Orofacial Pain Associated with Vasospastic Angina: A Case Report.

The primary symptom of ischemic heart disease is typically chest pain, but in some cases, this pain may radiate to the maxillofacial region. This article describes the case of a 44-year-old man with orofacial pain of cardiac origin. The patient was suspected to be suffering from cardiac disease by the oral and maxillofacial surgeon and was referred to a cardiologist, where he received a heart examination. The patient was diagnosed by means of cardiac catheterization as having coronary spastic angina. During catheterization, intracoronary ergonovine maleate induced orofacial pain that was almost the same in character and intensity as the patient's first episode. The orofacial pain was considered to be telalgia from coronary spastic angina. The patient started medication on the same day as the diagnosis. There was no recurrence of any symptoms. These findings indicate that in such cases, the dentist may contribute to identifying ischemic heart disease and should refer the patient to a cardiologist.

Correlation between renal function and common risk factors for chronic kidney disease in a healthy middle-aged population: a prospective observational 2-year study.

BACKGROUND/AIMS: Age, proteinuria, metabolic syndrome, and hyperuricemia are the reported risk factors for chronic kidney disease (CKD) and cardiovascular disease (CVD). However, the best predictor of changes in renal function in the early stages of renal disease in a healthy middle-aged population is still unknown. Our study evaluated the correlation between changes in renal function and common risk factors to determine such a predictor. METHODS: In total, 2,853 healthy persons aged ≤50 years participated in the study. They had no proteinuria and were not on medications for hypertension, diabetes mellitus, hyperlipidemia, or hyperuricemia. Over 2 years, participants underwent annual health screening. The relationship between changes in estimated glomerular filtration rate (eGFR) and changes in risk factors for CKD was evaluated using univariate and multivariate linear regression analyses. RESULTS: Over 2 years, eGFR showed a significant decrease. Univariate regression analysis revealed that changes in fasting plasma glucose (FPG), total cholesterol, LDL-cholesterol, serum uric acid levels, and hemoglobin showed a significant negative correlation with changes in eGFR. Multiple regression analysis confirmed that changes in FPG, serum uric acid levels, in particular, and hemoglobin had a significant negative correlation with changes in eGFR. CONCLUSION: The changes in eGFR and other variables over 2 years were small and could be within expected biologic variation. A longer observational study is needed to elucidate whether FPG, serum uric acid and hemoglobin represent the earliest markers of eGFR decline.

Comparison between integrated backscatter intravascular ultrasound and 64-slice multi-detector row computed tomography for tissue characterization and volumetric assessment of coronary plaques.

BACKGROUND: The purpose of this study was to determine the cut-off values of Hounsfield units (HU) for the discrimination of plaque components and to evaluate the feasibility of measurement of the volume of plaque components using multi-detector row computed tomography (MDCT). METHODS: Coronary lesions (125 lesions in 125 patients) were visualized by both integrated backscatter intravascular ultrasound (IB-IVUS) and 64-slice MDCT at the same site. The IB values were used as a gold standard to determine the cut off values of HU for the discrimination of plaque components. RESULTS: Plaques were classified as lipid pool (n =50), fibrosis (n =65) or calcification (n =35) by IB-IVUS. The HU of lipid pool, fibrosis and calcification were 18 ± 18 HU (-19 to 58 HU), 95 ± 24 HU (46 to 154 HU) and 378 ± 99 HU (188 to 605 HU), respectively. Using receiver operating characteristic curve analysis, a threshold of 50 HU was the optimal cutoff values to discriminate lipid pool from fibrosis. Lipid volume measured by MDCT was correlated with that measured by IB-IVUS (r =0.66, p <0.001), whereas fibrous volume was not (r =0.21, p =0.059). CONCLUSION: Lipid volume measured by MDCT was moderately correlated with that measured by IB-IVUS. MDCT may be useful for volumetric assessment of the lipid volume of coronary plaques, whereas the assessment of fibrosis volume was unstable.

Both stimulation of GLP-1 receptors and inhibition of glycogenolysis additively contribute to a protective effect of oral miglitol against ischaemia-reperfusion injury in rabbits.

