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Biomedical subjects

R Nohara

Publications and source records attributed to R Nohara.

At least 37 records · Page 2Linked to original sources

Pericardial fluid from patients with ischemic heart disease accelerates the growth of human vascular smooth muscle cells.

The strong association between severe coronary stenosis and collateral growth continues to be a paradigm in this field of investigation. The present study was based on the hypothesis that angiogenic growth factors are produced by ischemic cardiac tissue, are diffusible and more concentrated in pericardial fluid, and accelerate the growth of vascular smooth muscle cells (VSMC). Pericardial fluid from 17 patients with stable or unstable angina or acute myocardial infarction (group A) and from 10 patients with nonischemic heart disease (group B) were collected at the time of open heart surgery. Cultured human aortic VSMC were plated at the third passage at a density of 5x10(3)/100 microl and allowed to attach for 24 h. The 3-day growth assay was preceded by 72 h of growth arrest with 0.4% fetal calf serum (FCS). Growth was restarted by the addition of 90 microl of medium containing 0.4% FCS, and 1O microl of each pericardial fluid. Cell counts on triplicate wells were performed using a dimethylthiazol (MTT) method on days 0 and 3. The effect of pericardial fluid on the growth of VSMC was evaluated as a ratio (R) of cell numbers on day 3 to those on day 0. The concentration of basic fibroblast growth factor (bFGF) in pericardial fluid was measured by an enzyme-linked immunosorbent assay. The concentration of bFGF in pericardial fluid of group A was 633+/-127 pg/ml, and significantly (p=0.003) higher than that of group B (86+/-23 pg/ml). R in group A was 2.29+/-0.18 and significantly (p=0.019) higher than that in group B (1.68+/-0.11). The level of bFGF positively correlated with R (p=0.009). These findings indicate that pericardial fluid from patients with ischemic heart disease contains some substances that mediate collateral development, and bFGF might be one of them.

Aged↗

Heparin potentiates collateral growth but not growth of intramyocardial endarteries in dogs with repeated coronary occlusion.

Heparin accelerates coronary collateral development in various animal models of myocardial ischemia. The purpose of this study was to clarify the beneficial effect of heparin on canine collateral development. Seventeen adult mongrel dogs were instrumented for measurements of a subendocardial segment length in the central area perfused by the left circumflex coronary artery, its flow, and left ventricular pressure. A pulsed Doppler flow probe and an externally inflatable pneumatic occluder were placed around the proximal circumflex artery. After the recovery from surgery, 2-min circumflex coronary artery occlusions were repeated eight times at 58-min intervals daily. After excluding seven dogs with well-developed preexisting collateral circulation, ten dogs were randomized into two groups with (n = 5) and without (n = 5) heparin treatment. The total occlusion time until adequate collateral development (an index of collateral growth) was 164+/-34 (SD) min in dogs with heparin treatment, being significantly less than 289+/-49 min in dogs without heparin (p<0.01). In contrast, the extent of the reduction in resting blood flow of the repeatedly occluded circumflex artery (an index of neovascularization toward the ischemic area) was comparable in dogs with and without heparin (15.4+/-12.4% vs. 21.1+/-13.6%, p=NS). Heparin promotes nonsprouting angiogenesis (arteriogenesis) of preformed collateral vessels but not neovascularization toward the ischemic area in dogs with brief repetitive coronary occlusions.

Animals↗

Determinants of collateral development in patients with acute myocardial infarction.

