Cardiovascular deconditioning during long-term spaceflight through multiscale modeling

Human spaceflight has been fascinating man for centuries, representing the intangible need to explore the unknown, challenge new frontiers, advance technology, and push scientific boundaries further. A key area of importance is cardiovascular deconditioning, that is, the collection of hemodynamic changes—from blood volume shift and reduction to altered cardiac function—induced by sustained presence in microgravity. A thorough grasp of the 0G adjustment point per se is important from a physiological viewpoint and fundamental for astronauts’ safety and physical capability on long spaceflights. However, hemodynamic details of cardiovascular deconditioning are incomplete, inconsistent, and poorly measured to date; thus a computational approach can be quite valuable. We present a validated 1D–0D multiscale model to study the cardiovascular response to long-term 0G spaceflight in comparison to the 1G supine reference condition. Cardiac work, oxygen consumption, and contractility indexes, as well as central mean and pulse pressures were reduced, augmenting the cardiac deconditioning scenario. Exercise tolerance of a spaceflight traveler was found to be comparable to an untrained person with a sedentary lifestyle. At the capillary–venous level significant waveform alterations were observed which can modify the regular perfusion and average nutrient supply at the cellular level. The present study suggests special attention should be paid to future long spaceflights which demand prompt physical capacity at the time of restoration of partial gravity (e.g., Moon/Mars landing). Since spaceflight deconditioning has features similar to accelerated aging understanding deconditioning mechanisms in microgravity are also relevant to the understanding of aging physiology on the Earth.

Aquatic therapies in patients with compromised left ventricular function and heart failure

With water immersion, gravity is partly eliminated, and the water exerts a pressure on the body surface. Consequently there is a blood volume shift from the periphery to the central circulation, resulting in marked volume loading of the thorax and heart. This paper presents a selection of published literature on water immersion, balneotherapy, aqua exercises, and swimming, in patients with left ventricular dysfunction (LVD) and/or stable chronic heart failure (CHF). Based on exploratory studies, central hemodynamic and neurohumoral responses of aquatic therapies will be illustrated. Major findings are: 1. In LVD and CHF, a positive effect of therapeutic warm-water tub bathing has been observed, which is assumed to be from afterload reduction due to peripheral vasodilatation caused by the warm water. 2. In coronary patients with LVD, at low-level water cycling the heart is working more efficiently than at lowlevel cycling outside of water. 3. In patients with previous extensive myocardial infarction, upright immersion to the neck resulted in temporary pathological increases in mean pulmonary artery pressure (mPAP) and mean pulmonary capillary pressures (mPCP). 4. Additionally, during slow swimming (20-25m/min) the mPAP and/or PCP were higher than during supine cycling outside water at a 100W load. 5. In CHF patients, neck- deep immersion resulted in a decrease or no change in stroke volume. 6. Although patients are hemodynamically compromised, they usually maintain a feeling of well-being during aquatic therapy. Based on these findings, clinical indications for aquatic therapies are proposed and ideas are presented to provoke further research.

Determinants of exercise performance in normal men with externally imposed expiratory flow limitation

To understand how externally applied expiratory flow limitation (EFL) leads to impaired exercise performance and dyspnea, we studied six healthy males during control incremental exercise to exhaustion (C) and with EFL at ∼1. We measured volume at the mouth (Vm), esophageal, gastric and transdiaphragmatic (Pdi) pressures, maximal exercise power (W˙max) and the difference (Δ) in Borg scale ratings of breathlessness between C and EFL exercise. Optoelectronic plethysmography measured chest wall and lung volume (Vl). From Campbell diagrams, we measured alveolar (Pa) and expiratory muscle (Pmus) pressures, and from Pdi and abdominal motion, an index of diaphragmatic power (W˙di). Four subjects hyperinflated and two did not. EFL limited performance equally to 65%W˙max with Borg = 9–10 in both. At EFLW˙max, inspiratory time (Ti) was 0.66s ± 0.08, expiratory time (Te) 2.12 ± 0.26 s, Pmus ∼40 cmH2O and ΔVl-ΔVm = 488.7 ± 74.1 ml. From Pa and Vl, we calculated compressed gas volume (Vc) = 163.0 ± 4.6 ml. The difference, ΔVl-ΔVm-Vc (estimated blood volume shift) was 326 ml ± 66 or 7.2 ml/cmH2O Pa. The high Pmus and long Te mimicked a Valsalva maneuver from which the short Ti did not allow recovery. Multiple stepwise linear regression revealed that the difference between C and EFL Pmus accounted for 70.3% of the variance in ΔBorg. ΔW˙di added 12.5%. We conclude that high expiratory pressures cause severe dyspnea and the possibility of adverse circulatory events, both of which would impair exercise performance.

