Cardiorespiratory Responses to Acute Intermittent Hypoxia in Humans With Chronic Spinal Cord Injury.

Brief exposure to repeated episodes of low inspired oxygen, or acute intermittent hypoxia (AIH), is a promising therapeutic modality to improve motor function after chronic, incomplete spinal cord injury (SCI). Although therapeutic AIH is under extensive investigation in persons with SCI, limited data are available concerning cardiorespiratory responses during and after AIH exposure despite implications for AIH safety and tolerability. Thus, we recorded immediate (during treatment) and enduring (up to 30 min post-treatment) cardiorespiratory responses to AIH in 19 participants with chronic SCI (>1 year post-injury; injury levels C1 to T6; American Spinal Injury Association Impairment Scale A to D; mean age = 33.8 ± 14.1 years; 18 males). Participants completed a single AIH (15, 60-sec episodes, inspired O2 ≈ 10%; 90-sec intervals breathing room air) and Sham (inspired O2 ≈ 21%) treatment, in random order. During hypoxic episodes: (1) arterial oxyhemoglobin saturation decreased to 82.1 ± 2.9% (p < 0.001); (2) minute ventilation increased 3.83 ± 2.29 L/min (p = 0.008); and (3) heart rate increased 4.77 ± 6.82 bpm (p = 0.010). Considerable variability in cardiorespiratory responses was found among subjects; some individuals exhibited large hypoxic ventilatory responses (≥0.20 L/min/%, n = 11), whereas others responded minimally (<0.20 L/min/%, n = 8). Apneas occurred frequently during AIH and/or Sham protocols in multiple participants. All participants completed AIH treatment without difficulty. No significant changes in ventilation, heart rate, or arterial blood pressure were found 30 min post-AIH p > 0.05). In conclusion, therapeutic AIH is well tolerated, elicits variable chemoreflex activation, and does not cause persistent changes in cardiorespiratory control/function 30 min post-treatment in persons with chronic SCI.

Therapeutic acute intermittent hypoxia: A translational roadmap for spinal cord injury and neuromuscular disease.

We review progress towards greater mechanistic understanding and clinical translation of a strategy to improve respiratory and non-respiratory motor function in people with neuromuscular disorders, therapeutic acute intermittent hypoxia (tAIH). In 2016 and 2020, workshops to create and update a "road map to clinical translation" were held to help guide future research and development of tAIH to restore movement in people living with chronic, incomplete spinal cord injuries. After briefly discussing the pioneering, non-targeted basic research inspiring this novel therapeutic approach, we then summarize workshop recommendations, emphasizing critical knowledge gaps, priorities for future research effort, and steps needed to accelerate progress as we evaluate the potential of tAIH for routine clinical use. Highlighted areas include: 1) greater mechanistic understanding, particularly in non-respiratory motor systems; 2) optimization of tAIH protocols to maximize benefits; 3) identification of combinatorial treatments that amplify plasticity or remove plasticity constraints, including task-specific training; 4) identification of biomarkers for individuals most/least likely to benefit from tAIH; 5) assessment of long-term tAIH safety; and 6) development of a simple, safe and effective device to administer tAIH in clinical and home settings. Finally, we update ongoing clinical trials and recent investigations of tAIH in SCI and other clinical disorders that compromise motor function, including ALS, multiple sclerosis, and stroke.

Single-session effects of acute intermittent hypoxia on breathing function after human spinal cord injury.

After spinal cord injury (SCI) respiratory complications are a leading cause of morbidity and mortality. Acute intermittent hypoxia (AIH) triggers spinal respiratory motor plasticity in rodent models, and repetitive AIH may have the potential to restore breathing capacity in those with SCI. As an initial approach to provide proof of principle for such effects, we tested single-session AIH effects on breathing function in adults with chronic SCI. 17 adults (13 males; 34.1 ± 14.5 years old; 13 motor complete SCI; >6 months post injury) completed two randomly ordered sessions, AIH versus sham. AIH consisted of 15, 1-min episodes (hypoxia: 10.3% O2; sham: 21% O2) interspersed with room air breathing (1.5 min, 21% oxygen); no attempt was made to regulate arterial CO2 levels. Blood oxygen saturation (SpO2), maximal inspiratory and expiratory pressures (MIP; MEP), forced vital capacity (FVC), and mouth occlusion pressure within 0.1 s (P0.1) were assessed. Outcomes were compared using nonparametric Wilcoxon's tests, or a 2 × 2 ANOVA. Baseline SpO2 was 97.2 ± 1.3% and was unchanged during sham experiments. During hypoxic episodes, SpO2 decreased to 84.7 ± 0.9%, and returned to baseline levels during normoxic intervals. Outcomes were unchanged from baseline post-sham. Greater increases in MIP were evident post AIH vs. sham (median values; +10.8 cmH2O vs. -2.6 cmH2O respectively, 95% confidence interval (-18.7) - (-4.3), p = .006) with a moderate Cohen's effect size (0.68). P0.1, MEP and FVC did not change post-AIH. A single AIH session increased maximal inspiratory pressure generation, but not other breathing functions in adults with SCI. Reasons may include greater spared innervation to inspiratory versus expiratory muscles or differences in the capacity for AIH-induced plasticity in inspiratory motor neuron pools. Based on our findings, the therapeutic potential of AIH on breathing capacity in people with SCI warrants further investigation.