BACKGROUND AND PURPOSE: We previously reported that pre-ischaemic i.v. miglitol reduces myocardial infarct size through the inhibition of glycogenolysis during ischaemia. Oral administration of miglitol has been reported to produce glucagon-like peptide 1 (GLP-1). We hypothesized that p.o. administration of miglitol, an absorbable antidiabetic drug, reduces myocardial infarct size by stimulating GLP-1 receptors and inhibiting glycogenolysis in the myocardium. EXPERIMENTAL APPROACH: The effects of p.o. and i.v. administration of miglitol on myocardial infarct size were compared in a rabbit model of ischaemia induced by 30 min of coronary occlusion and 48 h of reperfusion. The levels of phospho(p)-PI3kinase and p-Akt were measured in cardiac tissue by use of Western blot analysis. RESULTS: Both p.o. and i.v. administration of miglitol reduced the infarct size, and this effect was greater after p.o. than after i.v. administration under similar plasma miglitol concentrations. The reduction in infarct size induced by p.o. miglitol but not that induced by i.v. miglitol was partially inhibited by treatment with exendin(9-39), a GLP-1 receptor blocker. Both p.o. and i.v. miglitol improved ejection fraction and ±dP/dt after myocardial infarction. Miglitol administered p.o. but not i.v. up-regulated the myocardial expression of phospho(p)-PI3kinase and p-Akt following myocardial infarction; an effect that was inhibited by exendin(9-39). CONCLUSIONS AND IMPLICATIONS: Administration of miglitol p.o. reduces myocardial infarct size through stimulation of GLP-1 receptors and activation of PI3kinase-Akt pathway in addition to the inhibition of glycogenolysis. These findings may have clinical implications for the p.o. administration of miglitol for the treatment of patients with diabetes mellitus combined with coronary artery disease.

Postconditioning effect of granulocyte colony-stimulating factor is mediated through activation of risk pathway and opening of the mitochondrial KATP channels.

Granulocyte colony-stimulating factor (G-CSF) has been reported to improve cardiac function after myocardial infarction. However, whether postinfarct acute effect of G-CSF is mediated through the same signaling pathways as those of ischemic postconditioning is still unclear. We examined the postinfarct acute effect of G-CSF on myocardial infarct size and its precise molecular mechanism. Japanese white rabbits underwent 30 min of ischemia and 48 h of reperfusion. Rabbits were intravenously injected 10 µg/kg of G-CSF (G-CSF group) or saline (control group) immediately after reperfusion. The wortmannin + G-CSF, PD-98059 + G-CSF, N(ω)-nitro-L-arginine methyl ester (l-NAME) + G-CSF, and 5-hydroxydecanoic acid sodium salt (5-HD) + G-CSF groups were respectively injected with wortmannin (0.6 mg/kg), PD-98059 (0.3 mg/kg), L-NAME (10 mg/kg), and 5-HD (5 mg/kg) 5 min before G-CSF administration. Myocardial infarct size was calculated as a percentage of the risk area of the left ventricle. Western blot analysis was performed to examine the signals such as protein kinase B (Akt), extracellular signal-regulated protein kinase (ERK), eNOS, p70S6 kinase (p70S6K), and glycogen synthase kinase-3ß (GSK3ß) in the ischemic myocardium after 48 h of reperfusion. The infarct size was significantly smaller in the G-CSF group (26.7 ± 2.7%) than in the control group (42.3 ± 4.6%). The infarct size-reducing effect of G-CSF was completely blocked by wortmannin (44.7 ± 4.8%), PD-98059 (38.3 ± 3.9%), L-NAME (42.1 ± 4.2%), and 5-HD (42.5 ± 1.7%). Wortmannin, PD-98059, L-NAME, or 5-HD alone did not affect the infarct size. Western blotting showed higher myocardial expression of phospho-Akt, phospho-ERK, phosho-eNOS, phosho-p70S6K, and phosho-GSK3ß at 10 min and 48 h after reperfusion in the G-CSF group than in the control group. In conclusion, postreperfusion G-CSF administration reduces myocardial infarct size via activation of phosphatidylinositol 3-kinase-Akt and ERK prosurvival signaling pathways and their downstream targets eNOS, p70S6 kinase, GSK3ß, and mitochondrial ATP-dependent K(+) channel.

