The impact of intermittent hypoxemia on type 1 retinopathy of prematurity in preterm infants.

BACKGROUND: Intermittent hypoxemia (IH) may influence retinopathy of prematurity (ROP) development in preterm infants, however, previous studies had mixed results. This study tests the hypothesis that increased IH is associated with Type 1 ROP; a stage beyond which treatment is indicated. METHODS: IH was quantified by continuously monitoring oxygen saturation (SpO2) using high-resolution pulse oximeters during the first 10 weeks of life. Statistical analyses assessed the relationship and predictive ability of weekly and cumulative IH for Type 1 ROP development. RESULTS: Most analyses showed no association between IH and Type 1 ROP adjusting for gestational age (GA) and birth weight (BW). However, cumulative IH of longer duration during weeks 5-10, 6-10, and 7-10 were significantly associated with Type 1 ROP adjusting for GA and BW, e.g., the adjusted odds ratio of Type 1 ROP was 2.01 (p = 0.03) for every 3.8 seconds increase in IH duration from week 6-10. IH did not provide statistically significant added predictive ability above GA and BW. CONCLUSIONS: For most analyses there was no significant association between IH and Type 1 ROP adjusting for GA and BW. However, infants with longer IH duration during the second month of life had higher risk for Type 1 ROP. IMPACT: The relationship and predictive ability of intermittent hypoxemia (IH) on retinopathy of prematurity (ROP) is controversial. This study shows no significant association between IH events and Type 1 ROP after adjusting for gestational age (GA) and birth weight (BW), except for cumulative IH of longer duration in the second month of life. In this cohort, IH does not provide a statistically significant improvement in ROP prediction over GA and BW. This study is the first to assess the cumulative impact of IH measures on Type 1 ROP. Interventions for reducing IH duration during critical postnatal periods may improve ROP outcomes.

Intermittent Hypoxemia in Preterm Infants: A Potential Proinflammatory Process.

OBJECTIVE: A major consequence of prematurity is intermittent hypoxemia (IH). Data from both adult studies and neonatal animal models suggest that IH is proinflammatory; however, there is limited data in preterm infants. Here, we assess the relationship between IH and systemic inflammation, namely, serum C-reactive protein (CRP) in preterm infants. STUDY DESIGN: Serum CRP was measured at 30 days of life, at the time of peak IH frequency. IH measures (e.g., per cent time in hypoxemia, frequency, duration) were calculated the week prior to CRP collection. Statistical analyses were based on Spearman's correlation. RESULTS: A total of 26 infants were included. Median gestational age and birth weight were 274/7 weeks and 980 g, respectively. There were positive correlations between primary IH measures and CRP levels, especially for events longer than 1-minute duration (r range: 0.56-0.74, all p < 0.01). CONCLUSION: We demonstrate that IH is associated with increased CRP for the first time in preterm infants. Our findings are consistent with studies from adults and neonatal animal models suggesting that IH is a proinflammatory process. KEY POINTS: · IH events are common.. · IH is associated with elevated C-reactive protein.. · Longer IH events (>1 min) are of most significance..

Blood transfusions in preterm infants: changes on perfusion index and intermittent hypoxemia.

BACKGROUND: Red blood cell (RBC) transfusion decreases intermittent hypoxemia (IH) events beyond the first week of life. This benefit may be related to improved perfusion to the respiratory control network. Perfusion index (PI) is a perfusion measure provided by the pulse oximeter. We hypothesized that the benefit in IH after RBC transfusion is associated with an increase in PI. In addition, we assessed the value of PI and clinical measures in predicting the effect of RBC transfusion on IH. STUDY DESIGN AND METHODS: We prospectively enrolled infants less than 30 weeks' gestation age. PI and oxygen saturation (SpO2 ) were monitored with high-resolution pulse oximeters 24 hours before and after RBC transfusion. Data were analyzed at three postnatal periods: Epoch 1, first week of life (1 to 7 days of life); Epoch 2, 2 to 4 weeks of life (8 to 28 days of life); and Epoch 3, 4 to 8 weeks of life. RESULTS: A total of 118 transfusions were analyzed. IH measures significantly decreased after transfusion in Epochs 2 and 3. PI significantly increased after transfusion, but it did not correlate with the decrease in IH measures. Mechanical ventilation, fraction of inspired oxygen (FiO2 ), and IH measures influenced the effects on oxygenation. CONCLUSIONS: RBC transfusion improved IH after the first week of life. The benefit in IH did not correlate with PI increase after transfusion. Pretransfusion respiratory support and IH measures predicted the effect of transfusion on oxygenation.

