Optimal criteria for rapid detection of myocardial reperfusion by creatine kinase MM isoforms in the presence of residual high grade coronary stenosis.

Analysis of isoforms of MM creatine kinase (CK) in plasma is being developed as a means for rapid detection of coronary recanalization in patients given thrombolytic agents. To determine whether flow-limiting residual stenosis typical of that seen in patients affects plasma isoform profiles, stenosis sufficient to preclude reactive hyperemia was induced in dogs before coronary occlusion, followed by recanalization in 2 h. Plasma activities of the MM CK isoform released from myocardium (MM3) and its two conversion products elaborated sequentially (MM2 and MM1) were assayed in serial samples with a rapid quantitative chromatofocusing procedure. Reperfusion in 10 dogs shortened the mean intervals (+/-SD) to the occurrence of peak MM3 activity (3.7 +/- 0.9 h), peak MM3 expressed as a percent of total CK activity (MM3%, 2.5 +/- 0.3 h) and the maximal ratio of MM3 to MM1 (2.7 +/- 0.3 h) compared with results in 10 control dogs without reperfusion. Nevertheless, the appearance of these peaks was delayed by 8% to 57% when residual stenosis was present. In contrast, the rate of increase of MM3% was delineated before the peak, was fivefold greater with recanalization (1.19 +/- 0.46 versus 0.26 +/- 0.11% min-1 in control dogs) and was not attenuated by residual stenosis. Thus, this criterion appears capable of delineating recanalization early after thrombolysis whether or not high grade residual stenosis is present.

Compromise of beneficial effects of reperfusion on myocardium supplied by vessels with critical residual stenosis.

Coronary thrombolysis in patients frequently unmasks high grade residual stenosis. To determine whether beneficial effects of reperfusion are compromised by critical residual coronary stenosis, 14 dogs were instrumented with an external left anterior descending coronary artery balloon occluder, Doppler flow probe and adjustable screw clamp. In eight of the dogs, critical stenosis (abolition of reactive hyperemia after a 20 s occlusion; 95.7 +/- 1.0% cross-sectional area reduction) was induced before occlusion and maintained. In the control group (n = 6), no stenosis was induced. Each dog was subjected to 2 h of myocardial ischemia followed by balloon deflation and 24 h of reperfusion. Myocardial blood flow assessed with microspheres was similar during balloon inflation in both groups and indicative of profound ischemia. Transmural blood flow to the reperfused zone assessed 1 min after balloon deflation was significantly greater in control dogs without residual stenosis (383% of normal compared with 120% of normal in dogs with stenosis) (p less than 0.01). Compromise of transmural flow persisted in dogs with stenosis (85% compared with 121% of normal in control dogs after 1 h, p less than 0.05; and 49% compared with 68% after 24 h of reperfusion, p less than 0.05). Diminution of subendocardial blood flow after reperfusion was particularly marked. The extent of infarction was greater in the heart of dogs with residual stenosis. Thus, residual critical coronary stenosis compromises nutritional perfusion and salvage of reperfused myocardium after recanalization. These observations underscore the need for prompt identification of patients with high grade residual stenosis early after coronary thrombolysis and the potential value of angioplasty or coronary surgery in selected patients soon after initial recanalization.

Fate of collateral vessels after successful coronary angioplasty in patients with effort angina.

