Iridium-catalyzed asymmetric addition of imides to alkenes.

Enantioselective addition of an imide N-H bond to alkenes was realized by use of a cationic iridium catalyst. Bulky diphosphine ligands such as DTBM-segphos, DTBM-MeO-biphep, and DTBM-binap were indispensable for the reaction. A variety of styrene derivatives, allylsilanes, and norbornene were good substrates to give the corresponding chiral adducts with high enantioselectivity.

The incidence of hypotension during general anesthesia: a single-center study at a university hospital.

BACKGROUND: Although intraoperative hypotension (IOH) has been emerging as a serious concern during general anesthesia, the incidence of IOH has not been demonstrated clearly in the Japanese population. METHODS: This single-center retrospective study investigated the incidence and the characteristics of IOH in non-cardiac surgery at a university hospital. IOH was defined as at least one fall of MAP during general anesthesia, which was categorized into the following groups: mild (65 to < 75 mmHg), moderate (55 to < 65 mmHg), severe (45 to < 55 mmHg), and very severe (< 45 mmHg). The incidence of IOH was calculated as a percentage of the number of events to the total anesthesia cases. Logistic regression analysis was performed to examine factors affecting IOH. RESULTS: Eleven thousand two hundred ten cases out of 13,226 adult patients were included in the analysis. We found moderate to very severe hypotension occurred in 86.3% of the patients for at least 1 to 5 min, and 48.5% experienced severe or very severe hypotension. The results of the logistic regression analysis indicated female gender, vascular surgery, American Society of Anesthesiologists physical status classification (ASA-PS) 4 or 5 in emergency surgery, and the combination with the epidural block (EDB) were significant factors of IOH. CONCLUSIONS: IOH during general anesthesia was very frequent in the Japanese population. Female gender, vascular surgery, ASA-PA 4 or 5 in emergency surgery, and the combination with EDB were independent risk factors associated with IOH. However, the association with patient outcomes were not elucidated.

Propofol anesthesia decreases the incidence of new-onset postoperative atrial fibrillation compared to desflurane in patients undergoing video-assisted thoracoscopic surgery: A retrospective single-center study.

BACKGROUND: Postoperative atrial fibrillation (POAF) increases postoperative morbidity, mortality, and length of hospital stay. Propofol is reported to modulate atrial electrophysiology and the cardiac autonomic nervous system. Therefore, we retrospectively examined whether propofol suppresses POAF in patients undergoing video-assisted thoracoscopic surgery (VATS) compared to desflurane. METHODS: We retrospectively recruited adult patients who underwent VATS during the period from January 2011 to May 2018 in an academic university hospital. Between continuous propofol and desflurane administration during anesthetic maintenance, we investigated the incidence of new-onset POAF (within 48 hours after surgery) before and after propensity score matching. RESULTS: Of the 482 patients, 344 received propofol, and 138 received desflurane during anesthetic maintenance. The incidence of POAF in the propofol group was less than that in the desflurane group (4 [1.2%] vs. 8 patients [5.8%], odds ratio [OR]; 0.161, 95% confidence interval (CI), 0.040-0.653, p = 0.011) in the present study population. After adjustment for propensity score matching (n = 254, n = 127 each group), the incidence of POAF was still less in propofol group than desflurane group (1 [0.8%] vs. 8 patients [6.3%], OR; 0.068, 95% CI: 0.007-0.626, p = 0.018). CONCLUSIONS: These retrospective data suggest propofol anesthesia significantly inhibits POAF compared to desflurane anesthesia in patients undergoing VATS. Further prospective studies are needed to elucidate the mechanism of propofol on the inhibition of POAF.

Iridium-Catalyzed Enantioselective Intermolecular Hydroarylation of 1,1-Disubstituted Alkenes.

