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BackgroundNeuraxial modulation, including spinal cord stimulation, reduces cardiac sympathoexcitation and ventricular arrhythmogenesis. There is an incomplete understanding of the molecular mechanisms through which spinal cord stimulation modulates cardiospinal neural pathways. The authors hypothesize that spinal cord stimulation reduces myocardial ischemia–reperfusion—induced sympathetic excitation and ventricular arrhythmias through γ-aminobutyric acid (GABA)–mediated pathways in the thoracic spinal cord.MethodsYorkshire pigs were randomized to control (n = 11), ischemia–reperfusion (n = 16), ischemia–reperfusion plus spinal cord stimulation (n = 17), ischemia–reperfusion plus spinal cord stimulation plus γ-aminobutyric acid type A (GABAA) or γ-aminobutyric acid type B (GABAB) receptor antagonist (GABAA, n = 8; GABAB, n = 8), and ischemia–reperfusion plus GABA transaminase inhibitor (GABAculine, n = 8). A four-pole spinal cord stimulation lead was placed epidurally (T1 to T4). GABA modulating pharmacologic agents were administered intrathecally. Spinal cord stimulation at 50 Hz was applied 30 min before ischemia. A 56-electrode epicardial mesh was used for high-resolution electrophysiologic recordings, including activation recovery intervals and ventricular arrhythmia scores. Immunohistochemistry and Western blots were performed to measure GABA receptor expression in the thoracic spinal cord.ResultsCardiac ischemia led to myocardial sympathoexcitation with reduction in activation recovery interval (mean ± SD, –42 ± 11%), which was attenuated by spinal cord stimulation (–21 ± 17%, P = 0.001). GABAA and GABAB receptor antagonists abolished spinal cord stimulation attenuation of sympathoexcitation (GABAA, –9.7 ± 9.7%, P = 0.043 vs. ischemia–reperfusion plus spinal cord stimulation; GABAB, –13 ± 14%, P = 0.012 vs. ischemia–reperfusion plus spinal cord stimulation), while GABAculine alone caused a therapeutic effect similar to spinal cord stimulation (–4.1 ± 3.7%, P = 0.038 vs. ischemia–reperfusion). The ventricular arrhythmia score supported these findings. Spinal cord stimulation during ischemia–reperfusion increased GABAA receptor expression with no change in GABAB receptor expression.ConclusionsThoracic spinal cord stimulation reduces ischemia–reperfusion—induced sympathoexcitation and ventricular arrhythmias through activation of GABA signaling pathways. These data support the hypothesis that spinal cord stimulation–induced release of GABA activates inhibitory interneurons to decrease primary afferent signaling from superficial dorsal horn to sympathetic output neurons in the intermediolateral nucleus.Editor’s PerspectiveWhat We Already Know about This TopicWhat This Article Tells Us That Is New

Background: Myocardial ischemia can lead to fatal ventricular arrhythmias by disrupting the cardiospinal neural network which controls the sympathoexcitation. Spinal neuromodulation techniques could decrease myocardial ischemia-induced sympathoexcitation by modulating the spinal neural network. Hypothesis: We hypothesize that spinal oxytocin (OXT) administration decreases myocardial ischemia-induced sympathoexcitation by suppressing spinal neural hyperactivity in the dorsal horn (DH) and intermediolateral nucleus regions (IML). Materials and Methods: Anesthetized pigs underwent laminectomy to expose the spinal T2 section and a sternotomy to expose the heart for performing left anterior descending coronary artery ischemia (LAD) with and without intrathecal oxytocin (90ug) treatment. Electrocardiograms were recorded using a 56-channel mesh electrode to evaluate the activation recovery interval (ARI) and dispersion of repolarization (DOR) which are the markers for sympathoexcitation and arrhythmogenecity. Extracellular in-vivo spinal neural recordings were done by using a 64-channel microelectrode array inserted at the T2 segment of the spinal cord to record the activity of DH and IML neurons. Oxytocin was administered intrathecally at T1-T3. Spinal neural activity, ARI, and DOR were evaluated during myocardial ischemia with vs. without intrathecal oxytocin administration. Results: Sixteen Yorkshire pigs entered into this study. In 13 animals (LAD:7, LAD+OXT:6) ARI and DOR were evaluated during long LAD ischemia (1hr). ARI shortening due to LAD was mitigated by OXT (LAD:-33 ± 4 ms; LAD+OXT: -15 ± 1 ms, P=0.001). OXT decreased the LAD-induced augmented DOR (LAD: 2194± 310 ms2; LAD+OXT: 1099± 305 ms2, P=0.029). We have further evaluated the effect of OXT on short LAD ischemia (5 mins) and the impact of intrathecal OXT agonist on the spinal cord neural processing of myocardial ischemia in 3 pigs. Out of 88 recorded neurons, LAD increased the firing rate of more neurons than the LAD+OXT (LAD: increased 52, decreased 12 neurons; LAD+OXT: increased 16, decreased 14 neurons, P=0.007). The LAD-induced spinal cord hyperactivity was mitigated after intrathecal OXT administration (LAD:1.57 ± 0.52 Hz to LAD+OXT: 0.02 ± 0.22 Hz, P=0.0001). OXT also mitigated the reperfusion-induced spinal neuronal hyperactivity (LAD:2.16 ± 0.59 Hz to LAD+OXT: -0.36 ± 0.28 Hz, P Funding: NIH (R01) HL136836 (Dr.Mahajan) and University of Pittsburgh Medical Center Competitive Medical Research Fund (Dr.Salavatian). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Acute kidney injury (AKI) is a common postoperative complication in bilateral orthotopic lung transplant (BOLTx) recipients, but the contribution of intraoperative variables is not well defined. The authors hypothesized that intraoperative hypotension as well as hypoxia and vasopressor use would be associated with the development of postoperative AKI after BOLTx in patients without pre-existing renal dysfunction.The authors performed a retrospective analysis of patients undergoing BOLTx at a single center between 2013 and 2017. Intraoperative variables of hemodynamics included duration of mean arterial pressure55,60, and65 mm Hg; duration of oxygen saturation90%; and vasoactive-inotropic score (VIS). Associations between the occurrence of AKI and intraoperative hypotension, hypoxemia, and VIS were evaluated while controlling for significant confounding variables.AKI occurred in 177 (72%) of 245 patients in postoperative days 1-7. Notable significant differences in univariate analyses included cumulative mechanical support time, maximum VIS, peripheral oxygen saturation90% for15 min, total minutes oxygen saturation90%, and surgery duration in minutes. There was no significant difference in intraoperative hypotension measured as a duration15 min for mean arterial pressure55,60, or65 mm Hg. Multivariate logistic regression revealed preoperative creatinine (Odds ratio [OR], 7.77; confidence interval [CI], 1.96-30.83; P = 0.004), surgery duration (OR, 1.004; CI, 1.002-1.007; P = 0.002), and oxygen saturation (OR, 2.06; CI, 1.01-4.24; P = 0.049)90% for15 min to be independently associated with AKI.This study revealed that15 min of intraoperative hypoxia was independently associated with postoperative AKI after BOLTx.

