Ñ.Å. Ìàì÷óð, Þ.Þ. Âå÷åðñêèé, Ì.Á. Áàñêàêîâ, À.Ò. Òåïëÿêîâ, È.Â. Êîâàëåâ,

ÁÞËËÅÒÅÍÜ ÑÎ ÐÀÌÍ, ¹ 1 (111), 2004 ã.
ÓÄÊ 616.12-008
Ñ.Å. Ìàì÷óð, Þ.Þ. Âå÷åðñêèé, Ì.Á. Áàñêàêîâ, À.Ò. Òåïëÿêîâ, È.Â. Êîâàëåâ,
ß.Äæ. Àíôèíîãåíîâà, Þ.Ë. Áîðîäèí
ÈÇÓ×ÅÍÈÅ ÊÎÍÒÐÀÊÒÈËÜÍÛÕ ÑÂÎÉÑÒ ÂÍÓÒÐÅÍÍÅÉ ÃÐÓÄÍÎÉ
ÀÐÒÅÐÈÈ IN VITRO
ÃÓ ÍÈÈ êàðäèîëîãèè ÒÍÖ ÑÎ ÐÀÌÍ, Òîìñê
Ñèáèðñêèé ãîñóäàðñòâåííûé ìåäèöèíñêèé óíèâåðñèòåò ÌÇ ÐÔ
Öåëü èññëåäîâàíèÿ – èçó÷èòü áèîôèçè÷åñêèå ìåõàíèçìû êîíòðàêòèëüíûõ ñâîéñòâ âíóòðåííåé ãðóäíîé àðòåðèè è âëèÿíèå íà íèõ íèòðîãëèöåðèíà. Îáúåêòîì èññëåäîâàíèÿ ãëàäêîìûøå÷íûõ êëåòîê
ñëóæèëè èçîëèðîâàííûå ãëàäêîìûøå÷íûå ïîëîñêè âíóòðåííåé ãðóäíîé àðòåðèè (ÂÃÀ) 10 ïàöèåíòîâ, ïåðåíåñøèõ îïåðàöèþ ìàììàðîêîðîíàðíîãî øóíòèðîâàíèÿ. Èçó÷åíèå ìûøå÷íîãî íàïðÿæåíèÿ
ïðîâîäèëîñü ïðè ïîìîùè ìåõàíîãðàôèè íà ìåõàíîýëåêòðè÷åñêîì ïðåîáðàçîâàòåëå; èçó÷åíèå ìåìáðàííîãî ïîòåíöèàëà – ïðè ïîìîùè ìåòîäèêè äâîéíîãî ñàõàðîçíîãî ìîñòà. Ïîêàçàíî, ÷òî ìûøå÷íîå
íàïðÿæåíèå äèñòàëüíûõ ñåãìåíòîâ ÂÃÀ â 3,5 ðàçà âûøå, ÷åì â ïðîêèìàëüíûõ. Âûÿâëåí âûðàæåííûé
êîíòðàêòèëüíûé îòâåò ÂÃÀ ïðè âîçäåéñòâèè àäðåíàëèíà è íèôëóìîâîé êèñëîòû è åãî îòñóòñòâèå
ïðè âîçäåéñòâèè ìåçàòîíîì. Íèòðîãëèöåðèí îêàçûâàë âûðàæåííîå äîçîçàâèñèìîå ðåëàêñèðóþùåå
âëèÿíèå ïðè èñõîäíî ïîâûøåííîé êîíòðàê- òèëüíîñòè ãëàäêîìûøå÷íûõ êëåòîê äèñòàëüíîãî ñåãìåíòà ÂÃÀ, èíäóöèðîâàííîé õëîðèäîì êàëèÿ, è íå îêàçàë âëèÿíèÿ íà âåëè÷èíó ìåìáðàííîãî ïîòåíöèàëà ãëàäêîìûøå÷íûõ êëåòîê.
