14C]7-ethoxycoumarin metabolism by precision-cut rat hepatic slices

It is recognized that iodine-123-labelled 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (123I-BMIPP) slowly washes out of the myocardium. The mechanism for the washout was investigated in normal rat hearts by analyses of the subcellular distribution and lipid classes based on the BMIPP metabolism. Rat hearts were excised at 1-120 min after intravenous injection of 123I-BMIPP. After counting the radioactivity, the hearts were digested with Nagarse and homogenized, and then fractionated into the cytosolic, mitochondrial, microsomal and crude nuclear fractions by centrifugations. The radioactivity of each fraction was counted, and the lipid classes were analysed by radio-thin-layer chromatographic and high-performance liquid chromatographic methods. The heart uptake of 123I-BMIPP was maximal at 5 min (6.81%+/-0.36% ID/g), and 41% of the radioactivity disappeared within 120 min. The myocardial radioactivity was immediately distributed into the cytosolic, mitochondrial, microsomal and crude nuclear fractions. The distribution (%) of each fraction was almost identical from 5 min through 120 min. The cytosolic fraction was always the major site of radioactivity deposition (60%), and the time-activity curve of the cytosolic fraction paralleled that of the whole heart throughout the 120-min study period. In the cytosolic fraction, most of the radioactivity was incorporated into the triglyceride class, and the rest was present in the free fatty acid, phospholipid (phosphatidylcholine) and diglyceride classes. In the mitochondrial fraction, the radioactivity was mostly incorporated into the phospholipid class (phosphatidylethanolamine), followed by free fatty acids. The final metabolite of 123I-BMIPP, 123I-p-iodophenylacetic acid (123I-PIPA), initially appeared in the mitochondrial fraction as early as 1 min, and subsequently in the cytosolic fraction at 5 min. Another intermediary metabolite, 123I-p-iodophenyldodecanoic acid (123I-PIPC12), was found only in the mitochondrial fraction after 5 min. In conclusion, the slow washout kinetics of 123I-BMIPP from the myocardium mainly reflects the turnover rate of the triglyceride pool in the cytosol. The BMIPP metabolism, i.e. initial alpha-oxidation followed by subsequent cycles of beta-oxidation, was confirmed in vivo. The participation of the mitochondria in the metabolism was also proven.     

Loss of regional ventricular postextrasystolic potentiation after coronary occlusion in dogs

Postextrasystolic potentiation following coronary artery occlusion was studied serially using pairs of ultrasonic crystals to measure regional myocardial function in control, marginally ischemic, and ischemic segments of the left ventricle in dogs. Prior to coronary occlusion (CO), percent shortening in control (normal) segments increased by an average of 51.4 +/- 4.6% in the beat after a premature ventricular contraction (post-PVC beat), and this response changed little after coronary occlusion. During the 1st min after CO, in ischemic segments, systolic expansion developed but was replaced by active shortening in post-PVC beats; however, after 3 min of CO (average) and thereafter, there was no net positive shortening in post-PVC beats. In marginally ischemic segments early after CO, hypokinesia developed, but there was marked augmentation of percent shortening (208.6 +/- 32.6%) which persisted in post-PVC beats even after 2 h. It is concluded that loss of postextrasystolic potentiation occurs rapidly in ischemic regions after CO and is not indicative of irreversible damage; partially ischemic regions retain this mechanism for prolonged periods.     

Evaluation of myocardial damage using 123I-BMIPP imaging in patients with vasospastic angina

The purpose of this study is to determine whether left ventricular dysfunction following coronary artery spasm by 123I-BMIPP myocardial imaging. To reveal the clinical efficacy of 123I-BMIPP SPECT, 20 patients with vasospastic angina were studied using resting, 3-hour delayed image with 123I-BMIPP and exercise, 3-hour delayed image with 201Tl SPECT. 123I-BMIPP uptake was decreased compared to 201Tl (discordant) in 12 patients (60%) and in 49/100 myocardial segments (49%). The extent and severity score in resting image with 123I-BMIPP were significantly larger than that in delayed image with 201Tl (p < 0.01). In 123I-BMIPP SPECT, the severity score in the latest ischemia were significantly larger than that in others. The incidence of a complete agreement of decreased 123I-BMIPP uptake and coronary artery spasm was significantly higher (75%) than that in 201Tl (28%, p < 0.01). Furthermore, compared to 201Tl uptake, decreased 123I-BMIPP uptake much more corresponded to reduced wall motion in 9 of patients with mismatching. The severity of regional wall motion abnormality was significantly correlated with severity score of 123I-BMIPP. Late redistribution in delayed image with 123I-BMIPP was seen in 6 patients. The regional washout rate and the severity of regional wall motion abnormality in 6 patients was significantly lower than that in others (p < 0.05). Thus, metabolic abnormality assessed by 123I-BMIPP is well associated with left ventricular asynergy and spastic region in patients with vasospastic angina. In conclusion, 123I-BMIPP SPECT may sensitively delineate the impaired myocardium following coronary artery spasm, and it is very useful in diagnosing and estimating the severity of vasospastic angina.     