Microvascular volume contribution to hemorrhage compensation

Regulation of systemic blood pressure during small changes in blood volume is partially achieved by blood volume shifts from microcirculation to macrocirculation that cause a decrease in systemic hematocrit [LaForte, A., L. Lee, G. Rich, T. Skalak, and J. Lee. Am. J. Physiol. 262 (Heart Circ. Physiol. 31): H190–H199, 1992]. Diameters of 4–100 microns arterioles and 5–80 microns venules in spinotrapezius muscles of anesthetized rats were measured during control conditions and immediately after a 13% (of total blood volume) hemorrhage to determine the role of the microvasculature in hemorrhage compensation. The Strahler orders, mean control diameters (microns), and posthemorrhage diameters (% of control) were as follows: TA2, 5.7 (91.2%); TA3, 8.7 (90.4%); TA4, 12.5 (85.4%); TA5, 31.4 (95.8%); AA, 39.6 (94.6%); CV2, 8.0 (94.7%); CV3, 14.8 (93.7%); CV4, 24.6 (95.2%); CV5, 41.5 (98.8%); and AV, 47.8 (97.8%), where TA, AA, CV, and AV designate transverse arteriole, arcade arteriole, collecting venule, and arcade venule, respectively. The diameter reductions were heterogeneous for arterioles and venules, with significant variation in small arterioles (< 25 microns), which exhibited dimensions ranging from 61 to 100% of control, whereas larger arterioles ranged from 81 to 100% of control. The data were used with an anatomic model to estimate the systemic hematocrit decrease (0.73%) and the blood volume shifted from the microcirculation to the macrocirculation (3.74% of total control blood volume). These results agree well with direct measurements of the systemic hematocrit decrease and thus provide the microvascular basis for the rapid blood volume shift during moderate hemorrhage.

Effects of adenosine on intestinal hemodynamics, oxygen delivery, and capillary fluid exchange

Systemic arterial pressure, superior mesenteric arterial and venous pressures, blood flow, arteriovenous oxygen difference, lymph flow, and intestinal volume were monitored continuously from an autoperfused loop of cat ileum to determine the effects of locally infused adenosine on intestinal hemodynamics, oxygen consumption, and capillary fluid exchange. The results indicate that adenosine, inosine, and hypoxanthine are vasodilators in the intestinal circulation. Local infusion of adenosine significantly reduces vascular resistance, but lymph flow, lymph oncotic pressure, and lymphatic protein flux remained unchanged from control, and the intestinal volume rapidly became constant after an initial blood volume shift. Intestinal oxygen consumption decreased significantly in both autoperfused and constant flow preparations. Pretreatment with aminophylline prevented the reduction in oxygen consumption and greatly attenuated the vasodilatory effect of adenosine. The reactive hyperemic response to 60-s arterial occlusions was virtually unchanged following aminophylline treatment. Adenosine depressed oxygen utilization of mucosal and muscularis strips in vitro and caused a significant redistribution of blood flow from the mucosal-submucosal layer to the muscularis in autoperfused preparations. The results of this study indicate that adenosine significantly reduces vascular resistance and oxygen consumption, yet does not alter fluid exchange in the small intestine.

Quantitation of cerebral ischemic pressor response in dogs

Using a surgical technique designed to isolate the cerebral arterial circulation from the systemic and extracranial circulations and also a servomechanism devised to prevent blood volume shift between a donor dog and an experimental dog, the experimental dog's brain was perfused at a succession of controlled arterial pressures ranging from 140 to 0 mm Hg for the purpose of investigating quantitatively the steady-state response of the systemic arterial pressure (SAP) to stepwise changes of cerebral perfusion pressure (CPP) and cerebral blood flow (CBF). The interrelationships between CPP and SAP suggested a rectangular hyperbolic curve, but this same relationship was more clearly demonstrated when SAP was plotted against CBF. These findings suggest a chemical rather than pressoreceptor basis for the ischemic response. The peak values of ΔSAP/ ΔCPP in individual cases varied from 11.4 to 3.1 and averaged 7.7; thus the response was found to be four or more times as powerful as the carotid sinus pressoreceptor reflex in dogs.

Pressure-flow relationships in isolated canine cerebral circulation

As a result of anatomic studies on the cerebral arteries and veins in the dog using vascular cast preparations, a surgical procedure was developed by which a) the cerebral arterial circulation can be completely isolated from the systemic circulation and b) the perfusion blood will flow only to the intracranial regions. Also devised was a servomechanism which controls the donor dog's body weight and thus prevents a blood volume shift between the donor and recipient dogs, within ± 5 cc of the original value. The cerebral perfusion pressure (C.P.P.) was controlled by a Starling's resistance and was altered stepwise from 140 to 0 mm Hg. At each C.P.P. level the cerebral blood flow (C.B.F.) was measured by a stromuhr. The mean and the standard deviation of C.B.F. values at 100 mm Hg C.P.P. in 10 dogs was 67.1 ± 19.5 cc/100 gm brain/min. Pressure-flow relationship over the C.P.P. range from 140 to 0 mm Hg did not show any evidence of autoregulation of the cerebral vessels, but instead suggested a linear proportional relationship.