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At least 199 records · Page 11
All sourcesNASA NTRSDOE OSTI
NASA NTRS1991

Effects of Weightlessness on Human Fluid and Electrolyte Physiology

The changes that occur in human fluid and electrolyte physiology during the acute and adaptive phases of adaptation to spaceflight are summarized. A number of questions remain to be answered. At a time when plasma volume and extracellular fluid volume are contracted and salt and water intake is unrestricted. ADH does not correct the volume deficit and serum sodium decreases. Change in secretion or activity of a natriuretic factor during spaceflight is one possible explanation. Recent identification of a polypeptide hormone produced in cardiac muscle cells which is natiuretic, is hypotensive, and has an inhibitory effect on renin and aldosterone secretion has renewed interest in the role of a natriuretic factor. The role of this atrial natriuretic factor (ANF) in both long- and short-term variation in extracellular volumes and in the inability of the kidney to bring about an escape from the sodium-retaining state accompanying chronic cardiac dysfunction makes it reasonable to look for a role of ANF in the regulation of sodium during exposure to microgravity. Prostaglandin-E is another hormone that may antagonize the action of ADH. Assays of these hormones will be performed on samples from crew members in the future.

Leach, Carolyn S.↗
NASA NTRS2001

Three-dimensional ballistocardiography and respiratory motion in sustained microgravity

BACKGROUND: We measured the three-dimensional ballistocardiogram (BCG) in a free-floating subject in sustained microgravity during spaceflight to test the usefulness of such measurements for future non-invasive monitoring of cardiac function, and to examine the effects of respiratory movement on the BCG in three axes. METHODS: Acceleration was measured using a three-axis accelerometer fastened to the lumbar region of the subject while simultaneous recordings of ECG, and respiratory motion via impedance plethysmography were also made. Data were recorded during a 146-s period of inactivity on the part of the subject during which time there was no contact with the spacecraft. RESULTS: Total body motion due to respiratory activity was consistent with that calculated from the known action of the diaphragm and conservation of momentum. The accelerations due to cardiac activity, ensemble averaged over the R-R interval, were greatest along the head-to-foot axis. Maximum amplitude of the HIJK complex of the BCG generated by ventricular ejection was greatest in the head to foot axis (approximately 70 x 10(-3) m x s(-2)), but there were also substantial accelerations along the dorsoventral axis of up to 43 10(-3) m x s(-2), that are not measured interrestrial two-dimensional studies. The amplitude of the BCG was strongly affected by lung volume, with accelerations being reduced 50 to 70% between end-inspiration and end-expiration. CONCLUSIONS: These data suggest a greatly reduced transmission of the cardiac motion to the body at end-expiration (FRC) than at higher lung volumes. The BCG might be further developed as a non-invasive means of monitoring parameters such as stroke volume in microgravity.

Flight Experiment↗
NASA NTRS1996

Augmented baroreflex heart rate gain after moderate-intensity, dynamic exercise

The occurrence of a sustained vasodilation and hypotension after acute, dynamic exercise suggests that exercise may alter arterial baroreflex mechanisms. Therefore, we assessed systemic hemodynamics, baroreflex regulation of heart rate, and cardiac vagal tone after 60 min of cycling at 60% peak oxygen consumption in 12 healthy, untrained men and women (ages 21-28 yr). We derived sigmoidal carotid-cardiac baroreflex relations by measurement of R-R interval changes induced by ramped, stepwise, R-wave-triggered changes in external neck pressure from 40 to -65 mmHg. We estimated tonic cardiac vagal control with power spectral analysis of R-R interval variability in the respiratory frequency band (0.2-0.3 Hz) during frequency- and tidal volume-controlled breathing. Both mean arterial pressure and total peripheral resistance were reduced postexercise [pressure: from 86 +/- 2 (mean +/- SE) to 81 +/- 2 mmHg; resistance: from 23 +/- 2 to 16 +/- 1 units; both P < 0.05]. Cardiac output was increased postexercise (from 3.9 +/- 0.3 to 5.5 +/- 0.5 l/min, P < 0.05). Both slope and range of the carotid-cardiac baroreflex relation were increased postexercise (slope: from 4.7 +/- 0.7 to 6.1 +/- 0.9 ms/mmHg; range: from 186 +/- 23 to 238 +/- 30 ms, P < 0.05). Respiratory R-R interval variability (cardiac vagal tone) was not changed at any time after exercise, whereas heart rate and plasma norepinephrine levels were elevated. Thus moderate-intensity, dynamic exercise increases heart rate and cardiac output, reduces peripheral vascular resistance, and augments baroreflex responsiveness. Our data suggest that augmented baroreflex heart rate gain restrains rather than contributes to postexercise hypotension, which appears to be mediated predominately by vasodilation.

