Ventilatory effects of the interaction between phrenic and limb muscle afferents.

We studied the effects on ventilation and ventilatory muscle activation of stimulation of the central ends of the left phrenic and gastrocnemius nerves separately and concurrently in 10 spontaneously breathing, alpha-chloralose anaesthetized dogs. The nerves were stimulated for 1 min, at a frequency of 40 Hz and pulse duration of 1 ms. The phrenic nerve was stimulated at 20 and 40 times twitch threshold (TT). During these stimulation periods ventilation increased by 39% and 79% of control values, respectively. The gastrocnemius nerve was stimulated at 20 times TT. This produced a 90% increase in ventilation. Stimulation of either nerve resulted in increases in the activity of the right diaphragm, parasternal intercostal and alae nasi muscles comparable in magnitude to the increase in tidal volume. The activities of the genioglossus and transversus abdominis muscle increased to a much greater extent than did the other muscles under all conditions. In contrast, triangularis sterni activity remained unchanged during stimulation of either nerve. The phrenic nerve was then stimulated at 40 times TT for 1 min with superimposed gastrocnemius nerve stimulation (20 times TT) during the last 30 s. Ventilation had risen by 66% after 30 s of phrenic nerve stimulation. With the addition of gastrocnemius nerve stimulation, ventilation rose by a further 84% for a total increase of 150% of the control value. Mathematical summation of the responses to individual nerve stimulation at these intensities predicted a 156% increase in ventilation. Similar degrees of summation were found with respect to respiratory muscle activation. We conclude that the interaction between phrenic and limb muscle (gastrocnemius) afferent is additive with respect to their effects on ventilation.     

COPD对大鼠膈神经放电和呼吸运动的影响探讨

目的探讨COPD对大鼠膈神经放电和呼吸运动的影响。方法随机将60只Wistar大鼠分为两组,30只/组。实验组:熏香烟联合气管内滴注猪胰蛋白酶建立大鼠COPD模型;对照组:不给予熏香烟,d15气管内滴注生理盐水20 u/100 g。结果实验组膈神经放电幅度增强且具有统计学意义(P0.05);两组吸气相时间和膈神经放电活动均呈正相关。结论 COPD可影响大鼠膈神经放电和呼吸运动,使膈神经放电活动增强,出现呼吸中枢吸气驱动增高的现象,提示大鼠呼吸中枢的活动可能发生了改变。     

The effect of antigen-induced bronchoconstriction on phrenic nerve activity

The effects of acute bronchoconstriction, produced by inhalation of Ascaris suum antigen, on both the amplitude and timing of phrenic nerve activity were studied in anesthetized dogs. Blood gas tensions and inspiratory air flow were maintained constant. Bronchoconstriction resulted in a significant increase in the magnitude and rate of rise of the phrenic neurogram during both normal respiratory cycles and cycles when lung inflation was prevented. The increase in the slope of the phrenic neurogram that results from lung inflation was further increased during bronchoconstriction. In addition, in half the animals, there was a significant increase in the tonic phrenic activity measured during expiration. All of these changes were abolished by bilateral cervical vagotomy. Antigen administration did not affect the timing of the different phases of the cycle equally; inspiratory duration was reduced by 51.8% and expiratory duration by 67.6%. Postinspiratory activity of the phrenic (PIIA) was reduced by only 34.7%; thus, during bronchoconstriction PIIA occupied a proportionally greater fraction of the expiratory phase. Vagotomy abolished the changes in respiratory timing and eliminated all PIIA.     

Reflex heart rate control via specific aortic nerve afferents in the rabbit.

