Single low-dose administration of human recombinant hepatocyte growth factor attenuates intimal hyperplasia in a balloon-injured rabbit iliac artery model.

BACKGROUND: Previous studies have shown that repeated systemic administration of human recombinant hepatocyte growth factor (hrHGF) in mg/kg levels modulates the wound-healing process in various diseases. Recently, HGF has been characterized as one of the most potent endothelial-cell-specific growth factors. We tested our hypothesis that local delivery of hrHGF, even at low microg/kg levels (> or =2 orders of magnitude lower than systemically administered doses), might attenuate neointimal hyperplasia in response to vascular injury via accelerated reendothelialization. METHODS AND RESULTS: The iliac artery was denuded in 16 New Zealand White rabbits (3 kg), followed by administration, via a drug delivery catheter, of either hrHGF (10 microg; n = 11) or control vehicle (n=5) over 20 minutes. In pilot studies using this device, the drug permeated into the medial tissues, where it persisted for > or =24 hours. Four weeks after the local delivery of hrHGF, computer-assisted morphometric analysis revealed significant reduction in the intimal area (hrHGF, 0.37+/-0.21 versus control, 0.68+/-0.16 mm(2), mean +/- SD; P<0.05) but no change in the medial area (hrHGF, 1.03+/-0.21 versus control, 1.10+/-0.52 mm(2)). Scanning electron microscopy revealed extensive endothelialization with regular and confluent endothelial cell layer regeneration in the hrHGF-treated vessels. CONCLUSIONS: Accelerated endothelialization after local delivery of hrHGF, a novel and potent endothelial cell mitogen, effectively attenuates neointimal proliferation even after single low-dose administration. This observation could have potential therapeutic implications in the prevention of restenosis after angioplasty.

Myocardial relaxation in atrial fibrillation.

Although myocardial contractility has been known to vary from beat to beat in atrial fibrillation, myocardial relaxation in this arrhythmia has not been investigated. In this study, left ventricular relaxation was examined in seven patients with atrial fibrillation (four with mitral valve disease, one with aortic regurgitation, one with secundum type atrial septal defect and one with apical left ventricular hypertrophy). The left ventricular pressure was measured with a micromanometer-tipped catheter and the time constant of isovolumic left ventricular pressure decline (the relaxation time constant) was calculated by means of exponential curve fitting from more than 20 consecutive beats in each patient. The maximal rate of rise of left ventricular pressure (dP/dt) and the relaxation time constant were examined in relation to the preceding RR interval (RR2) and to the ratio of the RR2 interval to the pre-preceding RR interval (RR2/RR1), and the correlation coefficients were obtained. The dP/dt correlated better with RR2/RR1 than with the RR2 interval (0.82 +/- 0.05 versus 0.48 +/- 0.2), but the relaxation time constant did not show any correlation with RR2/RR1 or the RR2 interval (0.03 +/- 0.21 and 0.06 +/- 0.21, respectively). The relaxation time constant was fairly constant in each patient even when the RR2 interval and RR2/RR1 varied greatly. Thus, relaxation in atrial fibrillation is independent of changes in contractility as seen in the relation between postextrasystolic relaxation and postextrasystolic potentiation of contractility.

Left ventricular pressure-length relation during exercise-induced ischemia.

The pressure-length relation in normal and ischemic segments was analyzed with use of left ventriculography and simultaneous micromanometry during supine exercise in 9 normal subjects and 12 patients with effort angina. Segmental analysis was done in the right anterior oblique projection using a long axis with three perpendicular, equidistant chords. The apical segment in the 12 patients with coronary artery disease represented the ischemic region. In 5 of the 12 patients with coronary artery disease, the basal segment that showed no exercise-induced deterioration in wall motion was used as an intrapatient control (nonischemic segment). In the 12 patients with coronary artery disease, left ventricular ejection fraction decreased (from 65% to 50%, p less than 0.001), end-diastolic pressure increased (from 24 to 40 mm Hg, p less than 0.001) and the lowest diastolic filling pressure increased (from 9 to 22 mm Hg, p less than 0.001) during exercise-induced ischemia. In normal subjects, ejection fraction increased (from 64% to 70%, p less than 0.01) with unchanged end-diastolic pressure, whereas the lowest diastolic filling pressure decreased during exercise (from 9 to 3 mm Hg, p less than 0.01). Global left ventricular diastolic pressure-volume curves showed an upward and rightward shift during exercise-induced ischemia. Regional pressure-length curves of both nonischemic (n = 5) and ischemic (n = 12) segments were shifted upward in early diastole, but moved to a higher portion of the rest pressure-length curve without an upward shift during mid- to end-diastole. In contrast, the apical segment in normal subjects showed a downward shift during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in diastolic properties of the regional myocardium during pacing-induced ischemia in human subjects.

