13the influence of laser blood photomodification

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Laser Physics, Vol. 13, No. 1, 2003, pp. 106111.Original Text Copyright 2003 by Astro, Ltd.English Translation Copyright 2003 byMAIK Nauka /Interperiodica (Russia).

1. INTRODUCTION

The therapeutic effect of laser radiation is deter-mined by physical processes occurring both in theorganism as a whole and at lower levels such as the

organ, cell, cell fragment, biomolecules, etc. The intra-venous laser exposure of blood (ILEB) holds a specialposition among the variety of laser biostimulationmethods due to the fact that blood is a biological com-ponent, which determines the functioning of the wholeof the organism. Blood is the liquid that provides theexchange of all the nutrients and gases. The laser influ-ence upon blood is apparently one of the most impor-tant aspects among the whole variety of laser-biostim-ulation effects. Thus, using data on the microcapillaryblood flow [1], one can estimate the blood volume,undergoing laser action during 10-min irradiation of1-cm

2

area of the finger skin, at 100 ml (whereas thetotal blood volume is 35 l). Therefore, the ILEB is evi-dently the most effective procedure with regard to ther-apeutic after-effects.

Though the effect of laser biostimulation of the cir-culatory system by means of the ILEB is now deter-mined and has found the widespread practical use, theprinciple of its action remains unclear. On the one hand,it is considered that the laser irradiation changes theconformational property of hemoglobin molecules,thus resulting in the increase of the efficiency of oxygenmetabolism. However, on the other hand, it stimulatesthe intensity of microcapillary circulation, what cannotbe explained merely by the change of conditions ofmacromolecules, inasmuch as in microcapillaries the

cooperative interaction of erythrocytes and vessel wallsis significant (as is known, in nondeformable stateerythrocyte sizes are larger than the microcapillarydiameter) [1].

Furthermore, the surgical stress unavoidable inoperative interventions is the permanently emergingfactor in the medical practice, and during the postoper-ative period, it can cause damaging and transform intothe pathogenesis factor. Although recently, the assort-ment of pharmaceuticals and pharmacological methods

of general anesthesia, which allow the restriction of thesurgical stress development, has significantly broad-ened, the problem as itself is still far from the ultimatesolution. The main method allowing the limitation of

the alteration effect of surgical stress at periods beforethe operation, during the operation and narcosis, aswell as at the postoperative period is the directionalactivation of stress-limiting systems of the organism.Pharmacological measures are usually aimed at bio-chemical activation of one or several vital-activity reg-ulation systems; however, at the same time the undesir-able, side actions on other systems and functions oftenoccur. Therefore, the problem of the combined applica-tion of methods of pharmacological narcosis and theILEB to lower surgical stress in operative intervention[2] is topical.

In this work, we discuss the results of investigationsof the ILEB application in the operative interventioncombined with the pharmacological anesthesia.

2. SURGICAL STRESS

The surgical stress, unavoidable in operative inter-ventions, can have a damaging effect during the postop-erative period and transform into the pathogenesis fac-tor. The main method allowing the limitation of thealteration effect of surgical stress before the operation,during the operation and narcosis, and at the postoper-ative period is the directional activation of stress-limit-ing systems of the organism [2]. Pharmacological mea-sures are usually aimed at biochemical activation of

one or several vital-activity regulation systems, how-ever, at the same time, the undesirable side action onother systems and functions often appear.

The critically important fact is that patients of anelderly and senile age, mostly often undergoing opera-tive interventions, have the significantly suppressedresistance and compensatory-adaptive potential oforganism. They more often suffer from different con-comitant diseases (atherosclerosis, ischemia, pancre-atic diabetes, etc.), which burden both the main disease

LASER METHODS IN MEDICINEAND BIOLOGY

The Influence of Laser Blood Photomodificationon Dynamic Characteristics of Surgical Stress

I. E. Golub, A. N. Malov, A. V. Neupokoeva, L. V. Sorokina, and Yu. N. Vygovsky

Institute for Laser Physics, Siberian Branch of RAS, 4038, Irkutsk-33, 664033 RussiaIrkutsk State Medical University, ul. Krasnogo Vosstaniya 1, Irkutsk, 664003 Russia

Received May 8, 2002

Abstract

Investigation of laser photomodification of blood has shown the possibility to reduce the number ofmedicaments required for a certain level of patients anesthesia. The blood laser photomodification alleviatesthe postoperative stress reactions, what manifests as a significant decay of amplitudes of 11 biochemical bloodparameters during the entire postoperative period.


