Kazumi Okuda

Regional myocardial perfusion and glucose metabolism in experimental left bundle branch block.

BackgroundSeveral authors have reported cases in which 201TI scintigraphy demonstrated perfusion abnormality in the septum of patients with left bundle branch block (LBBB) and normal coronary arteriogram. The mechanism of this abnormality, however, remains to be clarified. Methods and ResultsTo determine whether LBBB itself induces abnormal myocardial perfusion and ischemia and to elucidate its mechanism, we used an in vivo animal model. LBBB was induced by right ventricular pacing in 17 open-chest dogs. We examined myocardial perfusion and glucose uptake using 201T1 and 18F-labeled 2-fluoro-2-deoxy-D-glucose. 201T1 activity in the septum was reduced to 74.7±14.5% of its maximal activity, and mean activity was 86.5±5.3% in the free wall (p<0.05). 18F activity in the septum was also reduced compared with that in the free wall (67.4±12.1% versus 88.0plusmn;5.2%, p<0.05). Regional myocardial blood flow was significantly reduced in the septum compared with the free wall, averaging 0.53±0.18 ml/min/g versus 0.84±0.14 ml/min/g, respectively (p<0.01). Systolic thickening in the septum was reduced from 1.36±0.20 to 0.98±0.04 (p<0.01) after the induction of LBBB, and the intramyocardial pressure in the septum in diastolic phase, in which the major flow of left anterior descending coronary artery (LAD) exists, increased from 26.6±10.5 to 57.8±22.2 mm Hg (p<0.02). Mean aortic pressure, IAD flow, and lactate extraction rate showed no significant change. ConclusionsLBBB itself may reduce myocardial perfusion and glucose uptake in the septum because of impaired systolic thickening and augmented intramyocardial pressure in the septum; however, this is not necessarily related to septal ischemia.

Oxidative metabolism in the myocardium in normal subjects during dobutamine infusion.

To assess the biventricular response of the clearance rate of carbon-11 acetate as an index of myocardial oxidative metabolism to increase in work-load, dynamic positron emission tomography was performed at rest and during dobutamine infusion in 14 normal subjects. The clearance rate constant (Kmono) of the left ventricular (LV) myocardium increased during dobutamine infusion (0.112±0.020 min−1 vs 0.065±0.015 min−1 at rest) (P<0.001) in proportion to the increase in the pressure-rate product. Kmono in the right ventricular (RV) myocardium also increased (0.080±0.018 min−1 vs 0.034±0.013 min−1 at rest) (P<0.001), with an excellent correlation with the LV Kmono (r=0.920). The fact that the increase in RV Kmono during dobutamine infusion was greater (158%±81%) than that in LV Kmono (79%±39%) (P < 0.005) indicates a greater increase in oxidative metabolism in the RV in response to inotropic stimulation in normal subjects.

Combined assessment of regional perfusion and wall motion in patients with coronary artery disease with technetium 99m tetrofosmin

BackgroundTechnetium 99m tetrofosmin is a new99mTc-labeled myocardial perfusion agent that can be labeled easily and provides excellent myocardial perfusion images. In addition, bolus administration of the tracer allows first-pass radionuclide ventriculography.Methods and ResultsThis study examined the diagnostic value of combined assessment of regional perfusion by tetrofosmin tomography and wall motion by first-pass radionuclide ventriculography both at rest and during stress in 24 patients suspected of having coronary artery disease. All patients underwent stress-rest tetrofosmin tomography, stress-delayed thallium 201 tomography, and coronary angiography. Stress tetrofosmin tomography showed abnormal perfusion in all 23 patients with angiographic evidence of coronary artery disease, whereas stress201Tl tomography showed abnormal perfusion in 22 of the 23 patients. For detection of significant (≥50% diameter stenosis) stenotic coronary arteries, the two perfusion studies showed similar sensitivities (62% with201Tl and 69% with tetrofosmin) and specificities (88% and 100%, respectively). When analysis of regional wall motion was combined with perfusion study, a slightly higher sensitivity was obtained (77%), with similar specificity. The regional wall motion score was concordant with the regional perfusion score in only 42% of the segments at rest and 50% during exercise.ConclusionsThese results suggest that stress tetrofosmin perfusion tomography and stress201Tl tomography provided similar diagnostic accuracy for detection of coronary artery disease. The combined assessment of perfusion and function that is feasible with tetrofosmin may enhance diagnostic accuracy in patients with coronary artery disease.