Mechanisms related to alterations in the diastolic properties of the left ventricle during angina were studied in seven patients with coronary artery disease. Single plane left ventriculograms were obtained using a high fidelity micromanometer-tipped catheter in both the resting state and immediately after rapid cardiac pacing. In all patients, typical anginal pain developed with pacing stress. After atrial pacing, the left ventricular end-diastolic pressure increased from 10 +/- 3 to 21 +/- 7 mm Hg (+/- standard deviation) (p less than 0.005) regardless of the changes in the end-diastolic volume. The ejection fraction was reduced from 59 +/- 10 to 48 +/- 13% (p less than 0.05). The diastolic pressure-volume curves shifted upward in post-pacing beats in four patients, while in three the curves shifted more to the right. The regional myocardial function was expressed in quantitative terms by a radial coordinate system with the origin at the center of gravity of the end-diastolic silhouette. Two representative radial grids for normal and ischemic segments were selected. In the normal segment, the end-diastolic length was augmented by 15% (p less than 0.005) and was associated with a 24% increase in stroke excursion with pacing stress (p less than 0.05). The increase in diastolic pressure was accompanied by comparable increases in end-diastolic length, and the diastolic pressure-length relation moved up to the higher portion of the single curve. In the ischemic segment, the end-diastolic length remained unchanged in the post-pacing beat, but segment shortening was significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of asynchronous wall motion by regional pressure-length loops in patients with coronary artery disease.

The progression of regional dysfunction during angina pectoris was studied in eight patients with coronary artery disease. Single plane left ventriculograms were obtained using a high fidelity micromanometer-tipped catheter both at rest and immediately after rapid cardiac pacing. Each image of the left ventriculogram was digitized and transferred to a computer. The boundary of the ventricular cavity was automatically determined and sequentially superimposed. Regional shortening was quantified by a radial coordinate system originating at the center of gravity of the end-diastolic silhouette. Thirty-two radial grids were drawn around the center of gravity, and the length of each radial grid was measured to characterize the centripetal motion of a given surface point. Each radial length was then plotted simultaneously and continuously against left ventricular pressure to generate a pressure-length loop. The area of the pressure-length loop provided an index of regional myocardial work. In the ischemic ventricle, the loops exhibited a striking deformity in configuration. Prolonged relaxation of ischemic segments was associated with outward motion of the normal segments. Shortening of the normal segment occurred earlier than that of the ischemic segment associated with its stretch. Thus, the loops of the two areas inclined in opposite directions. Pacing stress increased the magnitude of hypofunction in the potentially ischemic area, the average extent of shortening being reduced by 30% and the segmental work by 25% (p less than 0.005). In the normal area, contrary to the significant increase in segmental shortening (20% above control values [p less than 0.005]), the average segmental work remained at 7% below control values because of an augmented deformation of the loop.(ABSTRACT TRUNCATED AT 250 WORDS)

Three-dimensional analysis of regional myocardial function in response to nitroglycerin in patients with coronary artery disease.

