Iodine-123 metaiodobenzylguanidine images reflect intense myocardial adrenergic nervous activity in congestive heart failure independent of underlying cause.

OBJECTIVES: This study was undertaken to assess myocardial adrenergic activity using iodine-123 metaiodobenzylguanidine (MIBG) imaging in patients with heart failure. BACKGROUND: In patients with congestive heart failure, adrenergic nerve activity is accelerated. However, whether myocardial adrenergic nerve activity reflects the severity of heart failure and its relation to the underlying cause have not yet been elucidated. METHODS: Planar MIBG images were obtained from 96 patients with heart failure and compared with images from 9 age-matched healthy subjects. Groups 1 and 2 included 65 patients with heart failure related to impaired myocardial function and whose left ventricular ejection fraction was < 40% (group 1 = 40 patients with dilated cardiomyopathy; group 2 = 25 patients with ischemic cardiomyopathy). Group 3 included 31 patients with heart failure related to a mechanical abnormality and whose left ventricular ejection fraction was > 40% (mitral regurgitation in 16, aortic regurgitation in 9, aortic and mitral regurgitation in 4, ruptured aneurysm of Valsalva in 2). Myocardial uptake of MIBG was calculated as the heart/mediastinal activity ratio. Storage and release of MIBG were calculated as percent myocardial MIBG washout from 15 min to 4 h after isotope injection. RESULTS: The heart/mediastinal activity ratio in the immediate images (15 min) showed a significant decrease only in patients with severe heart failure (groups 1 and 2). The myocardial washout was accelerated in all three heart failure groups. The level of myocardial washout was related to severity of heart failure and correlated well with New York Heart Association functional classification. CONCLUSIONS: In severe heart failure associated with cardiomyopathy, norepinephrine uptake is reduced. In addition, myocardial adrenergic nerve activity is accelerated in proportion to severity of heart failure, independent of the underlying cause.

Hyperreactivity of aortic smooth muscle to serotonin is related to the presence of atheroma in Watanabe heritable hyperlipidaemic rabbits.

OBJECTIVE: The aim was to elucidate the contribution of atheromatous plaque to alterations of smooth muscle contraction to vasoconstrictive agents, by examining vasoreactivity of vascular smooth muscle from the thoracic aorta of 10-13 month old Watanabe heritable hyperlipidaemic rabbits. METHODS: From the same vascular ring of the lower thoracic aorta, a pair of small medial smooth muscle strips was prepared from the sites beneath the atheroma (atherosclerotic medial muscle strip) and from those beneath the plaque-free intima (normal medial muscle strip), and isometric tension was measured. RESULTS: Contractions to 118 mM KCl, histamine (30 nM to 10 microM), and noradrenaline (3 nM to 0.3 microM) were similar between atherosclerotic and the normal medial muscle strip. The ED50 to serotonin was 49(SD 28) and 116(66) nM (p < 0.05, n = 7) and the maximum tension to serotonin was 125(29)% and 82(29)% of that induced by 118 mM KCl (p < 0.01, n = 7) in atherosclerotic and normal medial muscle strip, respectively. Serotonin specific hyperreactivity of the atherosclerotic strip disappeared in Ca(2+)-free solution or in the presence of 10 microM H-7, an inhibitor of protein kinase C. After incubation with 0.1 microM phorbol 12,13-dibutyrate, an activator of protein kinase C, the isometric contractions induced by Ca2+ were significantly greater in atherosclerotic than in normal medial muscle strip. CONCLUSIONS: These results indicate that medial smooth muscle located beneath the atheroma is specifically hyperreactive to serotonin and that altered protein kinase C activity may explain in part the augmented response to serotonin.

Augmentation of coronary responsiveness to serotonin at the site of X-ray-induced intimal thickening in miniature pigs.