Relationship between perfusion index and patent ductus arteriosus in preterm infants.

BACKGROUND: Perfusion index (PI) is a noninvasive measure of perfusion. ΔPI (difference between pre- and postductal PI) may identify hemodynamically significant PDA. However, studies are limited to brief and intermittent ΔPI sampling. Our objective is to assess the value of continuous high resolution ΔPI monitoring in the diagnosis of PDA. METHODS: Continuous ΔPI monitoring in preterm infants was prospectively performed using two high-resolution pulse oximeters. Perfusion Index measures (ΔPI mean and variability, pre- and postductal PI) were analyzed over a 4-h period prior to echocardiography. A cardiologist blinded to the results evaluated for PDA on echocardiography. Linear mixed regression models were utilized for analyses. RESULTS: We obtained 31 echocardiography observations. Mean ΔPI (-0.23 vs. 0.16; P < 0.05), mean pre-PI (0.86 vs. 1.26; P < 0.05), and ΔPI variability (0.39 vs. 0.61; P = 0.05) were lower in infants with PDA compared to infants without PDA at the time of echocardiography. CONCLUSION: Mean ΔPI, ΔPI variability, and mean pre-PI measured 4 h prior to echocardiography detect PDA in preterm infants. PI is dynamic and should be assessed continuously. Perfusion index is a promising bedside measurement to identify PDA in preterm infants.

Cardiovascular and cardiorespiratory phase synchronization in normovolemic and hypovolemic humans.

We investigated whether and how cardiovascular and cardiorespiratory phase synchronization would respond to changes in hydration status and orthostatic stress. Four men and six women were tested during graded head-up tilt (HUT) in both euhydration and dehydration (DEH) conditions. Continuous R-R intervals (RRI), systolic blood pressure (SBP) and respiration were investigated in low (LF 0.04-0.15 Hz) and high (HF 0.15-0.4 Hz) frequency ranges using a phase synchronization index (λ) ranging from 0 (complete lack of interaction) to 1 (perfect interaction) and a directionality index (d), where a positive value of d reflects oscillator 1 driving oscillator 2, and a negative value reflects the opposite driving direction. Surrogate data analysis was used to exclude relationships that occurred by chance. In the LF range, respiration was not synchronized with RRI or SBP, whereas RRI and SBP were phase synchronized. In the HF range, phases among all variables were synchronized. DEH reduced λ among all variables in the HF and did not affect λ between RRI and SBP in the LF region. DEH reduced d between RRI and SBP in the LF and did not affect d among all variables in the HF region. Increasing λ and decreasing d between SBP and RRI were observed in the LF range during HUT. Decreasing λ between SBP and RRI, respiration and RRI, and decreasing d between respiration and SBP were observed in the HF range during HUT. These results show that orthostatic stress disassociated interactions among RRI, SBP and respiration, and that DEH exacerbated the disconnection.

Acute cardiovascular autonomic responses to inhaled particulates.

PURPOSE: Harmful effects of inhaled particulates have been established in epidemiologic studies of ambient air pollution. In particular, heart rate variability responses to high levels of environmental tobacco smoke (ETS), similar to responses observed during direct smoking, have been reported. We sought to determine whether such responses could be observed at lower particulate concentrations. METHODS: We monitored cardiovascular responses of non-smoking 21 women and 19 men to work-place-relevant levels of: ETS, cooking oil fumes (Coil), wood smoke (WS), and water vapor as sham control. Responses, tested on three consecutive days (random order of aerosol presentation), were averaged for each subject. RESULTS: Low frequency spectral powers of heart rate and blood pressure rose during recovery from exposure to particulate, but not to sham exposures. At breathing frequencies, spectral power of men's systolic pressure doubled, and baroreflex effectiveness increased, following ETS exposure. An index of sympathetic control of heart rate was more pronounced in men than women, in response to ETS and Coil, compared to WS and sham. CONCLUSIONS: When measured under controlled conditions, autonomic activities in non-smoking men and women exposed to low level, short term, particulate concentrations were similar to those observed during longer term, higher level exposures to ETS and to direct smoking. These increased indexes of sympathetic control of heart rate and peripheral vasomotion followed introduction of particulates by about 15 min. Finally, coupling of heart rate and systolic pressure indicated an increase in baroreflex activity in the response to breathing ETS that was less effective in men than women.