NASA Discipline Cardiopulmonary↗
NASA NTRS1977

Cardiovascular studies using the chimpanzee (Pan troglodytes)

Despite the phylogenetic similarities between chimpanzees and man, there exists a paucity of reliable data on normal cardiovascular function and the physiological responses of the system to standard interventions. Totally implanted biotelemetry systems or hardwire analog techniques were used to examine the maximum number of cardiovascular variables which could be simultaneously monitored without significantly altering the system's performance. This was performed in order to acquire base-line data not previously obtained in this species, to determine cardiovascular response to specific forcing functions such as ventricular pacing, drug infusions, and lower body negative pressure. A cardiovascular function profile protocol was developed in order to adjust independently the three major factors which modify ventricular performance, namely, left ventricular performance, left ventricular preload, afterload, and contractility. Cardiac pacing at three levels above the ambient rate was used to adjust end diastolic volume (preload). Three concentrations of angiotensin were infused continuously to evaluate afterload in a stepwide fashion. A continuous infusion of dobutamine was administered to raise the manifest contractile state of the heart.

Hinds, J. E.↗
NASA NTRS1983

Human sinus arrhythmia as an index of vagal cardiac outflow

The human central vagal mechanisms were investigated by measuring the intervals between heartbeats during controlled breathing (at breathing intervals of 2.5-10 s and nominal tidal volumes of 1000 and 1500 ml) in six young men and women. It was found that as the breathing interval increased, the longest heart periods became longer, the shortest heart periods became shorter, and the peak-valley P-P intervals increased asymptotically. Peak-valley intervals also increased in proportion to tidal volume, although this influence was small. The phase angles between heart period changes and respiration were found to vary as linear functions of breathing interval. Heart period shortening began in inspiration at short breathing intervals and in expiration at long breathing intervals, while heart period lengthening began in early expiration at all breathing intervals studied. It is concluded that a close relationship exists between variations of respiratory depth and interval and the quantity, periodicity, and timing of vagal cardiac outflow in conscious humans. The results indicate that at usual breathing rates, phasic respiration-related changes of vagal motoneuron activity begin in expiration, progress slowly, and are incompletely expressed at fast breathing ratges.

Eckberg, D. L.↗
NASA NTRS2017

Risk of Cardiac Rhythm Problems During Spaceflight

NASA has concerns regarding the incidence and clinical significance of cardiac arrhythmias that could occur during long-term exposure to the spaceflight environment, such as on the International Space Station (ISS) or during a prolonged (e.g., up to 3 years) sojourn to Mars or on the Moon. There have been some anecdotal reports and a few documented cases of cardiac arrhythmias in space, including one documented episode of non-sustained ventricular tachycardia. The potential catastrophic nature of a sudden cardiac death in the remote space environment has led to concerns from the early days of the space program that spaceflight might be arrhythmogenic. Indeed, there are known and well-defined changes in the cardiovascular system with spaceflight: a) plasma volume is reduced, b) left ventricular mass is decreased, and c) the autonomic nervous system adapts to the weightless environment. Combined, these physiologic adaptations suggest that changes in cardiac structure and neuro-humoral environment during spaceflight could alter electrical conduction, although the evidence supporting this contention consists mostly of minor changes in QT interval (the time between the start of the Q wave and the end of the T wave on an electrocardiogram tracing) in a small number of astronauts after long-duration spaceflight. Concurrent with efforts by NASA Medical Operations to refine and improve screening techniques relevant to arrhythmias and cardiovascular disease, as NASA enters the era of exploration-class missions it will be critical to determine with the highest degree of certainty whether spaceflight by itself alters cardiac structure and function sufficiently to increase the risk of arrhythmias.