OBJECTIVE: X-irradiation is known to enhance atherosclerotic change. We tested whether coronary vasoconstrictor responses are augmented at the sites of X-ray-induced intimal thickening in Göttingen miniature pigs. METHODS: In 17 pigs, a major branch of the left coronary artery was denuded with a balloon catheter. In 10 pigs, the denuded portion of the left coronary artery was selectively irradiated with 15 Gy of X-rays twice at 3 and 4 months after denudation (group 1). The remaining 7 pigs were not irradiated (group 2). The effects of intracoronary administration of serotonin, histamine and phenylephrine on the coronary diameter were studied 3 (3M) and 5 months (5M) after denudation. After the angiographical study at 5M, the vessels were isolated and isometric tension was measured in an organ chamber. RESULTS: The percent reduction in coronary diameter evoked with 10 micrograms.kg-1 of serotonin increased from 39(s.e.m. 4)% before X-irradiation (3M) to 75(6)% after X-irradiation (5M) in group 1 (P < 0.01), while it did not differ in group 2 [39(6)% at 3M vs. 33(8)% at 5M[ [39(6)% at 3M vs. 33(8)% at 5M]. In group 1, serotonin-induced coronary constriction was frequently accompanied by ischemic ECG changes. Histamine (10 micrograms.kg-1)-induced vasoconstriction was also augmented but to a smaller degree [47(6)% at 3M vs. 62(4)% at 5M; P < 0.05] in group 1, while it remained unchanged in group 2[52(5)% at 3M vs. 44(7)% at 5M]. Phenylephrine did not cause detectable contraction in either group at 3M or 5M. Methysergide and ketanserin attenuated serotonin-induced hypercontraction in a dose-dependent fashion. In the in vitro studies, endothelium-dependent relaxation to serotonin was impaired at the denuded site with (group 1) and without (group 2) X-irradiation to a similar extent. Isometric tension of medial smooth muscle developed by serotonin was significantly greater at the denuded site with X-irradiation (group 1) than the control site and the denuded site without X-irradiation (group 2) (P < 0.05). Intimal thickening was significantly greater at the denuded sites with X-irradiation [group 1, 238(45) microns] than at the denuded sites without X-irradiation [group 2, 58(5) microns] (P < 0.05). CONCLUSIONS: These results indicate that X-irradiation augments the coronary vasoconstrictor responses to autacoids, predominantly to serotonin, and that this augmentation is accompanied by enhanced intimal thickening. Serotonin-induced hypercontraction after X-irradiation resulted mainly from the hyperreactivity of medial smooth muscle.

Influence of downscatter in simultaneously acquired thallium-201/technetium-99m-PYP SPECT.

UNLABELLED: Simultaneously acquired dual-isotope imaging is a unique and useful approach in SPECT. Photon spillover, however, is a potential limitation of this technique. METHODS: To investigate the degree of 99mTc downscatter into the 201Tl window in patients, simultaneously acquired dual-isotope 201Tl/99mTc-pyrophosphate imaging was performed in 17 patients with acute myocardial infarction (MI). Thallium-201 SPECT imaging was performed first, with a 201Tl photopeak window after the 201Tl injection (early 201Tl images), followed by 99mTc injection and SPECT acquisition using dual-isotope windows (dual 201Tl images). Twenty-four hours after the 99mTc injection, a third set of 201Tl images was obtained (24-hr 201Tl images). Thallium defect size (extent score) and defect severity (severity score) were calculated from these three sets of 201Tl images to quantify the MI. RESULTS: Technetium-99m accumulation of varying intensity was recognized in all patients. Extent scores and severity scores were identical in early 201Tl images and 24-hr 201Tl images. Both scores, however, in the dual 201Tl images were decreased by 36% and 53%, respectively. CONCLUSION: There in a considerable 99mTc downscatter into the 201Tl window, which prevents precise quantification of MI in simultaneously acquired dual-isotope 201Tl/99mTc-pyrophosphate imaging.

[The usefulness of dipyridamole stress myocardial scintigram as a preoperative test for detecting ischemic heart disease before vascular surgery].