OBJECTIVES: The purpose of the present study was to evaluate whether severe restenosis after percutaneous transluminal coronary angioplasty (PTCA) promotes collateral development and whether successful dilation regresses collateral vessels. BACKGROUND: It is well known that in the presence of severe coronary stenosis, native collateral arterioles mature to small coronary arteries with several layers of smooth muscle cells. However, it remains unclear whether well developed collateral vessels regress after removal of coronary stenosis. METHODS: The study group comprised 41 patients who underwent elective PTCA for effort angina due to single-vessel disease, followed by repeat PTCA to treat restenosis. We classified the patients into three groups depending on the change in baseline Thrombolysis in Myocardial Infarction (TIMI) flow grade of the ischemia-related artery at initial and repeat PTCA, and we compared the extent of ST segment elevation at 1 min of the first balloon inflation between the two procedures. The average interval from initial to repeat PTCA was 125 days. RESULTS: The three patient groups comprised group A, 12 patients with decreased flow grade because of severe coronary restenosis; group B, 12 patients with increased flow grade who had severe initial stenosis and relatively mild restenosis; and group C, 17 patients with unchanged flow grade. In the presence of comparable rate-pressure products at initial and repeat PTCA, patients in group A had significantly greater ST segment elevation (p < 0.01) at initial than at repeat PTCA (mean +/- SD 0.42 +/- 0.31 vs. 0.13 +/- 0.22 mV). In group B, ST segment elevation was significantly less at initial than at repeat PTCA (0.13 +/- 0.25 vs. 0.19 +/- 0.17 mV, p < 0.05), and in group C, it was comparable at the two procedures (0.37 +/- 0.32 vs. 0.35 +/- 0.33 mV, p = 0.50). CONCLUSIONS: These findings indicate that severe restenosis after PTCA promotes collateral development and that successful dilaton regresses collateral vessels during a relatively short period of time.

Marked elevation of brain natriuretic peptide levels in pericardial fluid is closely associated with left ventricular dysfunction.

OBJECTIVES: The purpose of this study was to investigate whether atrial and brain natriuretic peptides (ANP and BNP, respectively) represent autocrine/paracrine factors and are accumulated in pericardial fluid. BACKGROUND: ANP and BNP, systemic hormones produced by the heart, have elevated circulating levels in patients with heart failure. Recent evidence suggests that the heart itself is one of the target organs for these peptides. METHODS: With an immunoreactive radiometric assay, we measured the concentrations of these peptides in plasma and pericardial fluid simultaneously in 28 patients during coronary artery bypass graft surgery. RESULTS: The pericardial levels of BNP were markedly elevated in patients with impaired left ventricular function. We investigated the correlation of ANP and BNP levels in plasma or pericardial fluid with left ventricular hemodynamic variables. None of the hemodynamic variables correlated with ANP levels in plasma or pericardial fluid. Both plasma and pericardial fluid levels of BNP were significantly related to left ventricular end-diastolic and systolic volume indexes (LVEDVI and LVESVI, respectively). In addition, BNP pericardial fluid levels had closer relations with LVEDVI (r = 0.679, p < 0.0001) and LVESVI (r = 0.686, p < 0.0001) than did BNP plasma levels (LVEDVI: r = 0.567, p = 0.0017; LVESVI: r = 0.607, p = 0.0010). BNP levels in pericardial fluid but not in plasma correlated with left ventricular end-diastolic pressure (r = 0.495, p = 0.0074). CONCLUSIONS: BNP levels in pericardial fluid served as more sensitive and accurate indicators of left ventricular dysfunction than did BNP levels in plasma. Thus, BNP may be secreted from the heart into the pericardial space in response to left ventricular dysfunction, and it may have a pathophysiologic role in heart failure as an autocrine/paracrine factor.

Pericardial fluid from patients with unstable angina induces vascular endothelial cell apoptosis.

OBJECTIVES: The purpose of this study was to investigate whether pericardial fluid from patients with unstable angina (UA) would modulate vascular endothelial cell survival. BACKGROUND: Apoptosis of vascular endothelial cells promotes the coagulation process, playing an important role in the formation of coronary arterial thrombi. However, little is known about the mechanisms of vascular endothelial cell death in acute coronary syndrome. We hypothesized that factors inducing apoptosis are produced by the ischemic heart and accumulated in high concentrations in pericardial fluid. METHOD: Pericardial fluid was obtained during coronary artery bypass surgery from patients with UA (group A, n = 8) and those with stable angina (group B, n = 23). A survival assay of F2 cells from a mouse vascular endothelial cell line was performed in the presence of 10% pericardial fluid from each patient. RESULTS: Pericardial fluid levels of vascular endothelial growth factor were significantly higher in group A than in group B, indicating that group A had more ischemic insults than group B. Pericardial fluid from group A, but not from group B, markedly induced F2 cell death (cell survival relative to fetal bovine serum; group A: 33 +/- 26% vs. group B: 91 +/- 22%, p < 0.01). Cell death was associated with internucleosomal DNA fragmentation, a hallmark of apoptosis. Fractionation of pericardial fluid using a Centricon C-100 demonstrated that apoptosis-inducible activities exist in the Centricon C-100 retentates but not in the filtrates. CONCLUSIONS: Factors that induce vascular endothelial cell apoptosis are secreted into the pericardial space from the hearts of patients with UA. These factors are large complexes or unknown new proteins larger than 100 kDa.