Antidiabetic drug voglibose is protective against ischemia-reperfusion injury through glucagon-like peptide 1 receptors and the phosphoinositide 3-kinase-Akt-endothelial nitric oxide synthase pathway in rabbits.

Glucagon-like peptide 1 (GLP-1) reportedly exerts a protective effect against cardiac ischemia. We hypothesized that the alpha-glucosidase inhibitor voglibose, an unabsorbable antidiabetic drug with cardioprotective effects, may act through stimulation of GLP-1 receptors. The results of the present study suggest oral administration of voglibose reduces myocardial infarct size and mitigates cardiac dysfunction in rabbits after 30 minutes of coronary occlusion and 48 hours of reperfusion. Voglibose increased basal and postprandial plasma GLP-1 levels and reduced postprandial plasma glucose levels. The infarct size-reducing effect of voglibose was abolished by treatment with exendin(9-39), wortmannin, Nomega-nitro-L-arginine methylester, or 5-hydroxydecanoate), which inhibit GLP-1 receptors, phosphoinositide 3-kinase, nitric oxide synthase, and K(ATP) channels, respectively. Western blot analysis showed that treatment with voglibose upregulated myocardial levels of phospho-Akt, phosphoendothelial nitric oxide synthase after myocardial infarction. The upregulation of phospho-Akt was inhibited by exendin(9-39) and wortmannin. These findings suggest that voglibose reduces myocardial infarct size through stimulation of GLP-1 receptors, activation of the phosphoinositide 3-kinase-Akt-endothelial nitric oxide synthase pathways, and the opening of mitochondrial K(ATP) channels. These findings may provide new insight into therapeutic strategies for the treatment of patients with coronary artery disease.

Evaluation of left atrial degeneration for the prediction of atrial fibrillation: usefulness of integrated backscatter transesophageal echocardiography.

OBJECTIVES: The purpose of this study was to elucidate the usefulness of integrated backscatter (IBS) transesophageal echocardiography (TEE) for the evaluation of atrial degeneration and clarify whether atrial degeneration predicts the occurrence of atrial fibrillation (AF). BACKGROUND: One of the causes of AF is pathological degeneration of the left atrium (LA). However, there is no appropriate method to evaluate degeneration of the LA in the clinical setting. METHODS: The IBS images were acquired with TEE with a 4- to 7-MHz transducer. The IBS values were calculated as the average power of the backscattered signal from regions of interest (ROI). In the pathological study, we measured IBS values of 21 left atrial specimens obtained from 10 autopsied hearts. Relative interstitial area in the ROI was automatically calculated by a personal computer. In the clinical study, we measured IBS values of the entire LA wall at 5-mm intervals (except the posterior wall) in 42 patients (18 non-AF patients, 14 paroxysmal AF patients, and 10 chronic AF patients). Each IBS value was color-coded to construct 3-dimensional maps. RESULTS: There was a weak correlation between the relative interstitial area and IBS values (r = 0.45, p = 0.038). Average corrected IBS values of total voxels in color-coded maps in the AF group (24.4 +/- 6.4 dB) and the paroxysmal AF group (23.9 +/- 9.6 dB) were significantly greater than those in the non-AF group (15.6 +/- 7.4 dB, p = 0.007), whereas there was no significant difference in LA diameter between the paroxysmal AF group (39.4 +/- 6.5 mm) and the non-AF group (36.7 +/- 5.5 mm). CONCLUSIONS: With IBS-TEE, we can identify an increase in atrial degeneration that might predict the occurrence of AF before LA dilation.

Postinfarct treatment with oxytocin improves cardiac function and remodeling via activating cell-survival signals and angiogenesis.