BACKGROUND: The presence or absence of collateral circulation to the infarct-related coronary artery in acute myocardial infarction (AMI) significantly impacts on infarct size and resulting left ventricular function. However, the determinants of collateral development have not been clarified. HYPOTHESIS: The purpose of this study was to elucidate the determinants of collateral development in humans. METHODS: The study group consisted of 248 patients (178 men, 70 women; mean age 63 years) undergoing coronary angiography within 12 h after the onset of a first AMI. All patients exhibited complete occlusion of the infarct-related artery. The extent of collateral circulation to the area perfused by the infarct-related artery was graded as none, or poorly or well developed, depending on the degree of opacification of the occluded coronary artery on the contralateral injection of contrast. RESULTS: Well-developed collateral circulation was observed in 92 of the 248 patients (37.1%). The prevalence of well-developed collaterals was 57% in patients with a history of angina pectoris prior to AMI, which was significantly (p < 0.0001) higher than the 26% in those without a history of angina. Multivariate stepwise logistic regression analysis was then applied to identify predictors of collateral development. Possible determinants of collateral development were long-standing preinfarction angina, severity of coronary artery disease, age, gender, and coronary risk factors (hypertension, diabetes, hypercholesterolemia, smoking). This analysis revealed that only the presence of a history of angina pectoris prior to AMI was a significant predictor of collateral development (p < 0.0001). CONCLUSIONS: A history of angina pectoris prior to AMI is a clinical marker for coronary stenoses. Since severe coronary stenoses can provide stimuli that lead to collateral development, it is reasonable that a history of angina would also be a clinical marker for collateral vessels.

Age Factors↗

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 beta-oxidation and subsequent ATP production. Thus, myocardial viability was reflected on the BMIPP uptake in acute ischemia. In spite of insignificant 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.

Animals↗

A patient with hypertrophic cardiomyopathy accompanied by right ventricular dilation of unknown cause.

Hypertrophic cardiomyopathy (HCM) is a disease characterized by an unknown cause of hypertrophy in the left or right ventricle. The dilated phase of HCM shows disease conditions resembling dilated cardiomyopathy, such as ventricular dilation, thin ventricular wall, and reduction of the ejection fraction. A patient presented with left ventricular concentric hypertrophy accompanied by right ventricular dilatation of unknown cause. Right ventricular endomyocardial biopsy specimens showed characteristic myocardial disarray. Therefore, there is the possibility that the patient had right and left ventricular HCM in the process toward the dilated phase, in which dilatation first occurred in the right ventricle.

Atrial Fibrillation↗

Improvement of regional myocardial and coronary blood flow reserve in a patient treated with enhanced external counterpulsation: evaluation by nitrogen-13 ammonia PET.

Enhanced external counterpulsation (EECP) is a noninvasive treatment for chronic stable angina, which works by recruiting and developing the coronary collateral vessels. Coronary perfusion and coronary flow reserve (CFR) were evaluated by nitrogen-13 (13N) ammonia positron emission tomography (PET) in a patient who had undergone EECP. The patient, who had 3-vessel coronary artery disease, required a percutaneous transluminal coronary angioplasty (PTCA) for the right coronary artery. The PTCA was successful, but 6 months later he again felt chest oppression. The coronary angiography showed re-stenosis at the PTCA site, and other progressive coronary stenosis. The patient was again treated with EECP for 35 h. The 13N-ammonia PET was performed both at baseline and during dipyridamole provocation, before and after EECP treatment. Coronary perfusion of each myocardial wall increased at the baseline (anterior: 0.52-0.75; septal: 0.48-0.66; lateral: 0.61-0.68; inferior: 0.46-0.57 ml min(-1) g(-1), and the CFRs in the septal and inferior walls (septal: 2.07-2.15; inferior: 1.99-2.06) also increased after the treatment. Thus, the EECP treatment improved both coronary perfusion at baseline and CFR, which suggests that it may be one of the choices for treatment of angina.

Ammonia↗

Immune function and psychological factors in patients with coronary heart disease (I).

As part of studies on the effects, especially the preventive effects, of exercise and psychological factors on cardiovascular diseases, the association between psychological tendencies and immune response was evaluated in patients with coronary heart disease who were receiving exercise therapy. The Pearson's product-moment correlation coefficients between natural killer (NK) cell activity and various psychological scales were obtained. For the Moudsley Personality Inventory, NK cell activity had a significant positive correlation with the extraversion scale and a significant negative correlation with the neuroticism scale. NK cell activity also had a significant positive correlation with the playful humor scale and a significantly negative correlation with the Self-rating Depression Scale. The positive correlation of NK cell activity with the extraversion scale and the humor scale and its negative correlation with the neuroticism scale suggest an association between a positive-feeling tendency and high NK cell activity. The negative correlations of NK activity with the depression scale and neuroticism scale indicate that decreased or excessive expression of feelings inhibits NK cell activity. Thus, high NK activity appears to be associated with optimal expression of feelings.