Lee, Stuart M. C.↗
NASA NTRS1986

Validation and application of single breath cardiac output determinations in man

The results of a procedure for estimating cardiac output by a single-breath technique (Qsb), obtained in healthy males during supine rest and during exercise on a bicycle ergometer, were compared with the results on cardiac output obtained by the direct Fick method (QF). The single breath maneuver consisted of a slow exhalation to near residual volume following an inspiration somewhat deeper than normal. The Qsb calculations incorporated an equation of the CO2 dissociation curve and a 'moving spline' sequential curve-fitting technique to calculate the instantaneous R from points on the original expirogram. The resulting linear regression equation indicated a 24-percent underestimation of QF by the Qsb technique. After applying a correction, the Qsb-QF relationship was improved. A subsequent study during upright rest and exercise to 80 percent of VO2(max) in 6 subjects indicated a close linear relationship between Qsb and VO2 for all 95 values obtained, with slope and intercept close to those in published studies in which invasive cardiac output measurements were used.

Loeppky, J. A.↗
NASA NTRS1972

A multichannel electromagnetic flowmeter telemetry system.

An eight-channel biomedical telemetry system provides four channels of blood flow measurements in addition to blood-pressure and EKG data. Emphasis is placed on the amplifiers and signal conditioning circuitry required for interfacing of the electromagnetic flow transducers with the transmission and modulation subsystems. The large number of data channels permits measurement of flow distribution as well as total cardiac output. The batteries and electronics for four channels (blood flow) weigh about 500 g and have a volume of 250 cu cm.

Fryer, T. B.↗
NASA NTRS1997

Non-Invasive Measurement of Pulsatile Intracranial Pressures Using Ultrasound

Early detection of elevated intracranial pressure (ICP) will aid clinical decision-making for head trauma, brain tumor and other cerebrovascular diseases. Conventional methods, however, require surgical procedures which take time and are accompanied by increased risk of infection. Accordingly we have developed and refined a new ultrasound device to measure skull movements which are known to occur in conjunction with altered ICP. The principle of this device is based upon pulse phase locked loop (PPLL), which enables us to detect changes in distance on the order of microns between an ultrasound transducer on one side of the skull and the opposite inner surface of the cranium. The present study was designed to verify this measurement technique in cadavera. Transcranial distance was increased in steps of 10 mmHg from zero to 50 mmHg by saline infusion into the lateral ventricle of two cadavera. In separate experiments, pulsations of ICP with the amplitudes of zero to 2 mmHg were generated by rhythmic injections of saline using a syringe. When the ICP was stepwise increased from zero to 50 mmHg, transcranial distance increased in proportion with the ICP increase (y=12 x - 76, r=0.938), where y is changes in transcranial distance in microns and x is ICP in mmHg. In the data recorded while ICP pulsations were generated, fast Fourier transform analysis demonstrated that cranial pulsations were clearly associated with ICP pulsations. The results indicate that changes in transcranial distance is linearly correlated with those in ICP, and also that the PPLL device has sufficient sensitivity to detect transcranial pulsations which occur in association with the cardiac cycle. By analyzing the magnitude of cranial pulsations, we may be able to estimate the pressure-volume index in the cranium. As a result, estimates of intracranial compliance may be possible by using the PPLL device. Further studies are necessary in normal subjects and patients.

Ueno, Toshiaki↗
NASA NTRS1995

'Non-hypotensive' hypovolaemia reduces ascending aortic dimensions in humans

1. The notion that small, 'non-hypotensive' reductions of effective blood volume alter neither arterial pressure nor arterial baroreceptor activity is pervasive in the experimental literature. We tested two hypotheses: (a) that minute arterial pressure and cardiac autonomic outflow changes during hypovolaemia induced by lower body suction in humans are masked by alterations in breathing, and (b) that evidence for arterial baroreflex engagement might be obtained from measurements of thoracic aorta dimensions. 2. In two studies, responses to graded lower body suction at 0 (control), 5, 10, 15, 20 and 40 mmHg were examined in twelve and ten healthy young men, respectively. In the first, arterial pressure (photoplethysmograph), R-R interval, and respiratory sinus arrhythmia amplitude (complex demodulation) were measured during uncontrolled and controlled breathing (constant breathing frequency and tidal volume). In the second, cross-sectional areas of the ascending thoracic aorta were calculated from nuclear magnetic resonance images. 3. Lower body suction with controlled breathing resulted in an increased arterial pulse pressure at mild levels (5-20 mmHg; ANOVA, P < 0.05) and a decreased arterial pulse pressure at moderate levels (40 mmHg; ANOVA, P < 0.05). Both R-R intervals and respiratory sinus arrhythmia were negatively related to lower body suction level, whether group averages (general linear regression, r > 0.92) or individual subjects (orthogonal polynomials, 12 of 12 subjects) were assessed. 4. Aortic pulse area decreased progressively and significantly during mild lower body suction, with 47% of the total decline occurring by 5 mmHg. 5. These results suggest that small reductions of effective blood volume reduce aortic baroreceptive areas and trigger haemodynamic adjustments which are so efficient that alterations in arterial pressure escape detection by conventional means.