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THE INFLUENCE OF LASER BLOOD PHOTOMODIFICATION 107

course, and the tolerance to surgical stress unavoidablein operative interventions. These circumstances to asignificant degree influence the result of surgical treat-ment as well.

The response to stress, revealed by G. Selier anddesignated as the general adaptation syndrome, is thenecessary link in the adaptation of the organism todominant environment factors. Though a wide range of

pharmaceuticals and pharmacological methods, allow-ing somewhat of the restriction of the surgical stressdevelopment, is now available, yet no assurance of atotal lack of stress alteration effects and homeostasisderangements during and after the operative interven-tion exists.

As is known, the activity of stress-limiting systems,restricting the excessive effects of catecholamines, glu-cocorticoids and other agents capable of preventingdamaging stress effect, rises under stress concurrentlywith the activation of stress-realizing systems. It isascertained that two general methodsthe adaptationof organism to environment factors and the introduc-

tion of mediators and metabolites of stress-limiting sys-tems or their chemical analogscan increase thepower of these systems or modify their activity.

Clinical investigations [2] revealed that patients ofan elderly and senile age undergoing hepatobiliary-sys-tem operations suffer from the most evident surgicalstress. The dynamics of development of this stress hasthree main periods: preoperative, peroperative, andpostoperative. The nowadays methods of the anestheticprotection do not completely limit the development ofsurgical stress, what manifests in a multiple increase ofthe blood corticosteroid content during operative inter-ventions. General mechanisms, determining alterationeffects of surgical stress through all stages of its devel-opment, imply the increase of concentration of prod-ucts of glucose, aminotranspherase, histidase, etc., andthe disturbance of both hepatic blood flow and theimmune response. The revealed mechanisms of the sur-gical stress formation make it possible to optimize thealgorithm of the anesthetic protection including thedirectional increase of the activity and power of stress-limiting systems of the organism in operative interven-tions by using the complex of activators of stress-limitingsystems and the ILEB in schemes of the preoperativepreparation, narcosis and postoperative treatment [2].

As is known, surgical stress paves the way for func-tional disorders, which proceed in the postoperative

period as well. Apparently, the nociceptive impulsesincoming from the location of tissue damages in thecentral nervous system (CNS), the emotional tension,immobility, and painful medical procedures are deter-mining factors in the development of these disorders,thus resulting in the activation of stress-realizing sys-tems and the development of alteration effects of thestress.

The development of surgical stress determines thepathogenetic response of the organism to different

damaging effects. The surgical stress is the state ofpolyfunctional changes arising in patients organismunder the influence of aggressive factors, main ofwhich are the neurosis, therapeutic and diagnosticmanipulations, the wait for operation, preoperativefear, vegetative depression, pain, pathological non-algesic reflexes, posture effect of circulation, respira-tion, hemorrhage, and injuries of vital organs [3].

Under the pain stress, the shifts of interactionsbetween the pacemaker structures of the algesic moti-vation and the projective cortical area take place in theCNS, and only after that, the shifts between subcorticalstructures.

During the surgical stress, the synergism betweenactions of adrenocorticotropic hormones and the adre-nal medullary substance is observed; metabolic, ener-getic, and functional shifts, directed to the intensifica-tion of brain and heart blood supply, take place.

The stress stimulation of the sympathicoadrenalsystem results in the increase of brain and heart bloodsupply, owing to the enhancement of the amplitude and

frequency of heartbeats as well as to the spasm of arte-rioles of all organs and tissues under the action of cate-cholamines [4].

The spasm of arterioles caused by catecholaminesleads to the rise of the vascular resistance, disturbance ofmicrocirculation, and afterwards to the disorder of bloodflow properties, accompanied by the hypovolemia,ischemia of different organs and tissues, changes ofwater-electrolytic and acid-base states with the forma-tion of biologically aggressive metabolites. It also breaksthe reaction of bio-oxidation. These circumstances jus-tify the expediency of the ILEB application.

The inflammatory component of surgical stress is

now a prime consideration. As is supposed, this veryfactor provides the invariance of the stress state over along period. Repeatedly proven interdependences ofnervous, endocrine and immune systems of organismimply that under the homeostasis disturbance, causedby stress, these systems naturally engage into the action[5]. Under stress, adaptive resources of the organismbecome either sufficient for the adequate response orexhausted. This thesis can be equally well referred tothe immune system of the human organism.

The interdependency of the nervous, immune, andendocrine systems of the organism is caused not onlyby the commonality of a number of receptors and deter-minants of cells of these systems. As is known, the sec-

ondary immune response is the adaptation to the anti-gen. The organism responds to the repeated introduc-tion of antigen by the advanced immunoglobulinsynthesis. It is ascertained that the ILEB has the stabi-lizing influence on the immune system [6, 7].

