Wall thickening at rest and contractile reserve early after myocardial infarction: correlation with myocardial perfusion and metabolism

BACKGROUND: Abnormalities in wall thickening and their reaction to stimulation can be studied by magnetic resonance imaging. OBJECTIVE: To analyse the relationship between these abnormalities and changes in myocardial perfusion and fatty acid metabolism. METHODS: Fifteen patients with a myocardial infarction underwent low-dose dobutamine magnetic resonance imaging to assess their wall thickening and contractile reserve, and technetium-99m sestamibi (MIBI) and beta-methyl-iodophenyl-pentadecanoic acid (BMIPP) single-photon emission tomography to assess their myocardial perfusion and fatty acid uptake. For nine segments per patient, the wall thickening was scored as normal, hypokinetic or akinetic, and the myocardial perfusion as normal (> 65%), mildly to moderately reduced (35-65%) or severely reduced (< 35%). Abnormalities in fatty acid uptake were compared with the myocardial perfusion and defined as matched (difference < or = 10%) or mismatched (difference > 10%) reduction. RESULTS: Thirty-four segments had abnormal wall thickening (13 hypokinetic and 21 akinetic). The wall thickening at rest was significantly related to the uptake of MIBI (P < 0.001), but not to abnormalities in the uptake of BMIPP. All of the akinetic segments had an abnormal uptake of MIBI (15 severely and six mildly to moderately reduced), whereas 7 of 13 hypokinetic segments had a normal and five a midly to moderately reduced uptake. A significant relationship between abnormalities of fatty acid metabolism and the contractile reserve was also found (P < 0.002): 14 of 16 segments with and only six of 18 without contractile reserve had a mismatched reduction in uptakes of MIBI and BMIPP. CONCLUSION: This study confirms the relationship between the wall thickening at rest and the residual perfusion after infarction. On the other hand, the contractile reserve, which is an accepted indicator of the viability of the infarct region, is associated strongly with abnormalities of fatty acid metabolism.     

Evaluation of myocardial perfusion and fatty acid uptake using a single injection of iodine-123-BMIPP in patients with acute coronary syndromes

The purpose of this study was to clarify the possibility of simultaneous evaluation of myocardial perfusion and fatty acid metabolism using a single injection of 123I-beta-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) in patients with acute coronary syndromes. METHODS: Thirty patients with unstable angina pectoris (UAP group) and 15 patients with acute myocardial infarction (MI group) were studied. BMIPP dynamic SPECT was performed 2 min after the injection of BMIPP (185 MBq), and images were obtained every 3 min for 15 min with a three-head gamma camera. Conventional BMIPP SPECT was also performed 30 min after the injection. Serial BMIPP and resting 201TI images were compared. RESULTS: A 201TI-BMIPP mismatch between 30-min BMIPP and resting 201TI images was observed in 27 of 30 patients in the UAP group and 8 of 15 patients in the MI group, respectively. However, a 201TI-BMIPP mismatch between early (2-5-min) BMIPP and resting 201TI images was observed in only 2 of 30 patients in the UAP group and in only 2 of 15 patients in the MI group, respectively. The kappa statistics of tracer uptake between early BMIPP and resting 201TI images showed good concordance in UAP (kappa = 0.823) and MI (kappa = 0.765) groups, respectively. These results indicated that initial distribution of BMIPP reflects myocardial perfusion in patients with acute coronary syndromes. CONCLUSION: Myocardial perfusion and fatty acid metabolism can be evaluated simultaneously using a single injection of BMIPP, when images are taken soon (2-5 min) and long after the injection in patients with acute coronary syndromes.     

Vitamin A supplementation but not deworming improves growth of malnourished preschool children in eastern Zaire