Aged↗

Effect of long-term exercise training on regional myocardial perfusion changes in patients with coronary artery disease.

The cardiac rehabilitation of patients with coronary artery disease (CAD) promotes exercise tolerance, improves left ventricular function, and decreases the heart rate and systolic blood pressure at the same load intensity. Several studies have shown that cardiac rehabilitation improves myocardial perfusion in CAD patients. However, the long-term (> or = 1 year) effect of cardiac rehabilitation on myocardial perfusion is still controversial. The effect of long-term exercise training on myocardial perfusion in CAD patients was assessed using thallium-201 (201Tl) exercise studies at a baseline (4 months after the onset of CAD) and at a 1-year or more follow-up in 58 patients with stable CAD. The subjects had been divided into a training group (n=35) participating in supervised exercise 2 times per week for the follow-up period, and the control group (n=23). There was an improvement in the myocardial perfusion on stress 201Tl scintigraphy in 20 of the 35 (57.1%) trained patients and in 3 of the 23 (13.0%) of the control patients (p<0.001). The number of 201Tl stress myocardial perfusion defect segments was significantly decreased after the cardiac rehabilitation training (231 to 153 segments), but showed no change in the control group (158 to 156 segments) (p<0.01). In spite of no significant differences in the number of involved coronary arteries, it improved (12/17 patients: 70.6%) more in the patients who had trained for more than 2 years compared to the patients who had trained for less than 2 years. The exercise tolerance increased in 25 of the 35 training group patients (71.4%), and in only 3 of the 23 control group patients (13.0%). The peak double products increased from 20,131+/-6,010 to 28,370+/-5,600 (p<0.01) in the training group, and showed no change in the control group (20,567+/-5,112 to 20,964+/-7,728 (NS)). The results indicated that the long-term physical training increased exercise tolerance and the double products of CAD patients. In addition, the training resulted in improved cardiac perfusion as evidenced by 201Tl scintigraphy. The findings suggest that exercise training is an advisable and effective treatment for patients with CAD.

Aged↗

Myocardial metabolism of 123I-BMIPP in a canine model with ischemia: implications of perfusion-metabolism mismatch on SPECT images in patients with ischemic heart disease.

UNLABELLED: 123I-(rho-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) is a fatty acid analog for SPECT imaging. This radiopharmaceutical possesses the unique property, that is, perfusion-metabolism mismatch on SPECT images in patients with ischemic heart disease. However, the reason of this mechanism remains unclear. METHODS: Using open-chest dogs under anesthesia, we made a system to release all the blood of the great cardiac vein outside without recirculation, if necessary. Left anterior descending artery (LAD) was occluded for 30 min after reperfusion. After the injection of BMIPP into LAD, blood samplings from the cardiac vein and abdominal aorta (6 dogs) or serial biopsy specimens from the LAD region (5 dogs) were performed, and then compared with the normal control. The catabolites of BMIPP, including backdiffusion of nonmetabolized BMIPP, were evaluated with high-performance liquid chromatography (HPLC) in the efflux study. Thin-layer chromatography (TLC) technique was introduced in the tissue analytical study. RESULTS: Although the rapid extraction of BMIPP from the plasma into the myocardium and the subsequent retention were unchanged, the early washout (8 min) of radioactivity significantly increased (51% +/- 12% to 65% +/- 7%; P < 0.05) with ischemia. The metabolites from the myocardium consisted of backdiffusion of nonmetabolized BMIPP, alpha, intermediate, and full oxidation metabolites. Among these metabolites, backdiffusion of nonmetabolized BMIPP in blood significantly increased (27.9% +/- 7.7% to 42.3% +/- 8.1%; P < 0.05), especially in the early phase with ischemia. In tissue, the radioactivity was concentrated in the triglyceride pool even in the early phase, and in addition, BMIPP and alpha-oxidized metabolite significantly decreased in the early phase with ischemia (t = 1 min after BMIPP injection, 25.9% +/- 8.6% to 14.5% +/- 2.1%, P < 0.01; t = 2 min, 8.9% +/- 5.0% to 4.5% +/- 1.7%, P < 0.05). CONCLUSION: These results show that backdiffusion of nonmetabolized BMIPP from the myocardium increased and BMIPP (long-chain fatty acids) in tissue decreased with ischemia, suggesting backdiffusion of nonmetabolized BMIPP might play an important role in myocardial perfusion-metabolism mismatch on SPECT images in patients with ischemic heart disease.