Effect of acute intermittent hypoxia on cortico-diaphragmatic conduction in healthy humans.

Acute intermittent hypoxia (AIH) is a strategy to improve motor output in humans with neuromotor impairment. A single AIH session increases the amplitude of motor evoked potentials (MEP) in a finger muscle (first dorsal interosseous), demonstrating enhanced corticospinal neurotransmission. Since AIH elicits phrenic/diaphragm long-term facilitation (LTF) in rodent models, we tested the hypothesis that AIH augments diaphragm MEPs in humans. Eleven healthy adults (7 males, age = 29 ± 6 years) were tested. Transcranial and cervical magnetic stimulation were used to induce diaphragm MEPs and compound muscle action potentials (CMAP) recorded by surface EMG, respectively. Stimulus-response curves were generated prior to and 30-60 min after AIH. Diaphragm LTF was assessed by measurement of integrated EMG burst amplitude and frequency during eupnoeic breathing before and after AIH. Following baseline measurements, AIH was delivered from an oxygen generator connected to a facemask under poikilocapnic conditions (15 one minute episodes of 9% inspired oxygen with one minute room air intervals). There were no detectable changes in MEP (-1.5 ± 12.1%, p = 0.96) or CMAP (+0.1 ± 7.8%, p = 0.97) amplitudes across the stimulus-response curve. At stimulation intensities approximating 50% of the difference between minimum and maximum baseline amplitudes, MEP and CMAP amplitudes were also unchanged (p > 0.05). Further, no AIH effect was observed on diaphragm EMG activity during eupnoea post-AIH (p > 0.05). We conclude that unlike hand muscles, poikilocapnic AIH does not enhance diaphragm MEPs or produce diaphragm LTF in healthy humans.

Synergy between Acute Intermittent Hypoxia and Task-Specific Training.

Acute intermittent hypoxia (AIH) and task-specific training (TST) synergistically improve motor function after spinal cord injury; however, mechanisms underlying this synergistic relation are unknown. We propose a hypothetical working model of neural network and cellular elements to explain AIH-TST synergy. Our goal is to forecast experiments necessary to advance our understanding and optimize the neurotherapeutic potential of AIH-TST.

Kinematic Visual Biofeedback Improves Accuracy of Swallowing Maneuver Training and Accuracy of Clinician Cues During Training in Stroke Patients with Dysphagia.

BACKGROUND: Dysphagia (swallowing impairment) is a common and often life-threatening problem after stroke. Submental surface electromyography (ssEMG) visual biofeedback is a commonly used clinical tool to train novel swallowing maneuvers, even though its effectiveness has been questioned. OBJECTIVE: To compare the effect of ssEMG and videofluoroscopy (VF) visual biofeedback on swallowing airway protection accuracy when training the volitional laryngeal closure swallowing maneuver (vLVC) in poststroke patients with dysphagia. Researchers also examined whether clinicians accurately judged vLVC performance. The hypothesis was that patient vLVC accuracy and clinician verbal cue accuracy will be greatest with VF (kinematic) visual biofeedback. PATIENTS: Nineteen patients with dysphagia post stroke. SETTING: Outpatient swallowing research laboratory. DESIGN: Randomized clinical trial. METHODS: Patients underwent 2 study phases. Phase 1: first demonstrated ability to perform the vLVC accurately. Phase 2: vLVC training. Participants were randomized into three biofeedback groups including the ssEMG group (ssEMG biofeedback in both phases), the VF group (VF biofeedback in both phases), and the mixed group (VF phase 1, ssEMG phase 2). To promote the best vLVC performance, a clinician provided real-time, verbal cueing using only the visual biofeedback type also seen by the patient, although both VF and ssEMG were recorded for all participants. MAIN OUTCOME MEASURE: Patient performance accuracy and clinician feedback accuracy for performing the vLVC maneuver. RESULTS: Both accuracy of vLVC training performance and clinician feedback accuracy were worse in the ssEMG group compared with the VF and mixed groups (P < .001). CONCLUSIONS: Swallowing airway protection requires precisely timed movements of small, hidden laryngeal and pharyngeal structures. Kinematic biofeedback (VF) may be required, at some point, to ensure that target swallowing movements are being trained during rehabilitation, rather than maladaptive movements. LEVEL OF EVIDENCE: I.

A Survey of Clinician Decision Making When Identifying Swallowing Impairments and Determining Treatment.

