Toshihiko Ban

Positron emission tomography using fluorine-18 deoxyglucose in evaluation of coronary artery bypass grafting

To assess the clinical value of positron emission tomography (PET) in the evaluation of coronary artery bypass grafting (CABG), PET perfusion and metabolic imaging using nitrogen-13 ammonia and fluorine-18 deoxyglucose (FDG) was performed before and 5 to 7 weeks after CABG in 22 patients with coronary artery disease. Postoperative improvement in hypoperfusion was observed more often in the metabolically active segments (62%) than in the inactive segments (27%) on the preoperative PET study (p less than 0.05). Similarly, the postoperative lessening of wall motion abnormality was observed more often in the metabolically active segments (78%) than in the inactive segments (22%) (p less than 0.001). Of 19 asynergic segments showing increased FDG uptake before operation, the postoperative PET revealed a decrease in FDG uptake in 13 (68%) and persistent uptake in 6 (32%). The improvement in asynergy was observed in all the segments that showed a postoperative decrease in FDG uptake, but in only 50% of those with persistent uptake (p less than 0.01). On the other hand, 4 of 5 segments showing a new FDG uptake after operation revealed further wall motion abnormality. Furthermore, the segments metabolically active before operation were more likely to have patent grafts (95%) than the metabolically inactive segments (70%) (p less than 0.05). Thus, preoperative metabolic imaging using PET appears to be useful for predicting the response to CABG. Improvement in metabolic derangement was associated with improvement in regional function after CABG.

Clinical application of atrial natriuretic polypeptide in patients with congestive heart failure: beneficial effects on left ventricular function.

Synthetic alpha-human atrial natriuretic polypeptide was infused in patients with congestive heart failure (CHF) (New York Heart Association class III or IV) and in those without CHF. The infusion of atrial natriuretic polypeptide (ANP) at a rate of 0.1 microgram/kg/min significantly decreased pulmonary capillary wedge pressure and increased stroke volume index in all of the patients with CHF, whereas it decreased pulmonary capillary wedge pressure but caused no significant change in stroke volume index in the patients without CHF. Concomitant significant reductions in total systemic resistance were observed in both groups of patients. The ANP infusion significantly increased the urine volume, the excretion of sodium, and endogenous creatinine clearance in the patients without CHF. In the patients with CHF, it also showed a tendency to increase all these variables, but the urine volume did not correlate with the reduction in pulmonary capillary wedge pressure. The ANP infusion also decreased plasma aldosterone concentrations in these patients, although no significant difference was observed in the decrement of the plasma aldosterone concentration in the patients with and those without CHF. These findings indicate that the ANP infusion improves left ventricular function in patients with CHF, and suggest that this improvement results mainly from the vasodilating activity of ANP.

α-Human atrial natriuretic polypeptide is released from the heart and circulates in the body

In order to clarify whether or not atrial natriuretic polypeptides are hormones in man, we have measured plasma alpha-human atrial natriuretic polypeptide (alpha-hANP)-like immunoreactivity (alpha-hANP-LI) with or without extraction procedure. alpha-hANP-LI was detected in plasma extracts from all 5 normal subjects and 7 patients with heart diseases. The alpha-hANP-LI concentration in normal peripheral plasma was 37.7 +/- 7.0 pg/ml (mean +/- SE). Plasma concentrations of alpha-hANP-LI in the coronary sinus obtained by cardiac catheterization were 3 to 10 times higher than those in the peripheral vein, inferior vena cava, right atrium, pulmonary artery and aorta. High performance gel permeation chromatography coupled with a radioimmunoassay (RIA) for alpha-hANP revealed that alpha-hANP-LI in normal peripheral plasma eluted at the position corresponding to that of authentic alpha-hANP without detectable amounts of high molecular weight forms. alpha-hANP-LI extracted from plasma taken from the coronary sinus of two patients also showed a single peak of alpha-hANP-LI co-eluting with alpha-hANP. In contrast, not only alpha-hANP but gamma-hANP and beta-hANP, high molecular weight forms, were present in the human atrial tissue. These results indicate that alpha-hANP is the predominant form of alpha-hANP-LI in human plasma and that this form generated in the atrial cardiocytes is preferentially released from these cells and circulates in the body.

