Wave intensity, an index of ventriculo-arterial interaction, increases in hypertensive subjects but decreases in normotensive subjects during the cold pressor test.

PURPOSE: Cardiovascular reactivity to the cold pressor test (CPT) is considered to be a marker for apparent and potential hypertension. We aimed to elucidate the association between the changes in wave intensity (WI) during CPT and hypertension. METHODS: We recruited 85 volunteers, 33 of whom were hypertensive and 52 normotensive. Using ultrasonic equipment during CPT, we measured carotid arterial WI, which is defined in terms of blood pressure and velocity in the carotid artery. RESULTS: The peak WI (W1) increased during CPT in 70.6% of hypertensive individuals, but decreased in 72.6% of normotensive individuals. The chi-square (χ2) test showed that the association between the direction of change in W1 (increase or decrease) and the blood pressure (hypertensive or normotensive) was very strong (P < 0.0001). CONCLUSION: Direction of change in W1 during CPT is a clear marker to discriminate cardiovascular reactivity that does not vary depending on each investigator's subjective point of view.

Diagnostic Accuracy of Diastolic Fractional Flow Reserve for Functional Evaluation of Coronary Stenosis: DIASTOLE Study.

Background: In the resting conditions, narrowing the window of coronary pressure measurements from the whole cardiac cycle to diastole improves diagnostic performance of coronary pressure-derived physiological index. However, whether this also applies to the hyperemic conditions has not yet been thoroughly evaluated. Objectives: The purpose of this study was to assess whether diastolic fractional flow reserve (diastolic FFR) has better diagnostic performance in identifying ischemia-causing coronary lesions than conventional FFR in a prospective, multicenter, and independent core laboratory-based environment. Methods: In this prospective multicenter registry at 29 Japanese centers, we compared the diagnostic performance of FFR, diastolic FFR, resting distal to aortic coronary pressure (Pd/Pa), and diastolic pressure ratio (dPR) using myocardial perfusion scintigraphy (MPS) as the reference standard in 378 patients with single-vessel coronary disease. Results: Inducible myocardial ischemia was found on MPS in the relevant myocardial territory of the target vessel in 85 patients (22%). In the receiver-operating curve analyses, diastolic FFR had comparable area under the curve (AUC) compared with FFR (AUCdiastolic FFR: 0.66; 95% confidence interval [CI]: 0.58-0.73, vs AUCFFR: 0.66; 95% CI: 0.58-0.74, P = 0.624). FFR and diastolic FFR showed significantly larger AUCs than resting Pd/Pa (0.62; 95% CI: 0.54-0.70; P = 0.033 and P = 0.046) but did not show significantly larger AUCs than dPR (0.62; 95% CI: 0.55-0.70; P = 0.102 and P = 0.113). Conclusions: Diastolic FFR showed a similar diagnostic performance to FFR as compared with MPS. This result reaffirms the use of FFR as the most accurate invasive physiological lesion assessment. (Diagnostic accuracy of diastolic fractional flow reserve (d-FFR) for functional evaluation of coronary stenosis; UMIN000015906).

Changes in cardiac contractility during graded exercise are greater in subjects with smaller body mass index, and greater in men than women: analyses using wave intensity and force-frequency relations.

INTRODUCTION AND PURPOSE: Estimation of the contractility of the left ventricle during exercise is an important part of the rehabilitation protocol. It is known that cardiac contractility increases with an increase in heart rate. This phenomenon is called the force-frequency relation (FFR). Using wave intensity, we aimed to evaluate FFR noninvasively during graded exercise. METHODS: We enrolled 83 healthy subjects. Using ultrasonic diagnostic equipment, we measured wave intensity (WD), which was defined in terms of blood velocity and arterial diameter, in the carotid artery and heart rate (HR) before and during bicycle ergometer exercise. FFRs were constructed by plotting the maximum value of WD (WD1) against HR. We analyzed the variation among FFR responses of individual subjects. RESULTS: WD1 increased linearly with an increase in HR during exercise. The average slope of the FFR was 1.0 ± 0.5 m/s3 bpm. The slope of FFR decreased with an increase in body mass index (BMI). The slopes of FFRs were steeper in men than women, although there were no differences in BMI between men and women. CONCLUSIONS: The FFR was obtained noninvasively by carotid arterial wave intensity (WD1) and graded exercise. The slope of the FFR decreased with an increase in BMI, and was steeper in men than women.