Biplane cineventriculography was performed at rest and after sublingual nitroglycerin in 13 patients with coronary artery disease. In six patients (responders), there was a significant increase in ejection fraction [40 +/- 5 to 52 +/- 4% (p less than 0.001)], while in the other seven (nonresponders), there was no alteration in ejection fraction. To evaluate the extent of regional myocardial response to nitroglycerin, the contractile pattern of the regional myocardium over the entire ventricular surface was analyzed using a computer-generated three-dimensional model. The spatial coordinates that define the elliptic ventricular surface on a given horizontal plane cross section of the chamber were determined by four counter values in the two orthogonal silhouettes. Then, 32 points at equal angles around the center of gravity of the end-diastolic cavity were generated to form the border image. Repetition of this process for 16 successive cross sections allowed for reconstruction of the ventricular surface by the sequence of 32 X 16 (512) points. The regional wall motion was expressed as the percent change of the radial length, drawn from the center of gravity to each surface point. There was significant heterogeneity in regional response to nitroglycerin. In the responders, the normally contracting area was significantly increased (from 16.5 +/- 16.0 to 36.2 +/- 14.9% of the total surface area, p less than 0.001), largely mediated by the greater improvement in segmental shortening of each graded contractile pattern relative to its deterioration. In the nonresponders, a lessening of the severe dysfunction of the given area was associated with significant deterioration of segmental shortening of the other normally contracting area (49.1 +/- 19.7% of the area with a contractile pattern of grade 5 had deteriorated, p less than 0.05). Thus, the ratio of the area with respective graded segmental shortening was virtually unchanged. These differences in response of the ischemic ventricle to nitroglycerin appeared to be related to the development of adequate coronary collateral vessels as well as to an interaction of changes in preload and afterload.

Prevention of coronary vasoconstriction by diltiazem during dynamic exercise in patients with coronary artery disease.

Whether exercise-induced vasoconstriction of coronary artery stenoses is modified by the administration of calcium antagonists was examined in 14 patients with classic angina pectoris. In this group the effect of intracoronary diltiazem (2 to 3 mg) on luminal area was evaluated in normal and stenotic segments of epicardial coronary arteries during symptom-limited supine exercise. The luminal area of a normal and a stenotic coronary artery segment was determined by quantitative coronary arteriography with a computer-assisted system. Patients were studied at rest, 6 min after 2 to 3 mg of intracoronary diltiazem, during supine bicycle exercise (96 W) and 5 min after sublingual administration of 1.6 mg nitroglycerin. Heart rate, mean pulmonary and aortic pressure as well as the percent change of both normal and stenotic luminal area were determined. Intracoronary administration of diltiazem was associated with mild dilation of both normal (19%, p less than 0.01) and stenotic coronary luminal area (11%, p less than 0.05). During subsequent exercise, luminal area of the stenotic vessel segment increased by 23% (p less than 0.001) and that of the normal vessel segment by 24% (p less than 0.001), whereas in a previously reported control group, luminal area of the stenotic vessel segment decreased by 29% during exercise. After sublingual administration of nitroglycerin, the luminal area of both the normal and the stenotic vessel segment increased further by 19% (p less than 0.01) and 22% (p less than 0.01), respectively, compared with the values after intracoronary administration of diltiazem.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhanced secretion of cardiac hepatocyte growth factor from an infarct region is associated with less severe ventricular enlargement and improved cardiac function.

OBJECTIVES: We hypothesized that the hepatocyte growth factor (HGF) may play a cardioprotective role in human myocardial infarction (MI). BACKGROUND: The HGF is a novel, multifunctional growth factor implicated in wound healing, angiogenesis and promotion of cell survival. Recent animal studies have demonstrated the existence of an HGF system in the heart, where it is activated in response to myocardial ischemia and reperfusion. METHODS: We studied 40 patients with acute myocardial infarction (AMI), who underwent coronary reperfusion therapy upon admission. Approximately four weeks later, left ventricular (LV) catheterization was repeated to determine the LV ejection fraction (EF), end-diastolic volume index (EDVI) and pressure (EDP). The levels of HGF and brain natriuretic peptide (BNP) were measured by collecting blood samples from cardiac veins draining the infarcted region (MI region) and those draining the noninfarcted region (non-MI region). The ratio of the HGF level in the MI region to that in the non-MI region (= MI/non-MI ratio) was calculated in each patient as an index of the MI-related HGF secretion. The MI/non-MI ratio for BNP was also calculated. RESULTS: The MI/non-MI ratio for HGF correlated inversely with LVEDP (r = -0.644, p < 0.0001) and LVEDVI (r = -0.843, p < 0.0001) and positively with LVEF (r = 0.763, p < 0.0001). These correlations were completely opposite in direction from those for BNP and LVEDP (r = 0.678, p < 0.0001), LVEDVI (r = 0.783, p < 0.0001) and LVEF (r = -0.805, p < 0.0001). These findings indicate that cardiac HGF acts in contrast to BNP, a biochemical marker for the development of LV remodeling. CONCLUSIONS: Enhanced secretion of cardiac HGF from the MI region is associated with an attenuation of ventricular enlargement and an improvement in cardiac function. The HGF system may modulate the process of ventricular remodeling and thus have important clinical implications.

