Sequestration and activation of polymorphonuclear leukocytes in the myocardium following reperfusion during coronary artery surgery

J Mel

10

11

Cell

Cardiol

24 (Supplement

VI)

(1992)

CARDIOPROTECTIVE EFFECTS OF CARVEDILOL IN ANESTHETIZED YUCATAN MINIPIGS A &ii: M DiMartino2, GZ Feuersteinz, P Lin&‘, RH PO pep, RR Ruffofo Jr’, M Slivjak’, EF Smith W SmithKline Beecham Pharmaceuticais, ‘Saint-Gr&goire, France, 2King of Prussia, PA, %rockham Park, UK. The present study was designed to assess the cardioprotective effect of carvedilol, a R-adrenergic blocker with vasodilating properties, in a model of acute myocardial infarction in Yucatan minipigs In=6-7). The affects of carvedilol were compared to those of propranolol. Ischemia, induced by occlusion of the left anterior descending coronary artery for 45 min, was followed by 4 h of reperfusion. At the end of the reperfusion period, infart size was determined using Evans blue dye and triphenyltetrazolium chloride staining and computer assisted image inalysis. Polymorphonuclear leukocyte infiltration was evaluated by measuring myocardial myeloperoxidase (MPO) activity. Vehicle, carvedilol (0.3 and lmg/kg) and propranolol (1 mg/kg) were given i.v. 15 min before coronary occlusion. Infarct size, which represented 27.5 f 2.3 % of the area at risk in the vehicle treated group, was only 13.1 k4.0 % (p
the vehicle

and either

cardioprotective vasodilation,

effect or possibly

group

of carvedilol

of carvedilol from calcium

treated

could result antagonism

animals

during

ischemia

and reperfusion.

from the combined action of R-adrenoceptor or inhibition of lipid peroxidation.

SEQUESTRATION AND ACTIVATION OF POLYMORPHONUCLEAR MYOCARDIUM FOLLOWING REPERFUSION DURING CORONARY FABIANI, T. LECOMPTE, V.JEBARA, A. Carpentier, HBpital Broussais,

ARTERY

LEUKOCYTES SURGERY.

The greater blockade

and

IN B. FARAH,

THE J.N.

Paris,France. The aim of this study is to demonstrate in the clinical setting during coronary artcry bypass surgery (CABG), a specific activation of PMN inside the myocardium and at the time of reperfusion. 16 patients undergoing elective CABG were included in a prospective study. There were 14 men and 2 women. Mean age was 61+13,3 years. Mean number of bypass was 2,3/patient (2 to 4). Mean cross clamp time was 60,2113,3 minutes (46 to 86 mn). All patients received double caval canulation in order to obtain blood from coronary sinus (CS). Blood samples wcrc obtained simultaneously from peripheral vein (PV) and from the CS at the following times: TO: 5 mn prior to aortic cross clamp.Tl: 2 rnk after aor& unclamping.TZ: 10 mn after aortic unclampin& T3: 20 mn after aortic unclamping. Were analysed: PMN count, elastase and lactoferrin concentrations. All patients survived and no myocardial infarction were noted in this scrie. Statistical analysis (2 factors repcatcd analysis of variance) of thcsc results showed: At TO, no difference was noted bctwecn Pand CS with respect to the 3 variables. At Tl, T2, T3, a significant (p
12

THE ATP-SENSITIVE K+ CHANNEL OPENER NICORANDIL PROTECTS ISOLATED RAT HEARTS AGAINST ISCHEMIA/REPERFUSION DAMAGE. N. Khandoudi, A.C. Guo, D. Feuvray. Physiologie Cellulaire, URA CNRS 1121, Universit6 Paris-Xl, 9 1405 Orsay CBdex. Nicorandil (nice) has been shown to selectively activate ATP-sensitive-K+ channels mainly 1990) and to shorten the action by modulating the ATP-dependent gate (Takano & Noma, potential duration. We examined the effects of nice on cardiac function during global ischemia and reperfusion. Isolated buffer-perfused rat hearts were subjected to 30 min of no-flow ischemia with or without nice (10 to 100 PM) followed by 30 min of reperfusion (without nice). Preischemic function with or without drug and reperfusion function were measured at a constant flow rate using the double product of heart rate and left ventricular developed pressure. At the higher concentration used nice resulted in significant improvements in reperfusion function (81.2 f 4.8% vs 52.7 + 7.3%) with no change in ATP content. We also observed that the protective effect of nice occurred during the ischemic period because the K-channel opener significantly reduced diastolic pressure. In a second group of experiments a pre-ischemic intracellular acidification was induced by the NH,CI method before adding nice. In this latter group functional recovery on reperfusion was only 21 & 7.1% for hearts without nice vs. 89.1 + 3.1% for hearts receiving nice. These findings provide support for a protective effect of the KATP opener nice against ischemic injury. S.8