Wave Intensity Analysis: Sex-Specific Differences in Hemodynamic and Ventilatory Responses to Graded Exercise-Echocardiographic Measurements.

BACKGROUND: The differences in hemodynamic and ventilatory responses to graded exercise between men and women have not been well documented. Using wave intensity (WI) analysis, which is useful for analyzing ventriculo-arterial interaction, we aimed to elucidate the sex-specific differences. METHODS: We enrolled 48 healthy subjects (24 men and 24 women, age 21.3 ± 1.6 and 20.5 ± 0.9 years, n.s. [not significant]). Using ultrasonic diagnostic equipment, we measured WI, arterial stiffness parameter (ß), force-frequency relation (FFR) and other hemodynamic parameters in the carotid artery before and during graded bicycle exercise. We also analyzed expired gas volume (VE) during the exercise. The workload was increased stepwise by 20 W at 1-min intervals up to respiratory compensation (RC) point through the anaerobic threshold (AT). WI is defined as WI = (dP/dt) (dU/dt), where P is blood pressure, U is velocity, and t is time. The peak value of WI (W1) increases with left ventricular (LV) peak dP/dt, in other words, an index of cardiac contractility. The FFR was obtained as the linear regression line of W1 on heart rate. ß is defined as ß = ln (Ps/Pd)/[(Ds - Dd)/Dd], where D is the arterial diameter, and suffixes s and d indicate systolic and diastolic, respectively. RESULTS: There was no difference in the body mass index between men and women. Carbon dioxide outputs (VCO2) did not differ at rest, but those at AT and RC were greater in men. Oxygen consumptions (VO2) in men and women at rest did not differ, but those in men at AT and RC were greater. Workloads per body weight in men and women did not differ at AT, but they were greater in men at RC. Systolic pressures at rest, AT and RC were greater in men than women. Heart rates in men and women did not differ at any stage of the graded exercise. W1 did not differ at rest and AT, but it was greater in men than women at RC. The slope of the FFR during the period from rest to AT did not differ between men and women. However, the slope of the FFR during the period from AT to RC was greater in men. CONCLUSIONS: The reached values of workload/weight at RC, VCO2 at AT and RC, VO2 at AT and RC, W1 at RC, and the slope of the FFR during the period from AT to RC were greater in men than women.

Effects of Enteral Immunonutrition in Esophageal Cancer.

BACKGROUND: Immunonutrition (IN) significantly reduces the incidence of postoperative infectious complications and the length of hospitalization in patients undergoing major elective surgery for gastrointestinal malignances. However, the clinical benefit of IN in patients who have undergone esophagectomy for esophageal cancer is unclear. Moreover, the effect of enteral IN in patients during preoperative adjuvant chemoradiotherapy and in patients treated with concurrent chemoradiotherapy for advanced esophageal cancer is unknown. SUMMARY: This review analyzes the evidence supporting the enteral administration of IN in patients who have undergone esophagectomy and/or chemoradiotherapy for esophageal cancer. Twelve trials that evaluated IN exclusively in patients who underwent esophagectomy were published between January 1980 and August 2017. Two trials concerning IN during chemoradiotherapy for esophageal cancer were identified in the same period. However, the evidence is insufficient to recommend enteral IN in patients who have undergone esophagectomy and/or chemoradiotherapy for esophageal cancer. KEY MESSAGE: Further evidence from well-designed randomized controlled trials is required to verify the clinical benefits of enteral IN in patients undergoing esophagectomy and/or chemoradiotherapy for esophageal cancer. PRACTICAL IMPLICATIONS: Resolvins, which are generated from EPA, are novel anti-inflammatory lipid mediators and may play a key role in the resolution of acute inflammation when IN is supplemented with EPA in patients undergoing severely stressful operations.