Êëþ÷åâûå ñëîâà: âíóòðåííÿÿ ãðóäíàÿ àðòåðèÿ
Àêòóàëüíîñòü ïðîáëåìû âîçíèêíîâåíèÿ ñïàçìà
àóòîàðòåðèàëüíûõ ãðàôòîâ âî âðåìÿ è ïîñëå îïåðàöèé êîðîíàðíîãî øóíòèðîâàíèÿ àññîöèèðóåòñÿ ñ óâåëè÷åíèåì çàáîëåâàåìîñòè è ñìåðòíîñòè [6, 17], ñâÿçàííûì ñ âîçíèêíîâåíèåì îñòðûõ èøåìè÷åñêèõ ýïèçîäîâ, â òîì ÷èñëå ïåðèîïåðàöèîííûõ èíôàðêòîâ ìèîêàðäà. Ïàòîãåíåç è ïðè÷èíû ñïàçìà àóòîàðòåðèàëüíûõ, â ÷àñòíîñòè, ìàììàðîêîðîíàðíûõ øóíòîâ
(ÌÊØ) äî êîíöà íå èçó÷åíû.  êà÷åñòâå âîçìîæíûõ
ïðè÷èí óêàçûâàþò èõ äåñèìïàòèçàöèþ, âîñïàëèòåëüíóþ ðåàêöèþ â îáëàñòè îïåðàòèâíîãî âìåøàòåëüñòâà
ñ âûäåëåíèåì áîëüøîãî êîëè÷åñòâà ñïàçìîãåííûõ
ìåäèàòîðîâ âîñïàëåíèÿ è ïð. Ýòà ñèòóàöèÿ óòÿæåëÿåòñÿ åùå áîëüøå, êîãäà èñïîëüçóþòñÿ òàêèå èíîòðîïíûå àãåíòû, êàê ñèìïàòîìèìåòè÷åñêèå àìèíû, ÿâëÿþùèåñÿ ìîùíûìè ñïàçìîãåííûìè âåùåñòâàìè, êîòîðûå, ñ îäíîé ñòîðîíû, åùå áîëüøå óâåëè÷èâàþò
ïîòðåáíîñòü ìèîêàðäà â êèñëîðîäå, à ñ äðóãîé – óìåíüøàþò åãî äîñòàâêó [14].
Ñðåäè ïàòîãåíåòè÷åñêèõ ìåõàíèçìîâ, ïðåäðàñïîëàãàþùèõ ê âîçíèêíîâåíèþ ñïàçìà âíóòðåííåé ãðóäíîé àðòåðèè (ÂÃÀ), îñíîâíóþ ðîëü ïðèïèñûâàþò íåñîîòâåòñòâèþ îáúåìà êðîâè, ïîñòóïàþùåé ïî îòíîñèòåëüíî óçêîìó ÌÊØ, ñâåðõìàêñèìàëüíîé ïîòðåáíîñòè ðåâàñêóëÿðèçèðîâàííîãî ìèîêàðäà, êîòîðûé â
áëèæàéøåì ïîñëåîïåðàöèîííîì ïåðèîäå íàõîäèòñÿ
â ñîñòîÿíèè ôóíêöèîíàëüíîé íàãðóçêè [13, 21].
 íàñòîÿùåå âðåìÿ íàêîïëåí áîëüøîé îïûò èçó÷åíèÿ êîíòðàêòèëüíûõ ñâîéñòâ äðóãèõ àóòîàðòåðèàëüíûõ êîðîíàðíûõ òðàíñïëàíòàòîâ íà ôîíå âîçäåéñòâèÿ ðàçëè÷íûìè êîíòðàêòèëüíûìè àãåíòàìè: íîðàäðåíàëèíîì [2–5, 7, 10, 14, 20–23], ôåíèëýôðèíîì [4,
7, 18], òðîìáîêñàíàìè [2, 5, 25] èëè èõ àíàëîãîì
U46619 [7, 11, 15, 16, 18, 20, 22, 24, 25], ýíäîòåëè-
íîì-1 [3, 7, 10–12, 18, 22, 23, 25, ], êàëèåì [2, 4, 5, 7,
15, 22], íåêîíêóðåíòíûì àãîíèñòîì EDRF-ðåöåïòîðîâ – êàëüöèåâûì èîíîôîðîì A23187 [12, 18], ïðîñòàãëàíäèíîì F2α [11], ñóìàòðèïòàíîì [13], àíãèîòåíçèíîì-2 [3, 12] è ïð. Ñ ó÷åòîì ðàçëè÷íûõ àñïåêòîâ
ïàòîãåíåçà ñïàçìà ÂÃÀ äëÿ åãî ïðîôèëàêòèêè èëè ëå÷åíèÿ ïðåäëàãàëèñü ðàçëè÷íûå ïðåïàðàòû. Äàííûå
ýòèõ íåìíîãî÷èñëåííûõ èññëåäîâàíèé íåîäíîçíà÷íû, à ïîðîé è ïðîòèâîðå÷èâû.  êà÷åñòâå ïåðñïåêòèâíûõ ïðåïàðàòîâ äëÿ ïðîôèëàêòèêè ñïàçìà ÂÃÀ íà
ïåðâîì ìåñòå ñòîÿò íèòðàòû [8, 9, 19]. Â òî æå âðåìÿ
C. Huraux è äð. [24] óêàçûâàþò íà òî, ÷òî ìíîãèå áîëüíûå ÈÁÑ, ïîäâåðãøèåñÿ êîðîíàðíîìó øóíòèðîâàíèþ, èìåþò òîëåðàíòíîñòü ê íèòðàòàì. Ïîýòîìó íèòðàòû â êà÷åñòâå âàçîäèëàòàòîðîâ äëÿ ÂÃÀ ìîãóò íå
îêàçûâàòü ýôôåêòà âî âðåìÿ îïåðàöèè è â ïîñëåîïåðàöèîííîì ïåðèîäå.
