Value of iodine-123 metaiodobenzylguanidine scintigraphy in patients with vasospastic angina.

To assess the presence and location of presynaptic myocardial sympathetic abnormality in patients with vasospastic angina, iodine-123 labelled metaiodobenzylguanidine (MIBG) single-photon emission tomography (SPET) was performed. Fifty patients suspected of having vasospastic angina pectoris were enrolled in the study. All patients underwent a provocative test with intracoronary ergonovine infusion during coronary angiography, in which 99%-100% obstructive spasm was defined as a positive result. Twenty-five patients were diagnosed as having vasospastic angina based on a positive provocative test. MIBG SPET was performed at 20 min and 3 h after administration of 111 MBq or MIBG. On early images, only 5 of 25 patients with vasospastic angina showed a mild reduction in MIBG uptake, whereas 3-h delayed images demonstrated MIBG abnormality in 20 patients (80%). The location of the MIBG abnormality was completely or partially consistent with the spastic coronary territory in 18 patients. On the other hand, only 4 of 25 patients (16%) with negative provocative test demonstrated reduced MIBG uptake. Accordingly, positive and negative predictive values of MIBG SPET for the provocative test were 83% (20/24) and 81% (21/26) respectively. In conclusion, MIBG scintigraphy with SPET can permit the non-invasive detection and evaluation of suspected vasospastic angina.

Evolution of coronary vascular tone in vasospastic angina.

In general, anginal symptoms diminish with time in patients with vasospastic angina. We assessed changes in coronary vascular tone (CVT) in patients with vasospastic angina over a 4-year period to evaluate the time course of spastic activity. Vasospastic angina was evaluated in 39 patients in whom occlusive spasm was evoked by selective intracoronary injection of ergonovine maleate (ERG-S) 48 h after stopping all coronary vasodilator drugs. These patients had no organic coronary stenosis and developed no stenosis during follow-up. ERG-S was repeated 3 times at 2-year intervals. CVT was determined at each ERG-S study using the equation: CVT = 1-(coronary artery diameter before ERG-S/coronary artery diameter after intracoronary injection of isosorbide dinitrate). Thirty-four patients (87%) had no angina pectoris at the second ERG-S study and 28 (72%) had none at the third. Coronary spasm was induced in 25 patients at the second ERG-S study and in 20 at the third. The overall CVT was shown to decrease at each successive ERG-S study (p < 0.01). There was no correlation between changes in CVT and anginal symptoms or the coronary spasm induction rate. These results demonstrate that CVT decreases over time in patients with vasospastic angina, suggesting that myocardial ischemia may improve spontaneously.

Clinical features of prognosis of Japanese patients with anomalous origin of the coronary artery.

Anomalous origin of the coronary artery can lead to angina pectoris, acute myocardial infarction or even sudden death in the absence of atherosclerosis. However, in Japan, this anomaly is usually treated medically rather than surgically. To clarify the clinical features of anomalous origin of the coronary artery in Japanese and the prognosis of such patients who are treated medically, we reviewed 56 patients with anomalous origin of the coronary arteries. The mean age of these patients was 55.9 +/- 11.5 years. Anomalous origin of the right coronary artery from the left sinus of Valsalva was seen most frequently (78.6%). In contrast, we found no cases of anomalous origin of the left coronary artery from the right sinus of Valsalva traversing between the aorta and the pulmonary trunk. A history of syncope (14.3%) and aorta regurgitation (21.4%) was frequent and serious complications during exercise stress testing occurred in 5 patients. These patients were treated medically, such as by limiting exercise or by the oral administration of medicine. During the follow up period (mean 5.6 +/- 4.2 years), death directly related to anomalous origin of the coronary artery was not found despite the lack of surgical treatment. Our results suggest that the prognosis of these middle-aged-to-elderly patients without atherosclerosis is relatively good, despite the lack of surgical treatment.

[Evaluation of pulmonary perfusion in a patient with agenesis of the left pulmonary artery: usefulness of radionuclide angiography].

We reported a case with agenesis of the left pulmonary artery, in which radionuclide angiography with 99mTc-HSA and time activity curve (TAC) were useful in evaluating pulmonary perfusion in the effected lung. The case involved a 32-year-old male, who underwent nuclear medicine examination including 99mTc-MAA scanning, 81mKr scanning and 99mTc-HSA angiography. 99mTc-MAA and 81mKr scanning showed the perfusion defect and decreased ventilation in the effected lung, respectively. On the other hand, the delayed images of 99mTc-HSA angiography showed the existence of perfusion in the effected lung, although the early images showed the perfusion defect in the same lung. The TAC whose region of interest was placed on the hilus showed that the effected lung was gradually filled with the blood flow through the collateral pathways. In addition, the ratio of area under the TAC on the contralateral lung versus the effected lung was 4.6, while the volume ratio of the contralateral lung versus the effected lung obtained from X-ray CT images was 2.7. Therefore, it was suggested that the perfusion per volume in the effected lung was decreased, compared with that in the contralateral lung. It was concluded that 99mTc-HSA angiography was useful in evaluating the perfusion of the effected lung in a patient with agenesis of the left pulmonary artery.