Utility of Inflammatory Marker- and Nutritional Status-based Prognostic Factors for Predicting the Prognosis of Stage IV Gastric Cancer Patients Undergoing Non-curative Surgery.

BACKGROUND/AIM: The present study aimed to compare the utility of various inflammatory marker- and nutritional status-based prognostic factors, including many previous established prognostic factors, for predicting the prognosis of stage IV gastric cancer patients undergoing non-curative surgery. PATIENTS AND METHODS: A total of 33 patients with stage IV gastric cancer who had undergone palliative gastrectomy and gastrojejunostomy were included in the study. Univariate and multivariate analyses were performed to evaluate the relationships between the mGPS, PNI, NLR, PLR, the CONUT, various clinicopathological factors and cancer-specific survival (CS). RESULTS: Among patients who received non-curative surgery, univariate analysis of CS identified the following significant risk factors: chemotherapy, mGPS and NLR, and multivariate analysis revealed that the mGPS was independently associated with CS. CONCLUSION: The mGPS was a more useful prognostic factor than the PNI, NLR, PLR and CONUT in patients undergoing non-curative surgery for stage IV gastric cancer.

Surgical Resection of a Ruptured Pancreaticoduodenal Artery Aneurysm.

BACKGROUND: Ruptured aneurysms of the pancreaticoduodenal artery result in fatal hemorrhage and high mortality. Therefore, prompt diagnosis and treatment are required, but there are sometimes problems differentiating this specific diagnosis from other abdominal pathologies. CASE REPORT: We encountered a rare case of a ruptured pancreaticoduodenal artery aneurysm with an atypical clinical presentation that simulated acute pancreatitis. A 71-year-old woman was admitted to the emergency department with abdominal pain in the left upper quadrant, a slightly elevated level of pancreatic amylase, and cholelithiasis on ultrasonography. With persistent pain and progressively decreasing hemoglobin level, computed tomography with contrast showed fluid collection in the subphrenic space, a retroperitoneal hematoma, and a pancreaticoduodenal artery aneurysm that appeared to originate from a branch of the SMA. Urgent angiography indicated spontaneous rupture of a pancreaticoduodenal artery aneurysm. Emergent surgery was undertaken, and a simple aneurysmectomy was successfully performed. The patient's recovery was unremarkable. The prompt diagnosis of a pancreaticoduodenal artery aneurysm was difficult because the initial symptoms were vague and misleading in our case. CONCLUSIONS: A high level of suspicion, rapid diagnostic capability, and prompt surgical or endovascular intervention, as well as effective teamwork in the emergency department, are critical to avoid the devastating consequences of a ruptured visceral artery aneurysm.

Noninvasive evaluation of left ventricular force-frequency relationships by measuring carotid arterial wave intensity during exercise stress.

BACKGROUND AND PURPOSE: Estimation of the contractility of the left ventricle during exercise is important in drawing up a protocol of cardiac rehabilitation. It has been demonstrated that color Doppler- and echo tracking-derived carotid arterial wave intensity is a sensitive index of global left ventricular (LV) contractility. We assessed the feasibility of measuring carotid arterial wave intensity and determining force-frequency (contractility-heart rate) relations (FFRs) during exercise totally noninvasively. METHODS: We measured carotid arterial wave intensity with a combined color Doppler and echo tracking system in 25 healthy young male volunteers (age 20.8 ± 1.2 years) at rest and during exercise. FFRs were constructed by plotting the maximum value of wave intensity (WD1) against heart rate (HR). RESULTS: We first confirmed that HR increased linearly with an increase in work load in each subject (r (2) = 0.95 ± 0.04). WD1 increased linearly with an increase in HR. The goodness-of-fit of the regression line of WD1 on HR in each subject was very high (r (2) = 0.48-0.94, p < 0.0001, respectively). The slope of the WD1-HR relation ranged 0.30-2.20 [m/s(3) (beat/min)]. CONCLUSIONS: Global LV FFRs can be generated in healthy young volunteers with an entirely noninvasive combination of exercise and wave intensity. These data should show the potential usefulness of the FFR in the context of cardiac rehabilitation.