Evidence for the delayed effect in human ischemic preconditioning: prospective multicenter study for preconditioning in acute myocardial infarction.

OBJECTIVES: This study aimed to investigate prospectively the protective effect of a first preinfarction angina attack against acute myocardial infarction (AMI) in human hearts without significant collaterals. BACKGROUND: Several retrospective studies and the prospective studies have demonstrated the existence of the preconditioning (PC) effect in humans. However, collaterals were not examined in the prospective studies. In animal models, the PC effect on myocardial infarct size appears soon after PC reperfusion (classic) but disappears within 1 to 2 h. It then reappears 24 to 48 h after reperfusion (the delayed PC effect). Meanwhile, the PC effect on stunning appears 12 h after PC reperfusion (the delayed PC effect). The concept of the classic and delayed PC effects has not been investigated in human AMI studies. If the above concept is also correct in humans, the infarct size and/or impairment of the left ventricular function should be inversely correlated with the time interval between the first preinfarction angina attack and the onset of AMI when that time interval is limited to between 2 and 48 h. METHODS: The subjects were 25 patients with first AMI of the proximal left anterior descending artery who underwent successful direct percutaneous transluminal coronary angioplasty (PTCA) 2 to 6 h after the onset and with no (or poor) collateral circulation (grade 0 or 1). They were divided into two groups: preinfarction angina (PA)(+) group: 11 patients with new onset preinfarction angina from 2 to 48 h before the onset, PA(-) group: 14 patients without angina before infarction. Peak creatine kinase (CK) and cumulative CK were examined, and the left ventricular ejection fraction (LVEF) and the regional wall motion (RWM) were determined from the left ventriculograms during the acute (immediately after the coronary reperfusion) and chronic (four weeks after the onset of AMI) phases. The RWM index (RWMI) was then calculated as the mean motion of chords (standard deviation [SD]/chord) lying in the area of chords of RWM < or = -2 SD in the acute phase (ischemic risk area). RESULTS The increase in the RWMI between the acute and chronic phases was significantly larger in the PA(+) group than in the PA(-) group (1.55 +/- 1.32 and 0.69 +/- 0.75, p < 0.05, respectively) although no significant difference in the enzymatic infarct size was seen between the two groups. The increases in the LVEF and the RWMI were significantly correlated with the time interval from the first preinfarction angina attack to the onset of AMI (r = 0.622, p < 0.05 and r = 0.646, p < 0.05, respectively), but the enzymatic infarct size was not. CONCLUSIONS: The beneficial effect of preinfarction angina on left ventricular wall motion, independently of collateral flows, indicates the existence of the PC effect in humans. The greater protective effect of a longer time interval between angina pectoris and AMI suggests that the protection is due to a delayed PC effect.

Left ventricular systolic series elastic properties in aortic stenosis before and after valve replacement.

In seven patients with aortic valve disease the time course of an auxotonic beat was compared with that of an isovolumetric beat produced by aortic cross clamping during open heart surgery. The rate of systolic stress rise (dS/dt; g.cm-2) of the isovolumetric beat at peak meridional wall stress (Sp; g.cm-2) of the auxotonic beat was determined by tipmanometry and simultaneous sonomicrometry and was found to be 87% of maximum dS/dt. In the second part of the study the stiffness index (k) was calculated in patients undergoing cardiac catheterisation according to: k = 0.87.(max.dS/dt)/Sp.Vcf, where Vcf = normalised midwall circumferential fibre shortening velocity (circ.s-1). In 22 patients, 10 controls and 12 patients with aortic stenosis before (pre) and after (post) valve replacement the systolic stiffness index k (circ-1) was determined using tipmanometry and frame by frame angiocardiography. Muscle fibre diameter and interstitial fibrosis were assessed from left ventricular endomyocardial biopsies. The systolic stiffness index k was 15 circ-1 in controls, 14 in preoperative patients with aortic stenosis and 12 (p less than 0.01 v controls) in postoperative patients. There was a significant correlation between k and muscle fibre diameter (r = 0.55; p less than 0.01) but not between k and interstitial fibrosis or ejection fraction. We conclude that systolic stiffness index k is normal despite marked left ventricular hypertrophy in preoperative patients with aortic stenosis. Following successful valve replacement systolic stiffness index decreased and was significantly lower than in controls. Series elasticity appears to be determined by structures related to the muscle cell rather than to interstitial fibrosis.

