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Hypokalemia, an abnormally low level of potassium (K + ), is a electrolyte imbalance that commonly occurs in heart failure patients. Hypokalemia is well known to induce lethal ventricular arrhythmia. However, the effects of hypokalemia in failing hearts that have undergone electrophysiological remodeling, i.e., the reactivation of fetal-type ion channels, remain unexplored. We have examined the effect of hypokalemia in the myocytes of transgenic mice overexpressing the hyperpolarization-activated, cyclic nucleotide-sensitive (HCN) channel in the heart (HCN2-Tg mice). Perfusion with a mild hypokalemic solution containing 3 mM K + induced ectopic ventricular automaticity in 55.0% of HCN2-Tg mouse myocytes. In the remaining HCN2-Tg mouse myocytes, the resting membrane potential (RMP) was more depolarized than that of wild-type myocytes subjected to the same treatment and could also be hyperpolarized by an HCN channel blocker. We conclude that in hypokalemia in our mice model, the HCN2 channel was constitutively activated at the hyperpolarized RMP, thereby destabilizing the electrophysiological activity of ventricular myocytes.

Key Points: The contribution of HCN4 pacemaker channels in the autonomic regulation of the sino-atrial node (SAN) has been a matter of debate. The transgenic overexpression of HCN4 did not induce tachycardia, but reduced heart rate variability, while the conditional knockdown of HCN4 gave rise to sinus arrhythmia. The response of the SAN to β-adrenergic stimulation was not affected by overexpression or knockdown of HCN4 channels. When HCN4 channels were knocked down, the parasympathetic response examined by cervical vagus nerve stimulation (CVNS) was enhanced; the CVNS induced complete sinus pause. The overexpression of HCN4 attenuated bradycardia induced by CVNS only during β-adrenergic stimulation. We concluded that HCN4 pacemaker channels stabilize the spontaneous firing by attenuating the parasympathetic response of the SAN., Abstract: The heart rate is dynamically controlled by the sympathetic and parasympathetic nervous systems that regulate the sinoatrial node (SAN). HCN4 pacemaker channels are the well-known causative molecule of congenital sick sinus syndrome. Although HCN4 channels are activated by cAMP, the sympathetic response of the SAN was preserved in patients carrying loss-of-function mutations of the HCN4 gene. In order to clarify the contribution of HCN4 channels in the autonomic regulation of the SAN, we developed novel gain-of-function mutant mice in which the expression level of HCN4 channels could be reversibly changed from zero to ∼3 times that in wild-type mice, using tetracycline transactivator and the tetracycline responsive element. We recorded telemetric ECGs in freely moving conscious mice and analysed the heart rate variability. We also evaluated the response of the SAN to cervical vagus nerve stimulation (CVNS). The conditional overexpression of HCN4 did not induce tachycardia, but reduced heart rate variability. The HCN4 overexpression also attenuated bradycardia induced by the CVNS only during the β-adrenergic stimulation. In contrast, the knockdown of HCN4 gave rise to sinus arrhythmia, and enhanced the parasympathetic response; complete sinus pause was induced by the CVNS. In vitro, we compared the effects of acetylcholine on the spontaneous action potentials of single pacemaker cells, and found that similar phenotypic changes were induced by genetic manipulation of HCN4 expression both in the presence and absence of β-adrenergic stimulation. Our study suggests that HCN4 channels attenuate the vagal response of the SAN, and thereby stabilize the spontaneous firing of the SAN., (© 2018 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

We report a significant complication that occurred during double guidewire insertion. The first guidewire (GW1) was inserted under ultrasonographic guidance, whereas the second guidewire (GW2) was inserted by the landmark-based method. Subsequently, GW2 penetrated and entangled with GW1, which caused difficulty in removing both guidewires. A dilator was used to dilate the puncture site, allowing simultaneous removal of both guidewires with minimal invasion. The first guidewire was found to be pointing in a cranial direction, indicating the manner in which the second guidewire's puncture needle had penetrated it. Thus, when double cannulation is performed, guidewire position should be confirmed.

Cerebral venous sinus thrombosis (CVST) is rare but displays various and often dramatic clinical symptoms. Few cases of CVST have been reported in the field of anesthesiology. We encountered an unexpected case of CVST that presented with delayed emergence from anesthesia after resection of a brain tumor. A 55-year-old man was scheduled for resection of an oligoastrocytoma in his right frontal lobe. After smooth induction of general anesthesia, anesthesia was maintained uneventfully for about 7 h with target-controlled infusion (TCI) of propofol and remifentanil, except for a seizure generated when the right anterior central gyrus was stimulated to allow motor evoked potential monitoring. Immediately after the cessation of TCI, spontaneous respiration was restored. However, the patient was unexpectedly comatose, and no response to painful stimuli or coughing during tracheal suctioning was observed. A computed tomogram taken 2 h after surgery showed diffuse brain edema, even though the neurosurgeons did not notice any cerebral swelling during closing of the dura mater. A magnetic resonance venogram revealed thromboses in the superior sagittal and straight sinuses. On the 9th postoperative day, the patient died without recovering consciousness or his brainstem reflexes. Anesthesiologists should be aware of CVST as a cause of delayed emergence from anesthesia after craniotomy.