Background Cardiac sympathoexcitation leads to ventricular arrhythmias. Spinal anesthesia modulates sympathetic output and can be cardioprotective. However, its effect on the cardio-spinal reflexes and network interactions in the dorsal horn cardiac afferent neurons and the intermediolateral nucleus sympathetic neurons that regulate sympathetic output is not known. The authors hypothesize that spinal bupivacaine reduces cardiac neuronal firing and network interactions in the dorsal horn–dorsal horn and dorsal horn–intermediolateral nucleus that produce sympathoexcitation during myocardial ischemia, attenuating ventricular arrhythmogenesis. Methods Extracellular neuronal signals from the dorsal horn and intermediolateral nucleus neurons were simultaneously recorded in Yorkshire pigs (n = 9) using a 64-channel high-density penetrating microarray electrode inserted at the T2 spinal cord. Dorsal horn and intermediolateral nucleus neural interactions and known markers of cardiac arrhythmogenesis were evaluated during myocardial ischemia and cardiac load–dependent perturbations with intrathecal bupivacaine. Results Cardiac spinal neurons were identified based on their response to myocardial ischemia and cardiac load–dependent perturbations. Spinal bupivacaine did not change the basal activity of cardiac neurons in the dorsal horn or intermediolateral nucleus. After bupivacaine administration, the percentage of cardiac neurons that increased their activity in response to myocardial ischemia was decreased. Myocardial ischemia and cardiac load–dependent stress increased the short-term interactions between the dorsal horn and dorsal horn (324 to 931 correlated pairs out of 1,189 pairs, P < 0.0001), and dorsal horn and intermediolateral nucleus neurons (11 to 69 correlated pairs out of 1,135 pairs, P < 0.0001). Bupivacaine reduced this network response and augmentation in the interactions between dorsal horn–dorsal horn (931 to 38 correlated pairs out of 1,189 pairs, P < 0.0001) and intermediolateral nucleus–dorsal horn neurons (69 to 1 correlated pairs out of 1,135 pairs, P < 0.0001). Spinal bupivacaine reduced shortening of ventricular activation recovery interval and dispersion of repolarization, with decreased ventricular arrhythmogenesis during acute ischemia. Conclusions Spinal anesthesia reduces network interactions between dorsal horn–dorsal horn and dorsal horn–intermediolateral nucleus cardiac neurons in the spinal cord during myocardial ischemia. Blocking short-term coordination between local afferent–efferent cardiac neurons in the spinal cord contributes to a decrease in cardiac sympathoexcitation and reduction of ventricular arrhythmogenesis. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

