Study of effects of simulated space flight factors and use of infusion liquids on human hemodynamics with the use of the Cardiocode method

Materials and methods Test subjects were six men aged 20 to 35 without chronic somatic diseases. Antiorthostatic hypokinesia with an angle of 15 ° (ANOH-15) simulated the weightlessness was used. Diuretics were used to simulate hypovolemia in the test individuals. During ANOH-15 the colloid and crystalloid intravenous infusions were applied. Central hemodynamics parameters were measured by Cardiocode method.


Aims
The aim is to study the effect of simulated space flight factors on the human central hemodynamics and evaluate the effectiveness of colloid and crystalloid infusions in microgravity simulation using the Cardiocode method.

Materials and methods
Test subjects were six men aged 20 to 35 without chronic somatic diseases.Antiorthostatic hypokinesia with an angle of 15 ° (ANOH-15) simulated the weightlessness was used.Diuretics were used to simulate hypovolemia in the test individuals.During ANOH-15 the colloid and crystalloid intravenous infusions were applied.Central hemodynamics parameters were measured by Cardiocode method.

Results
Background quantitative and qualitative central hemodynamics parameters were obtained, several individual characteristics of blood flow regulation were identified.The effects of space flight factors, ground-based simulated with antiorthostatic hypokinesia, on the human hemodynamics were investigated.

Conclusion
The Cardiocode method allowed obtaining the information about the effects of simulated space flight factors and different infusion fluids on the human central hemodynamics.
The efficacy of crystalloid and colloid infusions for the correction of central hemodynamics abnormalities in test subjects in microgravity was positively evaluated.

Introduction
The further progress in cosmonautics, the prospects for long-term interplanetary missions dictate us today the necessity of the development and improvement of the system of medical services for orbital flights.Prolonged space missions require further adjustments and corrections of the preventive measure system, improving the system of medical selection of cosmonauts and astronauts, elaboration of absolutely new methods of diagnostics and treatment of cosmonauts both during their space missions and their adaptation to new tasks of the existing medical equipment systems already admitted to be used in space medicine (1).
One of the biggest challenges for the nearest future, which has been discounted up to the present day, is devising of new methods of intensive therapy and eventual surgical treatment to be used on board a space ship during long-term space missions in case of emergency.As to the orbital flights, in case of necessity of a surgical treatment, or in case some critical health conditions occur, there exists always the possibility to interrupt the space flight and return the critically ill person to the Earth within the possible shortest time.But it is just another case with interplanetary missions: there is no way of doing the same.Therefore, this makes the elaboration of a new reliable medical service system all the more important for its use during long-term space flights, including creation of new concepts and development of new methods of on-board surgical treatment of cosmonauts or astronauts in critical cases, if any.
One of the most significant components of surgery and intensive therapy during a space flight is infusion therapy.The existing equipment systems and facilities make possible to use the infusion therapy even under the weightlessness conditions.But at the same time, it should be noted that there are no data on impacts of various infusion liquids on parameters of the central and the peripheral hemodynamics, including data on their impacts on blood microcirculation and tissue gas exchange processes in the microgravity environment during a space flight.
There is a huge amount of data collected by experts which are related to issues on redistribution of liquids in the body under the microgravity conditions (2), changes in water-salt exchange in the organism (3,4), tissue metabolism, effects of weightlessness both on the central and the peripheral hemodynamics (5).An efficiency of the use of infusion liquids under the space flight conditions has not been studied until now.
In the microgravity environment, when the parameters of the central and the peripheral blood circulation, the volumes of circulated blood and microcirculation indices are changed and when liquids in the cosmonaut's body are re-distributed, the effects of the use of infusion liquids might differ significantly from those expected.This factor should be considered in specifying tactics of infusion therapy under the space flight conditions.
Upon investigations of effects of colloid and crystalloid intravenous infusions on various parameters of the central and peripheral hemodynamics, we are able to optimize to a large extent all algorithms of intensive therapy in some surgical cases and some cases of critical health states under the weightlessness conditions.
In this connection it should be noted that it is advisable to carry out a number of groundbased experiments in order to identify some impacts of a simulated space flight on the efficiency of different infusion liquids used there.
The ground-based simulation of the microgravity is widely used both for training of cosmonauts and conducting of medical and technological experimentation under the microgravity conditions.There exist some different ways of how to imitate and simulate the weightlessness conditions on ground.
In medical studies, for the purpose of the microgravity simulation, most commonly used are methods simulating a lack of blood hydrostatic pressure in the organism.In particular, one of the microgravity models is restricting of test subjects to head down tilt bed rest which is called antiorthostatic hypokinesia (ANOH).
This article is presenting some results of an experimental study on the effects of factors of a space flight with the use of a ground-based simulation on the organism, with the utilization of the antiorthostatic hypokinesia (ANOH) at a tilt angle of 15°.
For conducting of such studies, the issues on methods of assessment, control and monitoring of the state of the cardiovascular system are of great importance.
In pursuing these aims, obtaining of reliable measurement data on the central hemodynamics by noninvasive technologies is really a very challenging idea.
In the above ANOH studies, in order to evaluate the responses of the human cardiovascular system to the simulated space flight conditions in combination with the support of the infusion liquids, we applied a new diagnostics method based on an application of the Cardiocode device (6).
The Cardiocode device offers an innovative noninvasive measuring technology that delivers noninvasively volumetric parameters of hemodynamics, based on the heart cycle phase analysis.This technology has its origin in a new theoretical model of blood flow via blood vessels in the organism.
This noninvasive technology makes possible to obtain not only values of phase-related parameters of hemodynamics, but to provide qualitative assessments of functional and structural changes, including hemodynamic changes in various parts of the cardiovascular system, as well.

