To evaluate the effects of lipoprotein (a) [Lp (a)] on the fibrinolytic system in patients with acute myocardial infarction (AMI) who underwent thrombolytic therapy with recombinant tissue-type plasminogen activator, we examined serial changes in plasma levels of Lp (a), plasminogen activator inhibitor (PAI) activity, alpha 2-plasmin inhibitor-plasmin complex (PIC) and thrombin antithrombin III complex (TAT) in venous plasma samples from 25 patients with AMI for 3 weeks. Plasma Lp (a) levels were significantly increased 5, 7, and 14 days after admission and tended to decrease by the 2lst day. On the other hand, the ratio of PIC/TAT was significantly increased on the 7th day and remained high for 3 weeks (p<0.01), while plasma PAI activity was significantly decreased on the 5th day after admission (p<0.01). Thus, plasma fibrinolytic function is impaired in the early phase after AMI, and gradually improves over the course of 3 weeks. The increase in plasma Lp (a) levels is, therefore, not accompanied by a significant decrease in plasma fibrinolytic function in patients with AMI.

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In 40 patients with old myocardial infarction (MI), we evaluated the relationship between characteristics in endocardial electrograms and regional wall motion abnormalities at the MI site. Left ventricular ejection fraction (LVEF) was greater in the late-potentials (LPs) negative group (n=21) than in the LPs positive group (n=19), but this difference was not significant (57.6±19.8% vs 47.9±16.8%). Regional wall motion was assessed by the radial method. We used the percent left ventriculogram (%LVG) area change of each segment as a marker of regional wall motion. Correlation coefficients between electrographic amplitude and %LVG area change, electrographic duration and %LVG area change, and amplitude/duration ratio and %LVG area change were 0.3999 (p<0.001), -0.2319 (p<0.02), and 0.4312 (p<0.001), respectively. Thus, characteristics of endocardial electrograms were significantly related to regional wall motion abnormalities in MI sites. In MI sites, as regional wall motion was reduced, the electrographic amplitude became smaller and the electrographic duration became longer. However, this relationship was not linked to that between LPs and LVEF.

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The effects and problems of coronary thrombolysis (CT) were investigated in 652 patients with initial acute myocardial infraction (AMI). Nosocomial mortality obtained by matching factors which determined prognosis was significantly lower in patients treated by CT (8.3%) than in those who did not undergo CT (18.1%). Regardless of whether the treatment was intracoronary arterial (ICT) or intravenous (IVCT), the primary cause of the decreased mortality was reperfusion of the coronary artery responsible for infarction (mortality 6.1% in the reperfused group vs 21.5% in the ineffective group). CT therapy improved left ventricular ejection fraction (LVEF), the nosocomial mortality rate, and regional wall motion at the site of infarction in cases that were reperfused less than 3 h, 3-6 h, and even 6 or more hours after the therapy. The long-term prognosis was significantly better in the reperfused group than in the ineffective group for 5 years and 7 months after therapy. However, CT was accompanied by both (1) poor prognosis in the ineffective group; and (2) unfavorable effects on the prognosis and on the daily life of patients with severe stenosis even after treatment. Accordingly, supplemental ICT and rescue PTCA (strategy (A)) were performed to treat the first problem, and deferred PTCA (strategy (B)) was conducted to treat the second problem in 80 patients with initial AMI. As a result, strategy (A) increased the coronary reperfusion rate to 94.3%, and strategies (A) and (B) together decreased the nosocomial mortality rate of 8.5% to 3.8%, and reduced the risk of death by 55.3%.

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The present study was performed to determine whether the effects of ischemic preconditioning are mediated by a decrease in myocardial contractile activity or by a change in catabolite accumulation during the subsequent period of sustained ischemia. In ischemic preconditioning groups, crystalloid perfused rat hearts were subjected to 5 or 10 min of global ischemia before a 15-min reperfusion period and a subsequent 30 min period of ischemia, Non-preconditioned control hearts underwent a single 30-min ischemic period. In the 5-min preconditioned hearts, the onset of myocardial contracture was significantly delayed (22.0±1.6 min) compared with that in control hearts (14.7±0.7 min). Tissue ATP content of the myocardium during sustained ischemia was preserved better in 5-min preconditioned hearts than in control hearts. The time to contractile arrest during the sustained ischemic period was greater in the preconditioned hearts (3.9±0.3 and 3.1±0.2 min in PC5 and PC10 hearts respectively) than in controls (1.9±0.1 min). Thus, residual myocardial work during sustained ischemia (as estimated by the rate pressure product) was not decreased in the preconditioned hearts compared with that in control hearts. Extracellular acidosis was identical among the three groups during the subsequent period of sustained ischemia. The early rise in extracellular K⁺ during sustained ischemia progressively increased with the duration of preconditioning. We conclude that, in crystalloid perfused rat heart, 5 min of global ischemia had a salutary effect against cell damage caused by sustained ischemia. This "preconditioning" effect cannot be attributed to decreased myocardial work during ischemia nor to differences in extracellular H⁺ or K⁺ accumulation.

