The Roles of Cardiovascular H2-Histamine Receptors Under Normal and Pathophysiological Conditions

This review addresses pharmacological, structural and functional relationships among H2-histamine receptors and H1-histamine receptors in the mammalian heart. The role of both receptors in the regulation of force and rhythm, including their electrophysiological effects on the mammalian heart, will then be discussed in context. The potential clinical role of cardiac H2-histamine-receptors in cardiac diseases will be examined. The use of H2-histamine receptor agonists to acutely increase the force of contraction will be discussed. Special attention will be paid to the potential role of cardiac H2-histamine receptors in the genesis of cardiac arrhythmias. Moreover, novel findings on the putative role of H2-histamine receptor antagonists in treating chronic heart failure in animal models and patients will be reviewed. Some limitations in our biochemical understanding of the cardiac role of H2-histamine receptors will be discussed. Recommendations for further basic and translational research on cardiac H2-histamine receptors will be offered. We will speculate whether new knowledge might lead to novel roles of H2-histamine receptors in cardiac disease and whether cardiomyocyte specific H2-histamine receptor agonists and antagonists should be developed.

Fatigue-Related Effects in the Process of Task Interruption on Working Memory

Interruption generally has a negative effect on performance by affecting working memory (WM). However, the neural mechanism of interruption has yet to be understood clearly, and previous studies have largely ignored the role of fatigue state. To address these issues, the present study explores the behavioral and electrophysiological effects of interruption on WM performance using electroencephalography (EEG) data. The moderating effect of fatigue is also explored. The participants performed spatial 2-back tasks with math task interruption, suspension interruption, and non-interruption under different fatigue states. The results show that interruption led to increased alpha activity and P300 amplitude, indicating inhibitory control to interference from irrelevant information. Analysis of P200 amplitude revealed that interruption affected attentional reallocation when resuming the primary task. Increased theta power indicated an increased demand for information maintenance during the interruption. A speeding-up effect was discovered after interruption; however, fatigue impaired cognitive ability and further exacerbated the negative effects of interruption on WM and behavioral performance. These findings contribute to a better understanding of cognitive activity during the interruption and of the interaction with fatigue, and provide further support for the theory of memory for goals (MFG).

Species dependent cardiac electrophysiological effects elicited by various potassium channel blocking drugs

Rodents are commonly used as models in electrophysiology. However, distinct differences exist between large animals and rodents in terms of their ion channel expression and action potential shapes, possibly limiting the translational value of findings obtained in rodents. We aimed for a direct comparison of the possible impact of selective inhibition of ion channels on the cardiac repolarization in preparations from human hearts and from model species. We applied the standard microelectrode technique at 37°C on cardiac ventricular preparations (papillary muscles and trabecules) from human (n = 63), dog (n = 47), guinea pig (n = 53), rat (n = 43), and rabbit (n = 16) hearts, paced at 1 Hz. To selectively block the IKur current, 1 µM XEN-D101; IK1 current, 10 µM barium chloride; IKr current, 50 nM dofetilide; IKs current, 500 nM HMR-1556; and Ito current, 100 µM chromanol-293B were applied directly to the tissue bath. The block of IKur and IK1 elicited significantly more prominent prolongation of APD in rats (35.6% and 67.9%, respectively) when compared with the other species, including that of human (1.0% and 2.6%, respectively). On the other hand, IKr block did not affect APD in rat preparations (1.6%), whereas it elicited marked prolongation in other species (9.0–47.7%), especially being pronounced in human preparations (60.3%). IKs inhibition elicited similar but minor APD prolongation (0.3–11.4%) in all species. Inhibition of Ito moderately lengthened APD in dog (22.3%) and rabbit (17.5%) preparations but elicited no change of APD in human preparations. In contrast, block of Ito caused marked APD prolongation in rat preparations (33.2%). Our findings suggest that the specific inhibition of various ion channels elicits fundamentally different effects in rodent ventricular action potential when compared with those of other species, including human. Therefore, from a translational standpoint, rodent models in cardiac electrophysiological and arrhythmia research should be used with great caution.

A Neurochemical and Electrophysiological Study on the Combined Effects of Caffeine and Nicotine in the Cortex of Rats

Objective: Caffeine and nicotine are the most consumed psychostimulants worldwide. Although the effects of each drug alone on the central nervous system (CNS) were studied extensively, the literature on the neurochemical and electrophysiological effects of their combined treatments is scarce. The present study investigates the cortical electrophysiological and neurochemical alterations induced by acute administration of caffeine and nicotine in rats. Methods: Rats received caffeine and nicotine with 1h interval between the two treatments. Results: Caffeine and nicotine administration resulted in a significant decrease in the concentrations of cortical amino acid neurotransmitters namely glutamate, aspartate, glycine and taurine while γ-aminobutyric acid (GABA) was significantly increased. An increased cortical lipid peroxidation and decreased reduced glutathione and nitric oxide levels and acetylcholinesterase and Na+, K+-ATPase activities were also observed. The electroencephalogram (EEG) showed an increase in delta frequency power band while theta, beta-1 and beta-2 were decreased after caffeine and nicotine treatment. These findings suggest that caffeine and nicotine adversely exacerbate their stimulant effects. This was manifested by the EEG changes and mediated by increasing cholinergic transmission, disturbing the balance between the excitatory and inhibitory amino acids leading to oxidative stress.