OBJECTIVE To determine if implementation of a simplified enhanced recovery protocol (ERP) across multiple surgical specialties in different hospitals is associated with improved short and long-term mortality. Secondary aims were to examine ERP effect on LOS, 30-day readmission, discharge disposition, and complications. SUMMARY BACKGROUND DATA Enhanced Recovery After Surgery (ERAS) and various derivative ERPs have been successfully implemented. These protocols typically include elaborate sets of multi-modal and multi-disciplinary approaches, which can make implementation challenging or are variable across different specialties. Few studies have shown if a simplified version of ERP implemented across multiple surgical specialties can improve clinical outcomes. METHODS A simplified ERP with seven key domains (minimally invasive surgical approach when feasible, pre-/intra-operative multimodal analgesia, postoperative multimodal analgesia, postoperative nausea and vomiting prophylaxis, early diet advancement, early ambulation, and early removal of urinary catheter) was implemented in five academic and community hospitals within a single health system. Patients who underwent non-emergent, major orthopedic or abdominal surgery including hip/knee replacement, hepatobiliary, colorectal, gynecology oncology, bariatric, general, and urological surgery were included. Propensity-matched, retrospective case-control analysis was performed on all eligible surgical patients between 2014-2017 after ERP implementation or in the 12 months preceding ERP implementation (control population). RESULTS 9492 patients (5185 ERP and 4307 controls) underwent ERP eligible surgery during the study period. 3367 ERP patients were matched by surgical specialty and hospital site to control non-ERP patients. Short and long-term mortality was improved in ERP patients: 30 day: ERP 0.2% vs Control 0.6% (p = 0.002); 1-year: ERP 3.9% vs. Control 5.1% (p < 0.0001); 2-year: ERP 6.2% vs Control 9.0% (p < 0.0001). LOS was significantly lower in ERP patients (ERP: 3.9 ± 3.8 days; Control: 4.8 ± 5.0 days, p < 0.0001). ERP patients were also less likely to be discharged to a facility (ERP: 11.3%; Control: 14.8%, p < 0.0001). There was no significant difference for 30-day readmission. All complications except venous thromboembolism were significantly reduced in the ERP population (p < 0.02). CONCLUSIONS A simplified ERP can uniformly be implemented across multiple surgical specialties and hospital types. ERPs improve short and long-term mortality, clinical outcomes, length of stay, and discharge disposition to home.

Ventricular arrhythmias are associated with significant morbidity and mortality. In the perioperative period, more than 10% of patients undergoing a general anesthetic have an abnormal heart rhythm. Arrhythmia development is a dynamic interplay between an arrhythmogenic substrate, myocardial electrophysiologic properties, modifying factors, and triggering factors. Imbalances in the autonomic nervous system can lead to increased myocardial excitability, which is a major contributor to the pathophysiology of ventricular tachyarrhythmias. Myocardial excitability and ventricular arrhythmogenesis is modulated perioperatively through hemodynamic management, electrolyte balance, anesthetic agents, or regional anesthetic and surgical techniques.

BACKGROUND Socioeconomic status (SES) can be a powerful predictor of adverse outcomes among heart failure patients but its impact on survival and readmission following left ventricular assist device (LVAD) implantation surgery is poorly understood. We investigated if the LVAD recipients from more deprived neighborhoods experienced higher mortality and readmission rate after device implantation as compared to those from less deprived areas. METHODS This is a single center, retrospective analysis evaluating adults who received Heartmate III and Heartware HVAD implants between 2009 and 2018. SES indicators were area of deprivation index (ADI), race and income. Our cohort was grouped by ADI quartiles from least deprived (Q1), Q2, Q3 to the most deprived (Q4). Outcomes included overall mortality and readmission following surgery. RESULTS A total of 191 patients were included in the study. Demographics by SES indicators demonstrated that least deprived (Q1) patients were older than the most deprived (65 vs. 57, p

OBJECTIVE: This study investigated spinal cord neuronal and glial cell activation during cardiac ischemia-reperfusion (IR)-triggered ventricular arrhythmias and neuromodulation therapy by spinal cord stimulation (SCS) BACKGROUND: Myocardial ischemia induces changes in cardiospinal neural networks leading to sudden cardiac death. Neuromodulation with SCS decreases cardiac sympathoexcitation; however, the molecular mechanisms remain unknown. METHODS: Yorkshire pigs (n=16) were randomized to Control, IR, or IR+SCS groups. A 4-pole SCS lead was placed in T1–T4 epidural space with stimulation for 30 mins prior to IR (50 Hz, 0.4msec duration, 90% motor threshold). Cardiac electrophysiological mapping and Ventricular Arrhythmia Score (VAS) were recorded. Immunohistochemistry of thoracic spinal sections was used to map and identify Fos-positive neuronal and glial cell types during IR with and without SCS. RESULTS: IR increased cardiac sympathoexcitation and arrhythmias (VAS = 6.2±0.9) which were attenuated in IR + SCS (VAS = 2.8±0.5, p=0.017). IR increased spinal cellular Fos expression (#Fos+ cells Control= 23±2 vs. IR=88±5, p