Relation between preexistent coronary collateral circulation and the incidence of restenosis after successful primary coronary angioplasty for acute myocardial infarction.

OBJECTIVES: The purpose of this study was to test the hypothesis that the incidence of restenosis after primary percutaneous transluminal coronary angioplasty for acute myocardial infarction is largely influenced by the preexistent coronary collateral circulation to the infarct-related coronary artery. BACKGROUND: The occurrence of restenosis after coronary angioplasty is the most serious limitation of this procedure. However, prediction of restenosis is difficult. Severe preexistent stenosis of the infarct-related coronary artery causing the development of collateral circulation may result in a high frequency of restenosis. METHODS: The study group consisted of 152 consecutive patients undergoing primary coronary angioplasty within 12 h after the onset of a first acute myocardial infarction. Of this group, 124 patients were angiographically followed up during the convalescent period of infarction and were classified into two groups according to the extent of preexistent collateral circulation to the infarct-related coronary artery. RESULTS: Restenosis occurred in 26 (38%) of 69 patients with poor or no collateral circulation (group A) in contrast to 35 (64%) of 55 patients with good angiographic collateral circulation (group B, p < 0.005). The frequency of preinfarction angina was significantly lower (p < 0.05) in group A (26% [18 of 69]) than in group B (44% [24 of 55]). CONCLUSIONS: These findings indicate that the presence of well developed collateral circulation to the infarct-related coronary artery predicts a higher frequency of restenosis after primary coronary angioplasty. The difference in restenosis rates observed between the patients with and without good collateral circulation probably reflects the impact of underlying severity of stenosis on the long-term outcome after coronary angioplasty.

Improvement of exercise capacity by sarpogrelate as a result of augmented collateral circulation in patients with effort angina.

OBJECTIVES: The purpose of this study was to evaluate whether a serotonin blocker, sarpogrelate, improves exercise capacity as a result of vasodilation of coronary collateral channels in patients with effort angina. BACKGROUND: Serotonin has been reported to decrease coronary collateral blood flow by collateral vasoconstriction in a canine model, suggesting that platelet activation in feeding coronary arteries of the collateral network has the potential to cause collateral vasoconstriction. METHODS: The subjects consisted of 22 patients with effort angina and reproducible ischemic threshold (group A, 11 patients with thrombolysis in myocardial infarction (TIMI) grade 2 or 3 flow of the ischemia-related coronary artery and Rentrop's collateral index 0 or 1; group B, 11 patients with TIMI grade 0 or 1 flow and Rentrop's collateral index 2 or 3). We repeated the symptom-limited treadmill exercise test using the Balke-Ware protocol and exercise tetrofosmin myocardial perfusion scintigraphy with and without pretreatment with 200 mg orally administered sarpogrelate. Each exercise test was performed at 9:00 a.m. on different days. The order of tests with and without sarpogrelate was randomized. RESULTS: In group A, sarpogrelate increased neither exercise time at 0.1 mV ST depression nor double product at 0.1 mV ST depression. In contrast, in group B sarpogrelate increased the exercise duration at 0.1 mV ST depression from 181+/-112 (SD) to 248+/-131 s (p < 0.05) and also increased the double product at 0.1 mV ST depression by 21% (p < 0.01). The severity score using myocardial perfusion scintigraphy at the same workload was significantly (p < 0.01) decreased by 37% in group B, but not in group A (11%), due to the sarpogrelate treatment. CONCLUSIONS: Sarpogrelate augments flow reserve of the collateral circulation and improves exercise capacity in anginal patients with well-developed collaterals. These findings indicate that a serotonin blocker, sarpogrelate, is useful not only as an antiplatelet drugs, but as an antianginal drug.