14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid (FTHA) has been recently introduced as a new tracer for fatty acid metabolism. Myocardial [18F]FTHA uptake is believed to reflect mainly beta-oxidation of the circulating free fatty acids (FFAs), since it is trapped in the mitochondria because subsequent steps of beta-oxidation are inhibited by sulfur heteroatom. We investigated [18F]FTHA kinetics in myocardial and skeletal muscle in vivo. METHODS: Two dynamic PET studies were performed in seven patients with stable coronary artery disease, once in the fasting state and once during euglycemic hyperinsulinemia (serum insulin approximately 60 mU/liter). The fractional [18F] FTHA uptake rates (Ki) were multiplied with serum FFA concentrations and were considered to represent FFA uptake. RESULTS: Serum FFA concentration decreased by 80% during insulin clamp. After tracer injection, rapid myocardial uptake was identified both in the fasting state and during insulin stimulation. The cardiac image quality was excellent in both occasions. In addition, femoral muscles were clearly visualized in both studies. The fractional myocardial [18F]FTHA uptake rates (Ki) in the normal myocardial regions were similar in the fasting state (0.11 +/- 0.04 ml/g/min (mean +/- s.d.) and during insulin clamp (0.12 +/- 0.03 ml/g/min; ns). The calculated myocardial FFA uptake was four times higher in the fasting state than during insulin clamp (5.8 +/- 1.7 versus 1.4 +/- 0.5 micromol/100 g/min, p < 0.005). The femoral muscle fractional [18F]FTHA uptake rates (Ki) were lower (0.0071 +/- 0.0014 ml/g/min) in the fasting state than during insulin clamp (0.0127 +/- 0.0036 ml/g/min; p = 0.03), but the estimated femoral muscle FFA uptake was three times higher in the fasting state (0.38 +/- 0.09 micromol/100 g/min) as compared to that during insulin clamp (0.12 +/- 0.05 micromol/100 g/min, p < 0.005). CONCLUSION: Fluorine-18-FTHA PET appears to be a feasible method to estimate fatty acid kinetics in myocardial and skeletal muscle. Physiologically reasonable rates of FFA uptake in myocardium and skeletal muscle were obtained. Furthermore, the uptake rates were suppressed in response to insulin both in the myocardial and femoral muscle as expected.     

Impairment of regional fatty acid uptake in relation to wall motion and thallium-201 uptake in ischaemic but viable myocardium: assessment with iodine-123-labelled beta-methyl-branched fatty acid

In coronary artery disease, discrepancy in the uptake of thallium-201 and of methyl-branched fatty acid at rest has been described. The purpose of this study was to evaluate iodine-123 labelled beta-methyl-branched fatty acid (BMIPP) myocardial uptake and wall motion at rest in segments with stress-induced ischaemia identified by stress 201Tl tomography in patients with chronic coronary artery disease. 123I-BMIPP myocardial tomography was performed at rest and was compared with the findings of exercise-reinjection 201Tl tomography in 45 patients with chronic coronary artery disease. Regional wall motion was evaluated by contrast left ventriculography in 36 patients. Among 237 segments with reversible 201Tl defects, equally decreased uptake on both reinjection 201Tl and BMIPP images was observed in 93 (39%), more severely decreased uptake of BMIPP in 118 (50%) and more severely decreased uptake of reinjection 201Tl in 26 (11%). On the other hand, among 90 segments with non-reversible 201Tl defects, each pattern was observed in 71 (79%), 6 (7%) and 13 (14%) segments, respectively. When comparing the ischaemic segments with and without more severely reduced uptake of BMIPP than of reinjection 201Tl, wall motion was impaired to a greater extent in the segments with more severely reduced uptake of BMIPP than of reinjection 201Tl [severe hypo- or dyskinesis was present in 64 (70%) of 91 segments and in 24 (22%) of 110 segments, respectively, P<0.005]. In patients with chronic coronary artery disease, resting fatty acid uptake was frequently more reduced than reinjection 201Tl in the segments with stress-induced ischaemia, while in most of the fixed perfusion defects BMIPP and reinjection 201Tl uptake decreased concordantly. In ischaemic myocardium, wall motion was impaired to a greater extent in those segments which showed more severely reduced uptake of BMIPP than of reinjection 201Tl. In ischaemic but viable myocardium, discordant BMIPP uptake less than reinjection 201Tl uptake may indicate metabolic alterations and wall motion abnormality at rest independent of perfusion abnormalities. In conclusion, the combination of resting BMIPP and stress-reinjection 201Tl imaging may provide information on metabolic alterations and wall motion abnormality at rest independent of perfusion abnormalities.     

mRNA expression of glycolytic enzymes and glucose transporter proteins in ischemic myocardium with and without reperfusion