Materials and methods
The aim of the experimental study with the use of the Cardiocode device & technology was to reveal and assess impacts and effects of a simulated space flight on the human cardiovascular system and evaluate the efficiency of the use of colloid and crystalloid intravenous infusions under the microgravity conditions.Six individuals (males) without any chronic somatic diseases, aged from 20 to 35, participated in the experimental study.
The antiorthostatic hypokinesia at a tilt angle of 15° (ANOH-15°) during 21 hours was taken as the model simulating the weightlessness conditions (microgravity).
The state of hypovolemia in the hypokinetic subjects was produced with the use of diuretics (furocemide).
The study comprised three sets of the experiment as follows: • Changes in the central hemodynamic parameters during the experiment were recorded and evaluated with the utilization of the device Cardiocode.The experimental studies were carried out in line with the following testing schedule.On the basis of the recorded ECG and Rheo curves, the appropriate heart cycle phase structure for every individuals was automatically identified and the relevant parameters of the central hemodynamics were calculated (6).

Results
The basic (recorded before the experiment) quantitative and qualitative characteristics of the cardiovascular system performance in all test subjects were within the norm.Certain individual peculiarities of blood flow regulation not referring to pathology were noted.Heart rate, HR Hemodynamic parameters the values of which are given as percentage of stroke volume provide a better understanding of cardiac output formation than the absolute values.Thus, percentage ratio of volumes PV1 and PV2 shows the process of the heart filling with blood, in particular, whether the ventricle or the atrium are to a greater degree responsible for diastole.

