The paper presents data from a study of the neuroendocrine regulation of nonstriated muscles, bronchial tree and the gallbladder tones by means of an assessment of the adrenergic and cholinergic systems state in patients, suffering from bronchial asthma and chronic acalculous cholecystitis. Adrenergic and cholinergic activities as well as cortisol secretion have significantly changed

Dudka, T.V.

Khukhlina, O.S.

Цифровий Репозиторій - Інтелектуальні Фонди Буковинського державного медичного університету

201Îðèã³íàëüí³ äîñë³äæåííÿUDC 616.248:616.366-002]–008. 851O. S. KhukhlinaT. V. Dudka O. S. Khukhlina, T.V. Dudka, 2013CHANGES IN CHOLINERGIC ANDADRENERGIC REGULATIONS OFBRONCHIAL AND BILIARY WAYS TONESIN A COMBINED COURSE OF BRONCHIALASTHMA AND CHRONIC CHOLECYSTITISAbstract. The paper presents data from a study of the neuroendocrineregulation of nonstriated muscles, bronchial tree and the gallbladdertones by means of an assessment of the adrenergic and cholinergicsystems state in patients, suffering from bronchial asthma and chronicacalculous cholecystitis. Adrenergic and cholinergic activities as wellas cortisol secretion have significantly changed.Bukovinian state medical university,ChernivtsiKey words: bronchial asthma, chronicacalculous cholecystitis, adrenergicand cholinergic regulation,acetylcholinesterase.IntroductionBronchial asthma (BA) is a global problem in theinternal medicine, leading among respiratory diseases;therefore it remains an actual problem for a scientificresearch both in Ukraine and around the world [1, 6,7]. Unfavorable epidemiologic situation, severe,uncontrolled course of BA are caused by lack oftimely detection of sick people when the signs are notsignificant, by such factors as allergens, xenobiotics,chronic nidi of viral and bacterial infection, parasiticinvasions, use of enzymatic domestic chemicals,uncontrolled use of a great variety of drugs, active andpassive cigarette smoking as well as stresses [6, 8].According to data of different authors, a combinedcourse of BA and diseases of digestive organs occursin 8-50% of cases, and gastrointestinal diseasesoccur combined with atopic BA twice as often aswith infection-dependant BA [3].Different authors describe the development ofgastric ulcer, gastric and duodenal erosions, chronicgastritis, duodenitis, reflux esophagitis and slidinghiatal hernia, duodenogastric reflux, changes in theliver, inflammation of the biliary tract and pancreas inthe patients with chronic inflammatory diseases of thelungs and bronchi [2, 4]. Chronic acalculous cholecystitis(CAC) combined with BA, according to some authors, isknown for the prevalence of aseptic inflammation in thegallbladder (GB), interrelation of exacerbations with BAexacerbation, more torpid, compared to BA, and atypicalcourse with less intensive pain syndrome, prevalence ofdyskinetic phenomena over the inflammatory ones withformation of hypokinetic dyskinesias of the GB [3, 4].With hypokinetic dyskinesias of the GB and a basistherapy of BA, amplification of CAC is predominant [5].Using basic therapy and â-adrenoceptor agonists as wellas cholinergic antagonists contribute to GB hypokineticdyskinesias intensification [4, 9].ObjectiveTo study the features of adrenergic and cholinergicregulations of bronchial tone and that of the gall-bladder in patients with combined course of chronicacalculous cholecystitis and bronchial asthma.Material and methods92 patients were involved in the study: 30 patientswith mild and moderate persisting BA (1st group), 30patients with mild and