We evaluated the usefulness of dipyridamole 201Tl myocardial scintigraphy (DS) for detecting myocardial ischemia in 18 candidate for vascular surgery. DS indicated significant thallium redistribution in 6 patients. Coronary angiography was performed in 5 of these 6 patients and revealed significant coronary artery disease in all patients. As a result, operation was cancelled in 4 patients with severe coronary artery disease. One of these cases died of acute myocardial infarction after being discharged from hospital. One other patient was operated after percutaneous transluminal coronary angioplasty. Another patient was operated knowing that he had significant but mild coronary artery disease. Subsequently, operations were performed in 14 patients. No serious cardiac event occurred in these 14 patients except one case with T wave inversion without myocardial enzyme elevation. Thus, we concluded that DS was a useful method for detecting ischemic heart disease and prevent cardiac event associated with vascular surgery.

Smooth muscles from spastic coronary artery segments show hypercontractility to histamine.

An animal model of coronary spasm was produced in Göttingen miniature pigs by a selective endothelial denudation of the coronary artery. Five months after the denudation, intracoronary bolus administration of 10 micrograms/kg histamine reduced the luminal diameter angiographically by 57 +/- 16 and 17 +/- 10% (P less than 0.01) in the previously denuded and contralateral control coronary arteries. Muscle fibers of 0.08-0.1 mm wide were prepared from circumferential bundles of the medial smooth muscle in the spastic and nonspastic coronary arteries. Upward shifts of either dose-tonic contraction relationships in Ca2(+)-containing solution or dose-monophasic contraction relationships in Ca2(+)-free solution were noted in muscle fibers taken from the spastic site compared with those from the nonspastic site with no difference between the mean effective dose values. After skinning the muscle fibers with saponin, there was no significant difference in the Ca2+ concentration-tension relationships between the two fibers. These findings suggest that an increased number of histaminergic receptors and/or augmentation of signal transduction, but not Ca2+ sensitivity of the contractile proteins in the medial smooth muscle cells, cause histamine-induced coronary hypercontraction.

Mechanisms of ergonovine-induced hyperconstriction of coronary artery after x-ray irradiation in pigs.

Mechanisms of ergonovine-induced coronary hyperconstriction were examined in vivo and in vitro in miniature pigs. To provoke coronary hyperconstriction, the endothelium of a segment of a major branch of the left coronary artery was denuded in 19 Göttingen miniature pigs (4 to 6 months of age). In Group I (n = 12), the denuded site of the coronary artery was selectively irradiated with 15Gy of x-ray twice, 3 and 4 months after endothelial denudation. The remaining 7 pigs were not irradiated (Group II). The vasoconstrictive effect of intracoronary administration of ergonovine (1 to 1000 microgram) was examined angiographically 3 months (just before irradiation in group I) and 5 months after denudation in the two groups. After the angiographical study, the vessels were isolated and isometric tensions were measured in an organ chamber. In the in vivo studies, ergonovine-induced vasoconstriction at the denuded and x-ray irradiated site in Group I was significantly greater than that at the control site or that at the denuded site in Group II. Pretreatments with serotonin receptor blockers (ketanserin or methysergide) significantly attenuated ergonovine-induced hyperconstriction, while an alpha-adrenergic receptor blocker (prazosin) did not (% inhibition; ketanserin 74 +/- 9%, p < 0.01, methysergide 60 +/- 10%, p < 0.01, prazosin 9 +/- 5%, NS). In the in vitro studies, ergonovine produced significantly greater tension at the denuded and x-ray irradiated site (Group I) than at the control site or at the denuded site (Group II). Ergonovine-induced endothelium-dependent relaxation was impaired at the denuded site in both groups to a similar extent. These results suggest that ergonovine-induced hyperconstriction at the denuded and x-ray irradiated coronary artery resulted mainly from the hyperreactivity of medial smooth muscle mediated by serotonin receptors.

Glomerulocystic kidneys. Report of an adult case.