The prevention of surgical stress can be appropriatein that very case if the emotional arousal and disturbedfunctions of the organism, alleviating the narcosis real-ization, are sufficiently corrected at the preoperativeperiod. During the operation, the anesthesia should


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limit the stress reaction by decreasing the nociceptiveafferent pulsation [8]. At the postoperative period, thecare should include the correction of functional disor-ders noneliminated during the operation, the reductionof the pain response, the emotional arousal, and thecontrol of the organism function under emergent condi-tions [9].

3. THE INTRAVENOUS LASER EXPOSUREOF BLOOD AS THE ANTISTRESS-ACTING

FACTOR

When the electromagnetic field of laser radiationinteracts with intrinsic electromagnetic fields of a cell,the cell field changes and its free charge is being redis-tributed. In this connection, the structural changes of bio-logic liquids and membranes may take place [10, 11].

A number of biophysical and clinical investigationsshows that the low-intensity laser radiation activatesduring blood exposure the important metabolic

enzymes and the protein biosynthesis [3]. It improvesthe oxygen transport function of erythrocytes, bloodflow properties [13, 14], the tissue regeneration [15],and microcirculation [1, 7], increases the activity of theimmune system [7, 15], and activates the reparativeprocesses [6], the challicreinquinine system [16], anti-oxidant enzymes [17]. Under the low-intensity laserexposure, new capillaries can be formed, thus improv-ing the oxygen delivery to tissues and optimizing thetissue metabolism [6, 7]. It is determined that the laserexposure normalizes the biochemical blood rates [18].

According to the results of [7], the elimination of theemotional preoperative stress is obviously concerned

with the laser action on mechanisms of secretion andregulation of neuromediators and hormones of corticaladrenal substance. As is also determined, the low-inten-sity laser irradiation of blood has sedative and antistresseffects [17].

Some authors consider that the laser radiation obvi-ates the CNS imbalance disturbing the sanogeneticbrain function. Depending on the initial state, the pho-tobioactivation of tissues causes either the intensifica-tion or the suppression of their metabolism and func-tions, thus resulting in the decay of pathologic pro-cesses, normalization of organism functions, and therecovery of regulating functions of brain [6, 7]. Thereare some data indicating the enhancement of the oxy-gen metabolism under the low-energy laser irradiation,which also leads to the normalization of redox pro-cesses [12]. The low-intensity laser irradiation causesthe photodynamical effect implying the change of thestructure and function of cell membranes, the cellularapparatus activation, and the rise of the activity ofDNARNA-protein systems. These processes deter-mine the activation of cell functions and the stimulationof regeneration and metabolism.

The data given above testify that the laser radiationhas the many-sided therapeutic effect, and the ILEBapplication in the operative intervention can be efficient.

4. CLINICAL INVESTIGATION TECHNIQUEAND EXPERIMENTAL RESULTS

The experimental investigations included the com-

parison of surgical-stress manifestations among threegroups of patients. We selected 67 chronic cholecystitispatients including 14 men and 53 women and dividedthem into three groups. First-group patients (21 patients)underwent the conventional preoperative preparation(CP). For the second group (25 patients) the conven-tional preparation was combined with the ILEB. Thelaser power at the fiber output was 1.52.0 mW and thetime of exposure was 4060-min. The third group(21 patients) underwent the complex activation ofstress-limiting systems (CASLM) including the CP, theintroduction of gamma-oxybutyric acid, dalargin, alphatocopherol, and the ILEB.

To induce general anesthesia, several variants ofnarcosis were used, namely, the standard neuroleptan-algesia (NLA), the NLA combined with the ILEB, andthe NLA combined with the use of metabolites, whichare the chemical analogs of stress-limiting systems, andthe ILEB.

When applying the standard NLA, the total dose offentanyl was 7.2

0.1

g/kg/h, and droperidol, 15.0

2.5

g/kg/h. For the NLA combined with the ILEB, thetotal fentanyl dose was 5.0

0.3

g/kg/h, and the totaldroperidol dose was 6.8

2.1

g/kg/h. The laser powerat the fiber output was 1.52.0 mW and the exposuretime was 4560 min. For the NLA combined with theintroduction of mediators and metabolites of stress-lim-

iting systems, and the ILEB, the total dose of fentanylwas 0.70.8

g/kg/h, droperidol, 2.8

g/kg/h, alphatocopherol, 45 mg/kg. For two latter cases, the laserradiation power at the fiber output was 1.52.0 mW andthe time of exposure was 4560-min.