NASA Discipline Cardiopulmonary↗
NASA NTRS2004

Strategies for Small Volume Resuscitation: Hyperosmotic-Hyperoncotic Solutions, Hemoglobin Based Oxygen Carriers and Closed-Loop Resuscitation

Introduction: Logistic constraints on combat casualty care preclude traditional resuscitation strategies which can require volumes and weights 3 fold or greater than hemorrhaged volume. We present a review of quantitative analyses of clinical and animal data on small volume strategies using 1) hypertonic-hyperosmotic solutions (HHS); 2) hemoglobin based oxygen carriers (HBOCs) and 3) closed-loop infusion regimens.Methods and Results: Literature searches and recent queries to industry and academic researchers have allowed us to evaluate the record of 81 human HHS studies (12 trauma trials), 19 human HBOCs studies (3trauma trials) and two clinical studies of closed-loop resuscitation.There are several hundreds animal studies and at least 82 clinical trials and reports evaluating small volume7.2%-7.5% hypertonic saline (HS) most often combined with colloids, e.g., dextran (HSD) or hetastarch(HSS). HSD and HSS data has been published for 1,108 and 392 patients, respectively. Human studies have documented volume sparing and hemodynamic improvements. Meta-analyses suggest improved survival for hypotensive trauma patients treated with HSD with significant reductions in mortality found for patients with blood pressure < 70 mmHg, head trauma, and penetrating injury requiring surgery. HSD and HSS have received regulatory approval in 14 and 3 countries, respectively, with 81,000+ units sold. The primary reported use was head injury and trauma resuscitation. Complications and reported adverse events are surprisingly rare and not significantly different from other solutions.HBOCs are potent volume expanders in addition to oxygen carriers with volume expansion greater than standard colloids. Several investigators have evaluated small volume hyperoncotic HBOCs or HS-HBOC formulations for hypotensive and normotensive resuscitation in animals. A consistent finding in resuscitation with HBOCs is depressed cardiac output. There is some evidence that HBOCs more efficiently unload oxygen from plasma hemoglobin as well as facilitate RBC unloading. We analyzed one volunteer study, 15 intraoperative trials, and 3 trauma studies using HBOCs. Perioperative studies generally suggest ability to deliver oxygen, but one trauma trial using HBOCs (HemAssist) for treatment of trauma resulted in a dramatic increase in mortality, while an intraoperative trauma study using Polyheme demonstrated reductions in blood use and lower mortality compared to historic controls of patients refusing blood. Transfusion reductions with HBOC use have been modest. Two HBOCs (Hemopure and Polyheme) are now in new or planned large-scale multicenter prehospital trials of trauma treatment. A new implementation of small volume resuscitation is closed-loop resuscitation (CLR), which employs microprocessors to titrate just enough fluid to reach a physiologic target . Animal studies suggest less risk of rebleeding in uncontrolled hemorrhage and a reduction in fluid needs with CLR. The first clinical application of CLR was treatment of burn shock and the US Army. Conclusions: Independently sponsored civilian trauma trials and clinical evaluations in operational combat conditions of different small volume strategies are warranted.