It is known that ischemia commonly increases exogenous glucose utilization by accelerating glucose uptake and flux rates through the Embden-Meyerhof pathway. Constitutive enzymes regulate the rate of glycolysis and in turn are regulated by product inhibition and allosteric controls. The purpose of this report was to test whether mRNA abundance for select glycolytic enzymes, and glucose transport proteins, is also modified. Six intact working pig hearts with coronary flow controlled by extracorporeal perfusion were compared at the following conditions: (1) aerobic control perfusion; (2) ischemia affected by a 60% decrease in left anterior descending (LAD) coronary perfusion: (3) ischemia again affected by a 60% decrease in LAD flow followed by a 40-min interval of aerobic reflow; (4) an intermittent ischemia and reflow protocol including four cycles of similar LAD flow reductions (5 min per cycle) interspersed with 15-20 min of aerobic reperfusion; (5) a 4-day model designed to produce myocardial chronic hibernation: and (6) mild ischemia induced by a 40% decrease in LAD flow for 85 min to produce certain adaptations compatible with short-term hibernation. In each heart, mRNA abundance was measured from LAD and circumflex (LCF) perfused myocardium for hexokinase, phosphofructokinase, glyceraldehyde-3-phosphate dehydrogenase and the two glucose transporter isomers, GLUT 4 and GLUT 1. mRNA data from LAD myocardium in intervention hearts were normalized to those from LAD tissue in the control heart (LADc) and with LCF values in the same intervention hearts. Signal variance around unity in the LAD tissue, with respect to that of the LCF myocardium, in the control heart compared closely (44 and 41% in two separate runs, respectively). GLUT 1/GLUT 4 ratios in the LAD and LCF beds of this heart also agreed closely. LAD/LADc ratios were increased for hexokinase (1.69), phosphofructokinase (3.69), and glyceraldehyde-3-phosphate dehydrogenase (2.29) in the ischemia heart and for phosphofructokinase (3.90), glyceraldehyde-3-phosphate dehydrogenase (2.20), GLUT 4 (1.55) and GLUT 1 (2.20) in the ischemia/reflow heart. There was no evidence of excess signal in the intermittent ischemia/reflow, chronic hibernation, or mild ischemia hearts. Altered signal from LCF myocardium was also suggested. These data indicate that mRNA abundance for select glycolytic enzymes and transporter proteins is increased in ischemic myocardium with or without reperfusion and offers a possible mechanism for increased protein activity in settings of diminished regional coronary flow.     

Extraskeletal primary osteosarcoma of the frontal region]

This article presents two cases with preserved myocardial 201Tl uptake and absent uptake of two kinds of radioiodinated fatty acids: iodine-123-labeled 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) and iodine-123-labeled 15-(p-iodophenyl)-9-(R,S)-methylpentadecanoic acid (9MPA). Although coronary angiography showed no stenotic lesion and left ventriculography revealed no wall motion abnormality, no myocardial uptake of BMIPP and 9MPA was observed in the first case. In the second case, no myocardial accumulation was recognized even in the initial phase of dynamic SPECT acquired soon after the injection of 9MPA. The results suggest that the non-visualized myocardium was not specific for BMIPP imaging and that rather than the early back diffusion of the tracers from the myocardium, abnormality of the myocardial cell membrane was a possible mechanism accounting for the phenomenon.     

Children''s spiritual response: validation of the nursing diagnosis spiritual distress

A variety of new radiopharmaceutical agents have been introduced to probe myocardial function in vivo. This review will introduce these new techniques which have recently been available in Japan. Tc-99m perfusion imaging agents provide excellent myocardial perfusion images which may enhance diagnostic accuracy in the study of coronary artery disease. In addition, greater photon flux from the tracer permits simultaneous assessment of regional perfusion and function with use of first-pass angiography or ECG-gated acquisition. Positron emission tomography enables metabolic assessment in vivo. Preserved FDG uptake indicates ischemic but viable myocardium which is likely to improve regional dysfunction after revascularization. In addition, FDG-PET seems to be valuable for selecting a high risk subgroup. Recently I-123 BMIPP, a branched fatty acid analog, has been clinically available in Japan. Less uptake of BMIPP than thallium is often observed in the ischemic myocardium. Such perfusion metabolic mismatch which seems to be similarly observed in FDG-PET is identified in the stunned or hibernating myocardium with regional dysfunction. Both of them are likely to recover afterwards. Severe ischemia is identified as reduced BMIPP uptake at rest, suggesting its role as an ischemic memory imaging. I-123 MIBG uptake in the myocardium reflects adrenergic neuronal function in vivo. In the study of coronary artery disease, neuronal denervation is often observed around the infarcted myocardium and post ischemic region as well. More importantly, reduced MIBG uptake in these patients can identify high risk for ventricular arrhythmias and assess severity of congestive heart failure. These new techniques will provide insights into new pathological states in the ischemic heart disease and enable to select optimal treatment in these patients.     