Öåëüþ èññëåäîâàíèÿ ÿâèëîñü èçó÷åíèå ñîêðàòèòåëüíûõ ñâîéñòâ èçîëèðîâàííûõ ñåãìåíòîâ âíóòðåííåé
ãðóäíîé àðòåðèè è âëèÿíèÿ íà íèõ íèòðîãëèöåðèíà
(ÍÃ) in vitro.
Ìåòîäèêà. Îáúåêòîì èññëåäîâàíèÿ ñëóæèëè èçîëèðîâàííûå ãëàäêîìûøå÷íûå ïîëîñêè ÂÃÀ 10 ïàöèåíòîâ, ïåðåíåñøèõ îïåðàöèþ ìàììàðîêîðîíàðíîãî øóíòèðîâàíèÿ, ïðèãîòîâëåííûå â ðàñòâîðå Êðåáñà
ïðè òåìïåðàòóðå 20–25°Ñ. Äåýíäîòåëèçèðîâàííàÿ àðòåðèÿ ðàçðåçàëàñü ïî îêðóæíîñòè ïîä óãëîì 25° ïî
îòíîøåíèþ ê ïîïåðå÷íîé îñè ñîñóäà.  ðåçóëüòàòå
ïîëó÷àëàñü ñîñóäèñòàÿ ëåíòà, èç êîòîðîé âûðåçàëèñü
ïîëîñêè øèðèíîé 0,5 ìì è äëèíîé 14–16 ìì. Íà èõ
êîíöàõ çàâÿçûâàëèñü òîíêèå øåëêîâûå íèòè äëÿ
óêðåïëåíèÿ ïîëó÷åííîãî ïðåïàðàòà â ýêñïåðèìåíòàëüíîé óñòàíîâêå.
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Âñå èññëåäîâàíèÿ áûëè âûïîëíåíû íà îñíîâå ðàñòâîðà Êðåáñà, ñîäåðæàùåãî (â ìêÌ) 120,4 NaCl; 5,9
ÊÑl; 2,5 ÑàÑl2; 1,2 MgCl2; 5,5 ãëþêîçû è 15 C4H11O3N
[òðèñ(îêñèìåòèë)-àìèíîìåòàí], ïðè pH 7,4 è òåìïåðàòóðå 37°C. Ãëàäêîìûøå÷íûå ñåãìåíòû ïîìåùàëè â
1 ìë ðåçåðâóàð ñ ïðîòî÷íûì ôèçèîëîãè÷åñêèì ðàñòâîðîì è çàêðåïëÿëè ìåæäó ñòàëüíûìè êðþ÷êàìè.
Ïîñëå ïðåäâàðèòåëüíîãî ðàñòÿæåíèÿ íàãðóçêîé
500–1000 ìã ñåãìåíò ôèêñèðîâàëè íà øòîêå ìåõàíîýëåêòðè÷åñêîãî ïðåîáðàçîâàòåëÿ. Ñ öåëüþ àäàïòàöèè
ñåãìåíòîâ ê óñëîâèÿì ðåãèñòðàöèè ìûøå÷íîãî íàïðÿæåíèÿ (ÌÍ) èõ ïîñòîÿííî ïåðôóçèðîâàëè ïðîòî÷íûì òåðìîñòàòèðóåìûì (36,8–37°Ñ) ðàñòâîðîì Êðåáñà ñî ñêîðîñòüþ 1 ìë/ìèí, ïîñëå ÷åãî, ïî êðàéíåé
ìåðå äâàæäû, âûçûâàëè òåñòèðóþùåå ñîêðàùåíèå
ãèïåðêàëèåâûì ðàñòâîðîì (30 ìM KCl). Çàòåì ïðåïàðàòû îòìûâàëè â ðàñòâîðå Êðåáñà äî âîçâðàùåíèÿ
ÌÍ ê èñõîäíîìó è ïðîèçâîäèëè àïïëèêàöèþ òåñòèðóåìûõ àãåíòîâ.