Technetium-99m teboroxime regional myocardial washout in subjects with and without coronary artery disease

The aim of this study was to test the hypothesis that regional myocardial washout of technetium-99m teboroxime is slowed in the presence of coronary stenosis. Washout was assessed in 33 catheterized patients and in 13 with a low likelihood of coronary artery disease, using a triple detector camera and dynamic single-photon emission computed tomography, with serial 1-minute acquisitions after injection of 20 to 25 mCi of teboroxime at the third minute of adenosine-induced hyperemia. Washout was measured as the percent change in counts between the first, second and third minutes after injection, as measured in 6 short-axis myocardial regions of interest. Myocardial regions were classified as ischemic (> or = 50% diameter stenosis and no prior myocardial infarct), infarcted, normal (no significant coronary stenosis) or "low likelihood" (from the 13 patients with a low likelihood of coronary artery disease). Teboroxime washout was significantly (p < 0.001) slowed in the ischemic myocardium (12.7 +/- 8.3%) compared with the normal (18.5 +/- 5.7%), low-likelihood (17.8 +/- 6.1%) and infarcted (17.8 +/- 4.4%) zones. There was regional variability in washout rates (% washout/min), with the anterior wall having the lowest (13.8 +/- 3.4%/min) and the inferior wall the highest (20.7 +/- 7.9%/min) values. In regard to individual coronary territories, 21 of 41 ischemic, noninfarcted territories (51%) had abnormal washout compared with 3 of 43 normal territories (7%) (p = 0.001). In conclusion, regional washout of teboroxime is detectably slowed in ischemic, noninfarcted myocardium. The clinical value of washout analysis in teboroxime single-photon emission computed tomography warrants further investigation.     

A two-dimensional Kolmorogov-Smirnov test for binned data

Exercise leads to marked increases in muscle insulin sensitivity and glucose effectiveness. Oral glucose tolerance immediately after exercise is generally not improved. The hypothesis tested by these experiments is that after exercise the increased muscle glucose uptake during an intestinal glucose load is counterbalanced by an increase in the efficiency with which glucose enters the circulation and that this occurs due to an increase in intestinal glucose absorption or decrease in hepatic glucose disposal. For this purpose, sampling (artery and portal, hepatic, and femoral veins) and infusion (vena cava, duodenum) catheters and Doppler flow probes (portal vein, hepatic artery, external iliac artery) were implanted 17 d before study. Overnightfasted dogs were studied after 150 min of moderate treadmill exercise or an equal duration rest period. Glucose ([14C]glucose labeled) was infused in the duodenum at 8 mg/kg x min for 150 min beginning 30 min after exercise or rest periods. Values, depending on the specific variable, are the mean +/- SE for six to eight dogs. Measurements are from the last 60 min of the intraduodenal glucose infusion. In response to intraduodenal glucose, arterial plasma glucose rose more in exercised (103 +/- 4 to 154 +/- 6 mg/dl) compared with rested (104 +/- 2 to 139 +/- 3 mg/dl) dogs. The greater increase in glucose occurred even though net limb glucose uptake was elevated after exercise (35 +/- 5 vs. 20 +/- 2 mg/min) as net splanchnic glucose output (5.1 +/- 0.8 vs. 2.1 +/- 0.6 mg/kg x min) and systemic appearance of intraduodenal glucose (8.1 +/- 0.6 vs. 6.3 +/- 0.7 mg/kg x min) were also increased due to a higher net gut glucose output (6.1 +/- 0.7 vs. 3.6 +/- 0.9 mg/kg x min). Adaptations at the muscle led to increased net glycogen deposition after exercise [1.4 +/- 0.3 vs. 0.5 +/- 0.1 mg/(gram of tissue x 150 min)], while no such increase in glycogen storage was seen in liver [3.9 +/- 1.0 vs. 4.1 +/- 1.1 mg/(gram of tissue x 150 min) in exercised and sedentary animals, respectively]. These experiments show that the increase in the ability of previously working muscle to store glycogen is not solely a result of changes at the muscle itself, but is also a result of changes in the splanchnic bed that increase the efficiency with which oral glucose is made available in the systemic circulation.     