The catalytic enantioselective hydroarylation of 1,1-disubstituted alkenes proceeded by using a cationic iridium/(R)-binap complex to give the corresponding adducts in high yields with high enantioselectivity. The reaction of arenes substituted with heteroaromatic directing groups proceeded to give the addition products linear-selectively. Methallylamine derivatives were good acceptors to obtain high enantioselectivities. The adduct bearing maleimide moiety was readily transformed into the ß-chiral amine derivative without loss of the enantiomeric purity.

Potential usage of anterior nasal sampling in clinical practice with three rapid antigen tests for SARS-CoV-2.

INTRODUCTION: Anterior nasal sampling (AN) might be more convenient for patients than NP sampling to diagnose coronavirus disease. This study investigated the feasibility of rapid antigen tests for AN sampling, and the factors affecting the test accuracy. METHODS: This single-center prospective study evaluated one qualitative (ESP) and two quantitative (LUMI and LUMI-P) rapid antigen tests using AN and NP swabs. Symptomatic patients aged 20 years or older, who were considered eligible for reverse-transcription quantitative polymerase chain reaction using NP samples within 9 days of onset were recruited. Sensitivity, specificity, and positive and negative concordance rates between AN and NP samples were assessed for the rapid antigen tests. We investigated the characteristics that affected the concordance between AN and NP sampling results. RESULTS: A total of 128 cases were recruited, including 28 positive samples and 96 negative samples. The sensitivity and specificity of AN samples using ESP were 0.81 and 1.00, while those of NP samples were 0.94 and 1.00. The sensitivity of AN and NP samples was 0.91 and 0.97, respectively, and specificity was 1.00, for both LUMI and LUMI-P. The positive concordance rates of AN to NP sampling were 0.87, 0.94, and 0.85 for ESP, LUMI, and LUMI-P, respectively. No factor had a significant effect on the concordance between the sampling methods. CONCLUSIONS: ESP, LUMI, and LUMI-P showed practical diagnostic accuracy for AN sampling compared to NP sampling. There was no significant factor affecting the concordance between AN and NP sampling for these rapid antigen tests.

Association between surgical tracheostomy and chronic tracheal stenosis: A retrospective, single-center study.

Background: Tracheal stenosis is a major complication of tracheostomy. Accordingly, anesthesiologists tend to select a smaller endotracheal tube (ETT) than usual for patients with a prior tracheostomy history, regardless of the presence or absence of respiratory symptoms. However, it likely comes from our trial and error, not scientific evidence. Therefore, in this study, we retrospectively examined the association between traditional surgical tracheostomy and tracheal stenosis as assessed by transverse computed tomography (CT). Methods: Patients who underwent surgery for head and neck cancer from January 2010 to December 2013, with a temporary tracheostomy closed within a couple of months, were included. Exclusion criteria were tracheostoma before surgery, permanent tracheostomy, or insufficient CT follow-up. Transverse CT slices were measured 2 cm above and below the tracheostomy site (0.5 cm/slice for a total of 9 slices). The minimum cross-sectional tracheal area and horizontal and vertical diameters in transverse CT slices were compared before (baseline: BL), 6 months (6M) and 12 months (12M) after tracheostomy. Tracheal stenosis was defined as a decrease in the minimum cross-sectional tracheal area compared to BL. Results: Of 112 patients, 77 were included. The minimum tracheal area was significantly decreased at 6M and 12M compared to BL (BL: mean 285 [SD 68] mm2, 6M: 267 [70] mm2, P < 0.01 vs. BL, 12M: 269 [68] mm2, P < 0.01 vs. BL), and the localization was predominantly at or above the tracheostomy site at 6M and 12M. Tracheal stenosis was identified in 55 patients at 6M and in 49 patients at 12M without any respiratory symptoms. With regard to horizontal and vertical diameter, only horizontal diameter was significantly decreased at 6M and 12M compared to BL (BL: 16.8 [2.4] mm, 6M: 15.4 [2.7] mm, P < 0.01 vs. BL, 12M: 15.6 [2.8] mm, P < 0.01 vs. BL). Conclusion: Conventional surgical tracheostomy was associated with a decreased horizontal diameter of the trachea. It resulted in a decreased cross-sectional tracheal area in more than one-half of the patients; however, no patient complained of any respiratory symptoms. Therefore, even without respiratory symptoms, prior tracheostomy causes an increased risk of tracheal stenosis, and using a smaller ETT than usual could be reasonable.