Role of endogenous hydrogen peroxide during angiotensin type 1 receptor blockers administration in pacing-induced metabolic coronary vasodilatation in dogs in vivo.

BACKGROUND: We have previously demonstrated that endothelium-derived hydrogen peroxide (H2O2) is an endothelium-derived hyperpolarizing factor (EDHF) in canine coronary microcirculation in vivo. However, the role of H2O2/EDHF during angiotensin type 1 receptor blockers (ARB) administration in metabolic coronary dilatation in vivo remains to be examined. We examined whether H2O2 during ARB administration is involved in pacing-induced metabolic coronary vasodilatation in dogs in vivo and if so, whether such beneficial effects of ARB administration acutely improve coronary vasodilatation in diabetes mellitus (DM). METHODS: Canine subepicardial coronary small arteries (CSA,≥ 100 µm) and arterioles (CA, <100 µm) in left anterior descending artery area were continuously observed by an intravital microscope under cyclooxygenase blockade(ibuprofen, 12.5 mg/kg, intravenous infusion, iv). Experiments were performed during paired right ventricular pacing under the following 4 conditions (n=5 each); (i) control, (ii) DM(alloxan 40 mg/ kg, iv, 1 week prior to study), (iii) DM+ARB(olmesartan, 10 µg/kg/min, 10 min, intracoronary infusion,ic)+L-NMMA (NOS inhibitor, 2 !mol/min, ic) and (iv)DM+ARB+catalase (H2O2 discomposer, 1000 U/ml, 5 min, ic). RESULTS: Cardiac tachypacing (60 to 120 bpm) caused coronary vasodilatation in both-sized arteries under control conditions. DM significantly decreased the vasodilatation compared with control in CSA and there was a residual vasodilatation for the loss of NO in CA, whereas DM+ARB+L-NMMA improved the vasodilatation compared with DM alone in CA and was significantly decreased by DM+ARB+catalase in CA. CONCLUSIONS: These results indicate that H2O2 during ARB administration is involved in pacing-induced metabolic coronary vasodilatation in DM in vivo and that there are substantial compensatory interactions between NO and H2O2.

Intermittent, moderate-intensity aerobic exercise for only eight weeks reduces arterial stiffness: evaluation by measurement of stiffness parameter and pressure-strain elastic modulus by use of ultrasonic echo tracking.

BACKGROUND AND PURPOSE: Aerobic exercise has been reported to be associated with reduced arterial stiffness. However, the intensity, duration, and frequency of aerobic exercise required to improve arterial stiffness have not been established. In addition, most reports base their conclusions on changes in pulse wave velocity, which is an indirect index of arterial stiffness. We studied the effects of short-term, intermittent, moderate-intensity exercise training on arterial stiffness based on measurements of the stiffness parameter (ß) and pressure-strain elastic modulus (E p), which are direct indices of regional arterial stiffness. METHODS: A total of 25 young healthy volunteers (18 men) were recruited. By use of ultrasonic diagnostic equipment we measured ß and E p of the carotid artery before and after 8 weeks of exercise training. RESULTS: After exercise training, systolic pressure (P s), diastolic pressure (P d), pulse pressure, systolic arterial diameter (D s), and diastolic arterial diameter (D d) did not change significantly. However, the pulsatile change in diameter ((D s - D d)/D d) increased significantly, and ß and E p decreased significantly. CONCLUSIONS: For healthy young subjects, ß and E p were reduced by intermittent, moderate-intensity exercise training for only 8 weeks.