BACKGROUND: We investigated whether postinfarct treatment with oxytocin (OT) improves left ventricular (LV) function and remodeling via cardiac repair of myocardial ischemia-reperfusion injury. METHODS AND RESULTS: Experiments were performed with 30 minutes of coronary occlusion and 2 or 14 days of reperfusion rabbit model of myocardial infarction. LV function and remodeling were significantly improved in the OT group. The infarct size was significantly reduced in the OT group. The number of CD31-positive microvessels was increased significantly in the OT group. There were no Ki67-positive myocytes in either group. The expression of the OT receptor, phosphorylated (p)-Akt protein kinase, p-extracellular signal-regulated protein kinase, p-enodthelial NO synthase, p-signal transducer and activator of transcription 3, vascular endothelial growth factor, B-cell lymphoma 2, and matrix metalloproteinase-1 (MMP-1) were markedly increased in the OT group days 2 and 14 post myocardial infarction. CONCLUSIONS: Postinfarct treatment with OT reduces myocardial infarct size and improves LV function and remodeling by activating OT receptors and prosurvival signals and by exerting antifibrotic and angiogenic effects through activation of MMP-1, endothelial NO synthase, and vascular endothelial growth factor. These findings provide new insight into therapeutic strategies for ischemic heart disease.

Antidiabetic drug pioglitazone protects the heart via activation of PPAR-gamma receptors, PI3-kinase, Akt, and eNOS pathway in a rabbit model of myocardial infarction.

The insulin-sensitizing drug pioglitazone has been reported to be protective against myocardial infarction. However, its precise mechanism is unclear. Rabbits underwent 30 min of coronary occlusion followed by 48 h of reperfusion. Rabbits were assigned randomly to nine groups (n = 10 in each): the control group (fed a normal diet), pioglitazone group (fed diets containing 1 mg.kg(-1).day(-1) pioglitazone), pioglitazone + 5-hydroxydecanoic acid (HD) group [fed the pioglitazone diet + 5 mg/kg iv 5-HD, a mitochondrial ATP-sensitive K(+) (K(ATP)) channel blocker], pioglitazone + GW9662 group [fed the pioglitazone diet + 2 mg/kg iv GW9662, a peroxisome proliferator activated receptor (PPAR)-gamma antagonist], GW9662 group (fed a normal diet + iv GW9662), pioglitazone + wortmannin group [fed the pioglitazone diet + 0.6 mg/kg iv wortmannin, a phosphatidylinositol (PI)3-kinase inhibitor], wortmannin group (fed a normal diet + iv wortmannin), pioglitazone + nitro-l-arginine methyl ester (l-NAME) group [fed the pioglitazone diet + 10 mg/kg iv l-NAME, a nitric oxide synthase (NOS) inhibitor], and l-NAME group (fed a normal diet + iv l-NAME). All groups were fed the diets for 7 days. The risk area and nonrisk area of the left ventricle (LV) were separated by Evans blue dye, and the infarct area was determined by triphenyltetrazolium chloride staining. The infarct size was calculated as a percentage of the LV risk area. Western blotting was performed to assess levels of Akt and phospho-Akt and phospho-endothelial NOS (eNOS) in the myocardium following reperfusion. The infarct size was significantly smaller in the pioglitazone group (21 +/- 2%) than in the control group (43 +/- 3%). This effect was abolished by GW9662 (42 +/- 3%), wortmannin (40 +/- 3%), or l-NAME (42 +/- 7%) but not by 5-HD (24 +/- 5%). Western blotting showed higher levels of phospho-Akt and phospho-eNOS in the pioglitazone group. Pioglitazone reduces the myocardial infarct size via activation of PPAR-gamma, PI3-kinase, Akt, and eNOS pathways, but not via opening the mitochondrial K(ATP) channel. Pioglitazone may be a novel strategy for the treatment of diabetes mellitus with coronary artery disease.

Simvastatin reduces myocardial infarct size via increased nitric oxide production in normocholesterolemic rabbits.