After the operation, the complex intensive care,aimed at the correction of the emotional arousal, painsyndrome, inflammatory reactions, waterelectrolyticand acidbase states as well as at the maintenance offunctions of cardiovascular and respiratory systems,was carried out. The care included the conventionaltherapy, the conventional therapy combined with ILEB,and the conventional therapy with complex activationof stress-limiting systems of the organism by means ofintroduction of sodium oxybutyrate, dalargin, andalpha tocopherol and the ILEB.

According to the formulated purposes, the studiedrates were examined at different stages before, duringand after the operation:

(1) at the admission of a patient to hospital,

(2) after different variants of preoperative preparation,

(3) 20 min before the operation,

(4) at the traumatic stage of the operation,


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(5) after the operation and the narcosis termination,

(6) at first day after the operation, under the postop-erative therapy of different kinds,

(7) at third day after the operation, under the postop-erative therapy of different kinds,

(8) at the fifth to seventh day after the operation,under the postoperative therapy of different kinds,

(9) at the 1012th day after the operation, under thepostoperative therapy of different kinds.

The tested blood was centrifugalized. The bloodplasma was instantly congealed in polyethylene tubesand was stored in the frozen state until the examination.The probes for cortisol and alpha tocopherol werestored separately, what allowed us to avoid the repeatedunfreezing.

To estimate the antistress action of different variantsof general therapy before, during, and after the opera-tion, we used the clinical signs and biochemical factorsreflecting different sides of the metabolism, namely:

(1) cortisol,

(2) diene conjugates (DC),

(3) malonic dialdehyde (MDA),

(4) antioxygenic activity (AOA),

(5) alpha tocopherol,

(6) lactic acid (LA),

(7) pyruvic acid (PVA),

(8) glucose,

(9) alanine aminotransferase (ALT),

(10) aspartate aminotransferase (AST),

(11) histidase.

The data shown in Fig. 1 indicate the possibility tolower the dose of anesthetic by applying the ILEB.

According to the obtained data, the diagrams (Figs. 24)demonstrating the dynamics of the above-mentionedblood parameters during preoperative, operative andpostoperative periods are plotted. The above-men-tioned blood parameters denoted by correspondingnumbers are plotted on theX

-axis, stages of the therapy,on the Y

-axis, the content or activity of each parameter,expressed in percent of normal value, is plotted on the

Z

-axis. The control group, which characteristics wereassumed as the norma, includes 35 virtually healthypersons without any clinical and laboratory signs of

pathology in the past and at the examination moment.The first diagram represents the dynamics of bloodparameters in case of the conventional preoperativepreparation, standard NLA, and the conventional post-operative therapy. The second diagram shows thechange of blood parameters when applying the ILEB atall of three stages. The third diagram shows the dynamicsof those parameters when applying both the ILEB, andmediators and metabolites of stress-limiting systems.

Patients of all groups underwent the single-type,standard premedication according to the followingscheme: for the night before the operation they were

prescribed the 510-mg dose of one of tranquilizers,dimedrol or suprastin, and 20-mg pipolphen; an hourprior to the operation doses of antihistamines wererepeated; 40 min before the operation the 0.51.0-mgatropine sulfate and 20-mg promedol were subcutane-ously introduced. The 2.5% sodium hyopental or hexe-nal solution was used as the initial narcosis among allof the groups of patients. The intubation of trachea wasperformed against the background of a maximum effectof 100160-mg succinocholine.

40

0

60

0

20

60

80

100120

40

20

80

100

120

1 2 31 2 3

Fig. 1.

Dose of anesthetic agent for different methods ofanalgesia: (1) the standard NLA, (2) the NLA + ILEB,(3) the NLA + ILEB + CASLM. The left diagram showsproperidol dose; right diagram, fentanyl. The anestheticdose for the standard NLA is assumed to be 100%.

2800

2600

2400

2200

20001800

1600

1400

1200

1000

800

600

400

200

011

10

9 8 7 6 5 4 3 2 1 12

34 5

67

89

Z

-axis, percent of norma

Bloodparameters:

Time:1,

2,3,

preop

erativ

e;

PVA,LA,A

-tocopherol,AOA,MDA,DC,cortisol

histidase,AST,ALT,glucose,

4,pe

ropera

tive;5,

6,7,

8,9,

posto

perat

ive

Fig. 2.

The dynamics of blood parameters at different stagesof treatment under the conventional anesthesia scheme.


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All operations were accomplished by the mechani-cal ventilation of lungs, which was realized by means ofvolume respirators of RO-6 series over the half-closed

circuit or manually by the nitrous-oxideoxygen mix-ture with the 2:1 ratio in a moderate hyperventilationregime. The regime of ventilation and hemodynamicswas controlled by the pulsoxymetry and cardiomonitor-ing using the Optim-420 device and Elon-001rhythmocardiomonitor. The noted stages of investiga-tions provided the practically complete characteriza-tion of the dynamics of the formation and developmentof surgical stress.

