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001-es BibID:	BIBFORM046510
Első szerző:	Szilvássy Zoltán (belgyógyász, farmakológus, klinikai farmakológus)
Cím:	The effect of continuous versus intermittent treatment with transdermal nitroglycerin on pacing-induced preconditioning in conscious rabbits / Z. Szilvassy, P. Ferdinandy, I. Nagy, I. Jakab, M. Koltai
Dátum:	1997
ISSN:	0007-1188
Megjegyzések:	1 Tolerance to the hypotensive e?ect of nitroglycerin (NG) blocks preconditioning induced by rapidventricular pacing (RVP) in rabbits. In the present work the e?ect of continuous versus intermittenttreatment with transdermal nitroglycerin on the pacing-induced preconditioning phenomenon wasstudied in conscious rabbits.2 RVP (500 beats min71 over 5 min) increased left ventricular end-diastolic pressure (LVEDP) frombaseline 4.1+0.9 to postpacing 13.8+2.9 mmHg (P50.001) with a right intraventricular ST-segmentelevation of 1.25+0.13 mV, two indicators of myocardial ischaemia. These changes were signi?cantlyattenuated when the RVP period was preceded by a preconditioning pacing of the same rate andduration with an interpacing interval of 5 min.3 Protection by preconditioning was abolished when the animals had been made tolerant to thevasodilator e?ect of 30 mg kg71 NG by the application of transdermal NG (approx. 0.07 mg kg71 h71)over 7 days. Furthermore, transdermal NG per se attenuated both RVP-induced ST-segment elevationand LVEDP-increase over the 7 day period.4 With intermittent transdermal NG treatment (12 h 'patch on' vs 'patch o?'), neither development ofvascular tolerance nor attenuation of the NG- or preconditioning-induced anti-ischaemic e?ects wereobserved. However, the severity of pacing-induced myocardial ischaemia was signi?cantly increasedduring the 'patch o?' periods.5 In a second set of experiments, postpacing changes in cardiac cyclic GMP and cyclic AMP levelswere determined by means of radioimmunoassay in chronically instrumented anaesthetized open-chestrabbits with the same NG-treatment protocols. Preconditioning reduced postpacing increase in cyclicAMP with an increase in cyclic GMP concentrations in hearts of the untreated animals and in thosegiven patches intermittently during both 'patch on' and 'patch o?' periods. However, the preconditioninge?ect on either cyclic nucleotide was blocked in the tolerant animals.6 Transdermal NG increased resting levels of both cardiac cyclic nucleotides in the non-tolerant butnot in the tolerant state. The postpacing increase in cyclic AMP content was inhibited by transdermalNG, independent of vascular tolerance development, whereas, an increase in cyclic GMP content wasexclusively seen in the non-tolerant animals.7 We conclude that the anti-ischaemic effect of NG is independent of the cyclic GMP mechanism in thetolerant state. While intermittent NG therapy prevents development of vascular tolerance and preservespreconditioning, the nitrate-free periods yield an increased susceptibility of the heart to ischaemicchallenges.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Ischaemic preconditioning nitrate tolerance rapid pacing cyclic GMP intermittent nitrate therapy
Megjelenés:	British Journal of Pharmacology. - 121 : 3 (1997), p. 491-496. -
További szerzők:	Ferdinándy Péter Nagy I. Jakab Ildikó (farmakológus) Koltai Mátyás
Internet cím:	Szerző által megadott URL Intézményi repozitóriumban (DEA) tárolt változat
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