Animals↗

Importance of alpha 1-sympathetic activity for diurnal change in ischemic threshold in patients with stable angina.

BACKGROUND: Although ischemic threshold reportedly is lower in the early morning than in the afternoon, the mechanisms that account for the diurnal change in minimal coronary vascular resistance in the potentially ischemic area are unknown. HYPOTHESIS: We hypothesized that calcium-channel blockers and alpha 1 blockers may affect the ischemic threshold in the early morning and afternoon in patients with stable angina. METHODS: Before and after the administration of the calcium antagonist amlodipine (5 mg) alone and combined with the alpha 1 blocker prazosin (1 mg), a treadmill exercise test using the Balke-Ware protocol was undertaken in the morning (8:00 A.M.) and repeated in the afternoon (1:00 P.M.) with 15 stable angina patients. The ischemic threshold was defined as a reciprocal of minimal coronary vascular resistance in the presence of comparable levels of myocardial ischemia indicated by 0.1 mV ST depression. Minimal coronary vascular resistance was calculated as mean blood pressure divided by coronary blood flow. Since the coronary blood flow is closely related to myocardial oxygen consumption, which can be replaced by the double product of heart rate and systolic blood pressure, minimal coronary vascular resistance was approximated to 1/heart rate. RESULTS: At baseline, minimal coronary vascular resistance was significantly higher in the early morning than in the afternoon (8.5 +/- 0.3 x 10(-3) min/beats vs. 7.8 +/- 0.4 x 10(-3) min/beats, p < 0.01). Although treatment with amlodipine alone did not abolish the circadian pattern of minimal coronary vascular resistance (8.0 +/- 0.6 x 10(-3) min/beats vs. 7.7 +/- 0.6 x 10(-3) min/ beats, p < 0.05), the addition of prazosin virtually eliminated the diurnal difference in minimal coronary vascular resistance (7.4 +/- 0.5 x 10(-3) min/beats vs. 7.5 +/- 0.5 x 10(-3) min/beats, p = NS). CONCLUSIONS: These findings indicate that alpha 1-sympathetic activity may play a role in the pathogenesis of the diurnal change of ischemic threshold in patients with stable angina.

Adrenergic alpha-Antagonists↗

Effect of clarithromycin on renal excretion of digoxin: interaction with P-glycoprotein.

We present a digoxin-clarithromycin interaction in two patients in whom digoxin concentrations were unexpectedly increased. The ratio of renal digoxin clearance to creatinine clearance in one patient was lower during the concomitant administration of clarithromycin (0.64 and 0.73) than that after cessation of clarithromycin administration (1.30 +/- 0.20; mean +/- SD). Because P-glycoprotein could play an important role in the renal secretion of digoxin, we hypothesized that clarithromycin decreases renal digoxin excretion by inhibiting P-glycoprotein-mediated transport. Digoxin transport was evaluated with use of a kidney epithelial cell line, which expresses the human P-glycoprotein on the apical membrane by transfection with MDR1 complementary deoxyribonucleic acid. Clarithromycin inhibited the transcellular transport of digoxin from the basolateral to the apical side in a concentration-dependent manner and concomitantly increased the cellular accumulation of digoxin. These results suggest that clarithromycin may inhibit the P-glycoprotein-mediated tubular secretion of digoxin, and this interaction mechanism may contribute to an increase in the serum digoxin concentration.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Marked elevation of brain natriuretic peptide levels in pericardial fluid is closely associated with left ventricular dysfunction.