Àìïëèòóäà ñîêðàòèòåëüíûõ îòâåòîâ ãëàäêîìûøå÷íûõ ñåãìåíòîâ ðàññ÷èòûâàëàñü â ìÍ ëèáî â ïðîöåíòàõ îò àìïëèòóäû êîíòðîëüíîãî ñîêðàùåíèÿ, ÷òî
îïðåäåëÿëîñü öåëÿìè ýêñïåðèìåíòîâ.
Äëÿ îäíîâðåìåííîé ðåãèñòðàöèè ýëåêòðè÷åñêèõ è
ñîêðàòèòåëüíûõ ïàðàìåòðîâ èçîëèðîâàííûõ ïîëîñîê
ãëàäêîìûøå÷íûõ êëåòîê (ÃÌÊ) èñïîëüçîâàëàñü ìåòîäèêà äâîéíîãî ñàõàðîçíîãî ìîñòà [1]. Íà îñíîâå
ðàñòâîðà Êðåáñà ïðèãîòàâëèâàëèñü ãèïåðêàëèåâûå
ðàñòâîðû ñ êîíöåíòðàöèåé ÊÑl 40 ìÌ, à òàêæå òåñòèðóþùèå ðàñòâîðû ñ äîáàâëåíèåì Íà (“Ïåðëèíãàíèò”,
Schwarz Pharma, Ãåðìàíèÿ).
Ðåçóëüòàòû.  ðåçóëüòàòå èçó÷åíèÿ êîíòðàê- òèëüíûõ ñâîéñòâ ñåãìåíòîâ ÂÃÀ è ëó÷åâîé àðòåðèè
(ËÀ) in vitro áûëè ïîñòðîåíû êðèâûå ÌÍ, êîòîðûå
õàðàêòåðèçîâàëèñü íà÷àëîì êîíòðàêòèëüíîãî îòâåòà
ñïóñòÿ 2–3 ìèí ïîñëå àïïëèêàöèè âàçîêîíñòðèêòîðà
è äîñòèæåíèåì íà ïëàòî ìàêñèìàëüíîãî ÌÍ (20–30
ìèí), ñìåíÿâøåãîñÿ áûñòðîé ðåëàêñàöèåé ïðè îòìûâàíèè ïðåïàðàòà â ðàñòâîðå Êðåáñà èëè ïðè âîçäåéñòâèè íèòðîãëèöåðèíîì (ðèñ. 1 (À)).
Íà ðèñ. 2 ïðåäñòàâëåíû âåëè÷èíû ÌÍ (ìÍ) ñåãìåíòîâ àóòîàðòåðèé ïðè âîçäåéñòâèè íà íèõ ðàñòâîðàìè ðàçëè÷íûõ êîíòðàêòèëüíûõ àãåíòîâ.
Ìàêñèìàëüíîãî ÌÍ ñåãìåíòîâ ÂÃÀ è ËÀ óäàëîñü
äîñòè÷ü ïðè èõ ýêñïîçèöèè â ðàñòâîðå õëîðèäà êàëèÿ.
Ïðè ýòîì îòìå÷àëàñü ïàðàäîêñàëüíàÿ êîíòðàêòèëüíàÿ ðåàêöèÿ ïðåïàðàòîâ ÂÃÀ è ËÀ íà âîçäåéñòâèå íèôëóìîâîé êèñëîòû, ïðèáëèæàþùàÿñÿ ïî âåëè÷èíå ê
òàêîâîé ïðè èñïîëüçîâàíèè àäðåíàëèíà. Ïðè ïîñëåäîâàòåëüíîì âîçäåéñòâèè õëîðèäà êàëèÿ è íèôëóìîâîé êèñëîòû áûëî âûÿâëåíî, ÷òî ìàêñèìàëüíîå êàëèéèíäóöèðîâàííîå ÌÍ åùå áîëåå óñèëèâàåòñÿ ïðè
äîïîëíèòåëüíîì âîçäåéñòâèè íèôëóìîâîé êèñëîòîé
(ðèñ. 1 (Á)). Ïðè ýòîì äîïîëíèòåëüíîå ñîêðàùåíèå âî
âñåõ ñåðèÿõ ýêñïåðèìåíòîâ ñîîòâåòñòâîâàëî ïî âåëè÷èíå ñîêðàùåíèþ ïðè èçîëèðîâàííîì âîçäåéñòâèè
íèôëóìîâîé êèñëîòîé. Ïðè îäíîâðåìåííîì âîçäåéñòâèè îáîèõ âåùåñòâ ÌÍ òàêæå ñîîòâåòñòâîâàëî òàêîâîìó ïðè èõ ïîñëåäîâàòåëüíîì ïðèìåíåíèè (ðèñ. 1
(Â)). Ýòî ïîçâîëÿåò çàêëþ÷èòü, ÷òî ìåõàíèçìû êàëèé-
èíäóöèðîâàííîãî ñîêðàùåíèÿ è ñîêðàùåíèÿ, èíäóöèðîâàííîãî íèôëóìîâîé êèñëîòîé, ðàçíîðîäíû, íå
ñâÿçàíû äðóã ñ äðóãîì è ïðîÿâëÿþò àääèòèâíûé ýôôåêò ïðè ñîâìåñòíîì âîçäåéñòâèè.
