Kazuaki Kiyonaga

Early assessment of reperfusion therapy using cardiac troponin T

OBJECTIVES The purpose of this study was to investigate the utility of cardiac troponin T for early assessment of reperfusion therapy. BACKGROUND Several biochemical markers are used for early noninvasive detection of reperfusion during intravenous thrombolytic therapy. However, cardiac troponin T, a new myocardial-specific marker, has not been used previously for this purpose. METHODS We measured troponin T and creatine kinase, MB isoenzyme (CK-MB) levels in 38 patients with acute myocardial infarction whose infarct-related artery was totally occluded before reperfusion therapy. Subjects comprised 14 patients with successful angioplasty (group 1), 12 patients with successful thrombolytic therapy (group 2) and 12 patients with unsuccessful attempted reperfusion (group 3). Blood samples were taken every 15 min, and coronary angiography was performed every 5 to 8 min until 60 min after reperfusion (groups 1 and 2) or after the initiation of treatment (group 3). We calculated the increase in troponin T (delta troponin T) and CK-MB (delta CK-MB) 60 min after treatment was initiated and 60 min after reperfusion in groups 1 and 2. RESULTS Mean (+/- SD) delta troponin T and delta CK-MB levels were 9.35 +/- 7.83 ng/ml and 125 +/- 83 mU/ml in group 1 and 3.23 +/- 3.08 ng/ml and 130 +/- 137 mU/ml in group 2, respectively, 60 min after treatment and were 10.1 +/- 8.35 ng/ml and 131 +/- 84 mU/ml in group 1 and 6.84 +/- 8.30 ng/ml and 158 +/- 146 mU/ml in group 2, respectively, 60 min after reperfusion. These values were significantly higher than those 60 min after treatment in group 3: 0.16 +/- 0.19 ng/ml and 10 +/- 9 mU/ml, respectively. The predictive accuracy for detecting reperfusion using a threshold value of 0.50 ng/ml of delta troponin T and 25 mU/ml of delta CK-MB was 100% in group 1 and 92% in group 2 60 min after treatment, respectively. There was significant correlation between delta troponin T and delta CK-MB. CONCLUSIONS Serial measurements of cardiac troponin T as well as of CK-MB are useful for early assessment of reperfusion therapy.

Plasma Level of Triglyceride-rich Lipoprotein Remnants Is Closely Associated with the Activation of Coagulation Factor VII in Patients with Myocardial Infarction

Remnant-like particles, which have been recognized to be atherogenic derivatives of chylomicrons and very low density lipoproteins, can be measured using a new assay kit. The purpose of the present study was to investigate the association of remnant-like particles with the coagulation system that has an important role in the pathogenesis of myocardial infarction. We assayed blood levels of total cholesterol, triglyceride, HDL-cholesterol, apolipoproteins, remnant-like particles-cholesterol, remnant-like particles-triglyceride, fibrinogen, factor VII antigen, activated factor VII, and tissue factor in 111 patients with a history of myocardial infarction and 128 control subjects. In simple regression analysis, plasma levels of remnant-like particles-cholesterol and remnant-like particles-triglyceride showed a significant positive correlation with the levels of activated factor VII (r=0.319, p<0. 001, and r=0.286, p=0.002, respectively) and the activated factor VII/factor VII antigen ratio (r=0.241, p=0.011, and r=0.249, p=0.008, respectively) in patients with myocardial infarction. In contrast, there were no significant differences between remnant-like particles and activated factor VII in control subjects. In stepwise multivariate regression analysis, the significant determinants of activated factor VII were remnant-like particles-cholesterol (10.2%), apolipoproteins A-I (5.1%), and E (7.1%); for the activated factor VII/factor VII antigen ratio, remnant-like particles-triglyceride (6. 2%), age at blood sampling (5.1%), and apolipoprotein A-I (4.0%) in patients with myocardial infarction. However, the significant determinants of activated factor VII and the activated factor VII/factor VII antigen ratio were HDL-cholesterol (9.9% and 9.2%, respectively) in control subjects. It is concluded that remnant-like particles may be a risk factor for myocardial infarction by activating the extrinsic coagulation pathway.

The effect of digoxin on cardiovascular responses to hypoxia and reoxygenation in anesthetized dogs

To clarify the efficacy of digitalis in acute hypoxia and reoxygenation, we estimated the effects of digoxin on cardiovascular hemodynamics in anesthetized dogs. Hypoxia caused significant increases in aortic pressure, pulmonary artery pressure, left ventricular (LV) pressure, rate of change in LV pressure (LVdp/dt), cardiac output (CO) and plasma catecholamines. These changes in LVdp/dt, CO and plasma catecholamines induced by hypoxia were returned to the control levels within 3 min by reoxygenation with 70% O2. The injection of digoxin (0.05 mg/kg) in hypoxic dogs resulted in significant increases in LVdp/dt, CO and stroke volume (SV) but no changes in levels of plasma catecholamines, heart rate, mean aortic pressure and mean pulmonary artery pressure. However, the injection of digoxin resulted in no significant changes in cardiovascular response to reoxygenation. Our experiments demonstrate that digoxin caused significant increases in CO, SV and LVdp/dt in dogs with hypoxia but resulted in no significant changes in cardiovascular responses to reoxygenation.