Influence of simulated space flight factors and infusion liquid injection on hemodynamics of the test subjects
Volume PV5 characterizes the contribution of the aorta to blood ejection from the ventricle in the systole phase.
The diastole contributes to formation of cardiac output significantly.Without heart relaxation and diastole there would be no contraction and systole phase.An increase in the heart rate serves as a protection tool of the human body and assists in maintaining sufficient blood supply of body organs and tissues under conditions of increased loads.The inner structure of the cardiac cycle changes as well, and the functions are redistributed among the atria, ventricles and large vessels which take part in cardiac output formation.As investigations showed, under these conditions the interrelation of diastolic phase volumes changes, volume PV2 increases significantly and the atrium load on myocardium increases as well.In case of high pulse rate the ventricles are filled with blood only during the systole phase.Thus, the compensation mechanism works.
We will pay attention to the analysis of diastolic heart function considering the interrelation of volumes PV1 and PV2 as diagnostic criterion.The subject whose ventricles are filled in bed rest position during the early diastole phase possesses greater compensation capabilities.
Let us consider the general scheme of the dynamics of the central hemodynamic parameters of the test subjects during the experiment.Then we shall consider some individual characteristics.
It should be noted that the mentioned scheme can be observed in practically every test subject with only minor deviations.It is only the intensity of changes that is different.
A clear-cut response to orthostatic load preceding and following antiorthostatic hypokinesia (ANOH) as well as preceding and following the infusion therapy is typical for all test subjects.
The criteria for selection of test subjects best prepared to adaptation to the conditions of a space flight and re-adaptation upon return to the Earth When selecting the candidates for a space flight it is reasonable to take into account at least three criteria as listed below: • an acceptable ability to bear overloads during the start; • an acceptable ability of adaptation to weightlessness; • availability of a body compensatory reserve required for return to the Earth and readaptation to the normal gravity conditions.This is certainly a very difficult task.Much more information is needed to solve it.We can only offer a sort of prognostication, when using the results of the analysis of circulatory system response to the effects of simulated space flight factors in the above mentioned completed experiment.
The ability of every test individuals to be adapted to the weightlessness conditions is beyond any doubt.But their ability of re-adaptation to the Earth normal gravity conditions after a space flight raises far more questions.
Antiorthostatic hypokinesia at an angle of 15° (ANOH-15°) is a model of weightlessness in these experiments.The analysis of the data on hemodynamics changes during the ANOH showed that the ratio of diastolic phase volumes changes towards an increase in the PV1 blood volume and a decrease in the PV2 blood volume, i.e., the atria are discharged.
The orthostatic test carried out after the ANOH can be considered as a model of return to the normal gravity on the Earth after the weightlessness conditions.It is evident that it leads to a sharp increase in the heart rate and the PV2 parameter.It also implies a sudden overloading of atrial myocardium.
After a long-term stay in the weightlessness environment in a real space flight, the fact described above can play a significant role in the re-adaptation of a cosmonaut to the Earth gravity.
Taking it into account, a better ability to tolerate the orthostatic test under conditions of the simulated ground-based weightlessness can be considered as one of the criteria for the selection of test subjects for a real space flight.
This study allows drawing some general conclusions only and tracing some tendencies of the human cardiovascular system response to the space effects simulated in the experiment.

Discussion and conclusions
In conclusion, we would like to summarize the results of the conducted experimental study.
First, the Cardiocode method used for the experimental study allowed us to obtain most valuable qualitative and quantitative data on the effects of simulated space flight factors and infusion fluids on the human central hemodynamics.It has been found that the use of colloid and crystalloid infusions in the test subjects with hypovolemia in the microgravity environment is a very effective measure for coping with undesirable space flight effects.
Second, despite the complex theoretical concept of hemodynamics, the new noninvasive method of measuring phase-related volumetric parameters of hemodynamics has been successfully implemented in a very easy way, with the use of the small-sized portable PC-

Issue 1
was to reveal changes in the central hemodynamics of a human due to exposure factors of the simulated space flight (during a short-term ANOH and under conditions of in case of intentionally produced loss of fluid); Issue two was assessing the efficiency of the use of colloid and crystalloid intravenous infusions in test subjects with hypovolemia in order to correct abnormalities of the central and peripheral hemodynamics under conditions simulating microgravity effects (antiorthostatic hypokinesia at a tilt angle of 15° (ANOH -15°).

Figure 1 .
Figure 1.ECG, ECG first-order derivative and Rheogram recorded with the PC-assisted device Cardiocode.
Before evaluating the influence of infusion of colloid and crystalloid solutions on central hemodynamics, it is necessary to understand how hemodynamic parameters change under the influence of the simulated space flight factors.Analysis of parameters of central hemodynamics in the test subjects calculated with the Cardiocode device showed that the most significant changes during the experiment can be observed in the following parameters: SV -stroke volume, ml; MV -minute volume, l; www.cardiometry.netNo.2 May, 2013 130 PV1 -volume of blood entering the ventricle in the early diastole, which is the characteristic property of the suction function of the ventricle, % of SV; PV2 -volume of blood entering the left ventricle in the systole phase, which is the characteristic property of the contraction function of the atrium, % of SV;PV5 -volume of blood (SV fraction) pumped by the ascending aorta as peristaltic pump which is the characteristic property of the aortic tonus, % of SV.