Purpose: Speech-language pathologists (SLPs) are the primary providers of dysphagia management; however, this role has been criticized with assertions that SLPs are inadequately trained in swallowing physiology (Campbell-Taylor, 2008). To date, diagnostic acuity and treatment planning for swallowing impairments by practicing SLPs have not been examined. We conducted a survey to examine how clinician demographics and swallowing complexity influence decision making for swallowing impairments in videofluoroscopic images. Our goal was to determine whether SLPs' judgments of swallowing timing impairments align with impairment thresholds available in the research literature and whether or not there is agreement among SLPs regarding therapeutic recommendations. Method: The survey included 3 videofluoroscopic swallows ranging in complexity (easy, moderate, and complex). Three hundred three practicing SLPs in dysphagia management participated in the survey in a web-based format (Qualtrics, 2005) with frame-by-frame viewing capabilities. SLPs' judgments of impairment were compared against impairment thresholds for swallowing timing measures based on 95% confidence intervals from healthy swallows reported in the literature. Results: The primary impairment in swallowing physiology was identified 67% of the time for the easy swallow, 6% for the moderate swallow, and 6% for the complex swallow. On average, practicing clinicians mislabeled 8 or more swallowing events as impaired that were within the normal physiologic range compared with healthy normative data available in the literature. Agreement was higher among clinicians who report using frame-by-frame analysis 80% of the time. A range of 19-21 different treatments was recommended for each video, regardless of complexity. Conclusions: Poor to modest agreement in swallowing impairment identification, frequent false positives, and wide variability in treatment planning recommendations suggest that additional research and training in healthy and disordered swallowing are needed to increase accurate dysphagia diagnosis and treatment among clinicians.

Swallowing Kinematic Differences Across Frozen, Mixed, and Ultrathin Liquid Boluses in Healthy Adults: Age, Sex, and Normal Variability.

Purpose: The aim of this study was to examine the effects of frozen and mixed-consistency boluses on the swallowing physiology of younger and older adults. We also aimed to quantify factors that lead to increased variability in swallowing outcomes (i.e., age, sex, bolus type). Method: Forty-one healthy adults (18-85 years old) swallowed 5 blocks of 5 different boluses: 10-ml ultrathin liquid, a teaspoon of iced barium, a teaspoon of room-temperature pudding, a teaspoon of frozen pudding, and ultrathin barium with chocolate chips. All data were recorded with videofluoroscopy and underwent detailed timing kinematic measurements. Results: Neither barium ice nor frozen pudding sped up swallow responses. Many healthy adults initiated swallowing with the bolus as deep as the pyriform sinuses. Swallowing temporal kinematics for ultrathin liquid consistencies are most different from all others tested, requiring the best possible physiological swallowing performance in younger and older healthy individuals (i.e., faster reaction times, longer durations) compared with other bolus types tested. In each measure, older adults had significantly longer durations compared with the younger adults. More variability in swallowing kinematics were seen with age and laryngeal vestibule kinematics. Conclusion: This study provides important contributions to the literature by clarifying normal variability within a wide range of swallowing behaviors and by providing normative data from which to compare disordered populations.

A Novel Risk Score to Predict Dysphagia After Cardiac Surgery Procedures.

BACKGROUND: Although the exact cause of dysphagia after cardiac operations is unknown, timely diagnosis is critical to avoid a devastating aspiration event. Accordingly, we sought to generate the risk of dysphagia in cardiac surgery (RODICS) score to identify patients at risk for its development after heart surgery. METHODS: All adult heart surgery patients at our institution between January 2011 and March 2012 were analyzed. A videofluoroscopic swallow study stratified patients into two groups based on the presence or absence of dysphagia. Covariates (p < 0.20) were included in a multivariable model to determine the strongest independent predictors of postoperative dysphagia. Based on the relative odds ratios of significant variables, the RODICS score was generated. Risk cohorts were then created based on easily applicable, whole-integer score cutoffs. RESULTS: During the study period, 115 of 1,314 patients (8.8%) undergoing heart surgery were diagnosed with clinically significant dysphagia. The 38-point RODICS score comprises seven patient-specific characteristics and perioperative factors. The low risk (less than 4), intermediate risk (5 to 9), and high risk (more than 9) cohorts had postoperative dysphagia rates of 3.0%, 6.8%, and 21.6%, respectively (p < 0.001). The intermediate-risk cohort (odds ratio 2.3, 95% confidence interval: 1.33 to 4.27, p = 0.01) and high-risk cohort (odds ratio 8.9, 95% confidence interval: 5.22 to 15.32, p < 0.001) were at significantly higher risk of dysphagia developing. The RODICS score demonstrated excellent discriminatory ability (area under the curve 0.75). CONCLUSIONS: The incidence and impact of dysphagia after open cardiac operations is significant. This novel scoring system could lead to prompt identification of patients at high risk for postoperative dysphagia and potentially minimize the complications of aspiration.