Angiotensin-converting enzyme inhibition restores hepatocyte growth factor production in patients with congestive heart failure.

Endothelium-dependent vasodilation is impaired in patients with congestive heart failure. For vascular endothelium, hepatocyte growth factor (HGF) is one of the most potent and specific growth factors, which acts protectively against endothelial dysfunction. HGF production is downregulated by angiotensin II (Ang II) in vitro. We hypothesized that HGF production is impaired as the result of increased Ang II in patients with congestive heart failure, and that if so, the impaired production should be restored with angiotensin-converting enzyme inhibitors (ACE-I). We studied 16 patients with congestive heart failure caused by previous anterior myocardial infarction in whom left ventricular ejection fraction was 35+/-8% (mean+/-SD). Before and approximately 4 weeks after the treatment with ACE-I, blood samples were collected to measure the levels of HGF, Ang II, and brain natriuretic peptide as a biochemical marker for severity of heart failure. We also studied 5 control subjects, in whom heparin increased HGF production to 48+/-5-fold. However, in patients with heart failure, HGF response to heparin was significantly attenuated (24+/-5-fold, P<0.05 vs control). Therapy with ACE-I decreased the levels of Ang II and brain natriuretic peptide and restored HGF production in response to heparin by 43+/-7-fold, comparable to the control response. In conclusion, impaired HGF production was restored after the treatment with ACE-I probably by the mechanism of Ang II suppression. This novel effect of ACE-I may contribute to the clinical improvement in patients with heart failure and thereby may have an important therapeutic implication.

On whether there is a true increase in myocardial stiffness during myocardial ischemia.

In the experimental animal, acute ischemia by interruption of coronary blood supply is accompanied by a steepening of the slope of the left ventricular pressure-volume and pressure-segment length relations. This increase in chamber stiffness is associated with an increase in myocardial stiffness assessed from the slope of the diastolic stress-strain relation. Supply-type ischemia in humans brought about by balloon inflation during coronary angioplasty leads to an upward shift of the pressure-length relation of the ischemic and the adjacent segment combined with a steepening of the slope. In demand ischemia produced by rapid pacing in patients with coronary artery disease, an increased radial stiffness modulus at any level of radial stress was present when compared with that during the resting state. These alterations of the stress-strain relation suggest that the physical properties of the myocardium change during both supply and demand ischemia. The increased diastolic myocardial stiffness appears to result, at least in part, from increased residual interaction between actin and myosin filaments.

Alterations in left ventricular relaxation, early diastolic filling and passive viscoelastic properties during postpacing ischemia.

Alterations in left ventricular relaxation, early diastolic filling, regional myocardial dynamics and passive viscoelastic properties during postpacing ischemia were studied in 9 patients with coronary artery disease. In all patients typical anginal pain developed during pacing tachycardia, and in the postpacing beat, left ventricular end-diastolic pressure increased from 14 +/- 4 to 26 +/- 5 mm Hg (mean +/- standard deviation, p less than 0.01), relaxation time constant increased from 44 +/- 9 to 59 +/- 7 ms (p less than 0.01) and ejection fraction diminished from 63.1 +/- 9.1 to 52.8 +/- 10.8% (p less than 0.01). However, peak rate of early left ventricular filling obtained from frame-by-frame analysis of left ventriculograms did not change significantly. The time difference from segmental peak lengthening to left ventricular peak filling increased significantly in the ischemic segment (32 +/- 30 vs 77 +/- 49 ms, p less than 0.05). Chamber stiffness constant of a viscoelastic model increased significantly from 0.0177 +/- 0.01 to 0.0354 +/- 0.015 (p less than 0.01) without change in chamber viscosity constant. In the ischemic segment, peak rate of lengthening decreased by 45% with ischemia, and peak rate of lengthening normalized for the end-diastolic segment length by 36%. However, peak rate of lengthening normalized for the extent of systolic shortening did not change. The control segment showed a tendency to increase in these 3 parameters, but the changes were not statistically significant. Thus, peak rate of segmental myocardial lengthening decreased with ischemia because of a decrease in segmental shortening.(ABSTRACT TRUNCATED AT 250 WORDS)

Previous angina reduces in-hospital death in patients with acute myocardial infarction.