Myotrophic effects of muscle extracts obtained at different intervals after denervation

BACKGROUND: The assessment of return of function within dysfunctional myocardium after acute myocardial infarction (MI) using contractile reserve has been primarily qualitative. Magnetic resonance (MR) myocardial tagging is a novel noninvasive method that measures intramyocardial function. We hypothesized that MR tagging could be used to quantify the intramyocardial response to low-dose dobutamine and relate this response to return of function in patients after first MI. METHODS AND RESULTS: Twenty patients with a first reperfused MI (age, 53+/-12 years; 16 male; 11 inferior MIs) were studied. Patients underwent breath-hold MR-tagged short-axis imaging on day 4+/-2 after MI at baseline and during dobutamine infusion at 5 and 10 microg x kg(-1) x min(-1). At 8+/-1 weeks after MI, patients returned for a follow-up MR tagging study without dobutamine. Quantification of percent intramyocardial circumferential segment shortening (%S) was performed. Low-dose dobutamine MRI was well tolerated. Overall, mean %S was 15+/-11% at baseline (n=227 segments), increased to 16+/-10% at 5 microg x kg(-1) x min(-1) dobutamine (P=NS), 21+/-10% at peak (P<0.0001 versus baseline and 5 microg x kg(-1) x min(-1), and 18+/-10% at 8 weeks (P<0.004 versus baseline and peak). The increase in %S with peak dobutamine was greater in dysfunctional myocardium (103 segments, +9+/-10%) than in normal tissue (124 segments, +4+/-12%, P<0.0001). In dysfunctional regions, %S also increased from 6+/-7% at baseline to 14+/-10% at 8 weeks after MI (P<0.0001). In dysfunctional regions that responded normally to peak dobutamine (> or =5% increase in %S), the increase in %S from baseline to 8 weeks after MI (+9+/-9%) was greater than in those regions that did not respond normally (+5+/-9%, P<0.04). Midmyocardial and subepicardial response to dobutamine were predictive of functional recovery, but the subendocardial response was not. CONCLUSIONS: The response of intramyocardial function to low-dose dobutamine after reperfused MI can be quantified with MR tagging. Dysfunctional tissue after MI demonstrates a larger contractile response to dobutamine than normal myocardium. A normal increase in shortening elicited by dobutamine within dysfunctional midwall and subepicardium predicts greater functional recovery at 8 weeks after MI, but the response within the subendocardium is not predictive.     

Efficacy of coronary artery bypass grafting in patients with a dilated left ventricle due to myocardial infarction

This study was designed to clarify the efficacy of coronary artery bypass grafting (CABG) on left ventricular (LV) function in 16 patients with a dilated LV due to myocardial infarction (LV end-systolic volume index: LVESVI >60 ml/m2). All had attained complete revascularization. To estimate the LV wall motion quantitatively using echocardiography, a wall motion score (WMS) was used (LV was divided into 17 segments with a four-point scale: akinesis=3, severe hypokinesis=2, hypokinesis=1, normal=0 and then summed). Exercise stress tests were performed after surgery, revealing that anginal symptoms had vanished in all the patients. In 5 patients with a preoperative end-systolic volume index (ESVI) >100 ml/m2, the ejection fraction (EF) did not change, and both were under 30% (before to after: 26+/-4 to 26+/-4%). Neither the ESVI (148+/-50 to 133+/-39 ml/m2) nor the end-diastolic volume index (end-diastolic volume index (EDVI): 198+/-62 to 180+/-37 ml/m2) changed; the WMS did not change (33+/-2 to 33+/-3). During exercise, in spite of the increase in heart rate (HR) (at rest, 81+/-20; HR during exercise, 111+/-21 beats/min, p<0.005) and LV end-diastolic pressure (EDP) (22+/-9; 35+/-13 mmHg, p<0.02), both cardiac index (CI) (2.4+/-0.3; 2.6+/-0.4 L/min x m2) and minute work (MW: 4.0+/-1.1; 4.1+/-0.4 kg x M/min) did not increase. In 11 patients with a preoperative ESVI <100 ml/m2, EF was extremely increased in 5 patients (more than 10%, 35+/-4 to 60+/-6%, p<0.005=improved subgroup) in whom the EDVI (130+/-16 to 120+/-13 ml/m2) did not change whereas the ESVI (82+/-14 to 48+/-7 ml/m2) was reduced. However, in the 6 remaining patients (ie nonimproved subgroup), neither ESVI (78+/-8 to 74+/-12 ml/m2), EDVI (115+/-10 to 115+/-20 ml/m2) nor EF (31+/-7 to 35+/-3%) changed. During exercise, HR (at rest, 88+/-13; during exercise, 108+/-11 beats/min, p<0.005), LVEDP (20+/-6; 29+/-7 mmHg, p<0.01), CI (2.5+/-0.6; 3.3+/-0.5 L/min x m2, p<0.05), MW (4.6+/-1.0; 6.5+/-1.5 kg x M/min, p<0.05) increased. The WMS in the nonimproved subgroup did not change (29+/-6 to 27+/-2), but in the improved subgroup it reduced after surgery (27+/-3 to 19+/-4, p<0.01). These data suggested that CABG in patients with a dilated LV was effective against anginal symptoms, but was restricted to left ventricular function. It may be possible to estimate postoperative LV function, including exercise tolerance, from the preoperative LVESVI.     