Value of thallium-201 reinjection after delayed SPECT imaging for predicting reversible ischemia after coronary artery bypass grafting

The reinjection of a small dose (40 MBq) of thallium-201 after stress and delayed imaging often shows new redistribution in the regions with persistent defect. To assess whether these segments may represent reversible ischemia, reinjection thallium-201 single-photon emission computed tomography (SPECT) was performed after stress and 3-hour delayed imaging in 24 patients before coronary artery bypass grafting (CABG). The left ventricular myocardium was divided into 5 myocardial segments and regional wall motion was scored on a scale from 0 (normal) to 4 (dyskinesia). Thallium-201 findings were compared with improvement in regional perfusion and wall motion 1 to 2 months after CABG. The reinjection imaging identified new redistribution in 15 of 32 persistent defects (47%) on the 3-hour delayed images. In the study of stress and delayed SPECT imaging, the improvement in perfusion was observed in 34 of 43 segments (79%) exhibiting redistribution and 15 of 32 (47%) segments without redistribution (p less than 0.01). The reinjection SPECT identified new redistribution in 12 of the 15 improved segments that were not detected on the delayed images. Similarly, the improvement in wall motion was observed in 23 of 31 segments (74%) exhibiting redistribution and 14 of 30 segments (47%) without redistribution on the delayed images (p less than 0.05). The reinjection identified new redistribution in 10 of the 14 improved segments that were undetected on the delayed images. The predictive values for improvement in perfusion and wall motion by the reinjection imaging were significantly higher (92 and 89%) than those by the delayed imaging (69 and 62%, respectively, p less than 0.05 each).(ABSTRACT TRUNCATED AT 250 WORDS)

Prediction of reversible ischemia after revascularization: perfusion and metabolic studies with positron emission tomography

BACKGROUND Accurate noninvasive determination of myocardial viability is of paramount importance for the clinical identification of patients who will benefit most from revascularization. The preserved metabolic activity in the myocardium, as studied with positron emission tomography (PET), has been considered a gold standard for this purpose. However, recent reports show that moderate hypoperfusion or stress-induced ischemia may represent reversible ischemia. The present study was undertaken to compare the value of perfusion and metabolic studies with PET for predicting improvement in wall motion after revascularization. METHODS AND RESULTS Of 61 patients who had regional asynergy and underwent PET before revascularization, 43 patients who had successful revascularization were included in the study. Each patient underwent rest-stress 13N-ammonia perfusion scans and 18F-fluorodeoxyglucose (FDG) scan at rest while in a fasting state. Reversible ischemia was considered to be present when the resting perfusion was > or = 50% of the peak value, stress-induced hypoperfusion was present, or an increase in FDG uptake was observed. Of 130 asynergy segments, 51 segments had improved wall motion after revascularization. The positive and negative predictive values for improvement in asynergy were 48% and 87% by the rest perfusion study, 63% (P = .05 versus the rest value) and 87% by the rest-stress perfusion study, and 76% (P < .01 versus the rest value) and 92% by the FDG study. CONCLUSIONS FDG PET provided the best predictive value for improvement in wall motion after revascularization. On the other hand, 13N-ammonia PET is useful for predicting nonreversible myocardial scarring when it shows severe hypoperfusion at rest or hypoperfusion without stress-induced ischemia.

Prognostic value of an increased in flourine-18 deoxyglucose uptake in patients with myocardial infarction: Comparision 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.

Plasma levels of brain and atrial natriuretic peptides elevate in proportion to left ventricular end-systolic wall stress in patients with aortic stenosis.

Brain natriuretic peptide (BNP) is a novel cardiac hormone secreted predominantly from the ventricle. We examined the plasma levels of BNP and atrial natriuretic peptide (ANP) in 13 patients with aortic stenosis undergoing corrective surgery. Preoperative plasma BNP and ANP levels correlated highly with preoperative left ventricular end-systolic wall stress (ESS) (r = 0.96, p < 0.0001 and r = 0.95, p < 0.0001, respectively). Moreover, between preoperative and late postoperative states, the difference of the plasma levels of BNP and ANP correlated with the difference of ESS. In two patients with elevated ESS and quite high preoperative plasma BNP (> 1000 pg/ml), rapid decrease of the plasma level after operation was observed. These results suggest that synthesis and secretion of BNP and ANP are stimulated by the increase of left ventricular end-systolic wall stress in patients with aortic stenosis.