Evaluation of heart-to-organ ratios of 123I-BMIPP and the dimethyl-substituted 123I-DMIPP fatty acid analogue in humans

Radioiodinated fatty acid analogues modified by methyl-substitution are used for single photon emission tomography (SPET) imaging of the heart. The effect of mono- and dimethyl-substitution on heart-to-organ ratios was investigated in humans to evaluate their relative merits for SPET image quality. Planar total body scans were performed in fasting patients with coronary artery disease, but without heart failure, 1 h after administration of 111 MBq 15-(p-[I-123]-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP, n = 7) or 111 MBq 15-(p-[I-123]-iodophenyl)-3,3-dimethylpentadecanoic acid (DMIPP, n = 4). Because these branched fatty acids are used for cardiac imaging, we focused on heart-to-organ (heart/organ) ratios by comparing small regions of interest in heart, liver, lung, muscle and bladder. Both tracers showed good visualization of the heart. DMIPP showed a relatively high liver uptake: the heart/liver ratios for DMIPP and BMIPP were 0.39 +/- 0.05 and 1.00 +/- 0.12, respectively (P < 0.0001). Increased lung activity was found for BMIPP, with a heart/lung ratio of 1.63 +/- 0.17 versus 2.32 +/- 0.28 for DMIPP (P < 0.001). In contrast to DMIPP, BMIPP also showed increased activity in the bladder. In conclusion, BMIPP and DMIPP show different distribution patterns. Despite the more favourable heart/lung ratios for DMIPP, the high liver uptake affects cardiac SPET image quality and therefore BMIPP appears to provide superior cardiac SPET image quality in humans.     

Effect of metabolic substrate on BMIPP metabolism in canine myocardium

The lipid tracer 1 5-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) is clinically useful, and its basic metabolism is being analyzed. Because the pharmacokinetics of this lipid tracer may be affected by blood concentrations of fatty acid or glucose, this study evaluated the effects of excess levels of lipid or glucose on BMIPP uptake and metabolism. METHODS: A technique using an open-chest dog model was used. Blood sampling was performed from the left anterior descending coronary artery and great cardiac vein after an injection of 123I-BMIPP either with a glucose infusion (n = 6) or a lipid infusion (n = 5). High performance liquid chromatography and double-tracer kinetic analyses clarified the extraction, retention, backdiffusion and further metabolism of BMIPP. These results were compared with data from control dogs (n = 6). RESULTS: In this experiment, a 10-fold increase over the normal lipid blood concentration and twofold increase over the normal blood glucose concentration were evaluated with either intralipid or glucose infusion, respectively. In the lipid infusion studies, the extraction significantly decreased compared with the control values (74% +/- 12% to 58% +/- 8%; p < 0.05), and the washout increased from 50% +/- 13% to 68% +/- 16% (p < 0.05). The BMIPP backdiffusion increased (p < 0.05), and the levels of the further metabolites decreased (p < 0.05), while the retention level remained constant (normal, 89% +/- 9%; lipid infusion, 91% +/- 3%; ns). In the glucose infusion studies, the BMIPP extraction, retention and washout showed no statistical differences compared to controls; however, these parameters showed the same tendencies as those in the lipid infusion group. In addition, the BMIPP backdiffusion increased significantly (control, 25.1% +/- 8%; glucose infusion, 48.7% +/- 25.6%; p < 0.05) as it did after the lipid infusion. CONCLUSION: BMIPP metabolism and uptake are affected by excess concentrations of lipid and glucose in the blood. However, the retention of BMIPP was not affected by either type of infusion. The BMIPP backdiffusion and the further metabolite comprising 10% of the tracer extracted were affected both by the lipid and glucose infusions. These results indicate that an excess fat concentration and glucose affect BMIPP uptake, especially the extraction of BMIPP and BMIPP backdiffusion.     

99mTc-HL91: "hot spot" detection of ischemic myocardium in vivo by gamma camera imaging

BACKGROUND: 99mTc-HL91 is a new hypoxia imaging agent that demonstrates increased uptake and retention in globally hypoxic myocardium in vitro. The purpose of this study was to determine whether 99mTc-HL91 could detect regional ischemia in vivo by gamma camera imaging. METHODS AND RESULTS: Eight open-chest dogs with left circumflex (LCx) stenoses were studied. Injection of 5 mCi of 99mTc-HL91 and microspheres was followed by imaging over 4 hours. Heart slices were imaged, then stained with triphenyltetrazolium chloride (TTC), and tissues were well-counted. TTC staining demonstrated no injury. Mean LCx blood flow was 0.32+/-0.04 mL x min(-1) x g(-1), and mean left anterior descending coronary artery (LAD) flow was 0.96+/-0.02 mL x min(-1) x g(-1) (ratio, 0.33). "Hot spots" were detected in 8 of 8 experiments in vivo within 60 minutes and improved over 4 hours. Region of interest analysis of LCx/LAD activity ratios demonstrated significant increases within 30 minutes (final ratio, 3.0; P<0.05). LCx and LAD washout curves demonstrated significant differences within 15 minutes. Washout curves were biexponential over 1 hour, followed by linear retention from 1 to 4 hours. Four-hour fractional retention was 0.12 for LAD and 0.44 for LCx (P<0.01). Myocardial flow versus tracer uptake demonstrated 2 phases: phase 1 (flow, 0.05 to 0.7 mL x min(-1) x g(-1)) had an inverse linear correlation (r= -0.80); phase 2, (flow, >0.7 mL x min(-1) x g(-1)) had no correlation. Ischemic heart/liver ratios remained near 1.0 for 4 hours. CONCLUSIONS: 99mTc-HL91 positively identifies regional myocardial ischemia in a canine model using 99mTc imaging. Quantitative techniques allowed identification of ischemic myocardium within 15 minutes of tracer administration.     