Ìåçàòîí íå îêàçûâàë ñòàòèñòè÷åñêè çíà÷èìîãî
âëèÿíèÿ íà ÌÍ ñåãìåíòîâ ÂÃÀ äàæå â âûñîêèõ êîíöåíòðàöèÿõ. Àäðåíàëèí, íàïðîòèâ, âûçûâàë âûðàæåííûé ñîêðàòèòåëüíûé îòâåò èçîëèðîâàííûõ ñåãìåíòîâ ÂÃÀ, êîòîðûé ñðåäè äðóãèõ ïðåïàðàòîâ ìàêñèìàëüíî ïðèáëèæàëñÿ ê òàêîâîìó ïðè âîçäåéñòâèè
õëîðèäîì êàëèÿ. Ýòîò ôàêò êîñâåííûì îáðàçîì ñâèäåòåëüñòâóåò íå â ïîëüçó àäðåíàëèíà, øèðîêî ïðèìåíÿåìîãî â êà÷åñòâå ïîëîæè- òåëüíîãî èíîòðîïíîãî
àãåíòà â ïîñëåîïåðàöèîííîì ïåðèîäå.
Ðèñ. 1. Êðèâûå ÌÍ (ìåõàíîãðàììû) ñåãìåíòîâ ÂÃÀ ïðè
âîçäåéñòâèè êîíòðàêòèëüíûìè àãåíòàìè.
À – òèïè÷íàÿ êðèâàÿ ïðè âîçäåéñòâèè õëîðèäîì êàëèÿ; Á – àääèòèâíûé ýôôåêò ïðè ïîñëåäîâàòåëüíîì âîçäåéñòâèè õëîðèäîì
êàëèÿ è íèôëóìîâîé êèñëîòîé; Â – àääèòèâíûé ýôôåêò ïðè îäíîâðåìåííîì âîçäåéñòâèè õëîðèäîì êàëèÿ è íèôëóìîâîé êèñëîòîé
Ðèñ. 2. Âåëè÷èíû ÌÍ ñåãìåíòîâ ÂÃÀ è ËÀ ïðè âîçäåéñòâèè íà íèõ ðàñòâîðàìè ðàçëè÷íûõ êîíòðàêòèëüíûõ àãåíòîâ.
* – ð<0,05; îñòàëüíûå ðàçëè÷èÿ ñòàòèñòè÷åñêè íåçíà÷èìû
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ÁÞËËÅÒÅÍÜ ÑÎ ÐÀÌÍ, ¹ 1 (111), 2004 ã.
Îáíàðóæåíà çàâèñèìîñòü âåëè÷èíû èíäóöèðîâàííîãî õëîðèäîì êàëèÿ è ìåçàòîíîì ìàêñèìàëüíîãî
ÌÍ è ñêîðîñòè åãî äîñòèæåíèÿ îò ñåãìåíòà ÂÃÀ, èñïîëüçîâàííîãî äëÿ ïðèãîòîâëåíèÿ ïðåïàðàòà (ðèñ. 3).
Ïðè ýòîì ñòàòèñòè÷åñêîé çíà÷èìîñòè äîñòèãëè òîëüêî îòëè÷èÿ âåëè÷èí (â 3,5 ðàçà) èíäóöèðîâàííîãî
õëîðèäîì êàëèÿ ìàêñèìàëüíîãî ÌÍ â èññëåäîâàííûõ
ãðóïïàõ. Òàêæå îáíàðóæåíû ñòàòèñòè÷åñêè íåçíà÷èìûå îòëè÷èÿ â êîíòðàê- òèëüíîì îòâåòå ñåãìåíòîâ
ÂÃÀ, èññëåäîâàííûõ íà ïåðâûå è âòîðûå ñóòêè ïîñëå
îïåðàöèè (ðèñ. 4).
