Carbon monoxide is a rapid modulator of recombinant and native P2X2 ligand-gated ion channels

Background and purpose:

Carbon monoxide (CO) is a potent modulator of a wide variety of physiological processes, including sensory signal transduction. Many afferent sensory pathways are dependent upon purinergic neurotransmission, but direct modulation of the P2X purinoceptors by this important, endogenously produced gas has never been investigated.

Experimental approach:

Whole-cell patch-clamp experiments were used to measure ATP-elicited currents in human embryonic kidney 293 cells heterologously expressing P2X₂, P2X₃, P2X_2/3 and P2X₄ receptors and in rat pheochromocytoma (PC12) cells known to express native P2X₂ receptors. Modulation was investigated using solutions containing CO gas and the CO donor molecule, tricarbonyldichlororuthenium (II) dimer (CORM-2).

Key results:

CO was a potent and selective modulator of native P2X₂ receptors, and these effects were mimicked by a CO donor (CORM-2). Neither pre-incubation with 8-bromoguanosine-3′,5′-cyclomonophosphate nor 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (a potent blocker of soluble guanylyl cyclase) affected the ability of the CO donor to enhance the ATP-evoked P2X₂ currents. The CO donor caused a small, but significant inhibition of currents evoked by P2X_2/3 and P2X₄ receptors, but was without effect on P2X₃ receptors.

Conclusions and implications:

These data provided an explanation for how CO might regulate sensory neuronal traffic in physiological reflexes such as systemic oxygen sensing but also showed that CO could be used as a selective pharmacological tool to assess the involvement of homomeric P2X₂ receptors in physiological systems.     

Nurses' adoption of the AWHONN/NANN Neonatal Skin Care Project

The purpose of this project was to evaluate the nurses' adoption of the AWHONN/NANN Neonatal Skin Care Project Protocols that were implemented at 54 clinical sites across the United States, and to examine perceived barriers in the implementation process. One hundred thirty-six nurses from 26 hospitals returned the survey packets that included the Neonatal Nurse Opinion Survey and the Barriers Scale. Nurses had a higher-than-average level of education, describing themselves as leaders and innovators. In general, the protocols were well accepted and adopted into practice. Some protocols were not perceived as better than pre-existing practice, and nurses reported difficulty in the implementation of some protocols. The main barriers were a lack of skill in reading and understanding research, lack of authority, and lack of support from physicians and other staff. The project raised national awareness about neonatal skin care, involved nurses from the beginning and throughout the process, and removed several barriers to research utilization. Copyright © 2001 by W.B. Saunders Company     

Increased base rate of atrial pacing for prevention of atrial fibrillation after implantation of a dual-chamber pacemaker: insights from the Atrial Overdrive Pacing Study.

AIMS: Different pacing sites and various algorithms have been utilized to prevent atrial fibrillation (AF) in pacemaker recipients. However, the optimal pacing rate settings have not yet been established. In this randomized, prospective, multicentre, single-blinded, cross over study, rate-adaptive pacing at a high base rate (BR) in patients, age 60 years or above, or a history of paroxysmal AF, who underwent dual-chamber (DDD) pacemaker implantation for standard pacing indications, was evaluated for prevention of AF. METHODS AND RESULTS: In the study cohort of 145 patients implanted with DDD pacemakers with a programmable rest rate (RR) feature, the BR/RR settings were sequentially but randomly adjusted as follows: 60 bpm/Off for the baseline quarter (initial 3 months) and then to either 'A-B-C' or 'C-B-A' settings (A = 70/65 bpm, B = 70/Off, C = 80/65 bpm) for the subsequent quarters each of 3 months duration. Data on automatic mode switch episodes, device diagnostics, and a questionnaire evaluating pacemaker awareness and palpitations were collected. Ninety-nine patients, mean age 77 +/- 10 years, who completed the study protocol and followed for 12 months did not show significant differences in the number of mode switch episodes between any settings used. The percentage of atrial pacing was lower during baseline pacing compared to settings A, B, and C (P < 0.0001). Setting C produced a higher percentage of atrial pacing than A and B (P < 0.01). Although a higher percentage of atrial pacing correlated with a lower incidence of mode switch episodes, there was no statistically significant difference in the number of mode switch episodes between settings A, B, and C. There were no significant differences in the questionnaire scores relating to pacemaker awareness or palpitation. CONCLUSION: Overdrive single-site pacing in the right atrium achieved by programming analysed settings in the present study did not reduce AF as assessed by mode switch episodes. Additionally, no change in the symptoms of arrhythmia or awareness of pacing was seen.     

Electrical storm of monomorphic ventricular tachycardia after a cardiac-resynchronization-therapy-defibrillator upgrade.

In patients with significant left ventricular dysfunction and congestive heart failure despite optimal medical therapy, implantation of cardiac resynchronization therapy-defibrillation (CRT-D) devices has been shown to improve symptoms and mortality. In this report, we describe a case of a patient with ischaemic cardiomyopathy who developed incessant ventricular tachycardia (VT) after undergoing an upgrade from an implantable cardioverter defibrillator to a CRT-D device. The patient required multiple anti-arrhythmic agents, removal of the coronary sinus lead, and radiofrequency ablation to control VT. Thus, in rare patients, the CRT devices may potentially cause 'proarrhythmia' with serious consequences.