Saikosaponin b2 induces differentiation without growth inhibition in cultured B16 melanoma cells

Some patients of ischemic heart disease have low uptake in 123I-labeled beta methyl-iodophenyl penta-decanoic acid (BMIPP) SPECT in spite of normal uptake in thallium-201 (Tl) SPECT. To investigate their clinical significance, we performed both T1 and BMIPP myocardial SPECT in 26 cases with stable angina (n = 16) and unstable angina (n = 10), and compared with clinical backgrounds electrocardiogram (ECG) and left ventriculography (LVG). In 11 patients of them, the uptake of BMIPP was moderately reduced. We divided 26 cases into two groups according to uptake of BMIPP (normal/reduced). The two groups had no differences in length of angina attack and duration of disease, but they had a significant difference in the abnormality of either ECG or LVG. Three to six months after PTCA, we examined LVG in 18 cases, 12 of 16 cases with the abnormality of LVG showed the improvement of wall motion. We concluded the reduced uptake of BMIPP with normal uptake of Tl was related to more severe ischemia in cases with unstable angina.     

Propanil affects transcriptional and posttranscriptional regulation of IL-2 expression in activated EL-4 cells

OBJECTIVE: To determine the clinical and prognostic value of identifying metabolic abnormalities of myocardial fatty acid metabolism in idiopathic dilated cardiomyopathy using iodine-123 beta-methyl-iodophenyl pentadecanoic acid (123I BMIPP). SETTING: Cardiac care division in national hospital. PATIENTS: 32 consecutive patients with idiopathic dilated cardiomyopathy in whom both 123I BMIPP and thallium-201 myocardial single photon emission computed tomography were performed. METHODS: The uptake of each tracer was scored visually from 0 (normal) to 3 (defect) in 17 segments (eight basal, eight midventricular, and one apical). A total score for all 17 segments was compared with clinicopathological variables. Prognostic value of mismatches between the two tracers were also evaluated. RESULTS: The 123I BMIPP total score was correlated with pulmonary capillary wedge pressure (r = 0.68, p < 0.001), left ventricular end diastolic pressure (r = 0.65, p < 0.001), percentage fractional shortening at six months' follow up (r = -0.58, p = 0. 001), myocyte diameter (r = 0.66, p < 0.001), and percentage area of interstitial fibrosis (r = 0.69, p < 0.001) measured by morphometry in the biopsy specimens. During a mean (SD) follow up of 20 (11) months, deterioration of the New York Heart Association functional class was observed in 11 of the 32 patients; four of these died. Segments with a greater decrease in 123I BMIPP than thallium-201 uptake (type B mismatching) were often observed in patients with deterioration (88/187, 29% v 58/357, 16%; p < 0.001). CONCLUSIONS: The extent of the abnormality of myocardial fatty acid metabolism in idiopathic dilated cardiomyopathy reflects the severity of haemodynamic deterioration and histopathological changes. Type B mismatching is one of the important prognostic indicators in idiopathic dilated cardiomyopathy.     

Outcome significance of thallium-201 and iodine-123-BMIPP perfusion-metabolism mismatch in preinfarction angina