Iridium-Catalyzed Enantioselective Direct α-C-H Alkylation of Saturated Cyclic Amines with Alkenes.

Enantioselective direct α-C(sp3)-H alkylation of saturated cyclic amines having N-methylbenzimidazolyl as a directing group was realized by using a cationic iridium/chiral diphosphine catalyst. The alkylation of pyrrolidine derivatives with various terminal alkenes proceeded to give α-alkylated products in high yields with high enantioselectivities. Chiral α,α'-dialkylated pyrrolidine derivatives were also synthesized by using an excess of alkenes or by stepwise alkylation.

Characteristics and outcomes of unplanned intensive care unit admission after general anesthesia.

BACKGROUND: Unplanned ICU admission after surgery has been validated as a measure of a quality indicator of perioperative management because it may put surgical patients at risk of increased morbidity and mortality. Postoperative unscheduled admission to the ICU is usually determined either in the post-anesthesia care unit (PACU) or in the general surgical ward; however, it could be expected patient outcomes after ICU admission would be affected by the circumstances. The purpose of this retrospective observational study was to investigate the clinical characteristics and the outcome of unplanned admission to the ICU directly from the PACU or from the ward within 7 days after PACU discharge. METHODS: Forty-three thousand, five hundred fifty-three patients admitted to the PACU after general anesthesia were included in the study. Unplanned ICU admission was defined as the admission which was not anticipated preoperatively but was due to adverse events in the PACU (PACU group) or the ward after discharge from the PACU (Ward group). The following parameters were compared between the groups: patient characteristics, surgical characteristics, length of ICU and hospital stay, the principal adverse event for ICU admission, treatments in the ICU, and in-hospital mortality. The primary outcome was in-hospital mortality and the second was the length of ICU and hospital stay. RESULTS: Among 43,553 patients, 109 patients underwent unplanned ICU admission directly from the PACU (n= 73, 0.17%) or subsequently from the ward (n= 36, 0.08%). The length of both ICU and hospital stay was significantly longer in the Ward group than in the PACU group (1.4 and 19 days vs. 2.5 and 39 days, respectively). There was no significant difference in in-hospital mortality between the groups (4.1% vs. 8.3%, respectively). CONCLUSIONS: The incidence of unplanned ICU admission after PACU stay was low, however, delayed admission to the ICU from the ward may prolong the length of both ICU and hospital stay compared to those directly from the PACU.

Proarrhythmic Effects of Sympathetic Activation Are Mitigated by Vagal Nerve Stimulation in Infarcted Hearts.

OBJECTIVES: The goal of this study was to evaluate whether intermittent VNS reduces electrical heterogeneities and arrhythmia inducibility during sympathoexcitation. BACKGROUND: Sympathoexcitation increases the risk of ventricular tachyarrhythmias (VT). Vagal nerve stimulation (VNS) has been antiarrhythmic in the setting of ischemia-driven arrhythmias, but it is unclear if it can overcome the electrophysiological effects of sympathoexcitation in the setting of chronic myocardial infarction (MI). METHODS: In Yorkshire pigs after chronic MI, a sternotomy was performed, a 56-electrode sock was placed over the ventricles (n = 17), and a basket catheter was positioned in the left ventricle (n = 6). Continuous unipolar electrograms from sock and basket arrays were obtained to analyze activation recovery interval (ARI), a surrogate of action potential duration. Bipolar voltage mapping was performed to define scar, border zone, or viable myocardium. Hemodynamic and electrical parameters and VT inducibility were evaluated during sympathoexcitation with bilateral stellate ganglia stimulation (BSS) and during combined BSS with intermittent VNS. RESULTS: During BSS, global epicardial ARIs shortened from 384 ± 59 milliseconds to 297 ± 63 milliseconds and endocardial ARIs from 359 ± 36 milliseconds to 318 ± 40 milliseconds. Dispersion in ARIs increased in all regions, with the greatest increase observed in scar and border zone regions. VNS mitigated the effects of BSS on border zone ARIs (from -18.3% ± 6.3% to -2.1% ± 14.7%) and ARI dispersion (from 104 ms2 [1 to 1,108 ms2] to -108 ms2 [IQR: -588 to 30 ms2]). VNS reduced VT inducibility during sympathoexcitation (from 75%-40%; P < 0.05). CONCLUSIONS: After chronic MI, VNS overcomes the detrimental effects of sympathoexcitation by reducing electrophysiological heterogeneities exacerbated by sympathetic stimulation, decreasing VT inducibility.