Cardiomyoplasty: hemodynamic benefit to normal and depressed canine left ventricular function

This study examined the effects of cardiomyoplasty with vascular delay on canine normal and depressed left ventricular (LV) function. To improve viability of the latissimus dorsi muscle (LDM), vascular delay was performed 2 weeks before cardiomyoplasty in 10 mongrel dogs. Two weeks after cardiomyoplasty, LV function was evaluated by simultaneously measuring LV and aortic pressure, and aortic flow. The LDM was stimulated at a ratio of 1:4-1:7 synchronously with ventricular systole. Microspheres (90 mu) were sequentially injected into the left coronary artery to depress LV function. Data were acquired and analyzed on a beat to beat basis. Results were as follows: LDM stimulation significantly augmented LV systolic pressure (LVSP) from 138 +/- 2 to 161 +/- 2* mmHg, the peak rate of change of LV pressure (+dP/dt) from 1888 +/- 46 to 2584 +/- 43* mmHg/sec, aortic systolic pressure (AoSP) from 140 +/- 2 to 159 +/- 2* mmHg, stroke volume (SV) from 11.2 +/- 0.3 to 13.3 +/- 0.3* ml, stroke work (SW) from 19 +/- 1 to 26 +/- 1* gm.m, peak aortic flow (P Qa) from 5542 +/- 142 to 7190 +/- 161* ml/min, and decreased -dP/dt from -1683 +/- 31 to -1689 +/- 49* mmHg/sec (* = p < 0.05). Microsphere injections depressed LV function, but did not affect the magnitude of the net changes between stimulated and nonstimulated beats. However, the percent changes significantly increased. Preconditioning of LDM with vascular delay augments cardiac function in LDM assisted beats. This improved performance was present in both normal as well as depressed LV function groups. Thus, investigations of cardiomyoplasty may not necessarily require a model of severe myocardial dysfunction. Vascular delay offers an important preconditioning method of LDM to augment cardiac function in cardiomyoplasty.     

Comparison of persistent thallium perfusion defects by quantitative washout analysis with thallium reinjection in patients with coronary artery disease

Thallium reinjection can improve the detection of severely ischemic viable myocardium in patients with coronary artery disease. However, a disadvantage of this method is that it requires the acquisition of 3 separate sets of images and the administration of an additional dose of the radiotracer. Alternatively, quantitative analysis of the regional myocardial washout of thallium-201 can be easily obtained from the conventional postexercise and redistribution images without additional imaging time or radiation exposure to the patient. To determine whether this method can predict the results of thallium reinjection, this study analyzed thallium-201 images of 31 patients who had persistent perfusion defects in qualitative exercise/delayed redistribution single-photon emission computed tomographic thallium studies and who underwent thallium reinjection. The quantitative mean radioactive counts of each myocardial segment that had a persistent perfusion defect in the initial and delayed redistribution on 4-hour short-axis tomographic slices were measured to derive a delayed/initial ratio, and these values were compared with the results of thallium reinjection. The delayed/initial ratio was 1.06 +/- 0.22 in 39 segments that improved, versus 0.58 +/- 0.18 in 43 segments without improvement after reinjection (p < 0.001). Thirty-eight of the 39 segments that improved had a ratio of > or = 0.75, versus only 3 of the 43 segments that showed no improvement (sensitivity, 98%; specificity, 91%). The correlation between the delayed/initial ratio and reinjection results was equally high at any segment location or severity. It is concluded that quantitative regional thallium washout analysis predicts the results of thallium reinjection in segments with persistent thallium defects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship between mechanical properties of the carotid artery wall and baroreflex function in acutely treated hypertensive patients