There is little information on how previous angina influences in-hospital deaths secondary to acute myocardial infarction (MI). This study evaluated the causes of in-hospital deaths in MI patients with and without previous angina. A total of 2,264 consecutive patients were admitted to our hospital due to acute MI. These patients were divided into 2 groups according to the presence or absence of prior MI. Both groups were further divided according to the presence or absence of previous angina. The causes of in-hospital deaths were classified into 4 categories: (1) cardiogenic shock or congestive heart failure, (2) cardiac rupture, (3) arrhythmia, and (4) other causes. In patients with a first MI, the in-hospital mortality rate was lower in patients with previous angina than those without (6.9% vs 11.4%, p <0.01). There was no significant difference between these patients with and without previous angina in in-hospital deaths due to cardiogenic shock or congestive heart failure, arrhythmia, or other causes. Death due to cardiac rupture was less frequent in patients with previous angina (1.4% vs 5.0%, p <0.01). In patients with prior MI, the in-hospital mortality rate was lower in patients with than without previous angina (17.7% vs 25.3%, p <0.05). In contrast to patients with their first MI, there was a trend toward a lower incidence of in-hospital death due to cardiogenic shock or congestive heart failure in patients with previous angina (12.8% vs 19.0%, p = 0.05). There were no significant differences in in-hospital deaths due to cardiac rupture, arrhythmia, and other causes between the 2 subgroups. In multivariate analysis, previous angina was an independent predictor of in-hospital death. Thus, in-hospital deaths after acute MI in patients with previous angina were less because of less cardiac rupture in patients with a first MI and less cardiogenic shock or congestive heart failure in patients with prior MI.

Automated method for left ventricular volume measurement by cineventriculography with minimal doses of contrast medium.

Cineventriculography is of considerable value in the dimensional analysis of the left ventricular cavity, but conventional methods necessitate injection of large amounts of contrast medium. In this study, small dose left ventriculography, using only 5 ml of dye, was performed in order to minimize the untoward effects of contrast medium. A computer-aided image processing system was also developed to enhance the contrast of the ventricular image by subtracting the reference image to eliminate irrelevant background. The boundary of the left ventricular cavity was automatically determined to calculate the instantaneous volume change throughout the cardiac cycle. With use of this small dose of dye, the elevation of left ventricular end-diastolic pressure that consistently occurred 1 to 3 minutes after injection of conventional large doses could be avoided. (End-diastolic pressure at 1 minute after dye injection averaged 11.8 +/- 4.9 [mean +/- standard deviation] for small dose and 19.1 +/- 6.1 mm Hg for large dose injection.) Values for end-diastolic volume, end-systolic volume and ejection fraction calculated from the two consecutive small and large dose left ventriculograms in 16 patients were similar. Thus, minimal doses of contrast medium permit accurate measurement of left ventricular dimension and function without significant hemodynamic derangement. The optimal projection for regional wall motion analysis can easily be selected by this method with repeated exposure at various degrees of obliquity. With this technique, even noninvasive measurement of left ventricular volume can be provided by intravenous injection of small doses of contrast agent.

Diuretic effect of phosphodiesterase inhibitors depends on baseline renal function in patients with congestive heart failure.

We examined the diuretic effects of phosphodiesterase inhibitors in heart failure patients with and without renal failure. We found that, despite the improvement in central hemodynamics, phosphodiesterase inhibitors do not necessarily facilitate diuresis in heart failure in patients with concomitant renal failure.

Gadolinium-enhanced magnetic resonance imaging in acute myocardial infarction.

