Shigeto Namiuchi

Long-Term Right Ventricular Volume Overload Increases Myocardial Fluorodeoxyglucose Uptake in the Interventricular Septum in Patients With Atrial Septal Defect

BACKGROUND Several studies have shown that long-term right ventricular (RV) overload in animal models alters myocardial energy substrate metabolism. However, whether long-term RV volume overload alters this metabolism in the human is unclear. METHODS AND RESULTS We performed positron emission tomography with [(18)F]fluorodeoxyglucose (FDG) and single-photon emission tomography (SPECT) with [(201)Tl]TlCl (Tl) and [(123)I]15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) in 11 patients with atrial septal defect (ASD) and 11 control subjects. In the FDG study, we calculated myocardial metabolic rate of glucose (MMR) in interventricular septum (IVS) and left ventricular (LV) free wall. MMR was significantly increased in IVS compared with LV free wall in the ASD patients (420+/-35 versus 333+/-32 mol x kg(-1) x min(-1); P<0.05) but not in the control group (347+/-27 versus 357+/-25 mol x kg(-1) x min(-1)). In both ASD and control groups, SPECT count was not significantly different between IVS and LV free wall in Tl (ASD, 160+/-11 versus 177+/-12; control, 141+/-12 versus 157+/-14 counts per 15 minutes) and BMIPP studies (ASD, 203+/-14 versus 212+/-18; control, 162+/-16 versus 176+/-16 counts per 15 minutes). MMR in the IVS/LV free wall ratio in the ASD group significantly correlated with indices related to RV volume overload. CONCLUSIONS Given the assumption that long-term RV volume overload did not affect the lumped constant, the present study suggests that, unlike myocardial perfusion or fatty acid analogue uptake, myocardial glucose utilization in IVS relative to LV free wall is increased in relation to long-term RV volume overload in patients with ASD.

Nonselective endothelin receptor antagonist initiated soon after the onset of myocardial infarction may deteriorate 24-hour survival.

&NA; To investigate the effects of endothelin blockade initiated immediately after the onset of myocardial infarction on survival and left ventricular remodeling, treatment with the nonselective receptor antagonist TAK‐044 (n = 22) or saline (n = 19) for 3 weeks was initiated immediately after coronary ligation in rats. The 24‐h survival rate was significantly lower in the TAK‐044 group than in the saline group. The systolic blood pressure 24 h after the onset of myocardial infarction was similar in the saline and TAK‐044 groups, although it was significantly lower in the TAK‐044 group during the 3‐week protocol. Heart weight/tibial length was significantly increased in the TAK‐044 group compared with the saline group. As all deaths in the TAK‐044 group occurred within 24 h after myocardial infarction, we performed additional experiments using a separate group of rats 12–16 h after myocardial infarction. Plasma and myocardial endothelin‐1 levels were significantly increased, and a bolus injection of TAK‐044 significantly reduced left ventricular dP/dtmax in these rats that had had a myocardial infarction compared with sham‐operated rats. Endothelin receptor blockade initiated immediately after the onset of myocardial infarction may deteriorate acute‐phase survival and left ventricular remodeling. Inhibition of the positive inotropic action of endothlin‐1 may partially explain the increased 24‐h mortality.

The systemic inflammation-based Glasgow Prognostic Score as a prognostic factor in patients with acute heart failure.

Aims By combining C-reactive protein and serum albumin concentrations, the Glasgow Prognostic Score (GPS) provides valuable predictions of prognosis in patients with cancer. Both systemic inflammatory response and malnutrition are also common in patients with heart failure. We evaluated the efficacy of the GPS for predicting the prognoses of patients with acute decompensated heart failure (ADHF). Methods We investigated 336 patients who were admitted with ADHF. The GPS (0, 1, and 2) was defined as follows: patients with both elevated C-reactive protein (>1.0 mg/dl) and hypoalbuminemia (<3.5 g/dl) were allocated a score of 2, patients with only one of these biochemical abnormalities were allocated a score of 1, and patients with neither of these abnormalities were allocated a score of 0. Results During the follow-up period (mean ± SD: 504 ± 471 days), 71 patients (21.1%) died. Relative to a GPS of 0, the hazard ratios for all-cause death were 3.40 (95% confidence interval 1.81–6.45) for a GPS of 2 and 1.97 (95% confidence interval 1.06–3.66) for a GPS of 1, as determined using adjusted Cox proportional-hazards analysis. Conclusions The GPS, which is based on systemic inflammation, is useful for predicting the prognoses of hospitalized patients with ADHF.