Prognostic value of an increase in fluorine-18 deoxyglucose uptake in patients with myocardial infarction: comparison with stress thallium imaging.

OBJECTIVES: This study was undertaken to evaluate the prognostic value of an increase in fluorine (F)-18 deoxyglucose uptake compared with clinical, angiographic and stress thallium findings in patients with myocardial infarction. BACKGROUND: Positron emission tomography (PET) imaging using F-18 deoxyglucose has been applied to assess tissue viability in patients with coronary artery disease. We hypothesized that patients with a myocardial segment with augmented F-18 deoxyglucose uptake are at high risk for a future cardiac event. METHODS: One hundred fifty-eight consecutive patients with myocardial infarction referred for F-18 deoxyglucose PET and stress thallium scans were studied. Follow-up was obtained in 84 patients at a mean interval of 23 months to investigate prognostic implications of radionuclide studies. RESULTS: Seventeen patients had a cardiac event during the follow-up interval. Univariate analysis showed that an increase in F-18 deoxyglucose uptake was the best predictor of a future cardiac event (p = 0.0006), followed by the number of stenosed vessels (p = 0.008). In the multivariate analysis, when an increase in F-18 deoxyglucose uptake was entered into the model, only angiographic variables had an independent prognostic value, whereas no other radionuclide variables showed significant prognostic value. Among patients who did not show redistribution, a future cardiac event was observed more often in patients with than in those without an increase in F-18 deoxyglucose uptake (p < 0.05). CONCLUSIONS: Thus, an increase in F-18 deoxyglucose uptake seemed to be the best predictor of a future cardiac event among all clinical, angiographic and radionuclide variables in this study of stable patients with myocardial infarction. Even when a stress thallium-201 scan does not show redistribution, those patients who have an increase in F-18 deoxyglucose uptake in a PET study may be at risk for a future cardiac event, and these patients may need aggressive treatment to prevent a future cardiac event.

Effects of posture on cardiac autonomic nervous activity in patients with congestive heart failure.

OBJECTIVES: We aimed to clarify which recumbent position is preferred by patients with congestive heart failure (CHF) and to evaluate whether cardiac autonomic nervous activity is different among three recumbent positions (supine, left lateral decubitus, right lateral decubitus) in patients with CHF. BACKGROUND: It remains unclear whether cardiac autonomic nervous activity is different among three recumbent positions in patients with CHF. METHODS: We studied 17 male CHF patients (66+/-7 years) and 17 age- and gender-matched healthy subjects (66+/-7 years). Each subject underwent 24-h ambulatory electrocardiographic monitoring. A channel was used to record the CM5 lead, and another to record the signal of the patient's posture with use of a newly developed small-sized detector (3.2 cm x 3.2 cm). By using spectral analysis of heart rate variability, frequency-domain measures were calculated and compared among the three recumbent positions. Normalized high-frequency (HF: 0.15 to 0.40 Hz) power was used as an index of vagal activity and the low frequency (0.04 to 0.15 Hz)/HF power ratio was used as an index of sympathovagal balance. RESULTS: In patients with CHF, the time for the right lateral decubitus position was two-fold longer than that for the supine and left lateral decubitus positions. The increased cardiac sympathetic activity and decreased vagal tone in CHF patients were normalized in the right lateral decubitus position. CONCLUSIONS: The right lateral decubitus position in patients with CHF may be a self-protecting mechanism of attenuating the imbalance of cardiac autonomic nervous activity.

Effects of coronary artery reperfusion on relation between creatine kinase-MB release and infarct size estimated by myocardial emission tomography with thallium-201 in man.