Five-box thoracoscopic maze based on the Gemini-S bipolar ablation device to treat atrial fibrillation

Thoracoscopic atrial fibrillation ablation seeks to replicate the electrophysiological effects of more invasive, open surgical procedures. The authors present a lesion concept that includes isolation of the pulmonary veins, the left atrial posterior wall, and the superior vena cava, respectively, lines to inhibit perimitral and periauricular flutter circuits, and left atrial appendage closure. All lesions are tested for bidirectional block.

Beneficial Electrophysiological Effects of Rotigaptide Are Unable to Suppress Therapeutic Hypothermia-Provoked Ventricular Fibrillation in Failing Rabbit Hearts With Acute Ischemia–Reperfusion Injury

Aims: Whether therapeutic hypothermia (TH) is proarrhythmic in preexisting failing hearts with acute ischemia–reperfusion (IR) injury is unknown. Additionally, the effectiveness of rotigaptide on improving conduction slowing in hearts with IR injury is ambiguous. We investigated the electrophysiological effects of TH and rotigaptide in failing rabbit hearts with acute IR injury and determined the underlying molecular mechanisms.Methods and Results: Heart failure was induced by right ventricular pacing (320 beats/min, 4 weeks). Rabbits with pacing-induced heart failure were randomly divided into TH (n = 14) and non-TH (n = 7) groups. The IR rabbit model was created by ligating the coronary artery for 60 min, followed by reperfusion for 15 min in vivo. Then, the hearts were excised quickly and Langendorff-perfused for simultaneous voltage and intracellular Ca2+ (Cai) optical mapping. Electrophysiological studies were conducted, and vulnerability to ventricular fibrillation (VF) was evaluated using pacing protocols. TH (33°C) was instituted after baseline studies, and electrophysiological studies were repeated. Rotigaptide (300 nM) was infused for 20 min, and electrophysiological studies were repeated under TH. Cardiac tissues were sampled for Western blotting. TH increased the dispersion and beat-to-beat variability of action potential duration (APD), aggravated conduction slowing, and prolonged Cai decay to facilitate spatially discordant alternans (SDA) and VF induction. Rotigaptide reduced the dispersion and beat-to-beat variability of APD and improved slowed conduction to defer the onset of arrhythmogenic SDA by dynamic pacing and elevate the pacing threshold of VF during TH. However, the effect of rotigaptide on TH-enhanced VF inducibility was statistically insignificant. TH attenuated IR-induced dysregulation of protein expression, but its functional role remained uncertain.Conclusion: Therapeutic hypothermia is proarrhythmic in failing hearts with acute IR injury. Rotigaptide improves TH-induced APD dispersion and beat-to-beat variability and conduction disturbance to defer the onset of arrhythmogenic SDA and elevate the VF threshold by dynamic pacing, but these beneficial electrophysiological effects are unable to suppress TH-enhanced VF inducibility significantly.

Temporary device malfunction of an MR conditional cardiac resynchronization defibrillator when undergoing MRI without appropriate re-programming: a case report

Background Magnetic resonance (MR) imaging (MRI) for patients with implantable cardiac devices is becoming more routine, with the development of MR conditional devices allowing more patients access to the imaging they need. However, for this to be performed safely, strict protocols must be followed necessitating close collaboration between cardiology and radiology departments. We present a case where mandatory device re-programming of a cardiac resynchronization therapy defibrillator device into MRI mode was not performed pre-scan leading to temporary device dysfunction with no clinical consequences. Case summary A 72-year-old man presented to a device clinic for a routine device interrogation. An atrial tachycardia response episode was recorded at the same time as the patient reported having undergone an MRI scan at a local centre. The electrogram demonstrated temporary right ventricular loss of capture with standard output programming, and a short episode of oversensing on the atrial and ventricular channel which was not sustained for long enough to meet tachycardia detection. Discussion We demonstrate two potential electrophysiological effects of MRI on pacemakers, where the device had not been appropriately re-programmed pre-procedure. This illustrates that whilst MRI in patients with implantable cardiac devices is safe, strict protocols must be followed requiring robust multidisciplinary communication.