OBJECTIVE: To evaluate the relationship between the mechanical properties of the carotid artery wall and baroreflex function after acute reduction of blood pressure with lacidipine in essential hypertension. DESIGN: After 15 days of placebo washout, the hypertensive patients underwent a single-blind haemodynamic study before and 90 min after administration of 4 mg lacidipine (a dihydropyridine calcium antagonist). METHODS: Brachial intra-arterial blood pressure was recorded in eight mild-to-moderate essential hypertensive patients aged 40-53 years (mean +/- SEM 46.8 +/- 4.7 years). The carotid pulse diameter was recorded simultaneously by an echo-tracking technique. The mechanical properties of the carotid artery wall were evaluated by calculating Peterson's incremental elastic modulus (Ep) both as an averaged value of 10 heart cycles with stable blood pressure and was the dynamic correlation, on a beat-to-beat basis, of Ep and the systolic blood pressure during a 20 mmHg increase in blood pressure following a bolus injection of phenylephrine. The elastic properties of the carotid artery were investigated further by determining the correlation between the systolic pressure and systolic diameter, beat by beat, during a ramped increase of blood pressure after phenylephrine administration. The baroreceptor reflex sensitivity was measured simultaneously by the Oxford method and by correlating Ep and the electrocardiographic R-R' interval on a beat-to-beat basis during phenylephrine injections. RESULTS: After lacidipine administration Peterson's elastic modulus, measured under resting steady-state conditions, was reduced (18.7 +/- 7.4 versus 16.4 +/- 6 x 10(5) dyne/cm2), whereas the baroreflex sensitivity was unchanged (6.6 +/- 3.3 versus 6.3 +/- 0.2 ms/mmHg) and resetting of the baroreflex had occurred. At the same time, the correlations between the systolic blood pressure and Ep and between the systolic blood pressure and carotid systolic diameter over a 20 mmHg increase in blood pressure were unchanged. Moreover, the correlations between the systolic blood pressure and the R-R' interval and between Ep and R-R' interval during the phenylephrine-induced blood pressure increase did not differ statistically. CONCLUSIONS: The results suggest that the resetting of the baroreflex after the acute reduction in blood pressure caused by lacidipine is dissociated from mechanical changes in the carotid artery wall.     

Pulmonary metastasectomy for soft tissue sarcomas: is it justified?

beta-blocker therapy for mitral stenosis is controversial. This study compares right and left heart hemodynamics at rest and supine submaximal exercise in patients (n = 7) receiving chronic beta-antagonists with untreated patients (n = 17) matched for age (mean +/- SD = 51 +/- 12 years) and valve area (0.7 +/- 0.2 cm2/m2). Little benefit was observed with treatment at rest. Although pulmonary capillary wedge pressures (PCWP) were lower during exercise in the beta-blocker group (22 +/- 4 vs. 31 +/- 9 mmHg; P < 0.05), exercise performance was not enhanced and cardiac output response during exercise was reduced (control = 41% increase vs. 12% for beta-blockade). PCWP rose rapidly when diastolic filling periods were < 300 msec in both groups. Pulmonary capillary wedge pressure was found to be a nonlinear functions (P < 0.001) of diastolic filling period (PCWP = 15.9 + 5.84 x 10(5)/dfp2). These data suggest that there is a critical heart rate in patients with mitral stenosis above which hemodynamic compromise rapidly occurs.     

SPECT imaging of dopamine transporters in human brain with iodine-123-fluoroalkyl analogs of beta-CIT

