DELETERIOUS EFFECTS OF A SYSTEMIC LYTIC STATE ON REPERFUSED MYOCARDIUM - MINIMIZATION OF REPERFUSION INJURY AND ENHANCED RECOVERY OF MYOCARDIAL-FUNCTION BY DIRECT ANGIOPLASTY

Background The beneficial effects of flow restoration and the deleteri ous impact of reperfusion injury on ischemic myocardium are well known . However, most experimental studies have induced reperfusion by mecha nical release of nonthrombotic occlusions, only occasionally in the pr esence of a systemic lytic state. Conditions differ markedly in patien ts undergoing pharmacological or mechanical recanalization of thrombot ically occluded coronary arteries. Accordingly, this study was designe d to determine whether the method of coronary occlusion and mode of re canalization influence the response of the heart to reperfusion.Method s and Results The acute effects of reperfusion on right ventricular (R V) function and histology were studied in open-chest dogs subjected to right coronary artery (RCA) balloon occlusion and deflation alone (gr oup 1), pharmacological lysis of thrombotic occlusions (group 2), ball oon occlusion with reperfusion induced by balloon deflation in the pre sence of a systemic lytic state (group 3), and recanalization of throm botically occluded vessels by direct angioplasty (group 4). In all gro ups, 1 hour of RCA occlusion led to RV free wall (FW) dyskinesis. In g roup 1, reperfusion promptly improved RVFW function, with normal RVFW thickness and only minimal edema by microscopy. In contrast, in group 2, clot lysis led to acute RVFW swelling and impaired recovery of RVFW contraction associated with striking interstitial edema, contraction band necrosis, and hemorrhage by microscopy. In group 3, balloon defla tion in the presence of a lytic state led to a similar but less severe pattern of abrupt RVFW swelling and impaired recovery of RVFW functio n but lesser histological alterations than in group 2. However, mechan ical recanalization of thrombotically occluded vessels (group 4) led t o prompt recovery of RVFW function without significant RVFW swelling o r histological abnormalities. Conclusions Our observations indicate th at the responses of ischemic myocardium to reperfusion are influenced by factors beyond those effects attributable to ischemia and reperfusi on per se. Pharmacological lysis of coronary thrombi results in altera tions characteristic of reperfusion injury and associated with impaire d functional recovery. Such changes are also evident, although to a le sser extent, when reperfusion of nonthrombotic occlusions is induced b y mechanical recanalization in the presence of a systemic lytic state but not in its absence. However, such effects were not seen with direc t mechanical recanalization of thrombotically occluded vessels. In agg regate, these findings indicate that induction of a systemic lytic sta te, together with products released by lysis of introcoronary thrombi, generates an injurious milieu that exerts adverse effects on reperfus ed myocardium.