The comparison of results of biochemical monitor-ing of patient conditions under the ILEB with theparameters of patients undergoing the conventionalanesthesia testifies the positive influence of the laser

blood photomodification. The degree of surgical stress(the amplitude of fluctuation of all of 11 blood param-eters) recedes, and the dose of pharmaceuticals neces-sary to achieve the required anesthetic profunditydecreases. Dynamical characteristics of surgical stressunder the ILEB given in Figs. 3, 4 entail the followingconclusions:

the laser blood photomodification, in contrast tothe drug intervention, positively influences the entirefamily of blood parameters;

the dynamics of postoperative fluctuations ofblood parameters is significantly improved, what indi-cates the faster return of patient to the homeostasis;

the ILEB is compatible with pharmacological andother procedures of the general anesthesia and does notcause the suppression of any vital systems.

Generalizing given data, we can note that in the caseof the conventional postoperative therapy the endoge-nous alpha tocopherol is not completely mobilized atthe postoperative period, and the stress activation ofPOL processes is not limited, thus resulting in the sup-pression of the antioxidant activity and the deficiencyof alpha tocopherol. The use of metabolites and analogs

of stress-limiting systems, and their complex activationcan substantially prevent and limit the stress activationof POL, raise the antioxidant activity and normalize thealpha tocopherol content.

From the physical point of view, the highly mono-chromatic laser radiation falling into the nonlinear opti-cal medium (blood) generates a broad spectrum ofRaman frequencies (coinciding with frequencies of dif-ferent elementary biochemical subsystems). In thiscase, the sharpest resonance occurs at the frequencycommon for all of the oscillatory subsystems. Appar-ently, one of the brain and CNS rates is such a commonfrequency. The availability of the intense and structur-ally rich Raman spectrum in every of biochemical sub-systems facilitates the structural reconstruction of all ofoscillatory systems by tuning their frequencies to themaster rate of the organism as a whole. The nonspecificaction of laser radiation upon stress-forming systemstakes them out of the stress-homeostasis state (whichis characterized by significant fluctuations of ampli-tudes of blood parameters), thus facilitating the regulat-ing function of stress-limiting systems. The fact that thecoherent radiation acts upon all of subsystems (andblood parameters) at once is readily apparent from thestated above. The electromagnetic field influences allreactions proceeding in the organism just on the level ofthe interaction of ions and/or macromolecule frag-

ments, which is the fundamental and inevitable part inthe biochemical synthesis of enzymes, hormones, pro-teins, etc, induced by any subsystem.

Thus, the antistress effect of the combined therapyis caused by the fact that the employed stress-limitingsubstances and the ILEB increase the activity of theantioxidant stress-limiting system both directly and bymeans of the mediated action through other stress-lim-iting systems.

200

400

600

Z


11 109 8

7 6 5 4 3 21 1

23 4

56

78

9

Time

:1,2

,3,preop

erativ

e;

4,pe

ropera

tive;5,

6,7,8,

9,

posto

perat

iveBloodparameters:

PVA,LA,A

-tocopherol,

AOA,MDA,DC,cortisol


Fig. 3.

The dynamics of blood parameters at different stagesof treatment under the anesthesia with the ILEB.

200

400

600

Z


11 109

8 7 65 4 3 2

1 12

34 5

67

89

Time

:1,2

,3,preope

rative

;

4,pe

ropera

tive;5,

6,7,8,9

,

posto

perat

iveBloodparameters:

PVA,LA,A

-tocopherol,

AOA,MDA,DC,cortisol


Fig. 4.

The dynamics of blood parameters at different stagesof treatment under the anesthesia with the ILEB and theCASLM.


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5. CONCLUSIONS

The results represented above can be summarized inthe following way.

The conventional preoperative preparation andpostoperative therapy as well as the conventional anes-thesia employing neuroleptanalgetsia agents are notefficient enough to prevent the development and thealteration effect of surgical stress.

The HeNe laser irradiation of blood facilitatesthe decrease of the cortisol concentration level throughall stages of the surgical stress development, inhibitsthe hyperlipoperoxidation, stimulates the antioxygenicactivity, increases the alpha tocopherol content, abatesenzymology and the level of keto acids, and normalizesthe adrenal blood flow and immunity rate.

ACKNOWLEDGMENTS

This work was supported by the Russian Foundationfor Basic Research, project no. 01-02-17141a.

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