The quantitative relations between serum creatine kinase-MB isoenzyme (CK-MB) release and the final infarct size estimated by myocardial emission computed tomography with thallium-201 was assessed in 37 patients with a first acute transmural myocardial infarction who underwent intracoronary thrombolysis using urokinase 4.6 +/- 1.9 hours after the onset of symptoms. Serial CK-MB determinations were used to calculate the accumulated release of CK-MB (sigma CK-MB). Myocardial emission tomography with thallium-201 was performed 4 weeks after the onset, and infarct volume was measured from reconstructed tomographic images by computerized planimetry. The results are presented for two groups of patients: 11 patients with unsuccessful thrombolysis (group A) and 26 patients with successful thrombolysis (group B). An excellent linear relation was found for group A (sigma CK-MB = 6.4 X infarct volume + 47.7, r = 0.91), whereas a different linear relation was observed for group B (sigma CK-MB = 10.5 X infarct volume + 89.1, r = 0.80). Moreover, serum CK-MB activity reached a peak at 21.1 +/- 2.2 hours after the onset in group A and reached an earlier peak at 12.5 +/- 2.9 hours in group B (p less than 0.001). These data suggest that acute coronary recanalization alters the kinetics of CK-MB release, resulting in greater CK-MB release into the serum for equivalent infarct volume estimated by myocardial emission tomography with thallium-201. Thus, serum CK-MB time-activity curves after acute myocardial infarction may be influenced considerably by acute reperfusion, which is an important factor that should be incorporated in the interpretation of enzymatic estimates of infarct size in human patients.

Effect of clarithromycin on renal excretion of digoxin: interaction with P-glycoprotein.

We present a digoxin-clarithromycin interaction in two patients in whom digoxin concentrations were unexpectedly increased. The ratio of renal digoxin clearance to creatinine clearance in one patient was lower during the concomitant administration of clarithromycin (0.64 and 0.73) than that after cessation of clarithromycin administration (1.30 +/- 0.20; mean +/- SD). Because P-glycoprotein could play an important role in the renal secretion of digoxin, we hypothesized that clarithromycin decreases renal digoxin excretion by inhibiting P-glycoprotein-mediated transport. Digoxin transport was evaluated with use of a kidney epithelial cell line, which expresses the human P-glycoprotein on the apical membrane by transfection with MDR1 complementary deoxyribonucleic acid. Clarithromycin inhibited the transcellular transport of digoxin from the basolateral to the apical side in a concentration-dependent manner and concomitantly increased the cellular accumulation of digoxin. These results suggest that clarithromycin may inhibit the P-glycoprotein-mediated tubular secretion of digoxin, and this interaction mechanism may contribute to an increase in the serum digoxin concentration.

Technetium-99m-pyrophosphate uptake as an indicator of myocardial injury without infarct.

UNLABELLED: Technetium-99m-pyrophosphate (PYP) is bound to calcium in necrotic myocardium and has been used clinically to evaluate myocardial infarction. Technetium-99m-PYP is also reported to accumulate in myocardium with unstable angina pectoris and it is speculated that severe ischemia with noninfarcted tissue may also increase uptake of 99mTc-PYP. In this paper, 99mTc-PYP uptake was determined in various models of myocardial ischemia of short duration to examine its applicability to the assessment of myocardial viability. METHODS: In 23 open-chest dogs under anesthesia, models of ischemia-reperfusion of the left anterior descending artery (LAD) subjected to ischemia for 10, 30 or 60 min were produced. Wall motion was examined by echocardiography and myocardial blood flow was calculated using colored microspheres. Technetium-99m-PYP was injected after each ischemic intervention and reperfusion. RESULTS: Technetium-99m-PYP showed 1.18 +/- 0.009 in the uptake ratio (ischemic area/normal area) following 10-min ischemia (11 dogs). The uptake ratio following 30-min ischemia (8 dogs) showed a significantly higher increase than that following 10-min ischemia (4.09 +/- 1.75; p < 0.05), permitting in vivo and ex vivo imaging. After 60-min ischemia resulting in infarction (4 dogs), 99mTc-PYP uptake of the ischemic area showed an uptake ten times that of the normal area (transmural: 12.2 +/- 2.9, epicardium: 7.5 +/- 1.9, endocardium: 16.8 +/- 4.1). CONCLUSIONS: These findings indicate that since 99mTc-PYP accumulates in injured myocardium, its concurrent use with blood flow imaging is useful for the assessment of severity of ischemia, injured area and myocardial viability.