Reflex bradycardia was elicited in rabbits via repetitive electrical stimulation of the central end of the sectioned left aortic nerve. Supramaximal stimulation produced a 16.9 plus or minus 1.3% (SE) increase in the R-R interval when vagal and sympathetic efferent pathways were intact. Reducing the stimulation voltage allowed selective stimulation of the myelinated (A) fibers, and polarizing electrodes placed central to the stimulus site permitted A fiber blockade and selective stimulation of the unmyelinated (C) fibers. When afferent A fibers were selectively stimulated, 64% of the maximum response was obtained; selective C fiber activation elicited 63% of the maximum observed response. Selective stimulation of A or C fibers after either vagotomy or stellectomy indicated that A fiber afferents elicit heart rate responses via both vagal and sympathetic efferents, whereas C fiber afferent information is mediated predominantly via vagal efferents. This afferent-efferent specificity of the aortic baroreceptor pathways suggests baroreceptor mechanisms normally used to modulate heart rate. Small increments in blood pressure would activate low-threshold A fibers and result in reciprocal changes in vagal and sympathetic efferent activity. More substantial increases in blood pressure would activate afferent C fibers and produce additional heart rate effects via vagal efferents.     

Mechanisms of phrenic nerve injury during radiofrequency ablation at the pulmonary vein orifice

BACKGROUND: The phrenic nerve can be injured with radiofrequency energy delivery. Nevertheless, the mechanisms of injury are unknown. This study was undertaken to examine phrenic nerve tissue temperatures during ablation at the pulmonary vein (PV) orifice, assess the temperature dependence of injury, and to delineate the possible mechanisms of untoward nerve effects. METHODS: Ten dogs underwent ablation at the right superior PV (RSPV) orifice. Phrenic nerve temperatures were assessed with implanted thermocouples overlying the endocardial ablation site. Using an 8-mm ablation catheter tip, energy was titrated to 50 degrees C and incremented by 5 degrees C for 120 seconds. RESULTS: Phrenic nerve capture was achieved in nine (90%) dogs after thermocouple implantation. A RSPV orifice tissue temperature >60 degrees C occurred in 32 (84%) of energy deliveries with a power of 34 +/- 22 W. In three (33%) dogs, this resulted in nerve dysfunction (maximum nerve temperature: 41 degrees C, 41 degrees C, and 91 degrees C) with histology consistent with acute thermal injury. In four additional dogs, 17 energy deliveries were made directly to the phrenic nerve using a novel in situ model. In 5 (29%) energy deliveries, nerve function was impacted immediately by the generated current, with resolution simultaneous with discontinuing radiofrequency. Transient phrenic nerve injury occurred in all dogs at a temperature of 47 +/- 3 degrees C (range: 43-53 degrees C) after 38 +/- 32 seconds (range: 20-120 seconds). After termination of the energy delivery, nerve function returned in 15(88%) during 30 seconds of postablation pacing. In two (12%) ablation attempts, nerve recovery was delayed (>3 minutes). Permanent injury occurred in all dogs after 92 +/- 83 seconds (range: 20-280 seconds) of additional energy delivery at a temperature of 51 +/- 6 degrees C (range: 45-65 degrees C). CONCLUSION: Phrenic nerve injury can be more common than anticipated with RF ablation at the RSPV orifice. Relatively low tissue temperatures can injure the nerve. Immediate nerve effects suggest a second mechanism of nerve dysfunction related to electrical current. Transient nerve effects occur prior to permanent damage, providing an opportunity to discontinue energy delivery before permanent injury.     

3D mapping of phrenic nerve course for radiofrequency pulmonary vein isolation

Introduction

Phrenic nerve (PN) injury is a rare but severe complication of radiofrequency (RF) pulmonary vein isolation (PVI). The objective of this study was to characterize the typical intracardiac course of the PN with a three-dimensional electroanatomic mapping system, to quantify the need for modification of the ablation trajectory to avoid delivering an ablation lesion on sites with PN capture, and to identify very circumscribed areas of common PNC on the routine ablation trajectory of a RF-PVI, allowing fast and effective PN screening for everyday usage.

Methods

We enrolled 137 consecutive patients (63 ± 9 years, 64% men) undergoing PVI. A detailed high output (20 mA) pace-mapping protocol was performed in the right (RA) and left atrium (LA) and adjacent vasculature.