moderate persisting BA ofcomorbid CAC in the acute phase (2nd group), 32patients with CAC in the acute phase (3rd group) anda control group - 30 practically healthy individuals(PHI) of the respective age.Ventilation lung function was studied by means ofa computer Spirograph «Pneumoscope» company«Jaeger» (Germany), «Spirosift 3000» company«Fukuda Denshi» (Japan). The degree of disturbancein the respiratory function was evaluated through ananalysis of spirography findings and a curve «flow-volume» by comparing the findings obtained with theappropriate parameters for a given age, sex, heightand weight before and after pharmacological testswith salbutamol. The range of normative parameterswas considered 80-120% of appropriate. Ultrasono-graphic testing of the liver, the GB, and the pancreaswas carried out in 100% of patients by means of anultrasound scanner «Au-4 Idea» (Biomedica, Italy).The catecholamine depositing function of erythro-cytes (CDE) was studied according to the H.I.Mardar’s and D.P. Kladienko’s method. Thecholinergic system tone was assessed by the activityof acetylcholinesterase (AChE) in the blood serum.Results and discussionAll the patients with BA and BA combined withCAC had a marked predominance of the202Êë³í³÷íà òà åêñïåðèìåíòàëüíà ïàòîëîã³ÿ Òîì XII,  ¹3 (45), 2013parasympathetic nervous system, as evidenced by theestablished significant decrease of CDE (Table 1) inpatients with isolated asthma is 1.4 times (p <0.05), inpatients with asthma combined with CAC - there wasmore intense inhibition of enzyme activity – in 1.8times (p <0.05) and in patients with CAC of the 3rdgroup there were identical changes – a decreasedactivity of CDE in 1.6 times (p <0.05) with significantintergroup differences between the groups (p <0.05).These data suggest, that patients, suffering fromasthma combined with CAC, have a cholinergicimbalance due to, vagotonia, established on clinicalgrounds, and also due to AChE activity inhibition. Thisvegetative background promotes BA development,mucus hypersecretion by the bronchial glands, dyscriniaas was found in the patients under examination. It alsoleads to a lack of the GB contractility, development ofsphincter of Oddi hypertension dysfunction, and CAC.The distribution of patients according to the severity ofasthma and correlation analysis showed a directinterdependence between the severity of asthma (byFEV1 index-forced expiratory volume) of AChEactivity (r = 0.784, p <0.05).An analysis of the studies showed significantchanges in the CDE of the surveyed individuals. Forinstance, the CDA in the individuals of groups 1 and2 was lower by 1.6 and 2.4 times respectively (p<0.001) than in the group of PHI; in the patients ofthe 3rd group – the changes were minor – a declineof 14.6% (p<0.05) compared with practically healthyindividuals (Table 1). It should be noted, that theCDE in the first group was 64. 9% lower than in thesecond one. The patients of the first group had aparticular catecholamine (CA) depositing intensitydepending on the presence of the concomitant CAC.For instance, the patients with an isolated BA had asignificantly lower CA (by 1.5 times) per oneerythrocyte (ð<0.05). The patients, suffering fromBA combined with CAC, had by 3 times less CA perone erythrocyte (ð<0.05) than normal indices, andthat was by1.5 times less than in the first grouppatients (ð<0.05). The above mentioned changesoccur in the patients of the 3d group too. The numberof CA in an ordinary erythrocyte becomes a little less(for 13%) (ð<0.05). Participation of sympatho-adrenal