Iodine-123-2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane (beta-CIT) is a useful SPECT tracer for imaging the dopamine transporter. Its slow kinetics, however, necessitate imaging on the day after the injection. Two N-omega-fluoroalkyl analogs of beta-CIT, the fluoropropyl and fluoroethyl compounds (beta-CIT-FP and beta-CIT-FE, respectively), characterized by faster kinetics in baboons, were tested in humans as potential tracers for the dopamine transporter. Four healthy volunteers were injected with [123I]-beta-CIT-FP and another four were injected with [123I]beta-CIT-FE. SPECT data were acquired for 1149 +/- 590 min and 240 +/- 30 min, respectively. Both tracers demonstrated high brain uptake (6.37% +/- 0.37% and 7.8% +/- 1.5% of the injected dose, respectively). Activity concentrated with time in the striatal area, reaching a peak within 30 min, with little or no washout for [123I]beta-CIT-FP and a faster washout for [123I]beta-CIT-FE (14.7% +/- 6.9%). Occipital and midbrain activity showed similar patterns, displaying a peak within 15 min and rapid washout, followed by stable levels at approximately 100 min for both tracers. The ratio of peak specific striatal-to-peak specific midbrain activity was 9.1 +/- 1.8 for [123I]beta-CIT-FP and 7.7 +/- 0.7 for [123I]beta-CIT-FE, showing high in vivo selectivity for the dopamine transporter. These preliminary results suggest that both compounds could be used as SPECT (labeled with 123I) or PET (labeled with 18F) radiotracers to image the dopamine transporters in the living human brain.     

Oxygen consumption, lactate metabolism, and gastric intramucosal pH in an experimental liver transplantation model

We have evaluated whether myocardial uptake of the fatty acid analog 123I-15-(p-iodophenyl)-3-R,S-methyl pentadecanoic acid (BMIPP) is dependent on the dietary state. METHODS: We compared the biodistribution of 150 MBq of 123I-BMIPP in six healthy volunteers in two states: after at least 12 hr of fasting and after oral glucose loading (75 g) 60 min before tracer administration, followed by a meal enriched in carbohydrates and protein. Planar and tomographic acquisitions were performed over a 4-hr time period after tracer injection; data were corrected for radioactive decay and injected dose. Radioactivity was measured in blood samples drawn at several points. RESULTS: Significant increases of glycemia and insulinemia and a significant drop in plasma nonesterified acids were documented after glucose loading. Half-time values for plasma radioactivity were significantly shorter in the glucose-loaded state than in the fasted state (4.3 +/- 1.4 min compared to 6.3 +/- 1.3 min, p < 0.05). Activity in the heart and liver tended to be higher in the glucose-loaded state than in the fasted state. SPECT images at 0.5 hr after tracer injection demonstrated that the myocardial wall-to-cavity ratio was higher after glucose than in the fasted state (2.53 +/- 0.59 compared to 2.11 +/- 0.21, p = 0.15). Washout from the liver between 1 and 4 hr after injection increased from 18.6% +/- 4.4% in the fasted study to 24.1% +/- 2.4% after glucose (p = 0.04). Washout from the myocardium between 0.5 and 3.5 hr after injection increased from 13.1% +/- 8.8% in the fasted study to 24.0% +/- 3.7% after glucose (p = 0.05). CONCLUSION: These results indicate that fasting before BMIPP scintigraphy is not mandatory to obtain adequate SPECT images. At the tire when SPECT is usually performed, glucose loading may provide improved ratios between myocardial and blood pool activity.     

Scintigraphic assessment of silent myocardial ischaemia after early infarction using myocardial SPET imaging with 201Tl and 123I-MIBG

To test the hypothesis that myocardial sympathetic denervation reflects silent myocardial ischaemia early after infarction, 12 patients with myocardial infarction but without post-infarction angina pectoris underwent single photon emission tomography (SPET) at rest with 201Tl and 123I-metaiodobenzylguanidine (MIBG) shortly after and 3 months after infarction. Short-axis SPET images at the basal, mid-ventricular and apical portions of the left ventricle were selected, and each short-axis image was divided into eight segments. Tracer uptake in each of the 24 segments was scored using a 4-point scale. The total score in each segment was calculated as the defect score for each image, and the difference between the total defect score for the 201Tl and 123I-MIBG images was calculated as the delta defect score. All 12 patients underwent exercise stress 201Tl scintigraphy 1 month after infarction, and they were divided into two groups: those patients with (Group A, n = 7) and those patients without (Group B, n = 5) transient perfusion defects in the peri-infarcted region without chest pain. For the 123I-MIBG defect score, a marked reduction at 3 months was observed in Group A (24 +/- 12 vs 13 +/- 6; P < 0.01), whereas the defect score remained unchanged in Group B (25 +/- 7 vs 23 +/- 8; N.S.). The delta defect score was significantly reduced in Group A (10 +/- 5 vs 6 +/- 4; P < 0.05), whereas it remained unchanged in Group B. The 123I-MIBG defect score early after infarction was higher than the exercise-induced 201Tl defect score (24 +/- 12 vs 20 +/- 9; P < 0.01), whereas at 3 months post-infarction it was lower than the exercise-induced 201Tl defect score (13 +/- 6 vs 20 +/- 9; P < 0.05). Moreover, effort chest pain during daily activities was noted in 5 of the 7 (71%) patients in Group A within 3 months post-infarction. The results of this study suggest that viable but denervated myocardium (mismatched 123I-MIBG defects) is present in peri-infarcted regions, and that myocardial sensory nervous disturbance, which may co-exist with sympathetic nervous denervation, may induce silent myocardial ischaemia in patients with myocardial infarction.     