The relevance of brief antecedent ischemia to preservation of myocyte viability and cardiac function is still controversial in humans. Dysfunctioning but viable myocardium shows impaired fatty acid metabolism despite restored coronary perfusion. We asked whether preinfarction angina might be related to preservation of cell viability and better functional recovery in comparison with impaired fatty acid metabolism. METHODS: Tomographic imagings with thallium and beta-methyl-p-iodophenyl penta-decanoic acid (BMIPP) were performed in 32 patients with first acute myocardial infarction who received primary coronary angioplasty: 20 patients with preexisting angina before infarction (Group A) and 12 without (Group B). Thallium and BMIPP abnormalities were quantified as a severity index by a polar map. Regional function was quantified by ventriculography and followed up. RESULTS: Despite no significant difference in coronary risk factors, cardiac function and angiographic findings, the thallium severity index was significantly lower than that of BMIPP (62+/-45 versus 96+/-59) in Group A but not in Group B (104+/-65 versus 115+/-68); the thallium severity index in Group A was significantly lower than that in Group B, but there was no significant difference in BMIPP abnormality between them. The BMIPP severity index correlated significantly with that of thallium in both groups. However, the regression line in Group A shifted downward and was statistically different compared with that in Group B. Regional function at an acute stage was significantly improved from 107+/-31 to 70+/-31 s.d./chord during follow-up in Group A but not in Group B (109+/-62 versus 106+/-52). The ratio of the thallium severity index to that of BMIPP at an acute stage was significantly related to improved regional wall motion during follow-up in the reperfused patients (y=-53x + 65, r=0.667). CONCLUSION: Preinfarction angina preserves myocyte viability relative to fatty acid metabolism, resulting in augmented perfusion-metabolism mismatch and functional improvement in patients undergoing successful reperfusion, indicating cardioprotective effects of preinfarction angina.     

Assessment of 123I-beta-methyl iodophenyl pentadecanoic acid (BMIPP) myocardial scintigraphy in patients of chronic right ventricular overload--fatty acid metabolism in right ventricular myocardium

An investigation on the right ventricular pressure level and the abnormalities in the fatty acid metabolism of myocardium was made using 123I-beta-methyl-iodophenyl pentadecanoic acid (BMIPP) myocardial SPECT in patients with chronic right ventricular overloading. Twenty patients who presented with right ventricular systolic pressure (RVSP) of 35 mmHg or more were used as the subjects. Dual myocardial SPECT with 201TlCl (Tl) and BMIPP was carried out for the subjects and RVc/LVc, a ratio of radioactivity count incorporated in the right ventricular free wall to the left one was determined for Tl and BMIPP. And the correlations between RVc/LVc and RVSP, and RVc/LVc and RVSP/LVSP were examined. The subjects were classified into 3 groups based on the RVSP levels and the count ratio, BMIPP/Tl was compared among the three groups. With respect of Tl uptake, there were significant, positive correlations between RVc/LVc and RVSP (correlation coefficient r = 0.51, p < 0.05) and between RVc/LVc and RVSP/LVSP (correlation coefficient r = 0.59, p < 0.01). On the other hand, no significant correlation was found between them with respect of the uptake of BMIPP. The BMIPP/Tl ratio in the group with higher than 80 mmHg of RVSP was 0.82 +/- 0.06, which was significantly lower than the ratio's for two groups of less than 80 mmHg; 0.91 +/- 0.07 and 0.98 +/- 0.04 in the group with 35-49 and 50-79 mmHg of RVSP, respectively. These results show that when compared with BMIPP, Tl is superior for the estimation of right ventricular pressure. For the patients with right ventricular overloading, it was suggested that when RVSP reaches 80 mmHg or more, there appear some disorders in the fatty acid metabolism in the right ventricular myocardium.     

The relationship between discrepant areas on 201TlCl/123I-BMIPP myocardial scintigraphy, local wall motion, and glucose metabolism in patients with myocardial infarction

In order to clarify the significance of the discrepancy between myocardial blood flow and fatty acid metabolism on 201TlCl/123I-BMIPP SPECT after acute myocardial infarction, we examined 52 patients (278 segments) with their first acute myocardial infarction using two-dimensional echocardiography and FDG-PET. Patients with Tl/BMIPP discrepancy in the acute stage showed higher FDG accumulation than those without Tl/BMIPP discrepancy. In the chronic stage, however, there was no significant difference between both groups. Patients with Tl/BMIPP discrepancy in the chronic stage had lower wall motion scores than those without Tl/BMIPP discrepancy. Significant improvement of the wall motion score was recognized in patients who showed Tl/BMIPP discrepancy in the acute stage. Patients were classified into stenosis and non-stenosis groups by the presence of significant stenosis on coronary angiography in the chronic stage. In the stenosis group, the Tl/BMIPP discrepancy did not show much change from the acute to chronic stage, but there was a significant decrease in the non-stenosis group. It was concluded that 201TlCl/123I-BMIPP myocardial SPECT is useful for predicting future improvement of wall motion and determining the residual ischemia in the chronic stage based on the presence or absence of this discrepancy.     