system in the pathogenesis of asthma203Îðèã³íàëüí³ äîñë³äæåííÿoccurrence has been proved, however, in patientswith asthma and CAC, the ability to deposit CA,when combined with CAC has significantly dropped.The study of cortisol density in the blood serumof the patients under examination showed itssignificant drop in all groups observed (table 1). Forinstance, the first group patients’ blood contained 2.7times (ð<0,05) less cortisol than that of PHI; in thepatients of the second group the inhibition of thefunctional state of the adrenal cortex was even moreintense – cortisol was lower than its index in thecontrol group by 3.7 times (ð<0,05); the 3d grouppatients had the maximum drop in cortisol secretionby 1.7 times (ð<0,05) with reliable intergroupdifference (Table 1). Thus, one of the risk factors forBA development is a significant inhibition of cortisol-synthetic adrenocortical function. This is, probably,one of the pathogenic mechanisms of BA, and, inparticular, the progression of bronchial inflammationand formation of â-adrenergic mediators, insensible tothe influence of sympathoadrenal system, and offacilitating adrenergic imbalance. The results of thestudy of cortisol amount in patients, suffering fromBA combined with CAC depending on the BAseverity rate, prove this hypothesis.In particular, the patients with BA of ²² degree hadlower cortisol concentration in their blood than thoseof the PHI group by 2.3 times (ð<0,05), the sameindex in the patients with BA of ²²² degree was lowerby 2.8 times(ð<0,05), besides, in the patients withBA of ²² degree there was a reliably maximumdecrease of cortisol and of synthetic adrenocorticalfunction – by 3.7 times (p <0.05) with the presenceof reliable intergroup differences (p <0.05). Thecorrelation analysis indicates a significant directrelationship between the FEV1 index and cortisollevels in patients with BA combined with CAC (r =-0,725, p <0,05). Thus, the patients under the studyexperienced a significant inhibition of synthesis anddecrease in blood cortisol, which correlates with theseverity of asthma and is a risk factor for progressionof an inflammation in the GB. Table 2 shows amatrix of correlations between indices of CDE,AChE activity, cortisol levels and indices of lungfunction, morphological and functional properties oferythrocytes in patients with asthma and CAC.According to statistical data, there is a tight directcorrelation between FEV1indices and the cortisolamount in the blood, AChE and CDE activity, that is,adrenal insufficiency(cortisol deficiency in the blood),reduced AChE activity, intensifying vagotonia, as wellas an increasing resistance to CA (reduced CDE) allcontribute to BA and CDE development. CDE indicesare, to a considerable degree, interdependent with thecontractibility of the GB, of choleresis effort (CE)and lithogenic index (LI). A reciprocal proportionbetween AChE activity indices and a duration ofsphincter of Oddi spasm during the second phase ofcholeresis , as well as the direct interdependencebetween the AChE and LI activities which proves,that it is vagotonia which causes all above mentioneddisorders. A negative correlation between the indexof cortisol in the blood and sialic acid contentindicates a direct pathogenetic basis of inflammatorychanges in the GB and the bronchi.ConclusionThe base of regulatory neuroendocrine andparacrine mecganisms imbalance, contributing to adevelopment of bronchial asthma, is the cholinergicimbalance (reduction in blood acetylcholinesteraseactivity, hypertensive sphincter of Oddi dysfunction),adrenergic imbalance (reduction of reversibility ofbronchospasm with inhaled β-agonists underconditions of comorbidity (12-13% vs. 16-23% forisolated asthma)), reduction in catecholamine-depositing erythrocytes function, hypokineticgallbladder dysfunction, adrenal dysfunction(decreased cortisol levels) that contribute to thedevelopment and progression of chronic cholecystitisagainst a background of hypokinetic gallbladderdysfunction.References.  