Effect of metabolic substrate on BMIPP metabolism in canine myocardium.

UNLABELLED: The lipid tracer 1 5-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) is clinically useful, and its basic metabolism is being analyzed. Because the pharmacokinetics of this lipid tracer may be affected by blood concentrations of fatty acid or glucose, this study evaluated the effects of excess levels of lipid or glucose on BMIPP uptake and metabolism. METHODS: A technique using an open-chest dog model was used. Blood sampling was performed from the left anterior descending coronary artery and great cardiac vein after an injection of 123I-BMIPP either with a glucose infusion (n = 6) or a lipid infusion (n = 5). High performance liquid chromatography and double-tracer kinetic analyses clarified the extraction, retention, backdiffusion and further metabolism of BMIPP. These results were compared with data from control dogs (n = 6). RESULTS: In this experiment, a 10-fold increase over the normal lipid blood concentration and twofold increase over the normal blood glucose concentration were evaluated with either intralipid or glucose infusion, respectively. In the lipid infusion studies, the extraction significantly decreased compared with the control values (74% +/- 12% to 58% +/- 8%; p < 0.05), and the washout increased from 50% +/- 13% to 68% +/- 16% (p < 0.05). The BMIPP backdiffusion increased (p < 0.05), and the levels of the further metabolites decreased (p < 0.05), while the retention level remained constant (normal, 89% +/- 9%; lipid infusion, 91% +/- 3%; ns). In the glucose infusion studies, the BMIPP extraction, retention and washout showed no statistical differences compared to controls; however, these parameters showed the same tendencies as those in the lipid infusion group. In addition, the BMIPP backdiffusion increased significantly (control, 25.1% +/- 8%; glucose infusion, 48.7% +/- 25.6%; p < 0.05) as it did after the lipid infusion. CONCLUSION: BMIPP metabolism and uptake are affected by excess concentrations of lipid and glucose in the blood. However, the retention of BMIPP was not affected by either type of infusion. The BMIPP backdiffusion and the further metabolite comprising 10% of the tracer extracted were affected both by the lipid and glucose infusions. These results indicate that an excess fat concentration and glucose affect BMIPP uptake, especially the extraction of BMIPP and BMIPP backdiffusion.

Significance of fill-in after thallium-201 reinjection following delayed imaging: comparison with regional wall motion and angiographic findings.

To identify reversible defects, reinjection of a small amount of thallium-201 (201Tl) following 3-hr delayed imaging was performed in 60 patients with coronary artery disease who had perfusion abnormalities on their post-exercise 201Tl images. Thallium-201 uptake was visually scored and judged as normal (Group 1), reversible defect (Group II), new fill-in after reinjection (Group IIIa) and no fill-in even after reinjection (Group IIIb). New fill-in after reinjection was observed in 27 segments of the 85 segments (32%), showing persistent defect on the stress and delayed images. The wall motion in Group IIIa was worse than Group II but better than Group IIIb. Group IIIa showed Q-wave on ECG more often (69%) than Group II (27%) (p less than 0.01), but less often than Group IIIb (85%) (p less than 0.05). These data indicate that the reinjection 201Tl imaging often identifies new fill-in in the areas of no redistribution on the delayed images and it may hold promise for assessing tissue viability which the conventional imaging may underestimate.

Metabolic activity in the areas of new fill-in after thallium-201 reinjection: comparison with positron emission tomography using fluorine-18-deoxyglucose.