Íà ðèñ. 5 ïðåäñòàâëåíû äàííûå èçó÷åíèÿ ìåìáðàííîãî ïîòåíöèàëà (ÌÏ) è ìûøå÷íîãî íàïðÿæåíèÿ
íà ôîíå âîçäåéñòâèÿ ÍÃ ïîñëå êàëèéèíäóöèðîâàííîãî ñïàçìà ïðè ïîìîùè ìåòîäèêè äâîéíîãî ñàõàðîçíîãî ìîñòà. Ïîêàçàíà ïðÿìàÿ çàâèñèìîñòü âàçîäèëàòèðóþùåãî ýôôåêò íèòðîãëèöåðèíà îò åãî äîçû. Â êîíöåíòðàöèÿõ 10–8–10–7 Ì îí ñíèæàåò èíäóöèðîâàííîå
êàëèåì ÌÍ, íî íå äî èñõîäíûõ âåëè÷èí. Ïðè óâåëè÷åíèè êîíöåíòðàöèè äî 5·10–7 Ì ïðîèñõîäèò âûðàæåííîå ñíèæåíèå ÌÍ ñåãìåíòîâ ÂÃÀ äî âåëè÷èí
íèæå èñõîäíûõ. Ïîëíàÿ ðåëàêñàöèÿ ÂÃÀ ïðîèñõîäèò
ïðè êîíöåíòðàöèè íèòðîãëèöåðèíà 5·10–6 Ì.
Âàæíî îòìåòèòü, ÷òî íà ôîíå èñõîäíîãî ÌÍ ðåçåðâ êîíòðàêòèëüíîñòè, èíäóöèðîâàííîé êàëèåì,
îêàçàëñÿ ñóùåñòâåííî áîëåå íèçêèì, ÷åì ðåçåðâ ðåëàêñàöèè, èíäóöèðîâàííîé íèòðîãëèöåðèíîì, èç
÷åãî ñëåäóåò, ÷òî â ïåðâûå ñóòêè ïîñëå îïåðàöèè ÂÃÀ
èìååò âûðàæåííîå èñõîäíîå ÌÍ, áëèçêîå ïî ñâîèì
âåëè÷èíàì ê ìàêñèìàëüíîìó è ñîñòàâëÿþùåå ïî ìåíüøåé ìåðå 5/7 îò òàêîâîãî. Äðóãèì çàñëóæèâàþùèì
âíèìàíèÿ ôåíîìåíîì ÿâëÿåòñÿ òî, ÷òî íà ôîíå ìàêñèìàëüíîé ðåëàêñàöèè, èíäóöèðîâàííîé íèòðîãëèöåðèíîì, äàæå ïîñëå îòìûâàíèÿ ïðåïàðàòà â ðàñòâîðå
Êðåáñà íå ïðîèñõîäèò âîññòàíîâëåíèÿ åå ÌÍ äî èñõîäíûõ çíà÷åíèé. Ïðèìåíåíèå íèòðîãëèöåðèíà íå
îêàçàëî ñòàòèñòè÷åñêè çíà÷èìîãî âëèÿíèÿ íà ìåìáðàííûé ïîòåíöèàë ÃÌÊ.
Âûâîäû. Âåëè÷èíà èíäóöèðîâàííîãî õëîðèäîì
êàëèÿ è ìåçàòîíîì ìàêñèìàëüíîãî ÌÍ â äèñòàëüíûõ
ñåãìåíòàõ ÂÃÀ ñòàòèñòè÷åñêè çíà÷èìî îêàçàëàñü â
3,5 ðàçà âûøå, ÷åì â ïðîêèìàëüíûõ.
Íå âûÿâëåíî ñòàòèñòè÷åñêè çíà÷èìîãî ýôôåêòà
ìåçàòîíà íà ñòåïåíü ÌÍ èçîëèðîâàííûõ ñåãìåíòîâ
ÂÃÀ. Àäðåíàëèí è íèôëóìîâàÿ êèñëîòà, íàïðîòèâ,
âûçûâàþò âûðàæåííûé êîíòðàêòèëüíûé îòâåò ÂÃÀ è
ËÀ. Ïðè ýòîì ìåõàíèçìû êàëèéèíäóöèðîâàííîãî ñîêðàùåíèÿ è ñîêðàùåíèÿ, èíäóöèðîâàííîãî íèôëóìîâîé êèñëîòîé, ðàçíîðîäíû, íå ñâÿçàíû äðóã ñ äðóãîì
è ïðîÿâëÿþò àääèòèâíûé ýôôåêò ïðè ñîâìåñòíîì
âîçäåéñòâèè.