Intravenous infusion of rocuronium bromide prolongs emergence from propofol anesthesia in rats.

BACKGROUND: Neuromuscular blocking agents induce muscle paralysis via the prevention of synaptic transmission at the neuromuscular junction and may have additional effects at other sites of action. With regard to potential effects of neuromuscular blocking agents on the central nervous system, a definitive view has not been established. We investigated whether intravenous infusion of rocuronium bromide affects the emergence from propofol anesthesia. METHODS: Using an in vivo rat model, we performed propofol infusion for 60 minutes, along with rocuronium bromide at various infusion rates or normal saline. Sugammadex or normal saline was injected at the end of the infusion period, and we evaluated the time to emergence from propofol anesthesia. We also examined the neuromuscular blocking, circulatory, and respiratory properties of propofol infusion along with rocuronium bromide infusion to ascertain possible factors affecting emergence. RESULTS: Intravenous infusion of rocuronium bromide dose-dependently increased the time to emergence from propofol anesthesia. Sugammadex administered after propofol infusion not containing rocuronium bromide did not affect the time to emergence. Mean arterial pressure, heart rate, partial pressures of oxygen and carbon dioxide, and pH were not affected by rocuronium bromide infusion. Neuromuscular blockade induced by rocuronium bromide, even at the greatest infusion rate in the emergence experiment, was rapidly antagonized by sugammadex. CONCLUSIONS: These results suggest that intravenous infusion of rocuronium bromide dose-dependently delays the emergence from propofol anesthesia in rats. Future studies, such as detection of rocuronium in the cerebrospinal fluid or central nervous system, electrophysiologic studies, microinjection of sugammadex into the brain, etc., are necessary to determine the mechanism of this effect.

Antiarrhythmic effects of vagal nerve stimulation after cardiac sympathetic denervation in the setting of chronic myocardial infarction.

BACKGROUND: Neuraxial modulation with cardiac sympathetic denervation (CSD) can potentially reduce burden of ventricular tachyarrhythmia (VT). However, despite catheter ablation and CSD, VT can recur in patients with cardiomyopathy and the role of vagal nerve stimulation (VNS) in this setting is unclear. OBJECTIVE: The purpose of this study was to evaluate the electrophysiological effects of VNS after CSD in normal and infarcted hearts. METHODS: In 10 normal and 6 infarcted pigs, electrophysiological and hemodynamic parameters were evaluated before and during intermittent VNS pre-CSD (bilateral stellectomy and T2-T4 thoracic ganglia removal) as well as post-CSD. The effect of VNS during isoproterenol was also assessed pre- and post-CSD. Multielectrode ventricular activation recovery interval (ARI) recordings, a surrogate of action potential duration, were obtained. VT inducibility was tested during isoproterenol infusion after CSD with and without VNS. RESULTS: VNS increased the global ARI by 4% ± 4% pre-CSD and by 5% ± 6% post-CSD, with enhanced effects observed during isoproterenol infusion (10% ± 8% pre-CSD and 12% ± 9% post-CSD) in normal animals. In infarcted animals pre-CSD, VNS increased ARI by 6% ± 7% before and by 13% ± 8% during isoproterenol infusion. Post-CSD, VNS increased ARI by 6% ± 5% before and by 11% ± 7% during isoproterenol infusion. VT was inducible in all infarcted animals post-CSD during isoproterenol infusion; this inducibility was reduced by 67% with VNS (P = .01). In all animals, the hemodynamic effects of VNS remained after CSD. CONCLUSION: After CSD, the beneficial electrophysiological effects of VNS remain. Furthermore, VNS can reduce VT inducibility beyond CSD in the setting of circulating catecholamines, suggesting a role for additional parasympathetic modulation in the treatment of ventricular arrhythmias.