Light phase-restricted feeding slows basal heart rate to exaggerate the type-3 long QT syndrome phenotype in mice.

Long QT syndrome type 3 (LQT3) is caused by mutations in the SCN5A-encoded Nav1.5 channel. LQT3 patients exhibit time of day-associated abnormal increases in their heart rate-corrected QT (QTc) intervals and risk for life-threatening episodes. This study determines the effects of uncoupling environmental time cues that entrain circadian rhythms (time of light and time of feeding) on heart rate and ventricular repolarization in wild-type (WT) or transgenic LQT3 mice (Scn5a(+/ΔKPQ)). We used an established light phase-restricted feeding paradigm that disrupts the alignment among the circadian rhythms in the central pacemaker of the suprachiasmatic nucleus and peripheral tissues including heart. Circadian analysis of the RR and QT intervals showed the Scn5a(+/ΔKPQ) mice had QT rhythms with larger amplitudes and 24-h midline means and a more pronounced slowing of the heart rate. For both WT and Scn5a(+/ΔKPQ) mice, light phase-restricted feeding shifted the RR and QT rhythms ~12 h, increased their amplitudes greater than twofold, and raised the 24-h midline mean by ~10%. In contrast to WT mice, the QTc interval in Scn5a(+/ΔKPQ) mice exhibited time-of-day prolongation that was flipped after light phase-restricted feeding. The time-of-day changes in the QTc intervals of Scn5a(+/ΔKPQ) mice were secondary to a steeper power relation between their QT and RR intervals. We conclude that uncoupling time of feeding from normal light cues can dramatically slow heart rate to unmask genotype-specific differences in the QT intervals and aggravate the LQT3-related phenotype.

Simulations of gravitational stress on normovolemic and hypovolemic men and women.

BACKGROUND: Earth-based simulations of physiologic responses to space mission activities are needed to develop prospective countermeasures. To determine whether upright lower body positive pressure (LBPP) provides a suitable space mission simulation, we investigated the cardiovascular responses of normovolemic and hypovolemic men and women to supine and orthostatic stress induced by head-up tilt (HUT) and upright LBPP, representing standing in lunar, Martian, and Earth gravities. METHODS: Six men and six women were tested in normovolemic and hypovolemic (furosemide, intravenous, 0.5 mg x kg(-1)) conditions. Continuous electrocardiogram, blood pressure, segmental bioimpedance, and stroke volume (echocardiography) were recorded supine and at lunar, Martian, and Earth gravities (10 degrees, 20 degrees, and 80 degrees HUT vs. 20%, 40%, and 100% bodyweight upright LBPP), respectively. Cardiovascular responses were assessed from mean values, spectral powers, and spontaneous baroreflex parameters. RESULTS: Hypovolemia reduced plasma volume by approximately 10% and stroke volume by approximately 25% at supine, and increasing orthostatic stress resulted in further reductions. Upright LBPP induced more plasma volume losses at simulated lunar and Martian gravities compared with HUT, while both techniques induced comparable central hypovolemia at each stress. Cardiovascular responses to orthostatic stress were comparable between HUT and upright LBPP in both normovolemic and hypovolemic conditions; however, hypovolemic blood pressure was greater during standing at 100% bodyweight compared to 80 degree HUT due to a greater increase of total peripheral resistance. CONCLUSIONS: The comparable cardiovascular response to HUT and upright LBPP support the use of upright LBPP as a potential model to simulate activity in lunar and Martian gravities.