Basic kinetics of 15-(p-iodophenyl)-3-R, S-methylpentadecanoic acid (BMIPP) in canine myocardium

BMIPP is a radioiodinated fatty acid analogue used for myocardial single photon emission CT (SPECT) imaging based on high cardiac fatty acid metabolism. In normal dogs, 74% of the injected BMIPP was instantly extracted and was then retained in 65.3%. The washout of the retained radioactivity was low, and most of the washout was alpha- and beta-oxidation metabolites. ATP concentration plays an important role in the myocardial uptake and retention of BMIPP. The ATP-dependent BMIPP uptake at the TG pool was strongly regulated by etomoxir with modifying mitochondrial β-oxidation and subsequent ATP production. Thus, myocardial viability was reflected on the BMIPP uptake in acute ischemia. In spite of in-significant changes in early extraction and retention, BMIPP back diffusion (r=−0.92) and full-oxidation metabolite (r=0.78) were correlated with the severity of ischemia. Mismatched region of BMIPP with flow (Tl-201) showed decreased metabolic enzymes such as citrate synthase and 3-hydroxyacyl-CoA dehydrogenase. These data suggest that BMIPP would be feasible for detecting cellular energy state from lipid metabolism.

Improvement of myocardial ischemic dysfunction with dichloroacetic acid: experimental study by repeated ischemia in dogs.

We investigated metabolic factors related to the recovery of myocardial function during ischemia and after reperfusion using dichloroacetic acid (DCA) in canine models with repeated 10-min regional ischemia and reperfusion. Administration of 100 mg/kg DCA, which activates pyruvate dehydrogenase, improved regional wall motion significantly as compared with the nontreated controls (p < 0.05). The mechanism was studied by determining changes in myocardial levels of pH, glucose, lactate, and nonesterified fatty acids (NEFA). Glucose extraction was increased significantly during ischemia and reperfusion by the pretreatment of DCA (p < 0.01). the calculated contribution of glucose to myocardial oxidative metabolism during ischemia and reperfusion was greater than that of NEFA and lactate in case of DCA treatment. The uptake of [99mTc]pyrophosphate (PYP), which reflects myocardial injury, was also significantly suppressed by DCA (p < 0.01). pH was not affected by an infusion of DCA. These findings suggest that the activation of glucose metabolism by DCA, which is impaired and reduced during ischemia and reperfusion, may be responsible for the improved myocardial function after reperfusion.

Limitation of infarct size with preconditioning and calcium antagonist (Diltiazem): Difference in99mTc-PYP uptake in the myocardium

Ischemic cell injury and the uptake mechanism of99mTc-PYP (Pyrophosphate) were studied with preconditioning and calcium antagonist. Method: The coronary artery of an adult mongrel dog was clamped for 1 hour, followed by reperfusion and99mTc-PYP injection. A control group (group C, n = 8), a group in which continuous drip infusion of diltiazem (10 mg/kg) (group D, n = 7), and a group preconditioned by six 5-minute clampings and perfusions before occlusion (group P, n = 6) were compared. Results: Wall motion was fully recovered in group D but not in group P after 2 hours of reperfusion. The99mTc-PYP uptake ratio showed a significant (p < 0.05) reduction in group D (11.5: 3.6 compared with group C), but not in group P (11.5: 9.1, p = 0.25). The infarct area was 1.2 ± 0.6% of the left ventricle in group D, 1.3 ± 0.4 in group P, and 6.4 ± 1.0 in group C (p < 0.01 in groups D and P vs. group C). Conclusions: These findings suggest that preconditioning does not alleviate stunning, but it improves cell injury in spite of high uptake of99mTc-PYP. Diltiazem protects from both stunning and cell injury, suggesting a different mechanism of myocardial protection from that of preconditioning.