Kramer, George C.↗
NASA NTRS2002

Left ventricular outflow tract mean systolic acceleration as a surrogate for the slope of the left ventricular end-systolic pressure-volume relationship

OBJECTIVE: The goal of this study was to analyze left ventricular outflow tract systolic acceleration (LVOT(Acc)) during alterations in left ventricular (LV) contractility and LV filling. BACKGROUND: Most indexes described to quantify LV systolic function, such as LV ejection fraction and cardiac output, are dependent on loading conditions. METHODS: In 18 sheep (4 normal, 6 with aortic regurgitation, and 8 with old myocardial infarction), blood flow velocities through the LVOT were recorded using conventional pulsed Doppler. The LVOT(Acc) was calculated as the aortic peak velocity divided by the time to peak flow; LVOT(Acc) was compared with LV maximal elastance (E(m)) acquired by conductance catheter under different loading conditions, including volume and pressure overload during an acute coronary occlusion (n = 10). In addition, a clinically validated lumped-parameter numerical model of the cardiovascular system was used to support our findings. RESULTS: Left ventricular E(m) and LVOT(Acc) decreased during ischemia (1.67 +/- 0.67 mm Hg.ml(-1) before vs. 0.93 +/- 0.41 mm Hg.ml(-1) during acute coronary occlusion [p < 0.05] and 7.9 +/- 3.1 m.s(-2) before vs. 4.4 +/- 1.0 m.s(-2) during coronary occlusion [p < 0.05], respectively). Left ventricular outflow tract systolic acceleration showed a strong linear correlation with LV E(m) (y = 3.84x + 1.87, r = 0.85, p < 0.001). Similar findings were obtained with the numerical modeling, which demonstrated a strong correlation between predicted and actual LV E(m) (predicted = 0.98 [actual] -0.01, r = 0.86). By analysis of variance, there was no statistically significant difference in LVOT(Acc) under different loading conditions. CONCLUSIONS: For a variety of hemodynamic conditions, LVOT(Acc) was linearly related to the LV contractility index LV E(m) and was independent of loading conditions. These findings were consistent with numerical modeling. Thus, this Doppler index may serve as a good noninvasive index of LV contractility.

Non-NASA Center↗
NASA NTRS1997

The MR appearance of volume overload in the lower extremities

PURPOSE: Our goal was to describe the MR findings of volume overload (VO) in the lower extremities. METHOD: Fifteen individuals were studied, including eight healthy controls and seven patients with VO (four cardiac, three renal). MR evaluation included various SE techniques. Edema detection, localization, and symmetry were assessed subjectively. Relaxation time estimates were also made of the subcutaneous tissue, marrow, and three muscles. RESULTS: Subcutaneous tissue was markedly edematous in seven of seven patients and asymmetric in four of seven, whereas marrow was normal in all patients. Muscle edema was mild and asymmetric in six and two of seven patients, respectively. Perifascial fluid collections were identified in six of seven patients. CONCLUSION: Subcutaneous tissue edema is the dominant feature of VO in the lower extremities. Perifascial fluid is common but does not necessarily distribute symmetrically. Muscle edema is relatively mild. These findings should aid in identifying VO as the potential cause of swelling in patients with swollen legs.

Non-NASA Center↗
NASA NTRS2002

Pulmonary venous flows reflect changes in left atrial hemodynamics during mitral balloon valvotomy

Patients with mitral stenosis have usually blunted pulmonary venous (PV) flow, because of decreased mitral valve area and diastolic dysfunction. The authors compared changes in Doppler PV velocities by using transesophageal echocardiography (TEE) against hemodynamics parameters before and after mitral balloon valvotomy to observe relevance of PV velocities and endsystolic left atrial (LA) pressure-volume relationship. In 25 patients (aged 35 +/- 17 years) with mitral stenosis in sinus rhythm, changes in LA pressure and volumes were compared with PV velocities before and after valvotomy. Mitral valve area, mitral gradients, and deceleration time were obtained. Mitral valve area and mitral gradients changed from 1 +/- 0.2 cm2 and 14.6 +/- 5.4 mmHg to 1.9 +/- 0.3 cm2 and 6.3 +/- 1.7 mmHg, respectively (p<0.001). AR peak reverse flow velocity and AR duration decreased from 29 +/- 13 cm/s and 110 =/- 30 msec to 19 +/- 6 cm/s and 80 +/- 29 msec respectively (p<0.001). Transmitral Doppler E wave deceleration time decreased from 327 +/- 85 to 209 +/- 61 s and cardiac output increased from 4.2 +/- 1.0 to 5.2 +/- 1.1 L/minute (p<0.001). The changes in LA pressure were correlated with changes in S/D (r=0.57, p<0.05). The changes in endsystolic LA pressure-volume relationship were also correlated with changes in S/D (r=0.52, p<0.05). Endsystolic LA pressure-volume relationship decreased after mitral balloon valvotomy, as a result of a large decrease in pressure. PV systolic/diastolic (S/D) waves ratio reflects endsystolic LA pressure-volume relationship and may be used as another indicator of successful valvotomy.