Parasympathetic dysfunction and antiarrhythmic effect of vagal nerve stimulation following myocardial infarction.

Myocardial infarction causes sympathetic activation and parasympathetic dysfunction, which increase risk of sudden death due to ventricular arrhythmias. Mechanisms underlying parasympathetic dysfunction are unclear. The aim of this study was to delineate consequences of myocardial infarction on parasympathetic myocardial neurotransmitter levels and the function of parasympathetic cardiac ganglia neurons, and to assess electrophysiological effects of vagal nerve stimulation on ventricular arrhythmias in a chronic porcine infarct model. While norepinephrine levels decreased, cardiac acetylcholine levels remained preserved in border zones and viable myocardium of infarcted hearts. In vivo neuronal recordings demonstrated abnormalities in firing frequency of parasympathetic neurons of infarcted animals. Neurons that were activated by parasympathetic stimulation had low basal firing frequency, while neurons that were suppressed by left vagal nerve stimulation had abnormally high basal activity. Myocardial infarction increased sympathetic inputs to parasympathetic convergent neurons. However, the underlying parasympathetic cardiac neuronal network remained intact. Augmenting parasympathetic drive with vagal nerve stimulation reduced ventricular arrhythmia inducibility by decreasing ventricular excitability and heterogeneity of repolarization of infarct border zones, an area with known proarrhythmic potential. Preserved acetylcholine levels and intact parasympathetic neuronal pathways can explain the electrical stabilization of infarct border zones with vagal nerve stimulation, providing insight into its antiarrhythmic benefit.

Effect of Thoracic Epidural Anesthesia on Ventricular Excitability in a Porcine Model.

BACKGROUND: Imbalances in the autonomic nervous system, namely, excessive sympathoexcitation, contribute to ventricular tachyarrhythmias. While thoracic epidural anesthesia clinically suppresses ventricular tachyarrhythmias, its effects on global and regional ventricular electrophysiology and electrical wave stability have not been fully characterized. The authors hypothesized that thoracic epidural anesthesia attenuates myocardial excitability and the proarrhythmic effects of sympathetic hyperactivity. METHODS: Yorkshire pigs (n = 15) had an epidural catheter inserted (T1 to T4) and a 56-electrode sock placed on the heart. Myocardial excitability was measured by activation recovery interval, dispersion of repolarization, and action potential duration restitution at baseline and during programed ventricular extrastimulation or left stellate ganglion stimulation, before and 30 min after thoracic epidural anesthesia (0.25% bupivacaine). RESULTS: After thoracic epidural anesthesia infusion, there was no change in baseline activation recovery interval or dispersion of repolarization. During programmed ventricular extrastimulation, thoracic epidural anesthesia decreased the maximum slope of ventricular electrical restitution (0.70 ± 0.24 vs. 0.89 ± 0.24; P = 0.021) reflecting improved electrical wave stability. Thoracic epidural anesthesia also reduced myocardial excitability during left stellate ganglion stimulation-induced sympathoexcitation through attenuated shortening of activation recovery interval (-7 ± 4% vs. -4 ± 3%; P = 0.001), suppression of the increase in dispersion of repolarization (313 ± 293% vs. 185 ± 234%; P = 0.029), and reduction in sympathovagal imbalance as measured by heart rate variability. CONCLUSIONS: Our study describes the electrophysiologic mechanisms underlying antiarrhythmic effects of thoracic epidural anesthesia during sympathetic hyperactivity. Thoracic epidural anesthesia attenuates ventricular myocardial excitability and induces electrical wave stability through its effects on activation recovery interval, dispersion of repolarization, and the action potential duration restitution slope.