Mirror, mirror on the wall, who''s the thinnest one of all? Effects of self-awareness on consumption of full-fat, reduced-fat, and no-fat products

The aim of this study was to determine whether adenosine receptor blockade before ischemia would enhance the degree of stunning and induce a sustained decrease in glucose uptake after reperfusion. METHODS: Stunning was induced in 14 anesthetized swine by partially occluding the left anterior descending artery (LAD) for 20 min (> 80% flow reduction). Seven animals were pretreated with the nonspecific adenosine receptor blocker 8-phenyltheophylline (8-PT; 5 mg/kg), which decreased reactive hyperemia by an average of 38%. Myocardial glucose uptake was assessed 1 hr following reperfusion with PET and the glucose analog 18F-fluorodeoxyglucose (FDG). RESULTS: Before ischemia, systolic shortening in the LAD region was 15% +/- 6% in the control group and 16% +/- 4% in the 8-PT group and in both groups was reduced to - 1% +/- 2% during ischemia. After reperfusion, systolic shortening was 7% +/- 3% in the control group and 2% +/- 3% in the 8-PT group (p < 0.05). Myocardial oxygen consumption before ischemia was 4.58 +/- 3.03 micromol/min/g in the control group and 4.44 +/- 1.83 micromol/min/g in the 8-PT group (ns) and neither were different after reperfusion. In the postischemic LAD region, myocardial glucose uptake was 0.18 +/- 0.15 micromol/min/g in the control group and was similar to that of the 8-PT group (0.17 +/- 0.08 micromol/min/g; ns). CONCLUSION: The nonspecific adenosine blocker 8-PT enhanced the degree of stunning when given before ischemia but did not induce a sustained effect on myocardial glucose uptake after reperfusion.     

Mechanism of impaired left ventricular wall motion in the diabetic heart without coronary artery disease

OBJECTIVE: To elucidate whether impairment of the myocardial free fatty acid (FFA) metabolism and small vessel abnormalities in the myocardium are etiologic or contributory factors of myocardial dysfunction in patients with NIDDM without any significant coronary artery disease. RESEARCH DESIGN AND METHODS: We performed myocardial imaging with 123I-labeled beta-methyl-p-iodophenyl pentadecanoic acid (BMIPP), a branched analog of FFA, and dipyridamole-infusion 201thallium scintigraphy (Dip) in nine patients who demonstrated left ventricular wall motion abnormalities without any significant coronary artery disease and in fifteen control cases. As an index of myocardial FFA metabolism, the heart-to-mediastinum count ratio (H/M) of BMIPP was calculated from the mean count in the regions of interest at the heart and the upper mediastinum. RESULTS: Nine patients with reduced wall motion documented by left ventriculography (LVG), (hypokinetic group) demonstrated significantly lower BMIPP uptake (2.1 +/- 0.2, mean +/- SD) than fifteen patients with normal wall motion (normokinetic group) (2.3 +/- 0.2, P < 0.05). Regional ventricular wall motion observed by LVG, regional BMIPP uptake, and regional redistribution phenomenon (RD) were evaluated for five regions of the left ventricle: anterior, septal, apical, lateral, and inferoposterior regions. Wall motion was abnormal in 24 out of 120 regions. Regional BMIPP uptake was reduced in 47 regions. RD in Dip was observed in 23 regions. In regional analysis, the existence of defect in the BMIPP image showed significant correlation with wall motion abnormality (P < 0.01), but there was no significant relationship between the RD in Dip and regional wall motion abnormality (P = 0.16). Myocardial biopsy specimens obtained from the right ventricle of 20 patients showed no pathologic changes, with the exception of two patients. CONCLUSIONS: Our findings suggest that impairment of myocardial FFA metabolism rather than small vessel abnormalities in the myocardium is responsible for modest left ventricular dysfunction in patients with diabetes.     

Comparison between thallium-201 and technetium-99m-tetrofosmin uptake with sustained low flow and profound systolic dysfunction

Technetium-99m-tetrofosmin uptake was compared to that of 201Tl in the setting of low flow and systolic dysfunction. METHODS: In nine open-chested dogs, a severe left anterior descending (LAD) coronary artery stenosis resulted in a 54.3% mean flow reduction and decreased left ventricular thickening from 21% +/- 1% to -3 +/- 2%. After 30 min, 37 MBq (1 mCi) of 201Tl and microspheres were injected and initial and 2-hr redistribution images acquired. Two hours later, 370 MBq (10 mCi) of 99mTc-tetrofosmin and microspheres were injected and an image was obtained. LAD: left circumflex (LCX) count ratios for both tracers and flows were calculated by well counting postmortem, and 201Tl and 99mTc-tetrofosmin defect magnitudes were determined by quantitative image analysis. RESULTS: LAD:LCx flow ratios were similar during 201Tl and 99mTc-tetrofosmin injections (0.48 +/- 0.04 versus 0.49 +/- 0.05, p = n.s.). Final 201Tl activity (0.66 +/- 0.04) was significantly higher than 99mTc-tetrofosmin (0.55 +/- 0.05; p < 0.05). LAD/LCx 99mTc-tetrofosmin image defect count ratio was similar to 201Tl defect count ratio on the initial rest 201Tl scan (0.57 +/- 0.03 versus 0.56 +/- 0.02, p = ns), but significantly less than 201Tl defect count ratio at 2 hr (0.57 +/- 0.03 versus 0.65 +/- 0.02, p < 0.05). CONCLUSION: In a low-flow model with profound systolic dysfunction, myocardial 99mTc-tetrofosmin uptake ( > 50%) reflective of viability was observed in the asynergic zone perfused by the stenotic LAD.     