OBJECTIVE: Statins have been reported to be protective against myocardial infarction (MI). Moreover, statin drugs upregulate nitric oxide (NO) in coronary artery independent of lipid-lowering effects. However their precise mechanism for MI-protection is unclear. We investigated the effect of lipophilic statin administration in a normocholesterolemic rabbit MI model. METHODS: Nω-nitro-L-arginine methylester (L-NAME, 10 mg/kg) or vehicle alone was intravenously administered 20 min before inducing ischemia, followed by intravenous administration of simvastatin (5 mg/kg) or saline 10 min before ischemia. Rabbits then underwent 30 min of coronary occlusion followed by 48 h of reperfusion. The at-risk and infarct areas were calculated as a percentage of the total left ventricular slice area. RESULTS: Determination of infarct size revealed that pre-ischemic treatment with simvastatin reduced infarct size (30.5 ± 4%) in comparison to controls (45.0 ± 3%) (P < 0.05). This infarct size-reducing effect of simvastatin could be completely abrogated by pretreatment with L-NAME (42.0 ± 4%). CONCLUSIONS: Pre-ischemic treatment with simvastatin reduces MI size via NO production. Simvastatin could be a useful drug for coronary artery disease patients without dyslipidemia as it has direct protective effects.

Transcatheter embolization by autologous blood clot is useful management for small side branch perforation due to percutaneous coronary intervention guide wire.

A 75-year-old man underwent PCI for a bifurcation lesion with 90% stenosis in segment 6 and 75% proximal stenosis in segment 9 of the left coronary artery. We implanted a Duraflex coronary stent into segment 6 and kissing balloon inflation for segments 6 and 9. Although these 2 lesions were adequately dilated, we noticed coronary perforation caused by the guide wire in a small branch of segment 9. We tried to repair the perforation using a small balloon and long inflation, but unfortunately the perforation was not improved. We attempted to occlude the small branch including the perforation site with an autologous blood clot via a wire microcatheter inserted into the small branch. The autologous blood clot was suspended in contrast media and saline. Using this procedure, the small branch of segment 9 was occluded completely and the perforated site was repaired. After the procedure, no significant CPK elevation was detected, and 6 months later, we confirmed that small branch embolization was improved and coronary flow was good. Autologous blood clot is useful to occlude and repair perforations in small side branches of the coronary artery without myocardial damage.

Tissue characterization of coronary plaques: comparison of integrated backscatter intravascular ultrasound with virtual histology intravascular ultrasound.

BACKGROUND: Integrated backscatter (IB) intravascular ultrasound (IVUS) and IVUS Virtual Histology (VH) have been developed for tissue characterization, but have never been compared directly. The purpose of this study was to compare the overall agreement between IB-IVUS and IVUS-VH in the tissue characterization of plaques from the same coronary arterial cross-section. METHODS AND RESULTS: Images were acquired from 46 coronary arteries from 25 cadavers. Of a total of 392 histology/IVUS image pairs, 152 pairs were diagnosed as Stary's type III, IV, Va, Vb and Vc, and compared for IB-IVUS, IVUS-VH and histology. In the qualitative comparison, the overall agreement between histological and IB-IVUS diagnoses was higher (kappa = 0.81, 95% confidence interval (CI): 0.74-0.89) than that of the IVUS-VH diagnoses (kappa = 0.66, 95%CI: 0.56-0.75). The % fibrosis area determined by IB-IVUS was significantly correlated with the relative area of fibrosis based on histology (r = 0.67, p < 0.001). In the quantitative comparison, the overall agreement between the histological and IB-IVUS diagnoses was higher (kappa = 0.83, 95% CI: 0.75-0.91) than that of the IVUS-VH diagnoses (kappa = 0.73, 95% CI: 0.63-0.83). CONCLUSION: Based on histology as the gold standard, IB-IVUS provided higher diagnostic accuracy than IVUS-VH for tissue characterization of coronary plaques.

Can negative cardiac effect of proton pump inhibitor and high-dose H2-blocker have clinical influence on patients with stable angina?