OBJECTIVES: The purpose of this study was to investigate whether atrial and brain natriuretic peptides (ANP and BNP, respectively) represent autocrine/paracrine factors and are accumulated in pericardial fluid. BACKGROUND: ANP and BNP, systemic hormones produced by the heart, have elevated circulating levels in patients with heart failure. Recent evidence suggests that the heart itself is one of the target organs for these peptides. METHODS: With an immunoreactive radiometric assay, we measured the concentrations of these peptides in plasma and pericardial fluid simultaneously in 28 patients during coronary artery bypass graft surgery. RESULTS: The pericardial levels of BNP were markedly elevated in patients with impaired left ventricular function. We investigated the correlation of ANP and BNP levels in plasma or pericardial fluid with left ventricular hemodynamic variables. None of the hemodynamic variables correlated with ANP levels in plasma or pericardial fluid. Both plasma and pericardial fluid levels of BNP were significantly related to left ventricular end-diastolic and systolic volume indexes (LVEDVI and LVESVI, respectively). In addition, BNP pericardial fluid levels had closer relations with LVEDVI (r = 0.679, p < 0.0001) and LVESVI (r = 0.686, p < 0.0001) than did BNP plasma levels (LVEDVI: r = 0.567, p = 0.0017; LVESVI: r = 0.607, p = 0.0010). BNP levels in pericardial fluid but not in plasma correlated with left ventricular end-diastolic pressure (r = 0.495, p = 0.0074). CONCLUSIONS: BNP levels in pericardial fluid served as more sensitive and accurate indicators of left ventricular dysfunction than did BNP levels in plasma. Thus, BNP may be secreted from the heart into the pericardial space in response to left ventricular dysfunction, and it may have a pathophysiologic role in heart failure as an autocrine/paracrine factor.

Aged↗

Improvement of exercise capacity by sarpogrelate as a result of augmented collateral circulation in patients with effort angina.

OBJECTIVES: The purpose of this study was to evaluate whether a serotonin blocker, sarpogrelate, improves exercise capacity as a result of vasodilation of coronary collateral channels in patients with effort angina. BACKGROUND: Serotonin has been reported to decrease coronary collateral blood flow by collateral vasoconstriction in a canine model, suggesting that platelet activation in feeding coronary arteries of the collateral network has the potential to cause collateral vasoconstriction. METHODS: The subjects consisted of 22 patients with effort angina and reproducible ischemic threshold (group A, 11 patients with thrombolysis in myocardial infarction (TIMI) grade 2 or 3 flow of the ischemia-related coronary artery and Rentrop's collateral index 0 or 1; group B, 11 patients with TIMI grade 0 or 1 flow and Rentrop's collateral index 2 or 3). We repeated the symptom-limited treadmill exercise test using the Balke-Ware protocol and exercise tetrofosmin myocardial perfusion scintigraphy with and without pretreatment with 200 mg orally administered sarpogrelate. Each exercise test was performed at 9:00 a.m. on different days. The order of tests with and without sarpogrelate was randomized. RESULTS: In group A, sarpogrelate increased neither exercise time at 0.1 mV ST depression nor double product at 0.1 mV ST depression. In contrast, in group B sarpogrelate increased the exercise duration at 0.1 mV ST depression from 181+/-112 (SD) to 248+/-131 s (p < 0.05) and also increased the double product at 0.1 mV ST depression by 21% (p < 0.01). The severity score using myocardial perfusion scintigraphy at the same workload was significantly (p < 0.01) decreased by 37% in group B, but not in group A (11%), due to the sarpogrelate treatment. CONCLUSIONS: Sarpogrelate augments flow reserve of the collateral circulation and improves exercise capacity in anginal patients with well-developed collaterals. These findings indicate that a serotonin blocker, sarpogrelate, is useful not only as an antiplatelet drugs, but as an antianginal drug.

Aged↗

Marked elevation of vascular endothelial growth factor and basic fibroblast growth factor in pericardial fluid of patients with angina pectoris.

Although we reported that basic fibroblast growth factor (bFGF) levels in pericardial fluid of patients with unstable angina are apparently increased, it was unclear whether vascular endothelial growth factor (VEGF) is also increased in patients with myocardial ischemia. Using an enzyme-linked immunosorbent assay, we measured the concentrations of VEGF and bFGF in pericardial fluid of 51 patients with open heart surgery. Patients were divided into group A (n=10) with class III unstable angina (Braunwald's classification), group B (n=24) with class I or II unstable angina or stable angina and group C (n=17) with non-ischemic heart disease. The VEGF level in pericardial fluid in group A was 83+/-7 pg/ml, being significantly (p<0.001) higher than the 27+/-3 pg/ml in group B and the 28+/-5 pg/ml in group C. The concentrations of bFGF in pericardial fluid in groups A and B were 1461+/-579 and 1224+/-161 pg/ml, respectively, significantly (p<0.05) higher than the 292+/-97 pg/ml in group C. The level of VEGF in pericardial fluid was increased only in patients with severe rest angina within 2 days before emergency coronary artery bypass graft surgery (CABG), while bFGF was increased in all patients undergoing CABG for coronary artery disease. Thus VEGF and bFGF may play important roles in mediating collateral growth in humans.