Objective In this paper, the authors report their experience of perioperative transthoracic echocardiography (TTE) practice and its impact on perioperative patient management. Design Retrospective case series. Setting Single institution, tertiary university hospital. Participants A total of 101 adult ASA II-V male and female patients >18 years old who were scheduled for or having surgery were included in this retrospective case series. Interventions All patients underwent a focused perioperative TTE exam performed by cardiac anesthesiologists with significant TTE experience, and further clinical management was based on echocardiography findings discussed with the anesthesia care team. Measurements Significant echocardiographic findings and changes in patient management were reported. Step-up management was a new intervention that was executed based on echocardiographic findings (volume infusion, inotropic therapy, cardiology consultation, and other interventions), and step-down management was avoidance of an unnecessary intervention based on echocardiographic findings (proceeding to surgery without cancellation, delay, cardiology consultation, and additional investigations/interventions). Main Results Fifty-three percent of TTEs were performed in the preoperative setting, 34% were intra-operative, and 13% were postoperative. No significant findings were detected in 38 patients, leading to step-down management in all of them. Among patients with positive findings, left ventricular dysfunction (12.8%), hypovolemia (10.8%), and right ventricular dysfunction (7.9%) were the most common. Step-up therapy included inotropic/vasopressor therapy (24.8%), intensive care admission after surgery for further management (13.8%), volume infusion (12.8%), and other interventions (additional monitoring, surgical delay, cardiology consultation, and modification of surgical technique). Conclusion Perioperative focused TTE examination is useful in the diagnosis of new cardiac conditions for anesthesia management (intraoperative monitoring and hemodynamic therapy) and postoperative care (intensive care unit admissions). Perioperative TTE performed by anesthesiologists can also help avoid procedural delays and unnecessary consults.

The pathological consequences of ischemic heart disease involve signaling through the autonomic nervous system. Although early activation may serve to maintain hemodynamic stability, persistent aberrant sympathoexcitation contributes to the development of lethal arrhythmias and heart failure. We hypothesized that as the myocardium reacts and remodels to ischemic injury over time, there is an analogous sequence of gene expression changes in the thoracic spinal cord dorsal horn, the processing center for incoming afferent fibers from the heart to the central nervous system. Acute and chronic myocardial ischemia (MI) was induced in a large animal model of Yorkshire pigs, and the thoracic dorsal horn of treated pigs, along with control nonischemic pigs, was harvested for transcriptome analysis. We identified 32 differentially expressed genes between healthy and acute ischemia cohorts and 46 differentially expressed genes between healthy and chronic ischemia cohorts. The canonical immediate-early gene c-fos was upregulated after acute MI, along with fosB, dual specificity phosphatase 1 and 2 ( dusp1 and dusp2), and early growth response 2 (egr2). After chronic MI, there was a persistent yet unique activation of immediate-early genes, including fosB, nuclear receptor subfamily 4 group A members 1−3 ( nr4a1, nr4a2, and nr4a3), egr3, and TNF-α-induced protein 3 ( tnfaip3). In addition, differentially expressed genes from the chronic MI signature were enriched in pathways linked to apoptosis, immune regulation, and the stress response. These findings support a dynamic progression of gene expression changes in the dorsal horn with maturation of myocardial injury, and they may explain how early adaptive autonomic nervous system responses can maintain hemodynamic stability, whereas prolonged maladaptive signals can predispose patients to arrhythmias and heart failure. NEW & NOTEWORTHY Activation of the autonomic nervous system after myocardial injury can provide early cardiovascular support or prolonged aberrant sympathoexcitation. The later response can lead to lethal arrhythmias and heart failure. This study provides evidence of ongoing changes in the gene expression signature of the spinal cord dorsal horn as myocardial injury progresses over time. These changes could help explain how an adaptive nervous system response can become maladaptive over time.

Background Echocardiography-based speckle-tracking strain imaging is an emerging modality to assess left ventricular function. The aim of this study was to investigate the change in left ventricular systolic function after cardiac surgery with 3-dimensional (3D) speckle-tracking strain imaging and to determine whether preoperative 3D strain is an independent predictor of acute and long-term clinical outcomes after aortic valve, mitral valve, and coronary artery bypass grafting operations. Methods In total, 163 adult patients undergoing aortic valve, mitral valve, and coronary artery bypass surgeries were enrolled prospectively and had complete data sets. Demographic, operative, and outcome data were collected. 3D transthoracic echocardiograms were preformed preoperatively and on second to fourth postoperative day. Blinded off-line analysis was performed for left ventricular 2-dimensional (2D) ejection fraction (EF2D) and 3D ejection fraction (EF3D) and global peak systolic area, longitudinal, circumferential, and radial strain. Results 3D global strain correlated well with EF3D. Ventricular function as measured by strain imaging decreased significantly after all types of cardiac surgery. When preoperative EF3D was used, receiver operating characteristic curves identified reference values for 3D global strain corresponding to normal, mildly reduced, and severely reduced ventricular function. Normal ventricular function (EF3D ≥ 50%) corresponded to 3D global area strain -25%, with area under curve = 0.86 (0.81-0.89). Patients with reduced preoperative 3D global area strain had worse postoperative outcomes, including length of intensive care unit stay (4 vs 3 days, P = .001), major adverse events (27% vs 11%, P = .03), and decreased 1-year event-free survival (69% vs 88%, P = .005). After we controlled for baseline preoperative risk models including European System for Cardiac Operative Risk Evaluation score and surgery type, preoperative strain was an independent predictor of both short- and long-term outcomes, including length of intensive care unit stay, postoperative inotrope score, and 1-year event-free survival. Conclusions This study shows that cardiac surgery was associated with an acute reduction in postoperative left ventricular function, when evaluated with 3D strain imaging. In addition, preoperative 3D strain was demonstrated to be an independent predictor of acute and long-term clinical outcomes after cardiac surgery. The use of noninvasive 3D transthoracic echocardiogram strain imaging before cardiac surgery may provide added information to aid in perioperative risk stratification and management for these high-risk patients.