Íèòðîãëèöåðèí îêàçûâàåò âûðàæåííîå ðåëàêñèðóþùåå âëèÿíèå ïðè èñõîäíî ïîâûøåííîé êîíòðàêòèëüíîñòè ãëàäêîìûøå÷íûõ êëåòîê äèñòàëüíîãî ñåãìåíòà ÂÃÀ, èíäóöèðîâàííîé ýêñïîçèöèåé â õëîðèäå
êàëèÿ. Ìàêñèìàëüíîé ðåëàêñàöèè óäàëîñü äîáèòüñÿ
ïðè êîíöåíòðàöèè íèòðîãëèöåðèíà 5·10–6 Ì, ïîñëå
÷åãî äàëüíåéøåå ïîâûøåíèå êîíöåíòðàöèè íå óâåëè÷èâàëî ñòåïåíè ðåëàêñàöèè ÂÃÀ. Ïðè ýòîì ñíèæåíèå
Ðèñ. 3. Çàâèñèìîñòü ìàêñèìàëüíîãî ÌÍ, èíäóöèðîâàííîãî õëîðèäîì êàëèÿ è ìåçàòîíîì, è ñêîðîñòè åãî äîñòèæåíèÿ îò ñåãìåíòà ÂÃÀ, èñïîëüçîâàííîãî äëÿ ïðèãîòîâëåíèÿ
ïðåïàðàòà.
* – ð<0,05
Ðèñ. 4. Çàâèñèìîñòü ìàêñèìàëüíîãî ÌÍ, èíäóöèðîâàííîãî õëîðèäîì êàëèÿ è ìåçàòîíîì, è ñêîðîñòè åãî äîñòèæåíèÿ îò ïðîäîëæèòåëüíîñòè âðåìåíè, ïðîøåäøåãî ñ ìîìåíòà îïåðàöèè
ÌÍ, èíäóöèðîâàííîå 5·10–6 Ì ðàñòâîðîì íèòðîãëèöåðèíà, ïðåâûøàëî ñòåïåíü áàçàëüíîãî òîíóñà ÂÃÀ.
Ïðèìåíåíèå íèòðîãëèöåðèíà íå îêàçûâàëî ñòàòèñòè÷åñêè çíà÷èìîãî âëèÿíèÿ íà ìåìáðàííûé ïîòåíöèàë ÃÌÊ.
IN VITRO STUDY OF CONTRACTILE CHARACTERISTICS OF INTERNAL THORACIC ARTERY
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6. Cooper G.J., Locke T.J. Distension reduces the vasoreactivity of the internal mammary artery // European Journal of
Cardio-Thoracic Surgery. 1996. Vol. 10 (1). P. 26–31.
7. Direct vasodilator effect of milrinone, an inotropic drug, on
arterial coronary bypass grafts / Liu J.J., Doolan L.A., Xie
B. et al. // Journal of Thoracic and Cardiovascular Surgery.
1997. Vol. 113 (1). P. 108–113.
8. Effect of systemic vasodilators on internal mammary artery
flow. Implications for postoperative treatment after myocardial revascularization / Izzat M.B., West R.R., Ragoonanan C., Angelini G.D. // Journal of Thoracic and Cardiovascular Surgery. 1994. Vol. 108 (1). P. 82–85.
9. Effect of topical vasodilators on internal mammary arteries /
Sasson L., Cohen A.J., Hauptman E. Schachner A. // Annals
of Thoracic Surgery. 1995. Vol. 59 (2). P. 494–496.
10. Greater contractility of internal mammary artery bifurcation: possible cause of low patency rates / He G.W., Ryan
W.H., Acuff T.E. et al. // Annals of Thoracic Surgery. 1994.
Vol. 58 (2). P. 529–532.
11. He G.W., Yang C.Q., Starr A. Overview of the nature of vasoconstriction in arterial grafts for coronary operations //
Annals of Thoracic Surgery. 1995. Vol. 59 (3). P. 676–683.
12. He G.W., Yang C.Q. Radial artery has higher receptor-mediated contractility but similar endothelial function compared
with mammary artery // Annals of Thoracic Surgery. 1997.
Vol. 63(5). P. 1346–1352.
13. Hypertension increases the contractions to sumatriptan in
the human internal mammary artery / Yildiz O., Cicek S.,
Ay I. et al. // Annals of Thoracic Surgery. 1996. Vol. 62 (5).
P. 1392–1396.
14. Inhibitory effects of calcium antagonists on alpha-adrenoceptor-mediated contraction in the human internal mammary artery / He G.W., Acuff T.E., Ryan W.H. et al. // British
Journal of Clinical Pharmacology. 1994. Vol. 37 (2). P.
173–179.
15. Liu J.J., Johnston C.I., Buxton B.F. Synergistic effect of nisoldipine and nitroglycerin on human internal mammary artery // Journal of Pharmacology and Experimental Therapy.
