupling between cells remained intact. Despite normal electrophysiological properties of If in isolated patch clamped KO SAN cells, pacemaker activity was absent. Recurring Ca sparks were present in all KO SAN cells, suggesting that Ca cycling persists but is uncoupled from the sarcolemma. We conclude that NCX1 is required for normal pacemaker activity in murine SAN

Change in Systemic Arterial Pulsatility index (SAPi) during heart failure hospitalization is associated with improved outcomes

Study objective: To identify Change in Systemic Arterial Pulsatitlity index (∆SAPi) as a novel hemodynamic marker associated with outcomes in heart failure (HF). Design: The ESCAPE trial was a randomized controlled trial. Setting: The ESCAPE trial was conducted at 26 sites. Participants: 134 patients were analyzed (mean age 56.8 ± 13.4 years, 29 % female). Interventions: We evaluated the change in SAPi, (systemic pulse pressure/pulmonary artery wedge pressure) obtained at baseline and at the final hemodynamic measurement in the ESCAPE trial. Main outcome measures: Change in SAPi, (∆SAPi), was analyzed for the primary outcomes of death, heart transplant, left ventricular assist device (DTxLVAD) or hospitalization, (DTxLVADHF) and secondary outcome of DTxLVAD using Cox proportional hazards regression. Results: Median change in SAPi was 0.81 (IQR 0.20–1.68). ∆SAPi in uppermost quartile was associated with reductions in DTxLVADHF (HR 0.55 [95 % CI 0.32, 0.93]). ∆SAPi in the uppermost and lowermost quartiles combined was similarly associated with significant reductions in DTxLVADHF (HR 0.62 [95 % CI 0.41, 0.94]). ∆SAPi higher than 1.17 was associated with improved DTxLVADHF. ∆SAPi was also associated with troponin levels at discharge (regression coefficient p = 0.001) and trended with 6-minute walk at discharge (Spearman correlation r = 0.179, p = 0.058). Conclusion: ∆SAPi was strongly associated with improved HF clinical profile and adverse outcomes. These findings support further exploration of ∆ SAPi in the risk stratification of HF

Complete atrial-specific knockout of sodium-calcium exchange eliminates sinoatrial node pacemaker activity.

The origin of sinoatrial node (SAN) pacemaker activity in the heart is controversial. The leading candidates are diastolic depolarization by "funny" current (If) through HCN4 channels (the "Membrane Clock" hypothesis), depolarization by cardiac Na-Ca exchange (NCX1) in response to intracellular Ca cycling (the "Calcium Clock" hypothesis), and a combination of the two ("Coupled Clock"). To address this controversy, we used Cre/loxP technology to generate atrial-specific NCX1 KO mice. NCX1 protein was undetectable in KO atrial tissue, including the SAN. Surface ECG and intracardiac electrograms showed no atrial depolarization and a slow junctional escape rhythm in KO that responded appropriately to β-adrenergic and muscarinic stimulation. Although KO atria were quiescent they could be stimulated by external pacing suggesting that electrical coupling between cells remained intact. Despite normal electrophysiological properties of If in isolated patch clamped KO SAN cells, pacemaker activity was absent. Recurring Ca sparks were present in all KO SAN cells, suggesting that Ca cycling persists but is uncoupled from the sarcolemma. We conclude that NCX1 is required for normal pacemaker activity in murine SAN