BACKGROUND: Aspirin and anti-platelet drugs are used commonly for patients with coronary heart disease. Proton pump inhibitor (PPI) and high-dose H2-blocker were recommended for preventing NSAIDs-related ulcer. Previously H2-blocker reported to have some negative cardiovascular effects. Additionally, a recent in vitro study showed that PPI reduced cardiac contractility. In this study, we evaluated whether chronic administration of PPI and high-dose H2-blocker affects left ventricular function. METHOD: Fifty-two stable angina patients were enrolled and classified into PPI group ([P]; lansoprazole: 15 mg/day, n=28), H2-blocker group ([H]; famotidine: 40 mg/day, n=8), and control ([C]; none or mucosal-defense drug, n=16). Eligible patients showed normal cardiac function in initial catheterization without administrated PPI or H2-blocker. They received percutaneous coronary intervention and follow-up catheterization. We compared changes in ejection fraction (EF: %), end diastolic/systolic volume index (EDVI/ESVI: ml/m(2)), and peak positive/negative dp/dt (+/-dp/dt: mmHg/s) in left ventricular angiography series. RESULT: There were no significant differences among three groups regarding patient characteristics, backgrounds of angiographic and intervention, except for fewer smokers in [C]. Other drugs such as beta- and Ca-blocker did not have effects on cardiac function except for aspirin during 255+/-115 days follow-up. Rate of EF changes significantly decreased in [P], and tended to decrease in [H] (C: 3.8+/-9.8%, H: -1.6+/-7.6%, P: -2.1+/-5.9%; p<0.05 for [C] vs. [P]). Those of ESVI changes were significantly greater in [P], and tended to be greater in [H] (C: -4.5+/-16.2%, H: 4.9+/-15.5%, P: 7.3+/-16.2%; p<0.05 for [C] vs. [P]), though, EDVI changes' were similar (C: 2.5+/-8.9%, H: 2.6+/-3.6%, P: 1.6+/-6.1%; p=ns). Rate of +/-dp/dt-changes tended to decrease in [H] (+dp/dt: C: 3.9+/-15.5%, H: -10.0+/-25.2%, P: 0.3+/-19.6%; p=ns, -dp/dt: C: -0.1+/-19.5%, H: -8.5+/-20.4%, P: 5.7+/-27.7%; p=ns). CONCLUSION: In this study, PPI and high-dose H2-blocker have EF-reducing tendency. However, these changes were small and these drugs seemed to exhibit little influence clinically.

Post-infarct treatment with an erythropoietin-gelatin hydrogel drug delivery system for cardiac repair.

AIMS: We investigated the effect of an erythropoietin (EPO)-gelatin hydrogel drug delivery system (DDS) applied to the heart on myocardial infarct (MI) size, left ventricular (LV) remodelling and function. METHODS AND RESULTS: Experiments were performed in a rabbit model of MI. The infarct size was reduced, and LV remodelling and function were improved 14 days and 2 months after MI but not at 2 days after MI in the EPO-DDS group. The number of cluster of differentiation 31(CD31)-positive microvessels and the expression of erythropoietin receptor (EPO-R), phosphorylated-Akt (p-Akt), phosphorylated glycogen synthase kinase 3beta (p-GSK-3beta), phosphorylated extracellular signal-regulated protein kinase (p-ERK), phosphorylated signal transducer and activator of transcription 3 (p-Stat3), vascular endothelial growth factor (VEGF), and matrix metalloproteinase-1 (MMP-1) were significantly increased in the myocardium of the EPO-DDS group. CONCLUSION: Post-MI treatment with an EPO-DDS improves LV remodelling and function by activating prosurvival signalling, antifibrosis, and angiogenesis without causing any side effect.

Development of integrated backscatter intravascular ultrasound for tissue characterization of coronary plaques.

Tissue characterization of plaques of coronary arteries is important to clarify the process of acute coronary syndrome and prevent it. The purpose of this study is to develop an online integrated backscatter intravascular ultrasound (IB-IVUS) system and validate the diagnostic accuracy for the characterization of coronary plaques. A personal computer equipped with custom software was connected to an IVUS imaging system. Images were acquired from 242 segments of 46 coronary arteries from 25 cadavers obtained at autopsy. In the training study, a total of 724 regions-of-interests on color-coded maps were compared with histologic images. In the validation study, a total of 192 cross-sections of coronary arteries were evaluated. Receiver operating characteristic curve analysis showed that the cut-off points of -49 dB (area under curve = 0.98) and -29 dB (area under curve = 0.99) were the most reliable predictors of lipid pools, fibrosis and calcification. In the validation study, the analysis using IB values classified fibrous, lipid-rich and fibrocalcific plaque components with a high accuracy of 93%, 90% and 96%, respectively. The overall agreement between histologic and IB-IVUS diagnoses (n = 175) was high (Cohen's kappa = 0.81). The IB-IVUS system provides high diagnostic accuracy for analysis of tissue characteristics of coronary plaques.