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The effects of dietary supplementation with eicosapentaenoic acid (EPA) on ventricular arrhythmias during myocardial infarction were examined in a canine model. EPA was incorporated into cellular membranes after ingestion of EPA-ester (100 mg/kg body weight/day) for 8 weeks. The ratio of EPA to arachidonic acid (AA) in platelet cell membranes and myocardial microsomes was significantly increased (7% to 37% in platelet cell membranes; p<0.01, 3% to 12% in non-infarcted cardiac microsomes; p<0.01, and from 2% to 8% in infarcted cardiac microsomes; p<0.01). Dietary supplementation with EPA significantly reduced the incidence and severity of arrhythmias during coronary artery occlusion. Immediately after coronary artery occlusion, all of the animals in the control group that were given a toxic dose of digitalis developed ventricular tachycardia (VT) or ventricular fibrillation (Vf), whereas none of the animals in the EPA-supplement group developed VT or Vf within 15 min after administration of digitalis. Regardless of the presence of an infarcted area, the specific activity of the Ca²⁺-pump enzyme ((Ca²⁺-Mg²⁺)-ATPase) within the myocardial microsomal fraction of the EPA-supplemented group was significantly higher than in that of the control group (Vmax: 140.5±19.1 vs 94.8±28.9 nmol/mg/min in non-infarcted cardiac microsomes, p<0.01, 130.9±18.4 vs 90.2±26.4 nmol/mg/min in infarcted cardiac microsomes, p<0.01, EPA vs control group, respectively) . The specific activities of the Na⁺-pump enzyme ((Na⁺-K⁺)-ATPase) and NADPH-dependent cytochrome C reductase in infarcted and non-infarcted cardiac microsomes did not differ between these groups. These results indicate that EPA supplementation increases the (Ca²⁺-Mg²⁺)-ATPase activity within myocardial membranes that is involved in Ca²⁺ metabolism in myocardial cells by increasing the ratio of EPA to AA within cellular membranes. These cellular alterations are likely to reduce the severity of ventricular arrhythmias by inhibiting the rapid accumulation of intracellular Ca²⁺ following ischemia.

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To identify any differences in inhibitory G protein (Gi) attributable to species or the cause of heart failure, we studied the changes in this protein in different animal models of heart failure: 1) different species; rats vs. hamsters (F1B) with cardiomyopathy induced by adriamycin (ADR) and 2) different etiologies; rats with ischemic heart failure (IHD) due to coronary artery ligation vs. rats with cardiomyopathy induced by ADR and F1B (20-week-old) hamsters with cardiomyopathy induced by ADR vs Syrian hamsters BIO 14.6 (40-week-old) with genetic cardiomyopathy, using Western blotting methods and ADP-ribosylation. We also sought to determine whether changes in the amount of Gi protein reflected the regulation of adenylate cyclase. The amount of immunodetectable Gi rose by 35% (p<0.05) in ADR rats, 25% (p<0.05) in ADR hamsters, 15% (p<0.05) in IHD rats, and 28% (p<0.05) in BIO 14.6 hamsters, as compared with control rats, F1B (20-week-old) hamsters, sham-operated control rats, and F1B (40-week-old) hamsters, respectively. Assessment of Gi by pertussis toxincatalyzed ADP-ribosylation revealed increases in Gi of 24% (p<0.05) in ADR rats and of 44% (p<0.05) in BIO 14.6 hamsters, as compared with their respective controls. Gi function, as assayed by the acetylcholine-induced inhibition of adenylate cyclase, also increased. Thus, Gi protein appears to contribute to the changes in signal transduction in myocardium with heart failure.

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