Atrial fibrillation and delirium are common consequences of cardiac surgery. Dexmedetomidine has unique properties as sedative agent and might reduce the risk of each complication. This study coprimarily aimed to establish whether dexmedetomidine reduces the incidence of new-onset atrial fibrillation and the incidence of delirium.A randomised, placebo-controlled trial was done at six academic hospitals in the USA. Patients who had had cardiac surgery with cardiopulmonary bypass were enrolled. Patients were randomly assigned 1:1, stratified by site, to dexmedetomidine or normal saline placebo. Randomisation was computer generated with random permuted block size 2 and 4, and allocation was concealed by a web-based system. Patients, caregivers, and evaluators were all masked to treatment. The study drug was prepared by the pharmacy or an otherwise uninvolved research associate so that investigators and clinicians were fully masked to allocation. Participants were given either dexmedetomidine infusion or saline placebo started before the surgical incision at a rate of 0·1 μg/kg per h then increased to 0·2 μg/kg per h at the end of bypass, and postoperatively increased to 0·4 μg/kg per h, which was maintained until 24 h. The coprimary outcomes were atrial fibrillation and delirium occurring between intensive care unit admission and the earlier of postoperative day 5 or hospital discharge. All analyses were intention-to-treat. The trial is registered with ClinicalTrials.gov, NCT02004613 and is closed.798 patients of 3357 screened were enrolled from April 17, 2013, to Dec 6, 2018. The trial was stopped per protocol after the last designated interim analysis. Among 798 patients randomly assigned, 794 were analysed, with 400 assigned to dexmedetomidine and 398 assigned to placebo. The incidence of atrial fibrillation was 121 (30%) in 397 patients given dexmedetomidine and 134 (34%) in 395 patients given placebo, a difference that was not significant: relative risk 0·90 (97·8% CI 0·72, 1·15; p=0·34). The incidence of delirium was non-significantly increased from 12% in patients given placebo to 17% in those given dexmedetomidine: 1·48 (97·8% CI 0·99-2·23). Safety outcomes were clinically important bradycardia (requiring treatment) and hypotension, myocardial infarction, stroke, surgical site infection, pulmonary embolism, deep venous thrombosis, and death. 21 (5%) of 394 patients given dexmedetomidine and 8 (2%) of 396 patients given placebo, had a serious adverse event as determined by clinicians. 1 (1%) of 391 patients given dexmedetomidine and 1 (1%) of 387 patients given placebo died.Dexmedetomidine infusion, initiated at anaesthetic induction and continued for 24 h, did not decrease postoperative atrial arrhythmias or delirium in patients recovering from cardiac surgery. Dexmedetomidine should not be infused to reduce atrial fibrillation or delirium in patients having cardiac surgery.Hospira Pharmaceuticals.

Background Three-dimensional (3D) strain is an echocardiographic modality that can characterize left ventricular (LV) function with greater accuracy than ejection fraction. While decreases in global strain have been used to predict outcomes after cardiac surgery, changes in regional 3D longitudinal, circumferential, radial, and area strain have not been well described. The primary aim of this study was to define differential patterns in regional LV dysfunction after cardiac surgery using 3D speckle tracking strain imaging. Our secondary aim was to investigate whether changes in regional strain can predict postoperative outcomes, including length of intensive care unit stay and 1-year event-free survival. Methods In this prospective clinical study, demographic, operative, echocardiographic, and clinical outcome data were collected on 182 patients undergoing aortic valve replacement, mitral valve repair or replacement, coronary artery bypass graft, and combined cardiac surgery. Three-dimensional transthoracic echocardiograms were performed preoperatively and on the second to fourth postoperative day. Blinded analysis was performed for LV regional longitudinal, circumferential, radial, and area strain in the 17-segment model. Results Regional 3D longitudinal, circumferential, radial, and area strains were associated with differential patterns of myocardial dysfunction, depending on the surgical procedure performed and strain measure. Patients undergoing mitral valve repair or replacement had reduced function in the majority of myocardial segments, followed by coronary artery bypass graft, while patients undergoing aortic valve replacement had reduced function localized only to apical segments. After all types of cardiac surgery, segmental function in apical segments was reduced to a greater extent as compared to basal segments. Greater decrements in regional function were seen in circumferential and area strain, while smaller decrements were observed in longitudinal strain in all surgical patients. Both preoperative regional strain and change in regional strain preoperatively to postoperatively were correlated with reduced 1-year event-free survival, while postoperative strain was not predictive of outcomes. Only preoperative strain values were predictive of intensive care unit length of stay. Conclusions Changes in regional myocardial function, measured by 3D strain, varied by surgical procedure and strain type. Differences in regional LV function, from presurgery to postsurgery, were associated with worsened 1-year event-free survival. These findings suggest that postoperative changes in myocardial function are heterogeneous in nature, depending on the surgical procedure, and that these changes may have long-term impacts on outcome. Therefore, 3D regional strain may be used to identify patients at risk for worsened postoperative outcomes, allowing early interventions to mitigate risk.