Impact of chronic cyanosis and reoxygenation on the microheterogeneity of the myocardial blood flow: digital radiographic study in neonatal rats.

PURPOSE: This study sought to show the heterogeneity of myocardial blood flow in the chronically hypoxic infantile myocardium and its response to reoxygenation using a novel type of digital radiography. METHODS: Newborn rats were housed in a hypoxic chamber or in a normal chamber (controls). After 4 or 8 weeks, the control rats were ventilated with normoxic conditions, and the rats housed under hypoxia were ventilated with either hypoxic (cyanotic group) or normoxic conditions (reoxygenation group). Desmethylimipramine labeled with tritium (HDMI) was injected into the left ventricle, and both ventricular free walls were sectioned and sliced from the subepicardium to the subendocardium at 10 mm thickness. The within-layer distribution of HDMI density was measured by digital radiography, and its spatial heterogeneity (i.e., flow heterogeneity) was quantified by the coefficient of variation (CV) of flows. RESULTS: There were no differences in the CV between the groups in either ventricle at 4 weeks of age and no differences in the right ventricle at 8 weeks of age. There was a trend toward a higher left ventricular CV in the cyanotic group than in the control group at 8 weeks of age (0.637 ± 0.099 vs. 0.510 ± 0.060, P = 0.06). At 8 weeks of age, the CV was lower in both ventricles in the reoxygenation group than in those of the control and cyanotic groups. CONCLUSION: The chronically hypoxic infantile myocardium exhibits regional flow heterogeneity similar to that observed in the normal myocardium in both ventricles and exhibits reduced flow heterogeneity in response to reoxygenation.

Erythropoietin enhances hydrogen peroxide-mediated dilatation of canine coronary collateral arterioles during myocardial ischemia in dogs in vivo.

We have previously demonstrated that endothelium-derived hydrogen peroxide (H(2)O(2)) plays an important role in the canine coronary microcirculation as an endothelium-derived hyperpolarizing factor in vivo. However, it remains to be examined whether endogenous H(2)O(2) is involved in the dilatation of coronary collaterals during myocardial ischemia in vivo and, if so, whether erythropoietin (EPO) enhances the responses. Canine subepicardial native collateral small arteries (CSA; ≥ 100 µm) and arterioles (CA; <100 µm) were observed using an intravital microscope. Experiments were performed after left anterior descending coronary artery ischemia (90 min) under the following eight conditions (n = 5 each): control, EPO, EPO+catalase, EPO+N-monomethyl-l-arginine (l-NMMA), EPO+l-NMMA+catalase, EPO+l-NMMA+iberiotoxin [Ca(2+)-activated K(+) (K(Ca)) channel blocker], EPO+l-NMMA+apamin+charybdotoxin (K(Ca) channel blocker), and EPO+wortmannin (phosphatidylinositol 3-kinase inhibitor). Myocardial ischemia caused significant vasodilatation in CA but not in CSA under control conditions, which was significantly decreased by catalase in CA. After EPO, the vasodilatation was significantly increased in both sizes of arteries and was significantly decreased by catalase. The enhancing effect of EPO was reduced by l-NMMA but not by catalase in CSA and was reduced by l-NMMA+catalase in CA, where the greater inhibitory effects were noted with l-NMMA+catalase, l-NMMA+iberiotoxin, L-NMMA+apamin+charybdotoxin, or wortmannin. EPO significantly ameliorated ischemia-induced impairment of myocardial Akt phosphorylation, which was abolished by l-NMMA+catalase or wortmannin. EPO also ameliorated oxidative stress and myocardial injury, as assessed by plasma 8-hydroxydeoxyguanosine and troponin-T, respectively. These results indicate that EPO enhances H(2)O(2)-mediated dilatation of coronary collateral arterioles during myocardial ischemia in dogs in vivo.