1. Åâðîïåéñêàÿ ñåòü ïî ãëîáàëüíîé àëëåð-ãèè è àñòìå (GA2LEN) èçó÷àåò «ýïèäåìèþ» àëëåðãèè è àñ-òìû / Ä. Áóñêå, Ï.Ä. 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Ñ.². Ãåîðã³ºâñüêîãî ÌÎÇ Óêðà¿íè.-Ñ³ìôåðîïîëü, 2008.- 36 ñ. 6. Castro-Rodriguez J.A. TheAsthma Predictive Index: early diagnosis of asthma /J.A. Castro-Rodriguez // Curr. Opin. Allergy Clin. Immunol.-2011.- Vol.11, ¹3.- Ð.157-161. 7. Fanta C.H. Asthma /C.H. Fanta // N. Engl. J. Med.- 2009.- Vol.360, ¹10.- Ð.1002-1014. 8. Lang D.M. New asthma guidelines emphasize control,regular monitoring / D.M. Lang // Cleveland Clinic J. Med.-2008.- Vol.75, ¹9.- Ð.641-653. 9. Wang X.Y. Cholinergic andnitrergic innervation of ICC-DMP and ICC-IM in the humansmall intestine / X.Y. Wang, C. Paterson, J.D. Huizinga //Neurogastroenterol. Motil.- 2003.- Vol.15, ¹5.- Ð.531-543.204Êë³í³÷íà òà åêñïåðèìåíòàëüíà ïàòîëîã³ÿ Òîì XII,  ¹3 (45), 2013ÈÇÌÅÍÅÍÈß ÕÎËÈÍÅÐÃÈ×ÍÎÉ,ÀÄÐÅÍÅÐÃÈ×ÅÑÊÎÉ ÐÅÃÓËßÖÈÈ ÒÎÍÓÑÀÁÐÎÍÕÎÂ È ÆÅË×ÅÂÛÂÎÄßÙÈÕ ÏÓÒÅÉ ÏÐÈÑÎ×ÅÒÀÍÍÎÌ ÒÅ×ÅÍÈÈ ÁÐÎÍÕÈÀËÜÍÎÉÀÑÒÌÛ È ÕÐÎÍÈ×ÅÑÊÎÃÎ ÕÎËÅÖÈÑÒÈÒÀÎ.Ñ. Õóõëèíà, Ò.Â. ÄóäêàÐåçþìå. Â ñòàòüå ïðåäñòàâëåíû äàííûå èññëåäîâàíèÿñîñòîÿíèÿ íåéðîýíäîêðèííîé ðåãóëÿöèè òîíóñà ãëàäêèõìûøö áðîíõèàëüíîãî äåðåâà è æåë÷íîãî ïóçûðÿ ïóòåì îöåí-êè ñîñòîÿíèÿ ôóíêöèîíèðîâàíèÿ àäðåíåðãè÷åñêîé è õîëè-íåðãè÷åñêîé ñèñòåì ó áîëüíûõ áðîíõèàëüíîé àñòìîé è õðî-íè÷åñêèì íåêàëüêóëåçíûì õîëåöèñòèòîì, êîòîðîå ïîêàçàëîñóùåñòâåííûå èçìåíåíèÿ àäðåíîðåàêòèâíîñòè è õîëèíîðå-àêòèâíîñòè, à òàêæå èçìåíåíèÿ ñåêðåöèè êîðòèçîëà.Êëþ÷åâûå ñëîâà: áðîíõèàëüíàÿ àñòìà, õðîíè÷åñêèéíåêàëüêóëåçíûé õîëåöèñòèò, àäðåíåðãè÷åñêàÿ è õîëèíåðãè-÷åñêàÿ ðåãóëÿöèÿ, àöåòèëõîëèíýñòåðàçà.Áóêîâèíñêèé ãîñóäàðñòâåííûé ìåäèöèíñêèéóíèâåðñèòåò, ã. ×åðíîâöûÇÌ²ÍÈ ÕÎË²ÍÅÐÃ²×ÍÎ¯, ÀÄÐÅÍÅÐÃ²×ÍÎ¯ÐÅÃÓËßÖ²¯ ÒÎÍÓÑÓ ÁÐÎÍÕ²Â ÒÀÆÎÂ×ÎÂÈÂ²ÄÍÈÕ ØËßÕ²Â ÇÀ ÏÎªÄÍÀÍÎÃÎÏÅÐÅÁ²ÃÓ ÁÐÎÍÕ²ÀËÜÍÎ¯ ÀÑÒÌÈ ÒÀÕÐÎÍ²×ÍÎÃÎ ÕÎËÅÖÈÑÒÈÒÓÎ.Ñ. Õóõë³íà, Ò.Â. ÄóäêàÐåçþìå. Ó ñòàòò³ âèêëàäåíî äàí³ äîñë³äæåííÿ ñòàíóíåéðî-åíäîêðèííî¿ ðåãóëÿö³¿ òîíóñó íåïîñìóãîâàíèõ ì’ÿç³âáðîíõ³àëüíîãî äåðåâà òà æîâ÷íîãî ì³õóðà øëÿõîì îö³íêèñòàíó ôóíêö³îíóâàííÿ àäðåíåðã³÷íî¿ òà õîë³íåðã³÷íî¿ ñèñòåìó õâîðèõ íà áðîíõ³àëüíó àñòìó òà õðîí³÷íèé íåêàìåíåâèéõîëåöèñòèò, ÿêå ïîêàçàëî ³ñòîòí³ çì³íè àäðåíîðåàêòèâíîñò³òà õîë³íîðåàêòèâíîñò³, à òàêîæ çì³íè ñåêðåö³¿ êîðòèçîëó.Êëþ÷îâ³ ñëîâà: áðîíõ³àëüíà àñòìà, õðîí³÷íèéíåêàìåíåâèé õîëåöèñòèò, àäðåíåðã³÷íà òà õîë³íåðã³÷íàðåãóëÿö³ÿ, àöåòèëõîë³íåñòåðàçà.Áóêîâèíñüêèé äåðæàâíèé ìåäè÷íèé óí³âåðñèòåò, ì.×åðí³âö³Clin. and experim. pathol.- 2013.- Vol.12, ¹3 (45).-P.201-204.Íàä³éøëà äî ðåäàêö³¿ 03.09.2013Ðåöåíçåíò – ïðîô. Î.².Ôåä³â O. S. Khukhlina, T.V. Dudka, 2013___________

Changes in cholinergic and adrenergic regulations of bronchial and biliary ways tones in a combined course of bronchial asthma and chronic cholecystitis

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Changes in cholinergic and adrenergic regulations of bronchial and biliary ways tones in a combined course of bronchial asthma and chronic cholecystitis

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Цифровий Репозиторій - Інтелектуальні Фонди Буковинського державного медичного університету