Glomerulocystic kidney characterized by dilatation of Bowman's space occurs primarily in infants and children. We treated a normally developed 29-year-old Japanese man for hypertension and renal failure, who had been well up to 6 months before admission. Extrarenal malformations were not determined. A biopsy of both kidneys was done at the time of interdialysis, and the histology revealed diffuse glomerular cystic lesions. Electron-dense deposits were also observed in the mesangial area. Radiological studies of the kidneys showed numerous minute cysts in the cortical area, a normal architecture of the arterial trees, and negative evidence of urinary tract obstruction. This may be the first documentation of glomerulocystic kidney in an adult, without extrarenal anomalies.

Role of coronary artery spasm in progression of organic coronary stenosis and acute myocardial infarction in a swine model. Importance of mode of onset and duration of coronary artery spasm.

BACKGROUND: Coronary spasm may play an important role in progression of organic coronary stenosis and myocardial infarction, but the mechanisms responsible for these complications are not known. This study aimed to examine whether the mode of onset and the duration of coronary spasm influenced progression of organic coronary stenosis and acute myocardial infarction in a swine model of coronary spasm. METHODS AND RESULTS: Göttingen miniature pigs were subjected to cholesterol feeding, balloon-induced coronary arterial denudation, and x-ray irradiation. Five months later, coronary spasm was induced by intracoronary injection of serotonin. In 10 pigs, coronary spasm was provoked abruptly and maintained for 25 minutes by five repeated intracoronary injections of serotonin (10 micrograms/kg) every 5 minutes (group A, abrupt onset and short duration). In group B, coronary spasm was provoked gradually by intracoronary injections of serotonin at graded doses of 0.1, 0.3, and 0.6 microgram/kg every 5 minutes and was then maintained for 25 minutes in four pigs (group B1, gradual onset and short duration) and for 120 minutes in six pigs (group B2, gradual onset and long duration) by repeated intracoronary injections of serotonin (10 micrograms/kg) every 5 minutes. Intramural hemorrhage was noted histologically at the spastic site more frequently in group A with abrupt onset (nine of 10 pigs) than in group B with gradual onset (two of 10 pigs) (p < 0.01). Progression of organic coronary stenosis due to intramural hemorrhage was noted in seven pigs (six pigs in group A and one pig in group B), including three cases of total coronary occlusion. Evidence for the evolution of acute myocardial infarction (serial ECG findings, left ventriculograms, and histological findings) was noted in one pig (7%) of group A or B1 with short duration and in five of six pigs (83%) in group B2 with long duration (p < 0.01 versus group A and B1). CONCLUSIONS: These results indicate that: 1) intramural hemorrhage was frequently induced by coronary spasm of abrupt but not of gradual onset, 2) intramural hemorrhage resulted in acute progression of coronary stenosis and sometimes resulted in persistent total coronary occlusion leading to acute myocardial infarction, and 3) prolonged coronary spasm resulted in acute myocardial infarction without progression of organic coronary stenosis.

Safety and accuracy of dipyridamole thallium myocardial scintigraphy in elderly patients.

This study examined mainly the adverse effects of 201Tl myocardial scintigraphy with dipyridamole (D-Tl) in 73 elderly patients over 70 years old in comparison with those in 65 younger patients. Fifty-five of 73 elderly patients (75%) and 49 of 65 younger patients (75%) had a persistent or dipyridamole-induced perfusion defect on D-Tl. The hemodynamic changes induced by dipyridamole as well as the incidence of cardiac and noncardiac adverse effects were similar in both groups and no serious adverse effect occurred in either group. Secondly, we examined the procedure's usefulness for detecting ischemic heart disease in elderly and younger patients. Dipyridamole induced perfusion defect was noted in 21 elderly patients and in 24 younger patients (N.S.). Among the patients in whom coronary angiography was performed, significant coronary artery stenosis was found in 5 of 8 elderly patients and 17 of 20 young patients (N.S.). In patients with one or two-vessel disease, the area with dipyridamole induced ischemia was concordant with the stenotic area seen on coronary angiography in 3 of 3 elderly patients and 12 of 13 younger patients (N.S.). Thus, the safety and usefulness of D-Tl for detecting myocardial ischemia were comparable in elderly and young patients.