Coronary microcirculation in the beating heart.

The phase opposition of velocity waveforms between coronary arteries (predominantly diastolic) and veins (systolic) is the most prominent characteristic of coronary hemodynamics. This unique arterial and venous flow patterns indicate the importance of intramyocardial capacitance vessels and variable resistance vessels during a cardiac cycle. It was shown that during diastole the intramyocardial capacitance vessels have two functional components, unstressed volume and ordinary capacitance. Unstressed volume is defined as the volume of blood in a vessel at zero transmural pressure. In vivo observation of systolic narrowing of arterioles in mid-wall and in subendocardium indicates the increase in resistance by cardiac contraction.

Visualisation of the effects of dilazep on rat afferent and efferent arterioles in vivo.

Although the effects of dilazep hydrochloride (dilazep), a nucleoside transport inhibitor, have been examined, there have been no visualisation studies on the physiological effects of dilazep on the glomerular arterioles. The purpose of this study was to visualise and evaluate the effects of dilazep and consequently the effects of adenosine, which dilazep augments by measuring glomelurar diameters, renal blood flow and resistance in rats in vivo. We time-sequentially examined afferent and efferent arteriolar diameter changes using an intravital videomicroscope and renal blood flow. We administered dilazep at a dose of 300 microg/kg intravenously. To further investigate the effects of dilazep, rats were pre-treated with 8-p-sulfophenyl theophylline (a nonselective adenosine receptor antagonist), 8-cyclopentyl-1,3-dipropylxanthine (an A1 receptor antagonist), or 3,7-dimethyl-1-propargylxanthine (an A2 receptor antagonist). Dilazep constricted the afferent and efferent arterioles at the early phase and dilated them at the later phase, with the same degree of vasoconstrictive and vasodilatory effect on both arterioles. A1 blockade abolished vasoconstriction and augmented vasodilatation at the later phase and A2 blockade abolished vasodilatation and augmented vasoconstriction at the early phase. Non-selective blockade abolished both early vasoconstriction and later vasodilatation. In conclusion, adenosine augmented by dilazep constricted the afferent and efferent arterioles of the cortical nephrons at the early phase and dilated both arterioles at the later phase via A1 and A2 adenosine receptor activation, respectively. That the ratio of afferent to efferent arteriolar diameter was fairly constant suggests that intraglomerular pressure is maintained in the acute phase by adenosine despite the biphasic flow change.

Role of Cu,Zn-SOD in the synthesis of endogenous vasodilator hydrogen peroxide during reactive hyperemia in mouse mesenteric microcirculation in vivo.

We have recently demonstrated that endothelium-derived hydrogen peroxide (H2O2) is an endothelium-derived hyperpolarizing factor and that endothelial Cu/Zn-superoxide dismutase (SOD) plays an important role in the synthesis of endogenous H2O2 in both animals and humans. We examined whether SOD plays a role in the synthesis of endogenous H2O2 during in vivo reactive hyperemia (RH), an important regulatory mechanism. Mesenteric arterioles from wild-type and Cu,Zn-SOD(-/-) mice were continuously observed by a pencil-type charge-coupled device (CCD) intravital microscope during RH (reperfusion after 20 and 60 s of mesenteric artery occlusion) in the cyclooxygenase blockade under the following four conditions: control, catalase alone, N(G)-monomethyl-L-arginine (L-NMMA) alone, and L-NMMA + catalase. Vasodilatation during RH was significantly decreased by catalase or L-NMMA alone and was almost completely inhibited by L-NMMA + catalase in wild-type mice, whereas it was inhibited by L-NMMA and L-NMMA + catalase in the Cu,Zn-SOD(-/-) mice. RH-induced increase in blood flow after L-NMMA was significantly increased in the wild-type mice, whereas it was significantly reduced in the Cu,Zn-SOD(-/-) mice. In mesenteric arterioles of the Cu,Zn-SOD(-/-) mice, Tempol, an SOD mimetic, significantly increased the ACh-induced vasodilatation, and the enhancing effect of Tempol was decreased by catalase. Vascular H(2)O(2) production by fluorescent microscopy in mesenteric arterioles after RH was significantly increased in response to ACh in wild-type mice but markedly impaired in Cu,Zn-SOD(-/-) mice. Endothelial Cu,Zn-SOD plays an important role in the synthesis of endogenous H(2)O(2) that contributes to RH in mouse mesenteric smaller arterioles.