Non-NASA Center↗
NASA NTRS1972

Evaluation of the pulse-contour method of determining stroke volume in man.

The pulse-contour method for determining stroke volume has been employed as a continuous rapid method of monitoring the cardiovascular status of patients. Twenty-one patients with ischemic heart disease and 21 patients with mitral valve disease were subjected to a variety of hemodynamic interventions. The pulse-contour estimations, using three different formulas derived by Warner, Kouchoukos, and Herd, were compared with indicator-dilution outputs. A comparison of the results of the two methods for determining stroke volume yielded correlation coefficients ranging from 0.59 to 0.84. The better performing Warner formula yielded a coefficient of variation of about 20%. The type of hemodynamic interventions employed did not significantly affect the results using the pulse-contour method. Although the correlation of the pulse-contour and indicator-dilution stroke volumes is high, the coefficient of variation is such that small changes in stroke volume cannot be accurately assessed by the pulse-contour method. However, the simplicity and rapidity of this method compared to determination of cardiac output by Fick or indicator-dilution methods makes it a potentially useful adjunct for monitoring critically ill patients.

Alderman, E. L.↗
NASA NTRS1990

Baroreflex Responses to Acute Changes in Blood Volume in Humans

To test the hypothesis that acute changes in plasma volume affect the stimulus-response relations of high- and low- pressure baroreflexes, eight men (27-44 yr old) underwent measurements for carotid-cardiac and cardiopulmonary baro-reflex responses under the following three volemic conditions: hypovolemic, normovolemic, and hypervolemic. The stimulus- response relation of the carotid-cardiac response curve was generated using a neck cuff device, which delivered pressure changes between +40 and -65 mmHg in continuous steps of 15 mmHg. The stimulus-response relationship, of the cardio-pulmonary baroreflex were studied by measurements of Forearm Vascular Resistance (FVR) and Peripheral Venous Pressure (PVP) during low levels of lower body negative pressure (O to -20 mmHg). The results indicate greater demand for vasoconstriction for equal reductions in venous pressure during progressive hypovolemia; this condition may compromise the capacity to provide adequate peripheral resistance during severe orthostatic stress. Fluid loading before reentry after spaceflight may act to restore vasoconstrictive capacity of the cardiopulmonary baroreflex but may not be an effective countermeasure against potential post- flight impairment of the carotid-cardiac baroreflex.

Thompson, Cynthia A.↗
DOE OSTI2024

Myosin in autoinhibited off state(s), stabilized by mavacamten, can be recruited in response to inotropic interventions

Mavacamten is a FDA-approved small-molecule therapeutic designed to regulate cardiac function at the sarcomere level by selectively but reversibly inhibiting the enzymatic activity of myosin. It shifts myosin toward ordered off states close to the thick filament backbone. It remains elusive whether these myosin heads in the off state(s) can be recruited in response to physiological stimuli when required to boost cardiac output. We show that cardiac myosins stabilized in these off state(s) by mavacamten are recruitable by 1) Ca 2+ , 2) increased chronotropy [heart rate (HR)], 3) stretch, and 4) β-adrenergic (β-AR) stimulation, all known physiological inotropic interventions. At the molecular level, we show that Ca 2+ increases myosin ATPase activity by shifting mavacamten-stabilized myosin heads from the inactive super-relaxed state to the active disordered relaxed state. At the myofilament level, both Ca 2+ and passive lengthening can shift mavacamten-ordered off myosin heads from positions close to the thick filament backbone to disordered on states closer to the thin filaments. In isolated rat cardiomyocytes, increased stimulation rates enhanced shortening fraction in mavacamten-treated cells. This observation was confirmed in vivo in telemetered rats, where left-ventricular dP/dt max , an index of inotropy, increased with HR in mavacamten-treated animals. Finally, we show that β-AR stimulation in vivo increases left-ventricular function and stroke volume in the setting of mavacamten. Our data demonstrate that the mavacamten-promoted off states of myosin in the thick filament are at least partially activable, thus preserving cardiac reserve mechanisms.

59 BASIC BIOLOGICAL SCIENCES↗