Relation of left ventricular perfusion and wall motion with metabolic activity in persistent defects on thallium-201 tomography in healed myocardial infarction

Myocardial viability in persistent thallium (TI)-201 defect is a controversial subject. To assess metabolic activity in segments with persistent defect, stress TI-201 tomography and positron emission tomography using nitrogen-13 ammonia and fluorine-18 2-fluoro-deoxyglucose (FDG) were performed in 28 patients with healed myocardial infarction. The segments with TI-201 perfusion defect in electrocardiogram-determined infarcted areas were selected for assessment. Stress perfusion defect was detected in 61 segments by TI-201 tomography. Twenty-two patients (36%) showed transient defects with redistribution (group 1) and 39 showed persistent defects (group 2). Increase in FDG uptake was observed in 95% in group 1. Among group 2 patients, 15 segments (38%) showed an increase in FDG uptake (group 2A) while the remaining 24 (62%) did not have an increased uptake (group 2B). The decrease in nitrogen-13 ammonia perfusion was more severe in group 2B (-23 +/- 7%) than in group 2A (-13 +/- 9%) (p less than 0.005) and group 1 (-10 +/- 4%) (p less than 0.001). In addition, wall motion scores tended to be lower in group 2B (0.21 +/- 0.71), compared with group 2A (0.67 +/- 0.70) (p = 0.05) and group 1 (0.77 +/- 0.60) (p less than 0.01). These data indicate that metabolic viability was observed in approximately 40% of the segments with persistent TI-201 defect. Preservation of regional perfusion and wall motion in these areas was similar to that in areas with transient TI-201 defect.

Radioimmunoassay for α-human and rat atrial natriuretic polypeptide

Abstract Using a synthetic common carboxy-terminal fragment of α-human atrial natriuretic polypeptide (α-hANP) and α-rat atrial natriuretic polypeptide (α-rANP), we have produced an antiserum for α-ANP(17–28) and established a radioimmunoassay (RIA) for α-ANP that recognizes α-hANP and α-rANP equally. High performance gel permeation chromatography coupled with the RIA revealed that α-hANP-like immunoreactivity (α-hANP-LI) in the human atrium consists of three major components, γ-hANP, α-hANP and another. On the other hand, α-rANP-LI in the rat atrium comprised at least two components, 13K α-rANP-LI and 3K–5K α-rANP-LI, which were presumably γ-rANP and β-rANP, respectively. Thus, considerable amounts of γ-hANP and γ-rANP are present in human right auricles and rat atria, respectively. The RIA established in this study provides a useful tool to investigate the pathophysiological significance of α-ANP and related peptides in cardiovascular disorders and shows that γ-ANP is not only a precursor of α-ANP but acts as an important hormone.

Reactive Oxygen Species Play an Important Role in the Activation of Heat Shock Factor 1 in Ischemic-Reperfused Heart

BACKGROUND The myocardial protective role of heat shock protein (HSP) has been demonstrated. Recently, we reported that ischemia/reperfusion induced a significant activation of heat shock factor (HSF) 1 and an accumulation of mRNA for HSP70 and HSP90. We examined the role of reactive oxygen species (ROSs) in the induction of stress response in the ischemic-reperfused heart. METHODS AND RESULTS Rat hearts were isolated and perfused with Krebs-Henseleit buffer by the Langendorff method. Whole-cell extracts were prepared for gel mobility shift assay using oligonucleotides containing the heat shock element. Induction of mRNA for HSP70 and HSP90 was examined by Northern blot analysis. Repetitive ischemia/reperfusion, which causes recurrent bursts of free radical generation, resulted in burst activation of HSF1, and this burst activation was significantly reduced with either allopurinol 1 mmol/L (an inhibitor of xanthine oxidase) or catalase 2x10(5) U/L (a scavenger of H2O2). Significant activation of HSF1 was observed on perfusion with buffer containing H2O2 150 micromol/L or xanthine 1 mmol/L plus xanthine oxidase 5 U/L. The accumulation of mRNA for HSP70 or HSP90 after repetitive ischemia/reperfusion was reduced with either allopurinol or catalase. CONCLUSIONS Our findings demonstrate that ROSs play an important role in the activation of HSF1 and the accumulation of mRNA for HSP70 and HSP90 in the ischemic-reperfused heart.