Publications of the Space Physiology and Countermeasures Program, Cardiopulmonary Discipline: 1980-1990

A 10-year cumulative bibliography of publications resulting from research supported by the Cardiopulmonary Discipline of the Space Physiology and Countermeasures Program of NASA's Life Sciences Division is provided. Primary subjects included in this bibliography are Fluid Shifts, Cardiovascular Fitness, Cardiovascular Physiology, and Pulmonary Physiology. General physiology references are also included. Principal investigators whose research tasks resulted in publication are identified. Publications are identified by a record number corresponding with their entry in the Life Sciences Bibliographic Database, maintained at the George Washington University

Effect of Dietary Omega-3 Polyunsaturated Fatty Acids on Heart Rate and Heart Rate Variability in Animals Susceptible or Resistant to Ventricular Fibrillation

The consumption of omega-3 polyunsaturated fatty acids (n−3 PUFAs) has been reported to reduce cardiac mortality following myocardial infarction as well as to decrease resting heart rate (HR) and increase HR variability (HRV). However, it has not been established whether n−3 PUFAs exhibit the same actions on HR and HRV in individuals known to be either susceptible or resistant to ventricular fibrillation (VF). Therefore, HR and HRV (high frequency and total R–R interval variability) were evaluated before and 3 months after n−3 PUFA treatment in dogs with healed myocardial infarction that were either susceptible (VF+, n = 31) or resistant (VF−, n = 31) to ventricular tachyarrhythmias induced by a 2-min coronary artery occlusion during the last minute of a submaximal exercise test. HR and HRV were evaluated at rest, during submaximal exercise and in response to acute myocardial ischemia at rest before and after either placebo (1 g/day, corn oil, VF+, n = 9; VF− n = 8) or n−3 PUFA (docosahexaenoic acid + eicosapentaenoic acid ethyl esters, 1–4 g/day, VF+, n = 22; VF−, n = 23) treatment for 3 months. The n−3 PUFA treatment elicited similar increases in red blood cell membrane, right atrial, and left ventricular n−3 PUFA levels in both the VF+ and VF− dogs. The n−3 PUFA treatment also provoked similar reductions in baseline HR and increases in baseline HRV in both groups that resulted in parallel shifts in the response to either exercise or acute myocardial ischemia (that is, the change in these variables induced by physiological challenges was not altered after n−3 PUFA treatment). These data demonstrate that dietary n−3 PUFA decreased HR and increased HRV to a similar extent in animals known to be prone to or resistant to malignant cardiac tachyarrhythmias

Space medicine research publications: 1983-1984

A list of publications supported by the Space Medicine Program, Office of Space Science and Applications is given. Included are publications entered into the Life Sciences Bibliographic Database by The George Washington University as of October 1, 1984

Biomedical research publications: 1980 - 1982

Publications concerning the major physiological and psychological problems encountered by man when he undertakes space flight are listed. Nine research areas are included: cardiovascular deconditioning, motion sickness, bone alterations, muscle atrophy, blood cell alterations, fluid and eletrolyte changes, radiation effects and protection, behavior and performance, and general biomedical research

Kinetics of neuropeptide Y, catecholamines, and physiological responses during moderate and heavy intensity exercises.

Neuropeptide Y 1-36 (NPY1-36) is a vasoconstrictor peptide co-secreted with norepinephrine (NE) by nerve endings during sympathetic activation. NPY1-36 potentiates NE action post-synaptically through the stimulation of the Y1 receptor, whereas its metabolite NPY3-36 resulting from DPP4 action activates Y2 presynaptic receptors, inhibiting NE and acetylcholine secretion. The secretions of NPY1-36 and NPY3-36 in response to sympathetic nervous system activation have not been studied due to the lack of analytical techniques available to distinguish them. We determined in healthy volunteers NPY1-36, NPY3-36 and catecholamine kinetics and how these neurotransmitters modulate the physiological stress response during and after moderate- and heavy-intensity exercises. Six healthy males participated in this randomized, double-blind, saxagliptin vs placebo crossover study. The volunteers performed an orthostatic test, a 30-min exercise at moderate intensity and a 15-min exercise at heavy intensity each followed by 50 min of recovery in two separate sessions with saxagliptin or placebo. Oxygen consumption (V̇O <sub>2</sub> ), ventilation and heart rate were continuously recorded. NE, epinephrine, NPY1-36 and NPY3-36 were quantified by tandem mass spectrometry. We found that exercise triggers NPY1-36 and NE secretion in an intensity-dependent manner and that NE returns faster to the baseline concentration than NPY1-36 after exercise. NPY3-36 rises during recovery parallel to the decline of NPY1-36. Saxagliptin reverses the NPY1-36/NPY3-36 ratio but does not affect hemodynamics, nor NPY1-36 and catecholamine concentrations. We found that NPY1-36 half-life is considerably shorter than previously established with immunoassays. NPY1-36 and NE secretions are finely regulated to prevent an excessive physiological Y1 stimulating response to submaximal exercise