Redistribution of collateral blood flow from necrotic to surviving myocardium following coronary occlusion in the dog

Early changes in collateral blood flow after acute coronary occlusion may be critical for survival of ischemic myocardium. We used 15-mum radioactive microspheres to study myocardial blood flow in thoracotomized dogs 10 minutes and 24 hours after occlusion of the left anterior descending coronary artery (LAD). The ischemic area was delineated by dye injected into the distal artery, and indentification of potentially ischemic samples was confirmed by a newly developed technique in which microspheres were excluded from the normally perfused LAD. Layers were separated into necrotic or normal as defined by gross inspection and confirmed by histological examination and creatine phosphokinase assay. Infarction always involved endocardial layers and extended toward the epicardium. Average myocardial blood flow in 48 necrotic samples from 16 dogs either remained low (less than 0.05 ml/min g-1) or declined, falling from 0.11 +/-0.02(SE) at 10 minutes to 0.05 +/-0.01 ml/min g-1 at 24 hours (P less than 0.001). In contrast, in the 32 normal-appearing samples which were ischemic at 10 minutes, flow increased from 0.24 +/-0.03 to 0.39 +/-0.04 ml/min g-1 (P less than 0.001). Flow in control myocardium was 1.43 +/-0.12 and 1.04 +/-0.07 ml/min g-1, respectively. Peripheral mean coronary arterial pressure increased from 26 +/- 3 to 35 +/- 3 mm Hg, largely because of enlargement of collateral vessels; collateral conductance calculated from retrograde flow in 14 dogs increased from 0.023 +/- 0.005 after occlusion to 0.051 +/- 0.009 ml/min mm Hg-1 24 hours later (P less than 0.001). Thus, coronary collateral blood flow is redistributed from necrotic endocardial layers to surviving epicardial ones. In combination with a developing collateral supply this process may be essential for sparing myocardium after coronary occlusion.     

Capillary transfer constant of Gd-DTPA in the myocardium at rest and during vasodilation assessed by MRI

The purpose of this study was to determine whether the capillary transfer constant (Ki) of gadolinium-DTPA was sensitive to perfusion changes and whether ischemic regions in the myocardium could be identified using the modified Kety formula. Ki was measured at rest and during dipyridamole-induced vasodilation in 10 healthy volunteers and in 10 patients with ischemic heart disease. Ki increased by a factor of 2.5+/-1.2 (mean +/- SD) from 55+/-16 ml 100 g(-1)min(-1) at rest to 136+/-46 ml 100 g(-1)min(-1) (P < 0.01) during vasodilation in the healthy subjects. In the patients, there were no changes in Ki during vasodilation in ischemic regions (50+/-18 versus 49+/-30 ml 100 g(-1)min(-1) (P > 0.4)). Ki increased in nonischemic regions by a factor of 2.0+/-0.8 from 44+/-17 to 81+/-32 ml 100 g(-1)min(-1) during vasodilation (P < 0.02). It is concluded that the capillary transfer constant is sensitive to perfusion changes and that regional ischemia can be detected with MRI. This noninvasive and quantitative method may prove useful in the evaluation of patients with ischemic heart disease.     