Regional and temporal profiles of phorbol 12,13-dibutyrate binding after myocardial infarction in rats: effects of captopril treatment.

Phosphoinositide turnover and protein kinase C (PKC) mediate the signaling of angiotensin II, which plays a pivotal role in ventricular remodeling after myocardial infarction (MI). To determine whether PKC is activated after MI, rat hearts after MI were subjected to in vitro quantitative autoradiography with [3H]phorbol 12,13-dibutyrate (PDBu), which is highly selective for PKC. [3H]PDBu binding in the infarcted area increased significantly compared with the non-infarcted region 7 and 21 days after MI, but not 1 and 3 days and 10 months after MI. [3H]PDBu binding in the noninfarcted area was similar to that in the sham-operated rats. Immunohistochemical analysis revealed that abundant macrophages (7 days after MI), fibroblasts, and myofibroblasts (7 and 21 days after MI) occupied the infarcted region. To investigate whether myocardial [3H]PDBu binding is affected by captopril, hearts were subjected to in vitro autoradiography with [3H]PDBu after 1- or 3-week captopril treatment or no treatment. Captopril treatment significantly suppressed [3H]PDBu binding in the infarcted area 3 weeks after MI, but not 1 week after MI nor in the noninfarcted areas. These results suggest that PKC is upregulated during the healing and fibrogenic process after MI and that captopril treatment suppresses the upregulation in the infarcted area.

Effect of angiotensin converting enzyme inhibition on myocardial phosphoinositide metabolism visualised with 1-[1-11C]-butyryl-2-palmitoyl-rac-glycerol in myocardial infarction in the rat

Abstract. We recently reported that myocardial phosphoinositide (PI) metabolism can be visualised by 1-[1-11C]-butyryl-2-palmitoyl-rac-glycerol (11C-DAG) in rats with myocardial infarction (MI). Angiotensin II, the receptors for which are expressed predominantly in infarcted areas with active fibrogenesis rather than in non-infarcted regions, is involved in the upstream signalling systems of PI metabolism and plays an important role in the process of left ventricular (LV) remodelling after MI. We therefore hypothesised that the distribution of 11C-DAG after MI may be affected by the inhibition of angiotensin converting enzyme, which is one of the most important factors in the development of LV remodelling after MI. Rats were injected with 11C-DAG after 3 or 10weeks of treatment with captopril or no treatment following coronary artery ligation, and quantitative autoradiography was performed. Cells occupying the infarcted region were identified by immunohistochemistry. Compared with untreated rats, treatment with captopril for 3 weeks after MI elicited a reduction in the 11C-DAG uptake in the infarcted region (P<0.05) but not in the non-infarcted region, and was associated with a 22% decrease in the heart weight/body weight ratio. The thallium-201 distribution in the infarcted area was similarly low in the rats with and rats without the 3-week captopril treatment after MI. Abundant macrophages and myofibroblasts occupied the infarcted area in both rats with and rats without the captopril treatment for 3 weeks after MI. The 11C-DAG radioactivity in the infarcted region in the untreated rats was lower 10 weeks after MI than 3 weeks after MI (P<0.01). This finding was in agreement with the results of immunohistochemistry demonstrating that the number and size of macrophages and myofibroblasts were remarkably reduced in rats 10 weeks after MI compared with 3 weeks after MI. Captopril treatment for 10 weeks after MI did not decrease the 11C-DAG radioactivity in the infarcted area further. These data suggest that 11C-DAG is useful for visually detecting regions with activated PI metabolism after MI, and that captopril reduces PI metabolism in the infarcted region in the relatively early phase of MI, which might contribute to the attenuation of ventricular remodelling.

[18F] labeled diacylglycerol analogue as a potential agent to trace myocardial phosphoinositide metabolism.

Phosphoinositide metabolism plays an important role in cardiac pathophysiology. To investigate whether [18F]diacylglycerol could be used to trace myocardial phosphoinositide metabolism, lipids were extracted from rat myocardium after the injection. 1-[8-[18F]fluorooctanoyl]-2-palmitoylglycerol and 1-[8-[18F]fluoropalmitoyl]-2-palmitoylglycerol were predominantly metabolized to phosphatidylethanolamine and triacylglycerol, respectively. The radioactivity incorporated into phosphoinositide metabolism was 51, 44, 32, and 30% 3, 5, 10, and 30 minutes after the injection of 1-[4-[18F]fluorobutyryl]-2-palmitoylglycerol, respectively. 1-[4-[18F]fluorobutyryl]-2-palmitoylglycerol might be a potential tracer to evaluate myocardial phosphoinositide metabolism early after the injection.