The cardiomyocyte molecular clock, regulation of Scn5a, and arrhythmia susceptibility.

The molecular clock mechanism underlies circadian rhythms and is defined by a transcription-translation feedback loop. Bmal1 encodes a core molecular clock transcription factor. Germline Bmal1 knockout mice show a loss of circadian variation in heart rate and blood pressure, and they develop dilated cardiomyopathy. We tested the role of the molecular clock in adult cardiomyocytes by generating mice that allow for the inducible cardiomyocyte-specific deletion of Bmal1 (iCSΔBmal1). ECG telemetry showed that cardiomyocyte-specific deletion of Bmal1 (iCSΔBmal1(-/-)) in adult mice slowed heart rate, prolonged RR and QRS intervals, and increased episodes of arrhythmia. Moreover, isolated iCSΔBmal1(-/-) hearts were more susceptible to arrhythmia during electromechanical stimulation. Examination of candidate cardiac ion channel genes showed that Scn5a, which encodes the principle cardiac voltage-gated Na(+) channel (Na(V)1.5), was circadianly expressed in control mouse and rat hearts but not in iCSΔBmal1(-/-) hearts. In vitro studies confirmed circadian expression of a human Scn5a promoter-luciferase reporter construct and determined that overexpression of clock factors transactivated the Scn5a promoter. Loss of Scn5a circadian expression in iCSΔBmal1(-/-) hearts was associated with decreased levels of Na(V)1.5 and Na(+) current in ventricular myocytes. We conclude that disruption of the molecular clock in the adult heart slows heart rate, increases arrhythmias, and decreases the functional expression of Scn5a. These findings suggest a potential link between environmental factors that alter the cardiomyocyte molecular clock and factors that influence arrhythmia susceptibility in humans.

Machine learning based classification of mitochondrial morphologies from fluorescence microscopy images of Toxoplasma gondii cysts.

The mitochondrion is intimately linked to energy and overall metabolism and therefore the morphology of mitochondrion can be very informative for inferring the metabolic state of cells. In this study we report an approach for automatic classification of mitochondrial morphologies using supervised machine learning to efficiently classify them from a large number of cells at a time. Fluorescence microscopy images of the chronic encysted form of parasite Toxoplasma gondii were used for this development. Manually classifying these morphologies from the hundreds of parasites within typical tissue cysts is tedious and error prone. In addition, because of inherent biological heterogeneity in morphologies, there can be variability and lack of reproducibility in manual classification. We used image segmentation to detect mitochondrial shapes and used features extracted from them in a multivariate logistic regression model to classify the detected shapes into five morphological classes: Blobs, Tadpoles, Lasso/Donuts, Arcs, and Other. The detected shapes from a subset of images were first used to obtain consensus classification among expert users to obtain a labeled set. The model was trained using the labeled set from five cysts and its performance was tested on the mitochondrial morphologies from ten other cysts that were not used in training. Results showed that the model had an average overall accuracy of 87%. There was high degree of confidence in the classification of Blobs and Arcs (average F scores 0.91 and 0.73) which constituted the majority of morphologies (85%). Although the current development used microscopy images from tissue cysts of Toxoplasma gondii, the approach is adaptable with minor adjustments and can be used to automatically classify morphologies of organelles from a variety of cells.

The Impact of Intermittent Hypoxemia on Type 1 Retinopathy of Prematurity in Preterm Infants.

Background: Intermittent hypoxemia (IH) may influence retinopathy of prematurity (ROP) development in preterm infants, however, previous studies had mixed results. This study aims to assess the influence and evaluate the predictive ability of IH measures on Type 1 ROP, a stage beyond which ROP treatment is indicated. Methods: IH was quantified by continuously monitoring oxygen saturation (SpO2) using high-resolution pulse oximeters during the first 10 weeks of life. Statistical analyses assessed the relationship and predictive ability of weekly and cumulative IH variables for Type 1 ROP development. Results: Univariate analyses suggested that IH measures are greater in infants with Type 1 ROP and are predictive of Type 1 ROP development. Multivariable logistic regression analyses revealed that cumulative IH of longer duration during certain postnatal periods are associated with Type 1 ROP development after adjusting for gestational age (GA) or birth weight (BW). Although area under the curve (AUC) analyses revealed added predictivity of cumulative IH variables above GA or BW, these increments in AUC were not statistically significant. Conclusions: The duration of IH events was associated with Type 1 ROP development. Interventions for reducing the duration of IH events may potentially improve ROP outcomes.