Cardiac sympathetic innervation via middle cervical and stellate ganglia and antiarrhythmic mechanism of bilateral stellectomy.

Cardiac sympathetic denervation (CSD) is reported to reduce the burden of ventricular tachyarrhythmias [ventricular tachycardia (VT)/ventricular fibrillation (VF)] in cardiomyopathy patients, but the mechanisms behind this benefit are unknown. In addition, the relative contribution to cardiac innervation of the middle cervical ganglion (MCG), which may contain cardiac neurons and is not removed during this procedure, is unclear. The purpose of this study was to compare sympathetic innervation of the heart via the MCG vs. stellate ganglia, assess effects of bilateral CSD on cardiac function and VT/VF, and determine changes in cardiac sympathetic innervation after CSD to elucidate mechanisms of benefit in 6 normal and 18 infarcted pigs. Electrophysiological and hemodynamic parameters were evaluated at baseline, during bilateral stellate stimulation, and during bilateral MCG stimulation in 6 normal and 12 infarcted animals. Bilateral CSD (removal of bilateral stellates and T2 ganglia) was then performed and MCG stimulation repeated. In addition, in 18 infarcted animals VT/VF inducibility was assessed before and after CSD. In infarcted hearts, MCG stimulation resulted in greater chronotropic and inotropic response than stellate ganglion stimulation. Bilateral CSD acutely reduced VT/VF inducibility by 50% in infarcted hearts and prolonged global activation recovery interval. CSD mitigated effects of MCG stimulation on dispersion of repolarization and T-peak to T-end interval in infarcted hearts, without causing hemodynamic compromise. These data demonstrate that the MCG provides significant cardiac sympathetic innervation before CSD and adequate sympathetic innervation after CSD, maintaining hemodynamic stability. Bilateral CSD reduces VT/VF inducibility by improving electrical stability in infarcted hearts in the setting of sympathetic activation.NEW & NOTEWORTHY Sympathetic activation in myocardial infarction leads to arrhythmias and worsens heart failure. Bilateral cardiac sympathetic denervation reduces ventricular tachycardia/ventricular fibrillation inducibility and mitigates effects of sympathetic activation on dispersion of repolarization and T-peak to T-end interval in infarcted hearts. Hemodynamic stability is maintained, as innervation via the middle cervical ganglion is not interrupted.

Left ventricular endocardial and epicardial strain changes with apical myocardial ischemia in an open-chest porcine model.

Early detection of acute myocardial ischemia is critical to prevent permanent myocardial damage. The impact of apical ischemia on global left ventricular (LV) function can be difficult to characterize using traditional volume-based echocardiography measures. Myocardial strain imaging is a sensitive, quantitative marker of myocardial deformation that can measure ventricular function. Recent advances allow layer-specific measurement of endo- and epicardial strain, enhancing the ability to evaluate myocardial ischemia. This study investigates the effects of apical ischemia on LV function using epi- and endocardial strain. We hypothesize that myocardial strain will identify changes in regional and global myocardial function associated with focal apical ischemia as compared to ejection fraction (EF), and that longitudinal strain will be a better indicator of myocardial dysfunction compared to circumferential or radial strain. In a porcine model (n = 9), acute ischemia was induced by left anterior descending coronary artery occlusion. Echocardiograms were performed at baseline, during 15-min ischemia, and after reperfusion. Global longitudinal strain decreased with acute focal ischemia of the left ventricular apical region (baseline: -16.4% vs. ischemia: -12.2%; P = 0.010), with no change observed in global circumferential and radial strain or EF Both endocardial and epicardial longitudinal strain decreased by 68% (P < 0.001) in the ischemic and peri-ischemic zone, while circumferential and radial strain only decreased in endocardium of the ischemic zone. Longitudinal strain was more sensitive to ischemia, being able to detect changes in global LV function and thus may confer clinical diagnostic advantage in the evaluation of acute LV apical ischemia.

