Alterations in K+ channel expression and gating are thought to be the major cause of action potential remodeling in heart failure (HF). We previously reported the existence of a late Na+ current (INaL) in cardiomyocytes of dogs with chronic HF, which suggested the importance of the Na+ channel in this remodeling process. The present study examined whether this INaL exists in cardiomyocytes isolated from normal and failing human hearts.A whole-cell patch-clamp technique was used to measure ion currents in cardiomyocytes isolated from the left ventricle of explanted hearts from 10 patients with end-stage HF and from 3 normal hearts. We found INaL was activated at a membrane potential of -60 mV with maximum density (0.34+/-0.05 pA/pF) at -30 mV in cardiomyocytes of both normal and failing hearts. The steady-state availability was sigmoidal, with an averaged midpoint potential of -94+/-2 mV and a slope factor of 6.9+/-0.1 mV. The current was reversibly blocked by the Na+ channel blockers tetrodotoxin (IC50=1.5 micromol/L) and saxitoxin (IC50=98 nmol/L) in a dose-dependent manner. Both inactivation and reactivation of INaL had an ultraslow time course (tau approximately 0.6 seconds) and were independent of voltage. The amplitude of INaL was independent of the peak transient Na+ current.Cardiomyocytes isolated from normal and explanted failing human hearts express INaL characterized by an ultraslow voltage-independent inactivation and reactivation.
Abstract Background : The clinical impact of echocardiographic demonstration of a vegetation (Veg) in patients in whom infective endocarditis (IE) is not suspected has not previously been analyzed. Hypothesis : In this study, an echocardiographic database was interrogated to test whether discovery of a vegetation by echocardiography should result in treatment for endocarditis if IE is not suspected. Methods : In all, 2,750 serial transthoracic echocardiograms (TTE) were reviewed to generate a list of reports containing the word Veg or thickening (Thk). A chart review of cases identified the impact the report had on patient management. To analyze reader bias due to echocardiographic requests, stating “rule out Veg or IE” as the reason for the study, an additional 1,000 serial TTE requests were segregated into two groups with and without this term. The incidence of the terms Veg or Thk in TTE reports of these groups was tabulated. Results : Of 2,750 reports, 20 contained the word Veg. Blood cultures were drawn in 16 of 20, with 7 of 16 being positive. Therapy for IE was initiated in 5 of 7 patients with positive cultures. Of 1,000 requests reviewed in the second phase, 24% of those with rule out Veg as the indication for TTE (n = 29) had Veg and 7% had Thk, while in 971 cases with other indications for TTE 0.2% had Veg and 9.3% had Thk. Conclusions : Clinicians disregard TTE demonstration of Veg if clinical suspicion for IE is low. It is not clear whether the initial echo request biases the interpretation.
