Platelet hyperreactivity after coronary artery bypass grafting: the possible relevance to glycoprotein polymorphisms. A preliminary report.

Coronary artery bypass grafting (CABG) surgery impairs platelet function and reactivity to a considerable extent. However, variability in the individual patients' responses makes any generalised statement uncertain. The observed variability is nowadays thought to relate to platelet glycoprotein polymorphisms. Our objective was to investigate the association between platelet reactivity and the restoration of platelet functional response to agonists during the period following cardiosurgical operation and some genetic polymorphisms of selected platelet membrane glycoproteins. Platelet reactivity was monitored in 32 IHD patients (56 +/- 8 years) subjected to CABG surgery by means of whole blood impedance aggregometry and concurrently using the platelet function analyser (PFA-100 at four time intervals: prior to operation (A), 2 h after administration of protamine sulfate (B), 3 days after (C) and 7 days after CABG surgery (D). Three important findings were made. First, in all patients platelet reactivity became decreased 2 h postoperatively (aggregation with 20 microM ADP reduced by up to 49%, P < 0.02) and vastly increased 7 days after CABG surgery (CT(CADP) reduced down to 87% of initial value, P < 0.05, ADP-induced aggregation enhanced up to 167%, P < 0.001, and that with collagen up to 131% of the initial value, P < 0.01). Second, the frequencies of the 'prothrombotic' phenotype variants of platelet membrane glycoproteins were higher in patients referred to as the carriers of more reactive platelets compared to those with less reactive platelets (GPIa (807)T-positive, 50 vs. 28%; GPIIIa Pl(A2)-positive, 27 vs. 21%; GPIb Met(145)-positive and GPIb VNTR B-positive, 13 vs. 0%. Lastly, the restoration in platelet hyperreactivity in CABG surgery patients was recorded more often in patients who underwent postoperative myocardial ischaemic episode(s), and was associated with significantly higher frequency of the 'prothrombotic' allele (807)T of the collagen receptor glycoprotein Ia (GPIa) in these subjects (83 vs. 61%). In conclusion, in patients with ischaemic episodes after CABG, we demonstrated a fast postoperative restoration of haemostatic capacity and evidence of platelet hyperreactivity at 7 days after CABG surgery. The platelet hyperfunction seems to relate to the occurrence of platelet glycoprotein polymorphisms GPIa(807)C/T and GPIIIa PlA(1/A2) and may be important in predicting postoperative vascular complications in CABG patients.

Low doses of aprotinin in aortocoronary bypass surgery--advantages and disadvantages.

INTRODUCTION: Excessive blood loss, as a result of augmented postoperative drainage, is considered one of the most serious cardiosurgical complications. The compounding constitutive anemia seems particularly harmful for patients with coronary artery disease. Aprotinin (Trasylol), a non-specific serine protease inhibitor, is successfully used to reduce excessive postoperative bleeding in such patients. The aim of our study was to verify the hypothesis whether aprotinin used during cardiopulmonary bypass procedure affects hemostatic parameters, which might be crucial for the elevated risk of thromboembolic complications. MATERIAL AND METHODS: The group of 54 patients subjected to coronary artery surgical treatment included 30 patients, who were given intraoperatively 3 million KIU aprotinin each, and 24 subjects non-treated with aprotinin. Aliquots of blood were withdrawn at several time intervals, until the 5th day after the operation. Whole blood platelet activation and reactivity (the expressions of P-selectin and glycoprotein Ib) were monitored by means of flow cytometry. In addition, several plasma parameters, like PAI-1, t-PA, D-dimers, prothrombin fragment F1 + 2, fibrinogen, ATIII activity, troponin I and CK-MB, as well as platelet count were determined at each time point. RESULTS: In this study we confirmed the essential advantage of the use of aprotinin: both the postoperative blood drainage and the blood units to be transfused postoperatively to cardiosurgical patients were vastly reduced in the aprotinin-treated subjects. The enhanced overall frequency of perioperative myocardial infarction events was not attributed to this group of patients, nor the non Q-wave infarctions were observed more often in patients treated with aprotinin. In these patients, fibrinolysis parameters tended to be depressed (with increased PAI-1 dominating over elevated t-PA) on the first day after the operation, and no significant differences with regard to fibrinogen, prothrombin fragment F1 + 2, troponin I and platelet count. There was a continuous rise in D-dimers in all the postoperative patients, which lasted until the third day and tended to reach plateau at the 5th day after the operation. We failed to reveal the preventive effects of aprotinin on platelet function: both platelet activation and reactivity remained apparently unchanged. Overall, our results rather support the reasoning on the advantageous effects of low doses of aprotinin. The use of this inhibitor reduces the risk of postoperative undesirable bleeding and results in a decreased postoperative drainage and reduced transfused blood units. On the other hand, however, a higher incidence of perioperative Q-wave infarction in the aprotinin-treated patients, although purely apparent and not statistically significant, might question the unlimited safety of the use of aprotinin in cardiovascular operations.