Summary Preoperative cardiac function is an important predictor of postoperative outcomes. Patients with heart failure are at higher risk of perioperative morbidity and mortality. Left ventricular ejection fraction, derived by standard echocardiography, is most frequently used to assess cardiac function in the intraoperative and postoperative periods. Myocardial strain analysis, a measurement of myocardial deformation, can provide additional information to left venricular eject fraction estimation. Here, we provide an overview of myocardial strain and different methods used to evaluate strain, including speckle tracking echocardiography. Speckle tracking echocardiography is an imaging modality that can analyse and track small segments of the myocardium, which provides greater detail for assessing global and regional cardiac motion and function. We further review the literature to illustrate the value of speckle tracking echocardiography-derived myocardial strain in describing cardiac function and its association with adverse surgical outcomes in the perioperative period, including low cardiac output states, need for inotropic support, postoperative arrhythmias, subclinical myocardial ischaemia, and length of hospital stay.

Left ventricular (LV) dysfunction increases the risk for serious post-operative complications. Accurate assessment of LV wall motion is necessary to guide anesthetic management; however, traditional measures have a high degree of inter- and intra-observer variability. Myocardial deformation as measured by strain and strain rates is improving the diagnostic and prognostic utility of echocardiography to determine LV function in patients with cardiovascular disease. Strain can be measured using tissue Doppler and speckle tracking imaging from two-dimensional or three-dimensional echocardiography using various online and offline software packages. Tissue Doppler strain analysis provides excellent temporal resolution but is limited by the imaging angle of insonation. Speckle tracking strain imaging is angle independent and now the more commonly used modality. Strain has been demonstrated to guide therapy, monitor disease progression in various pathologic states, and is emerging as a strong predictor of clinical outcomes.

Heart failure refractory to medical therapy may be treated by heart transplantation. Given that the need for organs outpaces supply, ventricular assist devices (VADs) were developed to support hemodynamics in the patient with end-stage heart failure. Initially approved only in those patients awaiting transplantation, VADs are now implanted for long-term therapy in patients ineligible for transplantation. Many of these patients may subsequently present for non-cardiac surgery, possibly in a non-transplant center. General anesthesiologists may therefore be expected to care for these patients, especially in an emergency. This review presents an overview of current VADs as well as their unique preoperative and intraoperative anesthetic considerations.

Myocardial ischemia creates autonomic nervous system imbalance and can trigger cardiac arrhythmias. We hypothesized that neuromodulation by spinal cord stimulation (SCS) will attenuate local cardiac sympathoexcitation from ischemia-induced increases in afferent signaling, reduce ventricular arrhythmias, and improve myocardial function during acute ischemia. Yorkshire pigs ( n = 20) were randomized to SCS (50 Hz at 200-μs duration, current 90% motor threshold) or sham operation (sham) for 30 min before ischemia. A four-pole SCS lead was placed percutaneously in the epidural space (T1–T4), and a 56-electrode mesh was placed over the heart for high-resolution electrophysiological recordings, including activation recovery intervals (ARIs), activation time, repolarization time, and dispersion of repolarization. Electrophysiological and hemodynamic measures were recorded at baseline, after SCS/sham, during acute ischemia (300-s coronary artery ligation), and throughout reperfusion. SCS 1) reduced sympathoexcitation-induced ARI and repolarization time shortening in the ischemic myocardium; 2) attenuated increases in the dispersion of repolarization; 3) reduced ventricular tachyarrythmias [nonsustained ventricular tachycardias: 24 events (3 sham animals) vs. 1 event (1 SCS animal), P < 0.001]; and 4) improved myocardial function (dP/d t from baseline to ischemia: 1,814 ± 213 to 1,596 ± 282 mmHg/s in sham vs. 1,422 ± 299 to 1,380 ± 299 mmHg/s in SCS, P < 0.01). There was no change in ventricular electrophysiology during baseline conditions without myocardial stress or in the nonischemic myocardium. In conclusion, in a porcine model of acute ventricular ischemia, SCS reduced regional myocardial sympathoexcitation, decreased ventricular arrhythmias, and improved myocardial function. SCS decreased sympathetic nerve activation locally in the ischemic myocardium with no effect observed in the normal myocardium, thus providing mechanistic insights into the antiarrhythmic and myocardial protective effects of SCS. NEW & NOTEWORTHY In a porcine model of ventricular ischemia, spinal cord stimulation decreased sympathetic nerve activation regionally in ischemic myocardium with no effect on normal myocardium, demonstrating that the antiarrhythmic effects of spinal cord stimulation are likely due to attenuation of local sympathoexcitation in the ischemic myocardium and not changes in global myocardial electrophysiology.

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.