Blood pressure regulation in diabetic patients with and without peripheral neuropathy.

Cardiac and vascular dysfunctions resulting from autonomic neuropathy (AN) are complications of diabetes, often undiagnosed. Our objectives were to: 1) determine sympathetic and parasympathetic components of compromised blood pressure (BP) regulation in patients with peripheral neuropathy and 2) rank noninvasive indexes for their sensitivity in diagnosing AN. We continuously measured electrocardiogram, arterial BP, and respiration during supine rest and 70° head-up tilt in 12 able-bodied subjects, 7 diabetics without, 7 diabetics with possible, and 8 diabetics with definite, sensory, and/or motor neuropathy (D2). During the first 3 min of tilt, systolic BP (SBP) of D2 decreased [-10.9 ± 4.5 (SE) mmHg] but increased in able-bodied (+4.8 ± 5.4 mmHg). Compared with able-bodied, D2 had smaller low-frequency (0.04-0.15 Hz) spectral power of diastolic BP, lower baroreflex effectiveness index (BEI), and more SBP ramps. Except for low-frequency power of SBP, D2 had greater SBP and smaller RR interval harmonic and nonharmonic components at rest across the 0.003- to 0.45-Hz region. In addition, our results support previous findings of smaller HF RR interval power, smaller numbers of baroreflex sequences, and lower baroreflex sensitivity in D2. We conclude that diabetic peripheral neuropathy is accompanied by diminished parasympathetic and sympathetic control of heart rate and peripheral vasomotion and diminished baroreflex regulation. A novel finding of this study lies in the sensitivity of BEI to detect AN, presumably because of its combination of parameters that measure reductions in both sympathetic control of vasomotion and parasympathetic control of heart rate.

Computer Aided Image Processing to Facilitate Determination of Congruence in Manual Classification of Mitochondrial Morphologies in Toxoplasma gondii Tissue Cysts.

Toxoplasma gondii is a parasite that chronically infects about a third of the world's population. During chronic infection, the parasite resides within tissue cysts in the form of poorly understood bradyzoites which can number in the thousands. Our prior work showed that these bradyzoites are metabolically active exhibiting heterogeneous replication potential. The morphological plasticity of the mitochondrion potentially informs about parasite metabolic state. We developed an image processing based program to assist manual classification of mitochondrial morphologies by trained operators to collect data and statistics from the manual classification of shapes. We sought to determine whether certain morphologies were readily classifiable and the congruence among manual classifiers, i.e. the degree to which different operators would place the same objects within the same class. Results from three operators classifying mitochondrial morphologies from 5 tissue cyst images showed that among the four classes, one (Blobs) were the easiest to classify. There was remarkable congruence between 2 of the 3 operators in classifying the objects (96%), while the agreement among all 3 operators was somewhat modest (57%). Such information would be valuable for biologists studying these parasites as well as in development of fully automated methods of morphological classification.

The Effect of Severe Intraventricular Hemorrhage on the Biorhythms of Feeding in Premature Infants.