Reinjection of thallium-201 after recording the 3-hr delayed scan often demonstrates improvement in areas of persistent abnormalities. To determine the metabolic activity of these areas, the changes seen on stress/redistribution/reinjection thallium SPECT were compared with PET using fluorine-18-fluorodeoxyglucose (FDG) in 18 patients with coronary artery disease. Of 48 segments showing no redistribution on the delayed scan, the reinjection scan identified new fill-in in 20 segments (42%), all of which demonstrated FDG uptake. In contrast, only 7 of the 28 segments (25%) showing no fill-in after reinjection were PET viable (p less than 0.01). Eleven patients had coronary bypass graft surgery after the radionuclide study. The majority of the segments showing redistribution (87%) and new fill-in after reinjection (65%) improved in wall motion, whereas only eight segments (25%) without new fill-in improved after surgery. Of those without new fill-in, two segments showing PET ischemia improved in wall motion, whereas the remaining six segments showing PET scar did not improve after surgery. Thus, the segments showing new fill-in after reinjection are PET viable myocardium. However, reinjection thallium imaging still underestimates the extent of tissue viability compared to PET imaging.

Regional wall thickening of left ventricle evaluated by gated positron emission tomography in relation to myocardial perfusion and glucose metabolism.

Regional wall thickening was assessed by electrocardiographically gated positron emission tomography (ECG-gated PET) in 26 patients with coronary artery disease. The standardized percent count increase from end-diastole to end-systole (S-percent Cl) was calculated as an index of wall thickening. The S-percent Cl was 77.8% +/- 28.9% in the segments with normal perfusion at rest, 51.9% +/- 29.5% in those with mild hypoperfusion, and 32.8% +/- 30.9% in those with severe hypoperfusion (p less than 0.001, each). Among the segments with resting hypoperfusion, the S-percent Cl was 38.9% +/- 31.5% in those without stress-induced ischemia and 48.7% +/- 30.9% in those with ischemia (p less than 0.05). Furthermore, among resting severe hypoperfusion, the S-percent Cl was 23.0% +/- 23.9% in the segments without fluorine-18-fluorodeoxyglucose (FDG) uptake and 37.8 +/- 32.9% in those with FDG uptake (p less than 0.05). These results suggest that stress-induced ischemia and FDG accumulation correlated with wall thickening. Thus, quantitative analysis of regional wall thickening seems to be useful for combined analysis of regional function, perfusion and metabolism in coronary patients.

Simple quantification of regional myocardial uptake of fluorine-18-deoxyglucose in the fasting condition.

Quantitative measurement of myocardial uptake of fluorine-18-deoxyglucose (FDG) is required for assessing tissue viability in the fasting state due to suppressed FDG uptake in the normal myocardium. A simple FDG uptake index (% dose per 100 ml tissue) has been introduced to compare with the fractional FDG uptake in 21 patients who underwent serial arterial blood sampling (14 under fasting and 7 under post-prandial conditions) and to measure the normal range in each myocardial segment in the study of 10 normal subjects (all in the fasting condition). Since the integral of plasma FDG values correlated with the body-weight corrected injected FDG dose (r = 0.82), an excellent correlation was observed between the FDG uptake index and the fractional FDG uptake (r = 0.98) in the fasting condition. In addition, the FDG uptake index correlated well with the regional metabolic rate of glucose calculated with the Patlak graphic analysis (r = 0.99). But this correlation was different in the postprandial condition and in the fasting condition in diabetic patients. In the study of normal subjects, the FDG uptake index was slightly higher in the lateral and inferior segments, as compared to the septal and anterior segments (p less than 0.05, each). We conclude that the FDG uptake index is considered as a simple and reliable parameter for quantitative assessment of myocardial FDG uptake in the nondiabetic patients in the fasting condition. Since its uptake was heterogeneous, FDG uptake should be carefully evaluated for assessing myocardial viability by comparing normal values in each segment.

Interpolating scan and oblique-angle tomograms in myocardial PET using nitrogen-13 ammonia.