Effect of vitamin A on small intestinal brush border enzymes in a rat

To determine the utility of the myocardial tracer Tc-99m-tetrofosmin in the examination of patients with left bundle branch block (LBBB) and to investigate Tc-99m-tetrofosmin uptake and retention in the myocardium, early and delayed Tc-99m-tetrofosmin SPECT was performed in 10 patients having LBBB without coronary stenosis. METHODS: After 740 MBq of Tc-99m-tetrofosmin injection in the resting state, the early and delayed SPECT imaging was done at 30 min and 180 min, respectively. RESULTS: Decreased Tc-99m-tetrofosmin uptake in the septal segments was observed in 4 patients (40%) at 30 min and in 9 (90%) at 180 min. Reverse redistribution was seen in 9 of 10 patients. In patients with LBBB, the septal-to-lateral uptake ratio was lower in the delayed images than in the early images (0.80 +/- 0.09 vs. 0.89 +/- 0.09, p < 0.001). In patients with LBBB, the washout rate of Tc-99m-tetrofosmin was higher in the septal segments than in the lateral segments (28.3 +/- 4.3% vs. 22.8 +/- 3.3%, p < 0.001). CONCLUSION: The SPECT data indicate that in LBBB without coronary stenosis, the uptake of Tc-99m-tetrofosmin is decreased in the septal wall, and that reverse redistribution occurs frequently. Our results contribute to the elucidation of both the cellular biokinetics of Tc-99m-tetrofosmin in the myocardium and the hemodynamics of the septum in LBBB, and indicate the possible clinical utility of Tc-99m-tetrofosmin.     

Atrial septal defect in adults: cardiopulmonary exercise capacity before and 4 months and 10 years after defect closure

OBJECTIVES: The purpose of the study was to evaluate the cardiopulmonary exercise capacity and ventilatory function in adults with atrial septal defect (ASD) preoperatively and 4 months and 10 years postoperatively. BACKGROUND: Only few data are available on cardiopulmonary exercise tolerance after ASD closure, but detailed knowledge might be helpful for indication for defect closure in certain patients. METHODS: The study was performed in adult patients (mean [+/-SD] age at operation 39.9 +/- 11.5 years; left-right shunt 9.6 +/- 5.6 liters/min; pulmonary/systemic flow ratio 2.8 +/- 1.2; mean pulmonary artery pressure 18.2 +/- 6.2 mm Hg). Cardiopulmonary exercise testing was performed with a bicycle ergometer. We determined peak oxygen uptake, anaerobic threshold, performance at anaerobic threshold and maximal performance in relation to these variables in a normal group. Ventilatory function at rest was expressed by vital capacity, maximal voluntary ventilation and forced expiratory volume in 1 s. RESULTS: Preoperatively, ventilatory function at rest was only moderately reduced to approximately 75% to 85%. Four months postoperatively we found no significant improvement, but 10 years postoperatively ventilatory function at rest was normalized. Preoperative cardiopulmonary exercise capacity was markedly reduced to 50% to 60%; early postoperatively it was only slightly higher, but late postoperatively exercise capacity significantly improved and was completely normalized. CONCLUSIONS: Although preoperative cardiopulmonary capacity in adult patients with nonrestrictive ASD was significantly decreased, some improvement was seen at 4 months postoperatively, with complete restitution to normal at 10 years after shunt closure.     

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.     

Thermoregulatory effects of caffeine ingestion during submaximal exercise in men

BACKGROUND: The exclusive effect of caffeine ingestion on exercise thermoregulation is unclear; data indicate that caffeine may have a positive effect, a negative effect, or no effect. METHODS: Rectal (TRE) and mean skin (TSK) temperatures, skin heat conductance (HSK), and sweat rate (MSW) were measured during 30 min of rest and subsequent 70 min of submaximal cycle-ergometer exercise (67% VO2PEAK) in 11 aerobically conditioned men (mean +/- SD 29 +/- 6 yr, 49 +/- 6 mL x min(-1) x kg(-1) VO2PEAK) under two conditions: a caffeine (10 mg x kg(-1) ingestion (CI) session and a noncaffeine ingestion (NCI) control session. RESULTS: There were no significant differences in physiological or thermoregulatory parameters during exercise: X (+/-SE) end exercise levels for the NCI and CI sessions, respectively, were VO2 = 2.50 +/- 0.09 vs. 2.55 +/- 0.09 L x min(-1); heart rate = 145 +/- 7 vs. 145 +/- 5 bpm; HSK = 30 +/- 3 vs. 28 +/- 3 kcal x m(-2) x h(-1) x degrees C(-1); MSW = 393 +/- 35 vs. 378 +/- 36 g x m(-2) x h(-1); and TRE = 38.3 +/- 0.2 vs. 38.4 +/- 0.1 degrees C. Control TSK was lower than that for CI by 0.4 to 0.5 degrees C at rest and during exercise. CONCLUSION: Ingestion of a high level (10 mg x kg(-1) of caffeine has no effect on skin heat conductance, sweating, or the rate of increase and final level of rectal temperature during moderate, submaximal leg exercise.