Pravastatin reduces myocardial infarct size via increasing protein kinase C-dependent nitric oxide, decreasing oxyradicals and opening the mitochondrial adenosine triphosphate-sensitive potassium channels in rabbits.

BACKGROUND: Statins reportedly protect against myocardial infarction, but the precise mechanism is unclear. METHODS AND RESULTS: Rabbits underwent 30 min of coronary occlusion followed by 48 h of reperfusion. Pravastatin (1 or 5 mg/kg) or saline was intravenously administered 10 min before ischemia. Pravastatin (5 mg/kg) was also administered 10 min before reperfusion. N(omega)-nitro-L-arginine methylester (L-NAME, 10 mg/kg), chelerythrine (5 mg/kg) or 5-hydroxydecanoic acid sodium salt (5-HD, 5 mg/kg) was intravenously administered 10 min before pravastatin injection. The infarct size was determined. The myocardial interstitial levels of 2,5-dihydroxybenzoic acid (DHBA) and nitrogen oxide (NOx), and the intensity of myocardial dihydroethidium staining were measured. Pre-ischemic treatment with pravastatin reduced the infarct size (34+/-5% and 24+/-4%, 1 and 5 mg/kg, respectively), but not pre-reperfusion treatment (42.1+/-3.7%), compared with the control (45+/-3%). This effect was blocked by L-NAME (42.6+/-4%), chelerythrine (50.9+/-3%) and 5-HD (52.7+/-2%). Pre-ischemic treatment with pravastatin increased myocardial NOx levels, and attenuated both the 2,5-DHBA level and the intensity of dihydroethidium staining during reperfusion. Chelerythrine abolished the increase in NOx levels by pravastatin. CONCLUSION: Pre-ischemic treatment with pravastatin reduces the myocardial infarct size via protein kinase C-dependent nitric oxide production, decreasing hydroxyl radicals and superoxide, and opening the mitochondrial adenosine triphosphate-sensitive potassium channels.

Edaravone reduces myocardial infarct size and improves cardiac function and remodelling in rabbits.

1. In the present study, we investigated the effect of 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone), a free radical scavenger, on myocardial infarct (MI) size and cardiac function in an in vivo model of MI in rabbits. We further investigated the contribution of hydroxyl radicals, superoxide and nitric oxide (NO) to its effects. 2. Anaesthetized open-chest Japanese white male rabbits were subjected to 30 min coronary occlusion and 48 h reperfusion. The control group (n = 10) was injected with saline 10 min before reperfusion. The edaravone group (n = 10) was injected with a bolus of 3 mg/kg edaravone 10 min before reperfusion. The edaravone + N(G)-nitro-L-arginine methyl ester (L-NAME) group (n = 5) was given 10 mg/kg, i.v., L-NAME 10 min before the administration of 3 mg/kg edaravone. The L-NAME group (n = 5) was given 10 mg/kg, i.v., L-NAME 20 min before reperfusion. Infarct size was measured using the triphenyl tetrazolium chloride method and is expressed as a percentage of area at risk. Cardiac function was assessed by echocardiography 14 days after infarction. 3. In another series of experiments, rabbits were subjected to 30 min coronary occlusion and 30 min reperfusion and myocardial interstitial 2,3-dihydroxybenzoic acid (DHBA) and 2,5-DHBA levels, indicators of hydroxyl radical, were measured using a microdialysis technique. 4. Infarct size in the edaravone group was significantly reduced compared with that in the control group (27.4 +/- 6.8 vs 43.4 +/- 6.8%, respectively; P < 0.05). The edaravone-induced reduction of infarct size was abolished by pretreatment with L-NAME. Myocardial interstitial levels of 2,3-DHBA and 2,5-DHBA increased 20 and 30 min after ischaemia and peaked at 10 min reperfusion in the control group. Edaravone significantly inhibited the increase in 2,3-DHBA and 2,5-DHBA levels seen during reperfusion. Dihydroethidium staining showing in situ detection of superoxide was less intense in ischaemic myocardium in the edaravone-treated group compared with the control group. Edaravone improved cardiac function and left ventricular remodelling 14 days after infarction. 5. In conclusion, edaravone significantly reduces MI size and improves cardiac function and LV remodelling by decreasing hydroxyl radicals and superoxide in the myocardium and increasing the production of NO during reperfusion in rabbits.