[Use of platelet function analyzer PFA-100 and whole blood aggregometry to monitor blood platelet sensitivity to acetylsalicylic acid (aspirin). Is it possible to reliably monitor antiplatelet treatment using routine laboratory diagnostic methods?]. / Zastosowanie analizatora funkcji plytek PFA-100 oraz metody agregacji we krwi pelnej do oceny wrazliwosci plytek krwi na dzialanie kwasu acetylosalicylowego (aspiryny). Czy mozliwa jest wiarygodna laboratoryjna weryfikacja leczenia przeciwplytkowego?

Introduction of the antiplatelet agents of new generations and the occurrence of the phenomenon of "aspirin-resistance" triggered the search for better, simpler and more reliable routine diagnostic methods to monitor platelet reactivity. Our objective was to evaluate the usefulness and reliability of two simple methods: platelet function analyzer (PFA-100) and whole blood platelet aggregometry for monitoring of platelet function in 18 healthy blood donors and 35 patients with ischaemic heart disease (IHD) subjected to small doses/75 mg and 150 mg a day) of acetylsalicylic acid (aspirin). In 50% of healthy blood donors the intake of 75 mg ASA a day resulted in the prolongation of PFA-100 collagen/epinephrine closure time (CEPI = (relevant to reduced platelet reactivity) of over 150 s, whereas 75% donors responded to 150 mg ASA-. Otherwise, the daily dose of 150 mg ASA resulted in a prolonged CEPI merely in 23% of in IHD patients. At both doses ASA completely inhibited the arachidonic acid-induced whole blood platelet aggregation in all healthy donors and in all but 3 IHD patients. Collagen-induced platelet aggregation was only negligibly affected by either dose of ASA. Our results point that the simultaneous monitoring of the PFA-100 collagen/epinephrine closure time and whole blood platelet aggregometry (Chrono-Log) enables to reliably evaluate the inhibition of platelet function by ASA and discriminate the partial or complete platelet insensitivity to aspirin. The phenomenon of more frequent platelet aspirin-resistance in IHD patients requires to be verified in randomised clinical prospective studies.

[Metabolic changes in blood oxygen in the human heart under ischemic and reperfusion conditions]. / Zmiany metabolizmu tlenowego krwi z serca ludzkiego w warunkach niedokrwienia i reperfuzji.

The number of granulocytes, their capability to generate O2-. and the activity of SOD-1, GSH-Px, Cat as well as MDA concentrations in erythrocytes in the blood extracted from the venous sinus and aorta under coronary artery bypass with use of St. Thomas cardioplegic solution were determined. The blood for examination was obtained before the institution of cardiopulmonary bypass, in the period of the deepest ischaemia (just after declamping of the aorta) and between the 1-3 minute and the 10-13 minute of reperfusion. A rise in the number of granulocytes both in the venous sinus and aortal blood at all examined intervals was noted. Capability to produce superoxide anion radicals decreased at the peak of ischemia and during reperfusion. The activity of SOD-1 was lower both after the period of ischemia and reperfusion. A rise in aortal blood activity during reperfusion was characteristic for GSH-Px; the activity was greater in the blood sampled from the coronary sinus during ischemia and initial reperfusion. With the exception of the initial reperfusion the activity of Cat diminished in all observed cases. We did not observe any significant changes in MDA concentration with the exception of the initial reperfusion in the aortal blood and later during reperfusion in the blood from the coronary sinus. The results demonstrate that the applied cardioplegic solution may protect myocardium from harmful effects of active oxygen froms produced as a results of ischemia and reperfusion.

[Surgical treatment of secondary complications of myocardial infarction]. / Chirurgiczne leczenie wtórnych powiklan zawalu serca.

The results are presented od surgical treatment of 18 patients operated on in the Cardiosurgery Department, Institute of Cardiology, Medical Academy in Lódz, in the years 1985-1989, for complications of myocardial infarction. The material includes such complications as: post-infarction perforation of the septum, and post-infarction aneurysm of the left ventricle. The usefulness of specialized examinations is shown in qualifying the patients for operation, and the method is presented of carrying out operations in these patients in extracorporeal circulation. Good results of surgical treatment were achieved.

[Personal observations of dobutamine effectiveness after surgery with extracorporeal circulation]. / Wlasne spostrzezenia w stosowaniu dobutaminy po operacjach w krazeniu pozaustrojowym.

This report describes the use of dobutamine in patients presenting a low output syndrome after cardiosurgical operations i EEC. Of 565 patients operated on valvular heart defects and coronary artery disease in 89 patients (15.7%) a low output syndrome was diagnosed and treated. Dobutamine proved to be effective in patients with moderate impairment of the left ventricular contractility. In those with severe left ventricular dysfunction, dobutamine was ineffective and other catecholamines ought to be used. The authors support the view that combined administration of dobutamine (or other catecholamines) and nitroglycerin in patients with low output syndrome proves to be superior to the effect of each single drug.