To investigate the clinical application of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA)-enhanced magnetic resonance imaging (MRI) in the management of acute myocardial infarction (AMI), we examined 44 patients with AMI within 1 month after onset. Enhanced images were classified into 4 types: nontransmural (type 1), transmural and homogeneous (type 2), transmural and marginal (type 3), and no enhancement (type 4). Each enhancement pattern was correlated with angiographic and thallium-201 imaging results. The redistribution images of thallium were graded on a 4-point scale from 0 (normal) to 3 (markedly reduced or absent activity). The percentage of the perimeter affected by asynergy was obtained from the left ventriculogram. Peak creatine kinase and the percentage of asynergic perimeter were significantly higher in type 3 than in other type patients. End-diastolic volume index was significantly higher in type 3 than in type 2 patients. Left ventricular ejection fraction was lowest, and end-systolic volume index, thallium-201 score, and incidence of wall thinning on MRI were highest in type 3 patients. Therefore, the transmural and marginal enhancement pattern (type 3) was compatible with extensive myocardial infarction with infarct expansion and less viable myocardium. In the other types, the infarction was small to moderate in size and left ventricular function was well preserved. Thus, Gd-DTPA-enhanced MRI may be useful in the evaluation of left ventricular function and myocardial viability of the infarct region after AMI.

Effect on survival of previous angina pectoris after acute myocardial infarction.

Although the present study revealed that previous angina improved in-hospital outcome, no further benefit was observed once the patients left the hospital. The worse long-term prognosis was associated with multi-vessel coronary disease in patients with previous angina.

Usefulness of serum troponin T levels on day three or four in predicting survival after acute myocardial infarction.

The appearance of serum troponin T (tn-T) on day 1 after acute myocardial infarction (AMI) strongly depends on coronary reperfusion. In contrast, the kinetics of tn-T release after day 1 after AMI are unaffected by the reperfusion status, and reflect the degradation of myofilaments in irreversibly damaged cells. However, it is not known whether serum tn-T levels after day 1 after AMI can be used to predict the long-term outcome. The purpose of this study was to elucidate the prognostic value of determining the tn-T level on day 3 or 4 after AMI. Serum tn-T levels on day 3 or 4 after AMI were measured in 121 patients (92 men and 29 women, mean age 65 years). Mean follow-up period was 526 days. There were 12 deaths (9 cardiac and 3 noncardiac) during the follow-up period. By Kaplan-Meier analysis, patients with tn-T levels higher than the median level (6.9 ng/ml) had a significantly higher mortality rate than those with submedian levels (p <0.01). By multivariate Cox proportional-hazards regression analysis, the serum tn-T level was an independent predictor of the long-term outcome after AMI (p <0.01). Futhermore, in patients with a first AMI, the serum tn-T level exhibited a significant negative linear correlation with left ventricular ejection fraction assessed 4 weeks after AMI (r = -0.48, p <0.001). Increased serum tn-T levels on day 3 or 4 after AMI are a powerful noninvasive predictor of poor long-term prognosis, reflecting residual left ventricular function after AMI.

Effects of aspirin DL-lysine on thrombin generation in unstable angina pectoris.

To evaluate the effects of aspirin on thrombin generation in patients with unstable angina, plasma levels of thrombin-antithrombin III complex (TAT) as a new marker of thrombin generation and of 11-dehydro-thromboxane B2 (11-dehydro-TXB2) as an indicator of platelet activation were measured in 18 patients with unstable angina, including 8 patients with prolonged rest angina (> 15 minutes). Aspirin DL-lysine (900 mg) was administered intravenously to 9 of the 18 patients (aspirin group); the other 9 were not given aspirin during the first 24 hours of hospitalization (non-aspirin group). Clinical characteristics, angiographic features and medications other than aspirin were similar between the 2 groups. Levels of plasma TAT and 11-dehydro-TXB2 were significantly higher (p < 0.05) in patients with prolonged rest angina than in those without the condition (n = 10). In 5 patients with prolonged rest angina who received aspirin, plasma TAT levels (ng/ml) were significantly decreased (4.52 +/- 1.18 at baseline, 2.50 +/- 0.65 at 1 hour and 2.16 +/- 0.42 at 24 hours after aspirin administration, p < 0.01) with a significant decrease in plasma 11-dehydro-TXB2 levels. However, the reduction in TAT after aspirin administration was slight in patients without prolonged rest angina (n = 4). In contrast, levels of plasma TAT and 11-dehydro-TXB2 in the non-aspirin group remained unchanged during the study period. These results suggest that aspirin rapidly reduces thrombin generation through inhibition of platelet activity in patients with unstable angina with prolonged rest angina.