The effect of low sensitivity areas or gaps between adjacent slices of the multislice positron emission tomography on detection of myocardial perfusion abnormality with 13NH3 was evaluated segmentally in 36 patients with coronary artery disease at rest or during exercise. The detectability of the defects in RCA or LAD region was 80% in single-position scans in stress studies. The false-negative defects were located mainly in the inferior wall, apicoinferior wall, or high anterior wall. When the patients were moved half the slice interval to perform the interpolating scan, and the two sets of images were interlaced with each other, the detectability increased to 88%. The interpolating scan also allowed reconstruction of long-axis and short-axis tomograms in high quality, which further improved the detectability of perfusion defects (100% for RCA or LAD and 75% for LCX lesion) and helped in understanding the anatomic relationships to the coronary artery territories.

Regional metabolic abnormality in relation to perfusion and wall motion in patients with myocardial infarction: assessment with emission tomography using an iodinated branched fatty acid analog.

The clinical usefulness of single-photon tomography using both a beta-methyl-branched fatty acid analog, 123I-15-(p-iodophenyl)-3-methyl pentadecanoic acid (BMIPP) and 201TI was assessed in 4 normal subjects and 28 patients with myocardial infarction. A homogeneous distribution of the tracer in the left ventricular myocardium was observed in each normal subject. BMIPP uptake was decreased compared to 201TI (discordant) in 17/28 patients (61%) and in 49/196 myocardial segments (25%). Such discordant BMIPP uptake was observed more often in areas of acute myocardial infarction (59% at less than or equal to 4 wk versus 31% at greater than 4 wk after onset) (p less than 0.01) and areas supplied with revascularized arteries (74% for revascularized versus 28% for nonrevascularized areas) (p less than 0.01). In addition, the discordant BMIPP uptake was seen more often in the segments exhibiting a wall motion score lower than the perfusion score (46%) in comparison to segments showing a similar decrease in both the wall motion and perfusion scores (12%) (p less than 0.01). Thus, BMIPP imaging may play a major role in increasing our understanding of the relationship between perfusion and wall motion, particularly in patients with acute myocardial infarction and those who received revascularization therapy.

Myocardial lipid metabolism in compensated and advanced stages of heart failure: evaluation by canine pacing model with BMIPP.

UNLABELLED: The normal myocardium uses primarily fatty acid as its energy source, but, as heart failure develops, the myocardial fatty acid metabolism is limited. In this study, impairment of the lipid metabolism in heart failure was serially evaluated with 123I-(rho-iodophenyl)3-(R,S)-methylpentadecanoic acid (BMIPP), a radioiodinated fatty acid analog. METHODS: Rapid ventricular pacing was introduced in 10 beagle dogs. Dogs were subjected to hemodynamic assessment and measurement of catecholamine before and after pacing. After 1 wk (group A; n = 4) and 4 wk (group B; n = 6) of pacing, BMIPP was injected directly into the left anterior descending artery; its extraction, retention, and washout rate in the early phase were calculated, and the metabolites in the myocardium were evaluated using high-performance liquid chromatography. These factors were compared with those of healthy control animals (group C; n = 6). RESULTS: The left ventricular ejection fraction and cardiac output decreased significantly in groups A and B after pacing. The pulmonary capillary wedge pressure did not change in group A but increased significantly in group B. Plasma norepinephrine increased progressively as heart failure developed but did not reach statistical significance. The washout rate in the early phase increased, significantly in groups A and B compared with that of group C. Extraction and retention of BMIPP did not change in group A. In group B, extraction tended to decrease and retention decreased significantly compared with that of group C. The levels of full metabolite formed by complete oxidation of BMIPP decreased, and backdiffusion of BMIPP increased significantly in groups A and B compared with that of group C. Myocardial blood flow did not change among the three groups. CONCLUSION: Our study indicates that myocardial fatty acid oxidation begins to be inhibited and that washout of BMIPP increases in the compensated stage of left ventricular dysfunction but that myocardial extraction and retention of fatty acid are definitely impaired in the advanced stage of heart failure. Therefore, as assessed by BMIPP, the myocardial lipid metabolism is related to the pathophysiology of the development and worsening of heart failure.