Continuous Multi-Parameter Heart Rate Variability Analysis Heralds Onset of Sepsis in Adults

BACKGROUND: Early diagnosis of sepsis enables timely resuscitation and antibiotics and prevents subsequent morbidity and mortality. Clinical approaches relying on point-in-time analysis of vital signs or lab values are often insensitive, non-specific and late diagnostic markers of sepsis. Exploring otherwise hidden information within intervals-in-time, heart rate variability (HRV) has been documented to be both altered in the presence of sepsis, and correlated with its severity. We hypothesized that by continuously tracking individual patient HRV over time in patients as they develop sepsis, we would demonstrate reduced HRV in association with the onset of sepsis. METHODOLOGY/PRINCIPAL FINDINGS: We monitored heart rate continuously in adult bone marrow transplant (BMT) patients (n = 21) beginning a day before their BMT and continuing until recovery or withdrawal (12+/-4 days). We characterized HRV continuously over time with a panel of time, frequency, complexity, and scale-invariant domain techniques. We defined baseline HRV as mean variability for the first 24 h of monitoring and studied individual and population average percentage change (from baseline) over time in diverse HRV metrics, in comparison with the time of clinical diagnosis and treatment of sepsis (defined as systemic inflammatory response syndrome along with clinically suspected infection requiring treatment). Of the 21 patients enrolled, 4 patients withdrew, leaving 17 patients who completed the study. Fourteen patients developed sepsis requiring antibiotic therapy, whereas 3 did not. On average, for 12 out of 14 infected patients, a significant (25%) reduction prior to the clinical diagnosis and treatment of sepsis was observed in standard deviation, root mean square successive difference, sample and multiscale entropy, fast Fourier transform, detrended fluctuation analysis, and wavelet variability metrics. For infected patients (n = 14), wavelet HRV demonstrated a 25% drop from baseline 35 h prior to sepsis on average. For 3 out of 3 non-infected patients, all measures, except root mean square successive difference and entropy, showed no significant reduction. Significant correlation was present amongst these HRV metrics for the entire population. CONCLUSIONS/SIGNIFICANCE: Continuous HRV monitoring is feasible in ambulatory patients, demonstrates significant HRV alteration in individual patients in association with, and prior to clinical diagnosis and treatment of sepsis, and merits further investigation as a means of providing early warning of sepsis

GpaXItarl originating from Solanum tarijense is a major resistance locus to Globodera pallida and is localised on chromosome 11 of potato

Resistance to Globodera pallida Rookmaker (Pa3), originating from wild species Solanum tarijense was identified by QTL analysis and can be largely ascribed to one major QTL. GpaXItarl explained 81.3% of the phenotypic variance in the disease test. GpaXItarl is mapped to the long arm of chromosome 11. Another minor QTL explained 5.3% of the phenotypic variance and mapped to the long arm of chromosome 9. Clones containing both QTL showed no lower cyst counts than clones with only GpaXItarl. After Mendelising the phenotypic data, GpaXItarl could be more precisely mapped near markers GP163 and FEN427, thus anchoring GpaXItarl to a region with a known R-gene cluster containing virus and nematode resistance genes

Positive End-Expiratory Pressure may alter breathing cardiovascular variability and baroreflex gain in mechanically ventilated patients

<p>Abstract</p> <p>Background</p> <p>Baroreflex allows to reduce sudden rises or falls of arterial pressure through parallel RR interval fluctuations induced by autonomic nervous system. During spontaneous breathing, the application of positive end-expiratory pressure (PEEP) may affect the autonomic nervous system, as suggested by changes in baroreflex efficiency and RR variability. During mechanical ventilation, some patients have stable cardiorespiratory phase difference and high-frequency amplitude of RR variability (HF-RR amplitude) over time and others do not. Our first hypothesis was that a steady pattern could be associated with reduced baroreflex sensitivity and HF-RR amplitude, reflecting a blunted autonomic nervous function. Our second hypothesis was that PEEP, widely used in critical care patients, could affect their autonomic function, promoting both steady pattern and reduced baroreflex sensitivity.</p> <p>Methods</p> <p>We tested the effect of increasing PEEP from 5 to 10 cm H2O on the breathing variability of arterial pressure and RR intervals, and on the baroreflex. Invasive arterial pressure, ECG and ventilatory flow were recorded in 23 mechanically ventilated patients during 15 minutes for both PEEP levels. HF amplitude of RR and systolic blood pressure (SBP) time series and HF phase differences between RR, SBP and ventilatory signals were continuously computed by complex demodulation. Cross-spectral analysis was used to assess the coherence and gain functions between RR and SBP, yielding baroreflex-sensitivity indices.</p> <p>Results</p> <p>At PEEP 10, the 12 patients with a stable pattern had lower baroreflex gain and HF-RR amplitude of variability than the 11 other patients. Increasing PEEP was generally associated with a decreased baroreflex gain and a greater stability of HF-RR amplitude and cardiorespiratory phase difference. Four patients who exhibited a variable pattern at PEEP 5 became stable at PEEP 10. At PEEP 10, a stable pattern was associated with higher organ failure score and catecholamine dosage.</p> <p>Conclusions</p> <p>During mechanical ventilation, stable HF-RR amplitude and cardiorespiratory phase difference over time reflect a blunted autonomic nervous function which might worsen as PEEP increases.</p