Since the advent of neonatal cardiac surgery in the 1970s, an increasing number of patients suffering from congenital heart disease (CHD) have survived into adulthood. In 2010, it is estimated that 1.2 million or 1 in 150 of young adults have some form of CHD in the United States. Current birth, incidence, and survival rate predict an increase in the CHD population between 10,000 and 300,000 patients per year. Data from large adult CHD (ACHD) centers (UCLA, Toronto, Mayo Clinic) show that as many as 50% of these patients with complex physiology are 40 years of age or older and that two-thirds of them can be categorized as medium or high risk to demonstrate signs and symptoms of low cardiac output. As this population ages, it is very likely for hospital-based physicians to encounter such patients in their procedural and/or surgical practice. Risk stratification and interdisciplinary approach in the care of these patients will assure a safe outcome. The assessment of the patient must consider the variable expression of CHD. Because most lesions are "fixed but not cured," the periprocedural practitioner must consider the altered physiology of the heart in context of the physiological challenges of percutaneous and open surgical interventions. The 2008 American Heart Association/American College of Cardiology guidelines for the Management of Adults with CHD establish for the first time a streamlined approach to the care of these patients. This review will apply these guidelines to the patients with ACHD undergoing noncardiac surgery and intervention.

In 2010 it was estimated that 1.2 million young adults in the United States have some form of congenital heart disease (CHD). Data from large adult congenital heart disease (ACHD) centers show that as many as 50 % of these patients are over 40 years of age. As this population ages, physicians are likely to encounter such patients in their practice. Risk stratification and an interdisciplinary approach are paramount in achieving safe outcomes. The assessment of the patient must consider the variable expression of CHD. As most lesions are “fixed but not cured” the altered physiology of the heart and the physiological challenges of surgical interventions must be considered. The 2008 AHA/ACC guidelines for the Management of Adults with CHD establish for the first time a streamlined approach to the care of these patients. This review will apply these guidelines to the ACHD patient undergoing non-cardiac surgery.

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

Post-operative atrial fibrillation (AF) is the most common complication for cardiac surgery, with an incidence of 27-40% and is associated with increased 30-day mortality. Several models exist to predict post-op AF using clinical data, however none have been widely implemented, and all have room for improvement (average area under ROC curve is ~0.70). We tested whether DNA methylation, assayed from pre-operative blood draws, could add predictive value. We enrolled a cohort of 55 adult patients undergoing cardiopulmonary bypass, with a 36% incidence of post-op AF. Reduced representative bisulfite sequencing provided single-base resolution for an average of 3 million CpGs with 10x sequencing coverage per sample. We first tested whether these CpGs were correlated with AF. Of the 809,569 CpGs that passed thresholds in all samples, 16,774 were significantly correlated with AF (corrected p-value

The clinical utility of focused transthoracic echocardiography (TTE) is increasingly recognized in perioperative medicine. However its use is limited among anesthesiologists because of a lack of training. The most efficient training methods have not been determined. We hypothesized that simulation-based TTE training would be more effective than traditional lecture-based methods for teaching basic TTE skills to the anesthesiology residents.In this prospective randomized study, 61 anesthesiology residents (in anesthesia clinical training years 1 to 3) were randomized to either control (n = 30) or simulation groups (n = 31) for TTE training. A standardized pretest was administered before TTE training sessions of 45 minutes each. The first training session used a lecture-based video didactic in the control group or a TTE simulator in the simulation group. Comprehension in both groups was then assessed using a written posttest and by performing a TTE examination on a volunteer subject. TTE examinations were graded on the ability to acquire the correct image, image quality, anatomy identification, and time required to attain proper imaging by 2 blinded experts. A second training session incorporating "hands-on" training with a volunteer subject was conducted in a subset of 21 residents (n = 11 control, n = 10 simulation). The simulation group included additional simulator training. After the second session, another posttest on a volunteer subject was administered.Pretest scores revealed similar preintervention knowledge among residents (56.0% ± 11.9% vs 59.3% ± 11.0%, P = 0.25; control versus simulator group, respectively). The simulation group scored higher on all criteria after the first training session: written posttest (57.9% ± 8.8% vs 68.2% ± 10.1%; P0.001), volunteer subject posttest image quality scores (0 to 25 scale) (6.4 ± 3.5 vs 12.4 ± 4.2; P = 0.003), anatomy identification scores (0 to 25 scale) (8.3 ± 6.6 vs 17.8 ± 6.6; P = 0.003), and percentage correct views (50 ± 19 vs 78 ± 21; P0.001). After the second session, all scores were again improved in the simulation group: volunteer subject posttest image quality scores (9.6 ± 3.3 vs 15.6 ± 2.8; P = 0.002), anatomy identification scores: (17.6 ± 3.8 vs 22.8 2.4; P = 0.003), and percentage correct views (80 ± 16 vs 96 ± 8; P = 0.007).This prospective randomized study demonstrated that anesthesiology residents trained with simulation acquired better skills in TTE image acquisition and anatomy identification on volunteer subjects. The educational benefit of simulation persisted even with introduction of hands-on instruction with volunteer subjects in both groups. The impact of these short-term educational approaches on longer-term retention and actual clinical application warrants further investigation.

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.