Proarrhythmic proclivity of left-stellate ganglion stimulation in a canine model of drug-induced long-QT syndrome type 1

Background Left-stellate ganglion stimulation (LSGS) can modify regional dispersion of ventricular refractoriness, promote triggered activity, and reduce the threshold for ventricular fibrillation (VF). Sympathetic hyperactivity precipitates torsades de pointes (TdP) and VF in susceptible patients with long-QT syndrome type 1 (LQT1). We investigated the electromechanical effects of LSGS in a canine model of drug-induced LQT1, gaining novel arrhythmogenic insights. Methods In nine mongrel dogs, the left and right stellate ganglia were exposed for electrical stimulation. ECG, left- and right-ventricular endocardial monophasic action potentials (MAPs) and pressures (LVP, RVP) were recorded. The electromechanical window (EMW; Q to LVP at 90% relaxation minus QT interval) was calculated. LQT1 was mimicked by infusion of the KCNQ1/IKs blocker HMR1556. Results At baseline, LSGS and right-stellate ganglion stimulation (RSGS) caused similar heart-rate acceleration and QT shortening. Positive inotropic and lusitropic effects were more pronounced under LSGS than RSGS. IKs blockade prolonged QTc, triggered MAP-early afterdepolarizations (EADs) and rendered the EMW negative, but no ventricular tachyarrhythmias occurred. Superimposed LSGS exaggerated EMW negativity and evoked TdP in 5/9 dogs within 30 s. Preceding extrasystoles originated mostly from the outflow-tracts region. TdP deteriorated into therapy-refractory VF in 4/5 animals. RSGS did not provoke TdP/VF. Conclusions In this model of drug-induced LQT1, LSGS readily induced TdP and VF during repolarization prolongation and MAP-EAD generation, but only if EMW turned from positive to very negative. We postulate that altered mechano-electric coupling can exaggerate regional dispersion of refractoriness and facilitates ventricular ectopy

Baroreflex sensitivity and heart rate variability are predictors of mortality in patients with aneurysmal subarachnoid haemorrhage.

OBJECT: We aimed to investigate the link between the autonomic nervous system (ANS) impairment, assessed using baroreflex sensitivity (BRS) and heart rate variability (HRV) indices, and mortality after aneurysmal subarachnoid haemorrhage (aSAH). METHODS: A total of 57 patients (56 ± 18 years) diagnosed with aSAH were retrospectively enrolled in the study, where 25% of patients died in the hospital. BRS was calculated using a modified cross-correlation method. Time- and frequency-domain HRV indices were calculated from a time-series of systolic peak intervals of arterial blood pressure signals. Additionally, cerebral autoregulation (CA) was assessed using the mean velocity index (Mxa), where Mxa > 0 indicates impaired CA. RESULTS: Both BRS and HRV indices were lower in non-survivors than in survivors. The patients with disturbed BRS and HRV had more extensive haemorrhage in the H-H scale (p = .040) and were more likely to die (p = .013) when compared to patients with the intact ANS. The logistic regression model for mortality included: the APACHE II score (p = .002; OR 0.794) and the normalised high frequency power of the HRV (p < <.001; OR 0.636). A positive relationship was found between the Mxa and BRS (R = 0.48, p = .003), which suggests that increasing BRS is moderately strongly associated with worsening CA. CONCLUSION: Our results indicated that lower values of HRV indices and BRS correlate with mortality and that there is a link between cerebral dysautoregulation and the analysed estimates of the ANS in aSAH patients

Współczesne metody oceny czułości baroreceptorów tętniczych w praktyce klinicznej