Background: Suck-swallow rhythmicity and the integration of breathing into infant feeding are developmentally regulated. Neurological injury and breathing abnormalities can both impact feeding in preterm infants. Objective: To determine the effects of neurologic injury independent of effects of disordered breathing on feeding biorhythms in premature infants. Methods: Low-risk preterm infants (LRP), infants with Grade 3-4 Intraventricular Hemorrhage (IVH), those with bronchopulmonary dysplasia (BPD), and those with both BPD and IVH (BPD+IVH) were identified. Forty-seven infants, 32-42 weeks Postmenstrual Age (PMA) were evaluated on one or more occasions (131 studies). Of these, 39 infants (81 studies) were performed at >35 weeks PMA. Coefficient of variation (COV) (=standard deviation of the inter-event (e.g., suck-suck, swallow-breath, etc.) interval divided by the mean of the interval) was used to quantify rhythmic stability. Results: To adjust for PMA, only those infants >35-42 weeks were compared. Suck-suck COV was significantly lower (more rhythmically stable) in the LRP group [COV = 0.274 ± 0.051 (S.D.)] compared to all other groups (BPD = 0.325 ± 0.066; IVH = 0.342 ± 0.072; BPD + IVH = 0.314 ± 0.069; all p < 0.05). Similarly, suck-swallow COV was significantly lower in LRP babies (0.360 ± 0.066) compared to the BPD group (0.475 ± 0.113) and the IVH cohort (0.428 ± 0.075) (p < 0.05). The BPD+IVH group (0.424 ± 0.109), while higher, was not quite statistically significant. Conclusions: Severe IVH negatively impacts suck-suck and suck-swallow rhythms. The independent effect of neurological injury in the form of IVH on feeding rhythms suggests that quantitative analysis of feeding may reflect and predict neurological sequelae.

Response to first dose of inhaled albuterol in mechanically ventilated preterm infants.

BACKGROUND: Bronchodilator responses among preterm infants are heterogeneous. Bedside measurements may identify responders. STUDY DESIGN: Respiratory measurements (Resistance, Compliance, FiO2) and pulse oximetry (SpO2) patterns were downloaded from infants <30 weeks gestational age during the first 2 months of life. Mechanically ventilated infants who received albuterol were included (n = 33). Measurements were compared before and after first albuterol. Secondary analyses assessed subsequent doses. RESULTS: Median gestation and birthweight were 25 3/7 weeks and 730 g, respectively. Mean Resistance decreased post-albuterol (p = 0.007). Sixty-eight percent of infants were responders based on decreased Resistance. Compliance and FiO2 did not significantly differ. Percent time in hypoxemia (SpO2 < 85%) decreased post albuterol (p < 0.02). In responders, Resistance changes diminished with subsequent administration (all p = 0.01). CONCLUSIONS: Ventilator resistance decreased in two-thirds of preterm infants, consistent with studies that utilized formal pulmonary function testing. Albuterol had a variable effect on delivered FiO2; however, hypoxemia may be useful in evaluating albuterol response.

Prematurity and postnatal alterations in intermittent hypoxaemia.

Intermittent hypoxaemia (IH) events are well described in extremely preterm infants, but the occurrence of IH patterns in more mature preterm infants remains unclear. The objective of this study was to characterise the effect of gestational age on early postnatal patterns of IH in extremely (<28 weeks), very (28-<32 weeks) and moderately (32-<34 weeks) preterm infants. As expected, extremely preterm infants had a significantly higher frequency of IH events of longer durations and greater time with hypoxaemia versus very and moderately preterm infants. In addition, the postnatal decrease in IH duration was comparable in the very and moderately preterm infants. This progression of IH events should assist clinicians and families in managing expectations for resolution of IH events during early postnatal life.

Effects of changes in the L-type calcium current on hysteresis in restitution of action potential duration.

BACKGROUND: Electrical restitution and memory of action potential duration (APD) are considered key determinants of stability of activation. Calcium handling also impacts stability of activation via its modification of the above and independently. We determined the effects of reduction in an important calcium current, I(CaL), on hysteresis in restitution of APD, which provides assessment of restitution and memory. METHODS: Transmembrane potentials were recorded from isolated ventricular tissues from pigs. The pacing protocols consisted of sequential and oscillatory changes in diastolic intervals (DI). Two protocols were used, one where DIs ranged between 100 and 700 ms and the other where DIs ranged between 10 and 290 ms. Verapamil (2 microM/L) was used to reduce I(CaL). From the hysteresis observed in restitution, loop area, thickness, overall tilt, and the maximum and minimum delays between DIs and APDs were calculated to obtain measures of memory and restitution. RESULTS: Restitution during sequential and oscillatory changes in DI displayed hysteresis. All measures of hysteresis decreased after reduction in I(CaL). The decreases in area, thickness, and overall tilt were most pronounced (50%, 50%, and 33%). CONCLUSION: Sequential and oscillatory changes in DIs reveal that while the overall slope of restitution of APD decreases with decrease in I(CaL), so do measures of memory. Because slopes and memory are considered to have contrasting effects on stability, our results suggest that predicting effects of alteration in I(CaL) on stability of activation using slope alone may not be adequate. (PACE 2010; 451-459).