Targeted stellate decentralization: Implications for sympathetic control of ventricular electrophysiology.

BACKGROUND: Selective bilateral cervicothoracic sympathectomy has proven to be effective for managing ventricular arrhythmias in the setting of structural heart disease. In the procedure currently used, the caudal portions of both stellate ganglia along with thoracic chain ganglia down to T4 ganglia are removed. OBJECTIVE: The purpose of this study was to define the relative contributions of the T1-T2 and T3-T4 paravertebral ganglia in modulating ventricular electrical function. METHODS: In anesthetized vagotomized porcine subjects (n = 8), the heart was exposed via sternotomy along with right and left paravertebral sympathetic ganglia to the T4 level. A 56-electrode epicardial sock was placed over both ventricles to assess epicardial activation-recovery intervals (ARIs) in response to individually stimulating right and left stellate vs T3 paravertebral ganglia. Responses to T3 stimuli were repeated after surgical removal of the caudal portions of stellate ganglia and T2 bilaterally. RESULTS: In intact preparations, stellate ganglion vs T3 stimuli (4 Hz, 4-ms duration) were titrated to produce equivalent decreases in global ventricular ARIs (right side: 85 ± 6 ms vs 55 ± 10 ms; left side: 24 ± 3 ms vs 17 ± 7 ms). Threshold of stimulus intensity applied to T3 ganglia to achieve threshold was 3 times that of T1 threshold. ARIs in unstimulated states were unaffected by bilateral stellate-T2 ganglion removal. After acute decentralization, T3 stimulation failed to change ARIs. CONCLUSION: Preganglionic sympathetic efferents arising from the T1-T4 spinal cord that project to the heart transit through stellate ganglia via the paravertebral chain. Thus, T1-T2 surgical excision is sufficient to functionally interrupt central control of peripheral sympathetic efferent activity.

Central vs. peripheral neuraxial sympathetic control of porcine ventricular electrophysiology.

Sympathoexcitation is associated with ventricular arrhythmogenesis. The aim of this study was to determine the role of thoracic dorsal root afferent neural inputs to the spinal cord in modulating ventricular sympathetic control of normal heart electrophysiology. We hypothesize that dorsal root afferent input tonically modulates basal and evoked efferent sympathetic control of the heart. A 56-electrode sock placed on the epicardial ventricle in anesthetized Yorkshire pigs (n = 17) recorded electrophysiological function, as well as activation recovery interval (ARI) and dispersion in ARI, at baseline conditions and during stellate ganglion electrical stimulation. Measures were compared between intact states and sequential unilateral T1-T4 dorsal root transection (DRTx), ipsilateral ventral root transection (VRTx), and contralateral dorsal and ventral root transections (DVRTx). Left or right DRTx decreased global basal ARI [Lt.DRTx: 369 ± 12 to 319 ± 13 ms (P < 0.01) and Rt.DRTx: 388 ± 19 to 356 ± 15 ms (P < 0.01)]. Subsequent unilateral VRTx followed by contralateral DRx+VRTx induced no further change. In intact states, left and right stellate ganglion stimulation shortened ARIs (6 ± 2% vs. 17 ± 3%), while increasing dispersion (+139% vs. +88%). There was no difference in magnitude of ARI or dispersion change with stellate stimulation following spinal root transections. Interruption of thoracic spinal afferent signaling results in enhanced basal cardiac sympathoexcitability without diminishing the sympathetic response to stellate ganglion stimulation. This suggests spinal dorsal root transection releases spinal cord-mediated tonic inhibitory control of efferent sympathetic tone, while maintaining intrathoracic cardiocentric neural networks.