Baroreceptory (BR) zlokalizowane w ścianach tętnic szyjnych i aorty stanowią jedenz elementów układu sprzężenia zwrotnego między układem nerwowym a układem sercowo-naczyniowym, którego zadaniem jest utrzymywanie względnie stabilnych wartościciśnienia tętniczego. Choroby układu krążenia mogą powodować dysfunkcję BRw wyniku zmniejszenia hamującej aktywności układu przywspółczulnego oraz zaburzeniafizjologicznej równowagi między wpływem układu współczulnego i nerwu błędnegona mięsień sercowy. Opracowano wiele różnych metod do oceny czułości baroreceptorów(BRS). Wśród nich wyróżnia się metody inwazyjne (metoda z podaniem fenylefryny,metoda z podaniem nitrogliceryny lub nitroprusydku sodu) i nieinwazyjne (próba Valsalvy,metoda z użyciem komory szyjnej i analiza spontanicznych oscylacji ciśnieniatętniczego i odstępów RR). Celem prezentowanej pracy jest omówienie znaczenia ocenyBRS w praktyce klinicznej. Dane z piśmiennictwa oraz aktualne wytyczne podkreślająrolę pomiarów BRS w ocenie ryzyka u pacjentów po przebytym zawale serca, w niewydolnościmięśnia sercowego oraz u chorych z komorowymi zaburzeniami rytmu. Zaburzeniafunkcji adaptacyjnej BR mogą być również jednym z istotnych elementów złożonegopatomechanizmu omdleń wazowagalnych (VVS). Ocena BRS może być stosowanaw wybranych przypadkach klinicznych, ale rola dysfunkcji BR w patogenezie schorzeńukładu krążenia wymaga niewątpliwie dalszych badań

Potential Predictors of Sudden Cardiac Death in Aortic Valve Disease

Although sudden death continues to claim 15 to 20% of patients with aortic valve disease, the exact cause still remains speculative. It has been the assumption of many workers that these deaths result from ventricular tachyarrhythmias. The major aim of this thesis was therefore to assess the prevalence of ventricular arrhythmias in patients with aortic valve disease and to evaluate their significance by signal-averaged electrocardiography (SAECG). A total of 100 patients, 55 with predominant aortic stenosis (AS) with a mean transaortic gradient of 81+/-27 mmHg, 16 with predominant aortic regurgitation (AR) and 29 with combined AS and AR were studied prior to aortic valve replacement (AVR). Substantial left ventricular hypertrophy was present with a mean echocardiographic left ventricular mass index of 210+/-72 g/m2. Left ventricular systolic and diastolic function were normal in 94% and 61% of patients respectively. Coronary angiography was performed in 89 patients of whom 50 (56%) had chest pain typical of angina pectoris and 21 (24%) had significant coronary artery disease. Angina was present in 20 of these 21 patients (95%). Thus angina could predict the presence of significant coronary artery disease with 95% sensitivity and 54% specificity. In agreement with previous work, this study has shown a high prevalence of complex ventricular arrhythmias. Nonsustained ventricular tachycardia (NSVT) was detected by ambulatory electrocardiographic monitoring in 9 (9%) patients of whom only one had late potentials on SAECG. The frequency of ventricular arrhythmias was not related to the degree of left ventricular hypertrophy or the severity of aortic valve disease. Left ventricular function did not have any effect on ventricular arrhythmias. A high prevalence of complex ventricular arrhythmias was also seen in the early (5 to 7 days post AVR) and late (121+/-24 days post AVR) post-operative periods. The frequency of ventricular arrhythmias was not affected by AVR. In the late post-operative period, 4 patients had NSVT, but none of them had late potentials on SAECG. As with the pre-operative results, there was little to suggest the presence of an arrhythmogenic substrate in these patients in view of the absence of late potentials on SAECG. Furthermore, no sustained ventricular arrhythmias were detected in the 3 study periods. Aortic valve replacement was accompanied by a significant regression in echocardiographic left ventricular hypertrophy in patients with predominant AS and those with combined AS and AR. Of the total 100 patients in this study, 75 were on the cardiac surgical waiting list of whom 60 have already undergone operation. There have been 7 deaths (7%) during the study period, 3 of them occurring suddenly in patients awaiting surgery. Thus, the incidence of sudden death while awaiting operation was 4%. It has been suggested that patients with decreased heart-rate variability have decreased vagal tone, increased sympathetic activity or both and hence are at a higher risk of developing ventricular fibrillation and sudden death. Cardiovascular autonomic function was assessed in 47 patients prior to AVR and repeated in 10 patients 3 months following AVR. Abnormal heart-rate variation during deep breathing was detected in 18 (38%) patients. AVR was not accompanied by any improvement in cardiovascular autonomic function at least in the shortterm . Thus, despite a high prevalence of ventricular arrhythmias in aortic valve disease patients with substantial left ventricular hypertrophy, there was little to suggest the presence of an arrhythmogenic substrate. The potential mechanism of sudden death in these patients could be speculated on the basis of impaired cardiovascular autonomic function