Multiparameter monitoring and analysis of in vivo ischemic and hypoxic heart

We describe a unique in vivo technique which addresses the multifactorial function of the heart, i.e., simultaneous measurement of myocardial ion transport (two mini-electrode systems to measure K+e and Ca2+e), energy metabolism (NADH fluorescence to measure NADH redox state), and coronary flow (laser-Doppler perfusion) using a multiprobe assembly (MPA) which contains transducers for all measurements. The MPA (which is 6 mm in diameter) was applied to the external surface of the heart in an open chest dog model. To test MPA function, myocardial ischemia was produced by application of a balloon occluder to the left anterior descending coronary (LAD) artery, and hypoxia was produced by changing the inspired O2-N2 ratio until the PaO2 was 20-30 torr. The MPA simultaneously monitored changes in ion flux, heart metabolism, and tissue perfusion during pathophysiological intervention.     

Desflurane and isoflurane exert modest beneficial actions on left ventricular diastolic function during myocardial ischemia in dogs

BACKGROUND: Volatile anesthetics exert cardioprotective effects during myocardial ischemia. This investigation examined the regional systolic and diastolic mechanical responses to brief left anterior descending coronary artery (LAD) occlusion in the central ischemic zone and in remote normal myocardium in the conscious state and during desflurane and isoflurane anesthesia. METHODS: Eighteen experiments were performed in nine dogs chronically instrumented for measurement of aortic and left ventricular pressure, cardiac output, LAD coronary blood flow velocity, and LAD and left circumflex coronary artery subendocardial segment length. Regional myocardial contractility was evaluated with the slope of the preload recruitable stroke work relationship determined from a series of left ventricular pressure-segment length diagrams in the LAD and left circumflex coronary artery zones. Diastolic function was assessed with a time constant of isovolumic relaxation (tau), maximum segment lengthening velocity in LAD and left circumflex coronary artery regions, and regional chamber stiffness constants derived using monoexponential and three-element exponential curve fitting in each zone. On separate experimental days, hemodynamics and indices of regional functional were obtained in the conscious state and during 1.1 and 1.6 minimum alveolar concentration end-tidal desflurane or isoflurane before and during LAD occlusion. RESULTS: In conscious dogs, LAD occlusion abolished regional stroke work, increased chamber stiffness (monoexponential: 0.39 +/- 0.04 during control to 1.34 +/- 0.39 mm-1 during LAD occlusion), and decreased the rate of early ventricular filling in the ischemic zone. These changes were accompanied by increased contractility (slope: 103 +/- 8 during control to 112 +/- 7 mmHg during LAD occlusion), rapid filling rate (maximum segment lengthening velocity: 46 +/- 5 during control to 55 +/- 7 mm.s-1 during LAD occlusion), and chamber stiffness (monoexponential: 0.43 +/- 0.05 during control to 1.14 +/- 0.25 mm-1 during LAD occlusion) in the normal region. Increases in tau were also observed in the conscious state during the period of myocardial ischemia. Desflurane and isoflurane increased tau and decreased the slope and maximum segment lengthening velocity in a dose-related manner. Monoexponential and three-element element exponential curve fitting were unchanged by the volatile anesthetics in the absence of ischemia. Myocardial contractility and rapid filling rate were enhanced in the nonischemic region during LAD occlusion in the presence of desflurane and isoflurane. In contrast to the findings in the conscious state, ischemia-induced increases in tau and chamber stiffness in the ischemic and normal zones were attenuated during anesthesia induced by desflurane and isoflurane. CONCLUSIONS: The results indicate that increases in contractility of remote myocardium during brief regional ischemia were preserved in the presence of desflurane and isoflurane anesthesia. In addition, desflurane and isoflurane blunted ischemia-induced increases in tau and regional chamber stiffness in both the ischemic and nonischemic zones. These results demonstrate that the volatile anesthetics may exert important beneficial actions on left ventricular mechanics in the presence of severe abnormalities in systolic and diastolic function during ischemia.