Myocardial perfusion during transient slow-flow in the patient with old vein graft intervention: assessment by serial measurement of pressure-derived fractional flow reserve and thermodilution-derived coronary flow reserve.

A patient with distal slow-flow after stenting in the old vein graft intervention was reported. This case is a first in whom guidewire-based serial measurement of pressure-derived fractional flow reserve (FFR(myo)) and thermodilution-based coronary flow reserve (CFR(thermo)) clearly demonstrated the serial change of microvascular circulation. During slow-flow, CFR(thermo) remained in low value despite significant improvement of FFR(myo) from 0.61 to 0.90. After thrombus aspiration and nicorandil injection, coronary flow reestablished immediately. CFR(thermo) improved significantly from 1.3 during slow-flow to 3.6 after restoration of flow.

Evidence of pharmacologic preconditioning during PTCA by intravenous pretreatment with ATP-sensitive K+ channel opener nicorandil.

BACKGROUND: It is not known whether pretreatment with nicorandil, an ATP-sensitive K+ channel (K(ATP)channel) opener, induces a preconditioning effect independent of increased collateral recruitment. METHODS: Forty-four patients with angina who underwent percutaneous transluminal coronary angioplasty (PTCA) to proximal left anterior descending artery (LAD) stenosis were randomly allocated for pretreatment with an intravenous injection of 80 g/kg nicorandil 5 min before initial ballooning (n=22) or saline (n=22). 99mTc tetrofosmin was injected during balloon inflation, quantitative analysis of occlusion images by SPECT was conducted, and the defect severity score (SS) was calculated. An ECG was recorded during the 2-min inflation to calculate the sum of ST elevation (sigmaST). RESULTS: SigmaST levels were significantly reduced in patients with nicorandil pretreatment compared with control patients (control:1.89+/-0.85 mV nicorandil:1.24+/-0.57 mV, p=0.0052). However, no difference was observed in defect severity (control: 79.0+/-32.5, nicorandil: 98.7+/-48.9 ns). A close correlation was observed between SS and sigmaST in both groups (nicorandil group R(2)=0.505, control group R(2)=0.599). A multivariate regression model demonstrated that both defect severity (p<0.0001) and pretreatment with nicorandil (p<0.001) were significantly related to the level of sigmaST, suggesting a cellular protective effect against ischaemia by nicorandil, independent of myocardial blood flow. CONCLUSION: Nicorandil pretreatment resulted in the induction of myocardial preconditioning independent of the severity of ischaemia.

Evidence of a cellular protective effect by antecedent angina independent of collateral flow recruitment during coronary angioplasty in humans.

The main aim of this study was to elucidate whether the beneficial effect of antecedent angina is a cellular protective effect or the result of an increase of collateral flow. Of 42 patients with angina who underwent percutaneous transluminal coronary angioplasty (PTCA) for proximal left anterior descending artery (LAD) stenosis, 22 had experienced antecedent anginal pain (AP) within 7 days prior to PTCA. 99mTc-sestamibi was injected during balloon inflation, and quantitative analysis of ischemic severity during coronary occlusion was calculated (SS). An electrocardiogram was recorded during ballooning to calculate the sum of ST elevation (sumST). SumST was significantly reduced in patients with AP compared with patients without AP (1.88+/-0.89 mV vs 1.18+/-0.74 mV, p=0.0088); however, no difference was observed in defect severity. A close correlation was observed between SS and sumST in both groups. The multivariate regression model demonstrated that both a large SS (p<0.0001) and the absence of preceding AP (p=0.001) were significantly related to the elevation of sumST. Recent angina can render the myocardium more resistant to subsequent ischemia during angioplasty and is true preconditioning rather than simply an increase of flow.