Vagal nerve stimulation activates vagal afferent fibers that reduce cardiac efferent parasympathetic effects.

Vagal nerve stimulation (VNS) has been shown to have antiarrhythmic effects, but many of these benefits were demonstrated in the setting of vagal nerve decentralization. The purpose of this study was to evaluate the role of afferent fiber activation during VNS on efferent control of cardiac hemodynamic and electrophysiological parameters. In 37 pigs a 56-electrode sock was placed over the ventricles to record local activation recovery intervals (ARIs), a surrogate of action potential duration. In 12 of 37 animals atropine was given systemically. Right and left VNS were performed under six conditions: both vagal trunks intact (n = 25), ipsilateral right (n = 11), ipsilateral left (n = 14), contralateral right (n = 7), contralateral left (n = 10), and bilateral (n = 25) vagal nerve transection (VNTx). Unilateral VNTx significantly affected heart rate, PR interval, Tau, and global ARIs. Right VNS after ipsilateral VNTx had augmented effects on hemodynamic parameters and increase in ARI, while subsequent bilateral VNTx did not significantly modify this effect (%change in ARI in intact condition 2.2 ± 0.9% vs. ipsilateral VNTx 5.3 ± 1.7% and bilateral VNTx 5.3 ± 0.8%, P < 0.05). Left VNS after left VNTx tended to increase its effects on hemodynamics and ARI response (P = 0.07), but only after bilateral VNTx did these changes reach significance (intact 1.1 ± 0.5% vs. ipsilateral VNTx 3.6 ± 0.7% and bilateral VNTx 6.6 ± 1.6%, P < 0.05 vs. intact). Contralateral VNTx did not modify VNS response. The effect of atropine on ventricular ARI was similar to bilateral VNTx. We found that VNS activates afferent fibers in the ipsilateral vagal nerve, which reflexively inhibit cardiac parasympathetic efferent electrophysiological and hemodynamic effects.

Remodeling of stellate ganglion neurons after spatially targeted myocardial infarction: Neuropeptide and morphologic changes.

BACKGROUND: Myocardial infarction (MI) induces remodeling in stellate ganglion neurons (SGNs). OBJECTIVE: We investigated whether infarct site has any impact on the laterality of morphologic changes or neuropeptide expression in stellate ganglia. METHODS: Yorkshire pigs underwent left circumflex coronary artery (LCX; n = 6) or right coronary artery (RCA; n = 6) occlusion to create left- and right-sided MI, respectively (control: n = 10). At 5 ± 1 weeks after MI, left and right stellate ganglia (LSG and RSG, respectively) were collected to determine neuronal size, as well as tyrosine hydroxylase (TH) and neuropeptide Y immunoreactivity. RESULTS: Compared with control, LCX and RCA MIs increased mean neuronal size in the LSG (451 ± 25 vs 650 ± 34 vs 577 ± 55 µm(2), respectively; P = .0012) and RSG (433 ± 22 vs 646 ± 42 vs 530 ± 41 µm(2), respectively; P = .002). TH immunoreactivity was present in the majority of SGNs. Both LCX and RCA MIs were associated with significant decreases in the percentage of TH-negative SGNs, from 2.58% ± 0.2% in controls to 1.26% ± 0.3% and 0.7% ± 0.3% in animals with LCX and RCA MI, respectively, for LSG (P = .001) and from 3.02% ± 0.4% in controls to 1.36% ± 0.3% and 0.68% ± 0.2% in LCX and RCA MI, respectively, for RSG (P = .002). Both TH-negative and TH-positive neurons increased in size after LCX and RCA MI. Neuropeptide Y immunoreactivity was also increased significantly by LCX and RCA MI in both ganglia. CONCLUSION: Left- and right-sided MIs equally induced morphologic and neurochemical changes in LSG and RSG neurons, independent of infarct site. These data indicate that afferent signals transduced after MI result in bilateral changes and provide a rationale for bilateral interventions targeting the sympathetic chain for arrhythmia modulation.