Three-dimensional quantitation of mitral valve coaptation by a novel software system with transthoracic real-time three-dimensional echocardiography.

We investigated the degree of mitral valve coaptation with a custom quantitation software system using transthoracic three-dimensional (3D) echocardiography. With real-time 3D echocardiography, we obtained transthoracic volumetric images in 20 healthy subjects and 20 patients with dilated cardiomyopathy. With our novel software system, the surface area of mitral valve tenting in the onset of mitral leaflet closure [O] and the timing of maximum closure of mitral leaflet [M] were reconstructed for quantitative measurement. The coaptation index was calculated by the following formula: [(3D tenting surface area in O-3D tenting surface area in M)/3D tenting surface area in O]. The coaptation index in patients with dilated cardiomyopathy was significantly smaller than that in healthy subjects (11% +/- 4.1% vs. 18% +/- 8.0%, P = .004). The custom quantitation software system with 3D echocardiography allowed us to assess the degree of mitral valve coaptation.

Important role of endogenous hydrogen peroxide in pacing-induced metabolic coronary vasodilation in dogs in vivo.

OBJECTIVES: We examined whether endogenous hydrogen peroxide (H2O2) is involved in pacing-induced metabolic vasodilation in vivo. BACKGROUND: We have previously demonstrated that endothelium-derived H2O2 is an endothelium-derived hyperpolarizing factor in canine coronary microcirculation in vivo. However, the role of endogenous H2O2 in metabolic coronary vasodilation in vivo remains to be examined. METHODS: Canine subepicardial small coronary arteries (> or =100 microm) and arterioles (<100 microm) were continuously observed by a microscope under cyclooxygenase blockade (ibuprofen, 12.5 mg/kg intravenous [IV]) (n = 60). Experiments were performed during paired right ventricular pacing under the following 7 conditions: control, nitric oxide (NO) synthase inhibitor (N(G)-monomethyl-L-arginine [L-NMMA], 2 micromol/min for 20 min intracoronary [IC]), catalase (a decomposer of H2O2, 40,000 U/kg IV and 240,000 U/kg/min for 10 min IC), 8-sulfophenyltheophylline (SPT) (an adenosine receptor blocker, 25 mug/kg/min for 5 min IC), L-NMMA+catalase, L-NMMA+tetraethylammonium (TEA) (K(Ca)-channel blocker, 10 microg/kg/min for 10 min IC), and L-NMMA+catalase+8-SPT. RESULTS: Cardiac tachypacing (60 to 120 beats/min) caused coronary vasodilation in both-sized arteries under control conditions in response to the increase in myocardial oxygen consumption. The metabolic coronary vasodilation was decreased after L-NMMA in subepicardial small arteries with an increased fluorescent H2O2 production compared with catalase group, whereas catalase decreased the vasodilation of arterioles with an increased fluorescent NO production compared with the L-NMMA group, and 8-SPT also decreased the vasodilation of arterioles. Furthermore, the metabolic coronary vasodilation was markedly attenuated after L-NMMA+catalase, L-NMMA+TEA, and L-NMMA+catalase+8-SPT in both-sized arteries. CONCLUSIONS: These results indicate that endogenous H2O2 plays an important role in pacing-induced metabolic coronary vasodilation in vivo.