Results

The right PN was most commonly captured in the superior vena cava at a lateral (50%) or posterolateral (23%) position before descending along the RA either straight (29%) or with a posterolateral bend (20%). In the LA, beginning deep within the right superior pulmonary vein (RSPV), the right PN is most frequently detectable anterolateral (31%), then descends to the lateral proximal RSPV (23%), and further towards the lateral antral region (15%) onto the medial LA wall (12%). To avoid delivering an ablation lesion on sites with PN capture, modification of ablation trajectory was necessary in 23% of cases, most commonly in the lateral RSPV antrum (81%). No PN injury occurred.

Conclusion

PN mapping frequently reveals the close proximity of the PN to the ablation trajectory during PVI, particularly in the lateral RSPV antrum. Routine PN pacing should be considered during RF PVI procedures.     

Respiratory activity in the superior laryngeal nerve of the rabbit

We studied the respiratory modulation of laryngeal afferents and their response to transmural pressure in 24 anesthetized, spontaneously breathing rabbits. Laryngeal afferent activity has a predominant inspiratory augmentation during tracheal breathing or tracheal occlusion that can be accounted for by the respiratory movement transmitted to the larynx through the trachea. During upper airway breathing or upper airway occlusion SLN afferent activity increases in expiration and decreases in inspiration. This respiratory modulation is due to changes in upper airway pressure (Pua). In fact, positive pressure stimulates SLN afferent activity, while negative pressure inhibits it. Mechanical restriction of epiglottal movement reduced the response to Pua changes during upper airway occlusion and application of maintained positive (0.1-0.5 kPa) and negative (-0.1 to -0.5 kPa) pressures (P less than 0.005). Furthermore, surgical removal of epiglottis decreased the baseline activity of SLN to 16.5% of control. These experiments suggest that in the rabbit the epiglottis is the main source of SLN afferent activity and that its displacement, due to changes in Pua, is the most important factor for modulating SLN activity. Most of the laryngeal receptors showed an inspiratory augmentation with tracheal breathing and occlusion, were stimulated by positive pressure and inhibited by negative pressure, reflecting the behavior observed in the whole nerve.     

Inhibitory and excitatory effects on respiration by phrenic nerve afferent stimulation in cats

Respiratory effects of electrical stimulation of phrenic nerve afferents were studied in anesthetized cats, either spontaneously breathing or paralyzed and ventilated. The type of phrenic afferent fibers activated was controlled by recording the evoked action potentials from dorsal root fibers. In both preparations, stimulation at a strength sufficient to activate small diameter myelinated phrenic nerve afferents induced a biphasic response. The first phase lasted a few respiratory cycles and was inhibitory and consisted of a decrease in tidal volume (VT) or phrenic activity (NA), inspiratory time (TI), respiratory duty cycle (TI/Ttot) and instantaneous ventilation (VE) or minute phrenic activity (NMA). Expiratory time (TE) increased and breathing frequency (f) and mean inspiratory flow (VT/TI) or mean inspiratory neural activity (NA/TI) did not change. This short-term response was suppressed in animals pretreated with bicuculline. The second phase was a long-term excitation in which VT or NA, f, VE or NMA and VT/TI increased whereas both TI and TI/Ttot decreased and TE did not change. Unlike published data, our results suggest that small-diameter myelinated phrenic nerve afferents are involved in these responses. These phrenic fibers, like afferents from other muscles, affect respiratory output and may play a role in the control of breathing.     

First report of phrenic nerve injury during pulmonary vein isolation using the Ablation Frontiers pulmonary vein ablation catheter

In an attempt to improve procedural outcomes and reduce time and complications, there has been particular interest in alternative technologies specifically designed for atrial fibrillation (AF) ablation. One novel technique is isolation of the pulmonary veins using an over-the-wire multielectrode catheter delivering duty-cycled bipolar and unipolar radiofrequency energy. Phrenic nerve injury is a rare but significant complication of AF ablation. This is the first report of phrenic nerve injury following catheter ablation for AF using the Pulmonary Vein Ablation Catheter (Medtronic, Minneapolis, MN, USA).     

