[The prevention of an excitation-conduction block during acute myocardial ischemia: is there a role for prostacyclin or for histamine?].
We have investigated (multivariate Cox's model) the relative risk of stable excitation-conduction block (ECB) in right ventricular myocardial strips (2 x 5 x 1 mm) from 26 female guinea-pigs, bathed in a 2-compartment chamber (3 ml) on the anterior side of which modified Tyrode's solution (K+ 12 mM, HCO3- 9 mM, pH 7 +/- 0.05, pO2 80 +/- 10 mmHg and absence of glucose) is supraperfused (stimulation rate: 450 ms; wire in the posterior compartment), thus enabling simulation of electrophysiologic changes seen during acute myocardial ischemia. Using glass microelectrodes, action potential amplitude (APA), durations (APD50 and 90%), resting membrane potential (RMP) and upstroke velocity (Vmax) are investigated. The hypothesis was tested of prostacyclin and histamine involvement in the genesis of ischemia-induced ECB in this model. Either a weak prostacyclin stimulator (cicletanine 10(-5) M, IPSEN, Paris, F, in DMSO 1:100; n = 16) or a potent prostacyclin generation blocker (indomethacin 10(-5) M, Sigma, in DMSO 1:100; n = 10) and either DMSO alone (1:100; n = 16) or a specific histaminergic H1 receptor antagonist (terfenadine 10(-5) M, Sigma, in DMSO 1:100; n = 10) were supraperfused using a randomization scheme. Each animal was used twice and either a first or a second occlusion (supraperfusing the modified Tyrode's solution for 30 min) period was performed and the randomized substances were supraperfused, thus enabling obtention of n = 52 experiments for analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Monti
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F
Istituto di Chirurgia del Cuore e Grossi Vasi, Università degli Studi La Sapienza, Roma.
Schiariti
M
M
Dawodu
A A
AA
Lanti
M
M
Pulvirenti
G
G
Terracciano
C M
CM
Evangelista
E
E
Puddu
P E
PE
Marino
B
B
Campa
P P
PP
D000208:Acute Disease; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D003327:Coronary Disease / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D004121:Dimethyl Sulfoxide / Q000627:therapeutic use; D004232:Diuretics / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D011464:Epoprostenol / Q000502:physiology*; D005260:Female; D006168:Guinea Pigs; D006327:Heart Block / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D006632:Histamine / Q000502:physiology*; D006636:Histamine Release / Q000187:drug effects / Q000502:physiology; D007213:Indomethacin / Q000627:therapeutic use; D011725:Pyridines; D016593:Terfenadine / Q000627:therapeutic use
D000959:Antihypertensive Agents; D004232:Diuretics; D011725:Pyridines; D016593:Terfenadine; D006632:Histamine; C038068:cicletanine; D011464:Epoprostenol; D007213:Indomethacin; D004121:Dimethyl Sulfoxide
Prevenzione del blocco dell'eccitoconduzione durante ischemia miocardia acuta: esiste un ruolo per la prostaciclina o per l'istamina?