Modulation of human cardiac mechanical and electrophysiologic function by direct stellate ganglion stimulation has not been performed. Our aim was to assess the effect of low-level left stellate ganglion (LSG) stimulation (SGS) on arrhythmias, hemodynamic, and cardiac electrophysiological indices. Patients undergoing ablation procedures for arrhythmias were recruited for SGS. A stimulating electrode was placed next to the LSG under fluoroscopy and ultrasound imaging; and SGS (5-10Hz, 10-20mA) was performed. We measured hemodynamic, intracardiac and ECG parameters, and activation recovery intervals (ARIs) (surrogate for action potential duration) from a duodecapolar catheter in the right ventricular outflow tract. Five patients underwent SGS (3 males, 45±20years). Stimulating catheter placement was successful, and without complication in all patients. SGS did not change heart rate, but increased mean arterial blood pressure (78±3mmHg to 98±5mmHg, P&nbsp

The primary aim of this study was to use speckle-tracking strain imaging to evaluate the effect of general anesthesia (GA) and positive-pressure ventilation (PPV) on left atrial (LA) mechanics. The authors hypothesized that GA and PPV would be associated with a decrease in LA strain. The secondary aims were to investigate the effects of GA and PPV on traditional Doppler-derived measures of LA function and Doppler echocardiographic grade of diastolic function.A prospective observational study.A university hospital.Adult patients undergoing cardiac surgery.Transthoracic echocardiography was performed at baseline and under GA with PPV.Changes in LA function associated with GA and PPV were assessed using LA speckle-tracking strain imaging. A reduction was observed in LA peak longitudinal strain (24% v 18%, p0.001) and preatrial contraction strain (13% v 8%, p0.001). No difference was seen in LA contraction strain or atrial ejection fraction. Indexed LA volume and Doppler diastolic indices also were reduced significantly, and 39% of patients had a change in measured diastolic grade under GA with PPV.Speckle-tracking strain imaging of the left atrium demonstrated that GA and PPV had a significant impact on LA mechanics by decreasing strain measures of LA preload, with a lesser effect on LA contractility.

Red blood cell (RBC) transfusions are associated with increased morbidity. Children receiving heart transplants constitute a unique group of patients due to their risk factors. Although previous studies in nontransplant patients have focused primarily on the effects of postoperative blood transfusions, a significant exposure to blood occurs during the intraoperative period, and a larger percentage of heart transplant patients require intraoperative blood transfusions when compared with general cardiac surgery patients. We investigated the relationship between clinical outcomes and the amount of blood transfused both during and after heart transplantation. We hypothesized that larger amounts of RBC transfusions are associated with worsening clinical outcomes in pediatric heart transplant patients.A database comprising 108 pediatric patients undergoing heart transplantation from 2004 to 2010 was queried. Preoperative and postoperative clinical risk factors, including the amount of blood transfused intraoperatively and 48 hours postoperatively, were analyzed. The outcome measures were length of hospital stay, duration of tracheal intubation, inotrope score, and major adverse events. Bivariate and multivariate analyses were performed to control for simultaneous risk factors and determine outcomes in which the amount of blood transfused was an independent risk factor.Ninety-four patients with complete datasets were included in the final analysis. Eighty-eight percent received RBC transfusions, with a median transfusion amount of 38.7 mL/kg. A multivariate analysis correcting for 8 covariate risk factors, including the Index for Mortality Prediction After Cardiac Transplantation, age, weight, United Network for Organ Sharing status, warm and cold ischemia time, repeat sternotomy, and pretransplant hematocrit, showed RBC transfusions were independently associated with increased length of intensive care unit stay (means ratio = 1.34; 95% confidence interval, 1.03-1.76; P = 0.03), and increased inotrope score in the first postoperative 24 hour (mean ratio = 1.26; 95% confidence interval, 1.04-1.52; P = 0.04). Patients suffering major adverse events received significantly larger median amounts of blood RBC transfusions (P = 0.002). Transfusions60 mL/kg were also associated with increased risk of major adverse events (accuracy 76%) including postoperative sepsis, extracorporeal membrane oxygenation, open chest, dialysis, and graft failure.The majority of pediatric patients undergoing orthotropic heart transplantation receive RBC transfusions, with the largest amount transfused in the operating room. Escalating amounts of RBC transfusions are independently associated with increased length of intensive care unit stay, inotrope scores, and major adverse events. Since heart allografts are a limited resource, improvement in the blood transfusion and conservation practices can enhance clinical outcomes in pediatric heart transplant patients.

Background Anesthesiologists are responsible for the management of perioperative cardiopulmonary arrest in children. This study used simulation to assess the pediatric resuscitation skills of experienced anesthesia residents. Methods Nineteen anesthesia residents were evaluated using a pediatric pulseless electrical activity scenario. The authors used a standardized checklist to evaluate the residents' diagnostic and therapeutic interventions. Results After the onset of pulseless electrical activity, 79% of residents initiated cardiopulmonary resuscitation within 1 min. Approximately one third (31%) performed chest compressions at the recommended rate. Epinephrine was administered by 95% of residents, but only one third used the correct pediatric dose. All residents administered fluid boluses, but only 16% administered the recommended volume. Only one fourth of the residents considered hyperkalemia as a cause of pulseless electrical activity. None of the residents asked for dosing aids. Conclusion During this simulated pediatric emergency, anesthesia residents demonstrated an acceptable knowledge of general resuscitation maneuvers. However, a subset of resuscitation skills was incorrectly performed, mostly related to age or weight. Importantly, many residents did not consider the full differential diagnosis of pulseless electrical activity. Anesthesia residents may benefit from additional pediatric resuscitation training and practice using cognitive aids to access dosages and complicated diagnostic algorithms.