title: Inhibitors of the kinin system as an alternative method of prevention or reduction reperfusive damages within thrombolytic therapy in patients with acute myocardium infarction.
abstract: The aim is to show the effectiveness of inhibitors of the kallikrein-kinin system (KKS) to avoid early microcirculation impairment and low reperfusion damages in the ischemic area during systemic thrombolysis (T) in order to achieve optimal results of thrombolytic therapy (TLT) in patients with acute myocardium infarction. Patients (n=104) with acute myocardium infarction were divided into 4 groups: treatment with early TLT infusing Contrycal (Aprotinin) and Heparin (CH) during the first 2 hrs from the onset of disease (Gr. 1); treatment for isolated T at an early stage (Gr. 2); TLT with late T (in 3-6 hrs) (Gr. 3); and conventional therapy (Gr. 4). The dynamics of clinical and ECG data were evaluated for each of the groups. Before the clinical study was fully evaluated, an experimental-morphological, controlled study was carried out on dogs. These results showed improved retrograde blood flow of the acute ischemized myocardium and decrease in ischemia level, together with reduction of frequency and area of reperfused intramiocardial haemorrhages (RPIMH) in infarction areas under the TLT and CH infusion. When CH was infused a significant advantage was revealed in early T that showed high antianginal and antiarrhythmic effect, while no Q wave was observed or it was deepened non-significantly. More clinical dynamic problems with extrasystols and significant deepening of Q wave were seen in the earlier isolated T (Gr. 2) that were worse than those seen in Gr. 1 conditions, but the problems were more negative in the patients from Gr. 3 and 4. CH optimizes the situation causing suppression of the pathological activation of KKS, decreasing vessel permeability, and reducing reperfusion damage. The latest thrombolytic drugs ensure faster thromb lysing but do not prevent the reperfusion damage, as higher fibrinolytic activity at the moment of T causes enhanced activation of KKS and RPIMH development and prevents peroxide oxidation of the lipids but this may result in higher affectivity of antioxidant use. Earlier administration of KKS inhibitors optimizes the affectivity of TLT and widens the indication to the systemic and intracoronary T, minimizes complications, and may cause higher affectivity of coronary angioplasty (CAP) and aorta-coronary shunting in patients with acute myocardium infarction.
authors.affiliation: Institute of Therapy, Tbilisi, Georgia.
authors.forename: A
authors.initials: A
authors.lastname: Korotkov
authors.forename: A
authors.initials: A
authors.lastname: Kistauri
authors.forename: A
authors.initials: A
authors.lastname: Korotkova
authors.forename: M
authors.initials: M
authors.lastname: Jibladze
authors.forename: E
authors.initials: E
authors.lastname: Guchua
mesh_terms: D000328:Adult; D000368:Aged; D007611:Aprotinin / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D005343:Fibrinolytic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D005500:Follow-Up Studies; D006493:Heparin / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D007705:Kinins / Q000037:antagonists & inhibitors*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control*; D012720:Severity of Illness Index; D013300:Streptokinase / Q000009:adverse effects / Q000627:therapeutic use; D015912:Thrombolytic Therapy / Q000009:adverse effects*; D016896:Treatment Outcome; D014361:Trypsin Inhibitors
chemical_list: D005343:Fibrinolytic Agents; D007705:Kinins; D014361:Trypsin Inhibitors; C011475:gordox; D006493:Heparin; D007611:Aprotinin; D013300:Streptokinase