Heterogeneous memory in restitution of action potential duration in pig ventricles.

BACKGROUND: Restitution of action potential duration and memory importantly affect electrical stability in ventricles. Studies have reported heterogeneous restitution among different regions of the ventricles. However, existence of heterogeneity in memory is not as well investigated. METHODS: Transmembrane potentials were recorded in endocardial and epicardial tissues from both ventricles of farm pigs. Pacing protocols with sinusoidally changing diastolic intervals were used to reveal hysteresis in restitution, from which quantitative measures of memory were calculated. RESULTS: Larger measures of hysteresis were observed in the endocardium than the epicardium (P < .05): loop thickness (in milliseconds), 26.9 vs 16.2; overall tilt, 0.376 vs 0.249; and loop area (in square milliseconds), 7288 vs 4146. Except for overall tilt, no significant differences in these measures were observed between ventricles. CONCLUSION: Heterogeneity in memory exists in pig ventricles. Because regions with the steepest restitution may also have the largest memory, our results suggest that heterogeneity in memory should also be factored in when predicting electrical stability.

Swallow-breath interaction and phase of respiration with swallow during nonnutritive suck among low-risk preterm infants.

This study describes swallow-breath interaction and phase of respiration with swallow during nonnutritive suck (NNS) in low-risk preterm infants. Suckle and swallow, thoracic motion, and airflow were measured in 16 infants during NNS. Logistic regression models were used to describe swallow-breath interaction and phase of respiration with swallow. One hundred seventy-six swallows occurred in 35 NNS periods. Swallow-breath interaction occurred as: central apnea (CA), obstructive apnea (OA), or attenuated respiration (AR). AR was associated with increased weeks post-first nipple feeding. OA occurred less often in males and with increased weeks post-first nipple feeding. In looking at the phase of respiration, more swallows occurred at beginning expiration with increased gestational age, increased weeks post-first nipple feed, and increased weeks before first nipple feed. More swallows occurred at midexpiration with more swallows per study, increased birth weight (BWT), and weeks before first nipple feed. Fewer swallows occurred at end expiration with increased weeks before first nipple feed. Fewer swallows occurred at midinspiration with increased swallows per study. Fewer swallows occurred at apnea with increasing BWT, more occurred with increased swallows per study. In low-risk preterm infants, swallow-breath interaction progresses from CA and OA to AR. The phase of respiration with swallow shows a maturation progression.

Co-occurrence and phase relationship between alternans of the R wave amplitude (RWAA) and of the T wave (TWA) in ECGs.

Alternans of the T wave in ECG (TWA) has high negative but poor positive predictive value in the prediction of ventricular arrhythmia. Alternans of repolarization duration, i.e. of action potential duration (APD), causes TWA. Prior studies from our group showed that alternans of the maximum rate of depolarization also occurs when APD alternans occurs and the relationship between these two has the potential to affect formation of spatial discord, which may be more arrhythmogenic. Therefore, exploration of the co-occurrence of the alternans of depolarization and repolarization has the potential to improve the prediction. In the present study, we used a mathematical model to show that depolarization alternans appears as alternating amplitude of the R wave in the ECG. We also investigated the link between changes in R wave amplitude and TWA. Results from clinical grade ECGs available in the PhysioNet database show that amplitude of the R wave can change as predicted by our experimental results and the mathematical model. Using TWA as the marker of repolarization alternans and R wave amplitude alternans (RWAA) as the marker of depolarization alternans, we investigated the phase relation between them and observed that, similar to previous results from animals, the phase relation between the two can spontaneously change. That is, alternans of depolarization does co-occur with TWA and the phase relationship between the two is not invariant. These results support further investigation of the use of RWAA as a complementary method to TWA to improve positive predictive value for prediction of ventricular arrhythmia.