Journal Article↗

Impairment of BMIPP uptake precedes abnormalities in oxygen and glucose metabolism in hypertrophic cardiomyopathy.

UNLABELLED: Impairment of fatty acid uptake is shown to precede myocardial perfusion abnormality using 123I-labeled 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) in an experimental model of hypertrophic cardiomyopathy (HCM) and in human studies. We have recently demonstrated that abnormalities of both glucose and oxidative metabolism precede the reduction of blood flow in HCM. The main purposes of this study were to assess the frequency of abnormal findings in FDG uptake, BMIPP uptake and oxygen metabolism and to clarify the relationship among these metabolic parameters by using PET and SPECT. METHODS: Twenty-eight subjects with HCM underwent FDG- and acetate-PET and thallium- and BMIPP-SPECT studies at rest, respectively. After correcting for partial volume effect, real percentages of FDG and BMIPP uptake were calculated. In addition, the clearance rate constant (K mono) of acetate was measured and normalized (%) to estimate the oxygen metabolism. RESULTS: There were various metabolic abnormalities observed in patients with HCM. BMIPP uptake was often impaired without significant reduction of K mono values or FDG uptake. Thus, abnormality of BMIPP uptake was more frequently observed than that for FDG uptake or K mono values (p < 0.0001, respectively). FDG uptake was relatively maintained even in the segments with reduced K mono values and reduced BMIPP uptake. CONCLUSION: HCM shows a variety of metabolic patterns; however, the results of our study suggest that reduction of BMIPP uptake appears to be the most sensitive indicator of metabolic abnormalities followed by reduction of oxidative metabolism in patients with HCM.

Acetates↗

First-pass radionuclide angiography using iodine-123 myocardial tracers and a multicrystal gamma camera.

UNLABELLED: The purpose of this study was to validate the accuracy of the assessment of ventricular function by first-pass radionuclide angiography (FPRNA) with 123I myocardial tracers and a multicrystal gamma camera. METHODS: Left ventricular ejection fraction (LVEF) and right ventricular ejection fraction were measured in 69 patients by FPRNA using 123I myocardial tracers (126 +/- 7 MBq) and 99mTc tracers (541 +/- 141 MBq) on a multicrystal gamma camera with a high-sensitivity collimator. For 44 patients, ejection fraction values measured by 123I-FPRNA were compared to those estimated by equilibrium radionuclide angiography (ERNA). Visual wall-motion analysis was also performed to judge clinical acceptability of 123I-FPRNA images for identification of wall-motion abnormality. RESULTS: Mean LVEFs (%) estimated by 123I-FPRNA and by 99mTc-FPRNA were 49.6 +/- 13.6 and 49.1 +/- 14.1, respectively (nonsignificant p value). An excellent correlation was found between LVEFs estimated by 123I-FPRNA and 99mTc-FPRNA (r = 0.96, s.e.e. = 1.9%). Values of LVEF measured by 123I-FPRNA also demonstrated excellent correlation with those measured by ERNA (r = 0.95, s.e.e. = 2.2%). A good correlation was also noted between right ventricular ejection fractions measured by 123I-FPRNA and 99mTc-FPRNA (r = 0.72, s.e.e. = 4.0%). The Spearman rank correlation coefficient between 123I-FPRNA and ERNA wall-motion scores was 0.87 (n = 135, p < 0.001). CONCLUSION: Resting ventricular function can be reliably measured with 123I-FPRNA in combination with a multicrystal gamma camera. This indicates that the assessment of ventricular function is feasible in conjunction with 123I myocardial imaging without an increase in cost or radiation dose to patients.

Adult↗

Effect of metabolic substrate on BMIPP metabolism in canine myocardium.

UNLABELLED: 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.

Animals↗