Comparative effects of ultra-short-acting beta1-blockers on voltage-gated tetrodotoxin-resistant Na+ channels in rat sensory neurons.

BACKGROUND AND OBJECTIVE: To examine a possible mechanism for their antinociceptive actions, we compared the effects of two clinically used ultra-short-acting beta1-blockers, landiolol and esmolol, on tetrodotoxin-resistant sodium (TTX-r Na) channels in rat dorsal root ganglion neurons, which are important for nociception. METHODS: In small (<30 microm) dorsal root ganglion neurons from Sprague-Dawley rats, recordings of whole-cell membrane currents were made using the patch-clamp technique. To examine the effects of landiolol and esmolol on TTX-r Na currents, whole-cell membrane Na currents were evoked every 10 s by stepping for 50 ms from a holding potential of -70 to -10 mV. Each drug was applied at stepwise-increased concentrations every 2 min. The voltage dependence of the steady-state inactivation of the TTX-r Na current was investigated by using a conventional double-pulse protocol. To test for use-dependent blockade of TTX-r Na channels by beta-blockers, trains of depolarizing pulses (to -10 from a holding potential of -70 mV) were applied at one of three frequencies (0.2, 5 or 20 Hz) in the absence or presence of drug (landiolol 8 mmol l, esmolol 140 micromol l). RESULTS: Esmolol blocked TTX-r Na currents in a dose-dependent and use-dependent manner, but a very high concentration of landiolol was required to block TTX-r Na channel activities. The half-maximal inhibitory concentrations (IC50) for the TTX-r Na current were (holding potential, -70 mV) landiolol 7.66 +/- 0.62 mmol l (n = 6) and esmolol 145 +/- 7.5 micromol l (n = 6), and the Hill coefficients were landiolol 1.06 +/- 0.09 (n = 6) and esmolol 0.96 +/- 0.05 (n = 6). CONCLUSION: Esmolol, but not landiolol, may have useful effects against pain related to TTX-r Na channel activity.

Analysis of concentration characteristics in ultrasonic atomization by droplet diameter distribution.

The droplet diameter distribution and concentration characteristics in ultrasonic atomization were experimentally studied. The samples were aqueous solutions of methanol, ethanol and 1-propanol. The diameter distribution of atomized droplets showed the normal distribution, and the median diameter and standard deviation were expressed by means of the ultrasonic condition and the liquid properties. The concentration characteristic in ultrasonic atomization was analyzed by using the model of shell and core to the atomized droplet, where the former and latter consist of solute and solution, respectively. The value, which was surface solute amount in droplet multiplied by the molecular volume, increased with increasing solute molar fraction in bulk liquid and was independent of alcohol kinds. The rate of accompanying liquid and the solute molar fraction in accompanied liquid were estimated from the diameter distribution and the surface solute amount in droplet.

The effects of class Ic antiarrhythmics on tetrodotoxin-resistant Na+ currents in rat sensory neurons.

IV or oral administration of antiarrhythmics has been reported to be effective for relieving neuropathic pain. Recent reports have indicated that tetrodotoxin-resistant (TTX-R) Na(+) channels play important roles in the nerve conduction of nociceptive sensation. In the present study, we investigated the effects of flecainide, pilsicainide (class Ic antiarrhythmics), and lidocaine (a class Ib drug) on TTX-R Na(+) currents in rat dorsal root ganglion neurons using the whole-cell patch-clamp method. Flecainide, pilsicainide, and lidocaine reversibly blocked the peak amplitude of TTX-R Na(+) currents in a concentration-dependent manner with half-maximum inhibitory concentration values of 8.5 +/- 6.6 microM (n = 7), 78 +/- 6.9 microM (n = 7), and 73 +/- 6.8 microM (n = 7), respectively. Each drug shifted the inactivation curve for the TTX-R Na(+) currents in the hyperpolarizing direction and caused a use-dependent block. We also studied an interaction between these antiarrhythmics on TTX-R Na(+) channels. Additional application of flecainide or pilsicainide to lidocaine resulted in an additive increase of tonic and use-dependent block. These results suggest that the inhibition of TTX-R Na(+) currents of dorsal root ganglion neurons by such antiarrhythmics is attributable, at least partly, to their antinociceptive effects.

Automated cardiac output measurement by transesophageal color Doppler echocardiography.

UNLABELLED: Automated cardiac output measurement (ACOM), which integrates digital color Doppler velocities in space and in time, has been validated using transthoracic echocardiography but has not been tested using transesophageal echocardiography (TEE). Therefore, we determined the feasibility of the ACOM method by TEE in 36 patients undergoing cardiovascular surgery. Regions of interest for ACOM were placed within a color sector across the main pulmonary artery (PA), the mitral annulus, and the left ventricular outflow tract. Cardiac output was determined from the PA flow, the mitral flow, and the left ventricular ejection flow at each view using the ACOM method. We compared measurements of cardiac output derived from the ACOM method with measurements simultaneously obtained by thermodilution (TD). In the mitral flow analysis, the values derived from ACOM correlated well with those from TD (R(2) = 0.85; mean difference = 0.01 +/- 0.58 L/min in the 2-chamber view; R(2) = 0.78; mean difference = -0.10 +/- 0.68 L/min in the 4-chamber view). In the PA flow analysis, the values derived from ACOM did not correlate with those from TD (R(2) = 0.30). In the left ventricular outflow tract analysis, it was very difficult to obtain the optimal view (44%) in which color Doppler flow signals adequately appeared. Using the ACOM method, we obtained good correlation and agreement for cardiac output measurements in the mitral flow analysis compared with TD. The ACOM method is a practical and rapid method to measure cardiac output by TEE analysis of mitral flow. IMPLICATIONS: Automated cardiac output measurement by transesophageal color Doppler echocardiography is a practical and rapid method to measure cardiac output. This technique is a promising new approach to echocardiographic quantification in the intraoperative setting.