Carvedilol Analogue Modulates both Basal and Stimulated Sinoatrial Node Automaticity

The membrane voltage clock and calcium (Ca(2+)) clock jointly regulate sinoatrial node (SAN) automaticity. VK-II-36 is a novel carvedilol analog that suppresses sarcoplasmic reticulum (SR) Ca(2+) release but does not block the β-receptor. The effect of VK-II-36 on SAN function remains unclear. The purpose of this study was to evaluate whether VK-II-36 can influence SAN automaticity by inhibiting the Ca(2+) clock. We simultaneously mapped intracellular Ca(2+) and membrane potential in 24 isolated canine right atriums using previously described criteria of the timing of late diastolic intracellular Ca elevation (LDCAE) relative to the action potential upstroke to detect the Ca(2+) clock. Pharmacological interventions with isoproterenol (ISO), ryanodine, caffeine, and VK-II-36 were performed after baseline recordings. VK-II-36 caused sinus rate downregulation and reduced LDCAE in the pacemaking site under basal conditions (P < 0.01). ISO induced an upward shift of the pacemaking site in SAN and augmented LDCAE in the pacemaking site. ISO also significantly and dose-dependently increased the sinus rate. The treatment of VK-II-36 (30 μmol/l) abolished both the ISO-induced shift of the pacemaking site and augmentation of LDCAE (P < 0.01), and it suppressed the ISO-induced increase in sinus rate (P = 0.02). Our results suggest that the sinus rate may be partly controlled by the Ca(2+) clock via SR Ca(2+) release during β-adrenergic stimulation

Selective sinoatrial node optical mapping and the mechanism of sinus rate acceleration

BACKGROUND: Studies using isolated sinoatrial node (SAN) cells indicate that rhythmic spontaneous sarcoplasmic reticulum calcium release (Ca clock) plays an important role in SAN automaticity. In the intact SAN, cross-contamination of optical signals from the SAN and the right atrium (RA) prevent the definitive testing of Ca clock hypothesis. The aim of this study was to use a novel approach to selectively mapping the intact SAN to examine the Ca clock mechanism. METHODS AND RESULTS: We simultaneously mapped intracellular Ca (Ca(i)) and membrane potential (V(m)) in 10 isolated, Langendorff-perfused normal canine RAs. The excitability of the RA was suppressed with high-potassium Tyrode's solution, allowing selective optical mapping of V(m) and Ca(i) of the SAN. Isoproterenol (ISO, 0.03 µmol/L) decreased the cycle length of the sinus beats, and shifted the leading pacemaker site from the middle or inferior SAN to the superior SAN in all RAs. The Ca(i) upstroke preceded the V(m) in the leading pacemaker site by up to 18 ± 2 ms. ISO-induced changes to SAN were inhibited by ryanodine (3 µmol/L), but not ZD7288 (3 µmol/L), a selective I(f) blocker. CONCLUSIONS: We conclude that, in the isolated canine RA, a high extracellular potassium concentration can suppress atrial excitability thus leading to SAN-RA conduction block, allowing selective optical mapping of the intact SAN. Acceleration of Ca cycling in the superior SAN underlies the mechanism of sinus tachycardia during sympathetic stimulation

Huge splenic epidermoid cyst with elevation of serum CA19-9 level

A 30-year-old female was referred to our hospital for further examination of liver dysfunction. A huge, soft mass was noted in her left upper quadrant on physical examination. Abdominal ultrasonography and computed tomography revealed a huge cystic tumor of 20 cm in the hilus of the spleen. Serum CA19-9 was 491 U/ml, and splenectomy was performed under suspicion of a malignant cystic tumor. The inner surface of the cyst was lined by squamous epithelial cells that were immunohistochemically positive for CA19-9. Serum CA19-9 level was normalized after the surgery. Our case of a very rare, huge epidermoid cyst of the spleen suggests that measurement of the serum CA19-9 level is useful for evaluating therapeutic efficacy of a splenic epidermoid cyst

Chronic Low-Level Vagus Nerve Stimulation Reduces Stellate Ganglion Nerve Activity and Paroxysmal Atrial Tachyarrhythmias in Ambulatory Canines

poster abstractIntroduction: Left sided low-level vagus nerve stimulation (LL-VNS) is used clinically for epilepsy and depression. We hypothesize that LL-VNS can suppress sympathetic outflow and reduce atrial tachyarrhythmias in ambulatory dogs. Methods: We implanted in 12 dogs a neurostimulator in left cervical vagus nerve and a radiotransmitter for continuous recording of left stellate ganglion nerve activities (SGNA), left thoracic vagal nerve activities (VNA) and electrocardiograms. The first 6 dogs (Group 1) underwent 1 week continuous LL-VNS. Another 6 dogs (Group 2) underwent intermittent rapid atrial pacing followed by active or sham LL-VNS on alternate weeks. Results: Integrated SGNA was significantly reduced during LL-VNS (7.8±0.9 mV-s vs. 9.4±0.9 mVs at baseline, P<0.05) in Group 1.The reduction was most apparent from 7 to 9 AM, (31% reduction, 10.8±2.5 mV-s versus 15.6±2.9 mV-s at baseline, P<0.01), along with a significantly reduced heart rate (P<0.05). SGNA-induced heart rate acceleration averaged 107.9±9.0 bpm during LL-VNS and 129.2±9.3 bpm at baseline (P<0.05). LL-VNS did not change VNA. The tyrosine hydroxylase-positive nerve structures in the left stellate ganglion were 99,684±22,257 µm2/mm2 in LL-VNS dogs and 186,561±11,383 µm2/mm2 (P<0.01) in normal control dogs. In Group 2, the frequencies of paroxysmal atrial fibrillation and atrial tachycardia during active LLVNS were 1.4±2.5/d and 8.0±5.8/d, respectively, significantly lower than during sham stimulation (9.2±6.2/d, P<0.01 and 22.0±4.4/d, P<0.001, respectively). Conclusion: LL-VNS suppresses SGNA and reduces the incidences of paroxysmal atrial tachyarrhythmias in ambulatory dogs. Significant neural remodeling of the left stellate ganglion is evident one week after cessation of chronic LL-VNS

Correction Method of Estimated Distance Using Geometrical Information on Sound Source and Microphone

In many engineering fields, distance to target is very important and fundamental information. Acoustical signal often plays an essential role in measurement of distance. Though there are distance measurement methods using a time delay between transmitted and reflected waves, it is difficult to measure short distance because the transmitted wave suppresses the reflected waves for short distance. Recently, in a research field of microwave, a method for measuring the short distance has been proposed using interference (i.e., standing wave) of transmitted and reflected waves. We applied the fundamental principle of this method to the estimation of short distance using audible sound as a transmitted wave. Until now, this method supposed that microphone was set at the straight line between a sound source and a target. However, we can not estimate exactly the distance between the microphone and target when the microphone is not set on the straight line due to the restriction of measuring environment. This paper describes a principle and its correction method for the distance estimation when a microphone is not set on the straight line between the sound source and microphone. Then, we perform a computer simulation under the condition that audible sound is used as a transmitted wave. Finally, we experimentally confirm the validity and effectiveness of the method proposed by applying it to the distance estimation problem in an actual sound field.APSIPA ASC 2009: Asia-Pacific Signal and Information Processing Association, 2009 Annual Summit and Conference. 4-7 October 2009. Sapporo, Japan. Poster session: Audio and Electroacoustics (5 October 2009)