Recruitment and discharge frequency of phrenic motoneurones during inspiration.

The discharges of 107 phrenic motor axons were recorded from cats under chloralose-urethane anaesthesia with spinal cords transected at T1 or with intact neuraxis. During inspiratory occlusions in spinal cats, each motoneurone was recruited at a mouth pressure constant at a given end tidal CO2; no motoneurone was recruited at a pressure greater than 70% of maximum. In eupnoea (32.3 torr CO2) 73% of motoneurones were recruited during the first 30% of inspiration; during CO2 rebreathing (60.8 torr CO2), 89% were recruited in the first 30% of inspiration. Neurones recruited earlier in inspiration had a lower onset frequency than later recruited units; all increased instantaneous frequency in a linear relation to pressure. Early recruited units showed a smaller increase in frequency per unit change in pressure than did later recruited units. During CO2 rebreathing, mean and peak frequencies increased on average 0.92 and 1.78 spikes.sec(-1) (%CO2)(-1), respectively, these increases being significantly less for early than for late recruited neurones. The data show that a stable order of recruitment of phrenic motoneurones exists during inspiration, the excitability of each motoneurone likely determining its time of recruitment. Above threshold, later recruited motoneurones are more 'sensitive' to a change in input. Recruitment of motoneurones is responsible for pressure generation at the start of inspiration and increase in discharge frequency (rate coding) is the dominant mechanism in the second half of inspiration.     

Dynamics of brain extracellular fluid pH and phrenic nerve activity in cats after end-tidal CO2 forcing

Ventilation is influenced by the interstitial [H+] of the brain. The pHecf, which in turn is determined largely by ventilation (via PaCO2) is sensed by the central chemoreceptors. In order to investigate the dynamics of both pHecf and neural tidal volume, we measured in cats with cut vagi and sinus nerves the dynamic medullary pHecf changes and the associated changes in integrated phrenic nerve activity after end-tidal CO2 forcing. The medullary surface ecf pH was measured with a glass electrode with a flat pH-sensitive surface. After CO2 up-steps, the pHecf changed with a time constant of about 43 sec, after down-steps 30 sec was found. The central time constant of the neural tidal volume response was 50 sec (mode) in both cases, whereas the overall response had a (modal) time constant of 80 sec. The results indicate that pHecf dynamics and the dynamic characteristics of the central neural respiratory organization are about equally important in determining the dynamic neural tidal volume response. It is argued that when PaCO2 changes, the dynamic pHecf change is perfusion limited and macroscopically homogeneous within the brainstem. Therefore, in our view it seems that the location of the central chemoreceptors within the brainstem is of minor importance in determining the dynamic neural tidal volume response to PaCO2 changes.     

Use of intracardiac echocardiography for early detection of phrenic nerve injury during cryoballoon pulmonary vein isolation

Use of Intracardiac Echocardiography for Early Detection of Phrenic Nerve Injury. Cryoballoon catheter ablation has recently emerged as an effective tool to achieve pulmonary vein isolation (PVI). Right-sided PVI with cryoballoon ablation has been associated with a significant incidence of phrenic nerve palsy. Multiple modalities are currently utilized to monitor phrenic nerve function during ablation. We describe a novel approach toward monitoring and diagnosing phrenic nerve palsy using intracardiac echocardiography (ICE) during cryoballoon ablation of the right pulmonary veins. This technique of monitoring has the advantage of continuous direct diaphragmatic visualization without the use of fluoroscopy, hence significantly minimizing radiation to both the patient and the operator. In addition, this technique does not require extra personnel to monitor the diaphragm using manual palpation. Further prospective studies of our and other methods for prevention of phrenic nerve palsy are required. (J Cardiovasc Electrophysiol, Vol. 23, pp. 874-876, August 2012).