1994. Vol. 268 (1). P. 434–440.
16. Nitroglycerin is superior to diltiazem as a coronary bypass
conduit vasodilator / Shapira O.M., Xu A., Vita J.A. et al. //
Journal of Thoracic and Cardiovascular Surgery. 1999. Vol.
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17. Palerme L.P., De Varennes B., Steinmetz O.K. Intraoperative duplex study of internal thoracic artery spasm during coronary bypass // Journal of Cardiac Surgery. 1997. Vol. 12
(6). P. 403–405.
18. Papaverive abolishes endothelium-dependent dilatation of
human internal mammary arteries in vitro / Schyvens C.G.,
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P. 223–228.
19. Pharmacologic dilatation of the internal mammary artery
during coronary bypass grafting / He G.W., Buxton B.F.,
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20. Salmenpera M., Levy J.H. The in vitro effects of phosphodiesterase inhibitors on the human internal mammary artery //
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21. Spence P.A., Montgomery W.D., Santamore W.P. High flow
demand on small arterial coronary bypass conduits promotes graft spasm // Journal of Thoracic and Cardiovascular
Surgery. 1995. Vol. 110 (4/1). P. 952–962.
22. The comparison of the responsiveness of human isolated internal mammary and gastroepiploic arteries to levcromakalim: an alternative approach to the management of graft
Ðèñ. 5. Ýëåêòðîìåõàíè÷åñêîå ñîïðÿæåíèå ñåãìåíòîâ
ÂÃÀ íà ôîíå âîçäåéñòâèÿ ðàñòâîðàìè íèòðîãëèöåðèíà (ÍÃ)
â âîçðàñòàþùèõ êîíöåíòðàöèÿõ ïîñëå êàëèéèíäóöèðîâàííîãî ñïàçìà.
Âñå ðàçëè÷èÿ ÌÍ ñòàòèñòè÷åñêè çíà÷èìû ïðè p<0,05;
âñå ðàçëè÷èÿ ÌÏ ñòàòèñòè÷åñêè íåçíà÷èìû
S.E. Mamchur, Yu.Yu. Vecherscki, M.B. Baskakov,
A.T. Teplyakov, I.V. Kovalyov, Ya.J. Anfinogenova,
Yu.L. Borodin
The aim of the study is to carry out the research of biophysical mechanisms and influence of nitroglycerine on internal thoracic artery (ITA) contractility. The object of the study was the
isolated segments of ITA taken from 10 patients underwent coronary artery bypass grafting. The investigation of muscular intention prosecuted by mechanography with mechanic-electrical
transducer use. Membrane potential was studied with a double-sacñharose bridge method. 3,5 times increasing of muscle intension of distal segments of ITA in comparison with proximal
ones was demonstrated. Adrenaline and niflumic acid made a
pronounced contractile effect unlike mesatone. Nitroglycerine
produced a dose-depended relaxation in a base kalium-induced
increased contractility of smooth muscle cells of an ITA’s distal
segment, but has no influence on membrane potential of a smooth muscle cells.
ËÈÒÅÐÀÒÓÐÀ
1. Óðàçàåâ À.Ì. Àêòèâíûå è ïàññèâíûå ýëåêòðè÷åñêèå
ñâîéñòâà áèîëîãè÷åñêèõ îáúåêòîâ: Ìåòîä. ðåêîìåíä. /
À.Ì. Óðàçàåâ, È.Â. Êîâàëåâ, È.Â. Ïåòðîâà. Òîìñê, 1987.
49 ñ.
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P. 1654–1659.
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4. Comparative reactivity and mechanical properties of human
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Research. 1998. Vol. 37 (3). P. 811–819.
5. Comparative vasoreactivity of the radial, internal mammary
and gastroepiploic arteries. Implications in coronary surgery / Chardigny C., Jebara V., Acar C. et al. // Chirurgie.
1994. Vol. 120 (9). P. 494–502.
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spasm / Akar F., Uydes–Dogan B.S., Tufan H. et al. // British Journal of Clinical Pharmacology. 1997. Vol. 44 (1). P.
49–56.
23. The comparison of vascular reactivities of arterial and venous grafts to vasodilators: management of graft spasm /
Uydes-Dogan B.S., Nebigil M., Aslamaci S. et al. // International Journal of Cardiology. 1996. Vol. 53 (2). P. 137–145.
24. The vasodilator effects of clevidipine on human internal
mammary artery / Huraux C., Makita T., Szlam F. et al. //
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25. Vasorelaxant properties of nicorandil on human radial artery / Sadaba J.R., Mathew K., Munsch C.M., Beech D.J. //
European Journal of Cardio-Thoracic Surgery. 2000. Vol.
17. P. 319–324.
89