[Endovascular stenting for a recurrent angina patient].

We report successful Palmaz-Schatz stenting for recurrent angina. Coronary arteriography in a 65-year-old man with recurrent angina six months after coronary artery bypass grafting (CABG) showed stenosis in the right coronary artery and in the saphenous vein graft to the left anterior descending artery. For both stenotic lesions, balloon dilatation was performed. However, both lesions recoiled after dilatation. Therefore, Palmaz-Schatz stents were inserted in both stenotic lesions. After stenting, the patient did not experience any further chest pain. Three months later coronary arteriography showed the stents remained patient. Balloon angioplasty for post-CABG angina is technically easier than additional surgery. However, angioplasty by balloon dilatation alone can induce dangerous complications during the acute phase and restenosis frequently develops. This method is not sufficiently effective or safe for recurrent angina. To prevent these problems, the stent was developed as a useful adjunct to balloon dilatation for the native artery. Using this new device, angioplasty for recurrent angina will be safer and more effective than additional surgery.

Two cases of Fabry's disease: a hemizygote with a point mutation in the alpha-galactosidase A gene and his relative.

A 34-year-old Japanese male had leg pain, edema of the legs, hypohidrosis, whorl-like opacities of the bilateral cornea, bilateral subcapsular cataracts, and chest discomfort on exercise. He had no characteristic angiokeratomas but did have telangiectases. The electrocardiogram revealed high voltage. The echocardiogram revealed mild mitral regurgitation. The alpha-galactosidase A activity in cultured lymphoblasts was deficient (0.5 nmol/h/mg protein). Electron microscopic examination of the skin revealed lamellar cytoplasmic inclusions in the endothelial cells, pericytes, and fibroblasts. He had a G--> A transition at nucleotide 982 in the coding sequence of the alpha-galactosidase A gene which resulted in a glycine to arginine amino acid substitution at residue 328. His uncle also had leg pain, edema of the legs, hypohidrosis, and chest pain on exercise. He had no characteristic angiokeratomas but did have telangiectases. Cardiovascular examination revealed hypertrophic cardiomyopathy and stenoses of coronary arteries. Electron microscopic examination of the skin revealed lamellar cytoplasmic inclusions in the endothelial cells, pericytes, and fibroblasts.

Enhanced blood pressure response to isometric handgrip exercise in patients with essential hypertension: effects of propranolol and prazosin.

To elucidate whether a difference exists in blood pressure (BP) elevation during isometric handgrip exercise (IHG) between essential hypertensives (EHT) and normotensives (NT), IHG was carried out in 12 NT and 46 EHT under constant sodium intake using a new instrument. The acute effects of propranolol and prazosin on IHG were also examined in EHT. The change in systolic BP (delta SBP) during IHG in EHT, delta SBP = 61 +/- 21 mmHg, was markedly greater than that in NT, delta SBP = 28 +/- 4 mmHg. Among EHT, delta BP increased with increasing severity of hypertension. Neither the changes in plasma norepinephrine nor in epinephrine during IHG showed significant differences between EHT and NT. The pressor response during IHG could not be suppressed by propranolol, but about 30% suppression of BP was observed during IHG with prazosin. It is concluded from these findings that EHT have an exaggerated BP response to IHG that is due to increased post-junctional alpha 1-adrenoceptors.

Effect of methyldopa, clonidine, and hydralazine on cardiac mass and haemodynamics in Wistar Kyoto and spontaneously hypertensive rats.

Prolonged treatment of spontaneously hypertensive (SHR) rats with either methyldopa or clonidine significantly and similarly reduced mean arterial pressure. Heart rate increased with methyldopa but decreased with clonidine; other haemodynamic effects were similar. SHR treated methyldopa, but not clonidine, had significantly reduced cardiac masses and heart weight to body weight ratios than did rats receiving the vehicle. Normotensive Wistar Kyoto (WKY) rats treated with methyldopa also had lower cardiac masses than their controls, but exhibited no significant changes in systemic haemodynamics. Treatment with the vasodilator hydralazine increased cardiac output and decreased total peripheral resistance in both SHR and WKY, but the decrease in mean arterial pressure was significant only in SHR. Heart rate was decreased and heart weight to body weight in WKY was elevated. Cardiac mass did not change. Minimal changes in regional haemodynamics were noted, with hydralazine eliciting a decrease in most organ vascular resistances. The data indicate that regression of hypertrophy following antihypertensive therapy was not solely dependent upon haemodynamic factors; nor was it necessarily the effect of suppression of the adrenergic system, since the results obtained with methyldopa and clonidine was similar.

Hemodynamic responses to bilateral lesions of the nucleus tractus solitarii in spontaneously hypertensive and normotensive rats.

Systemic and regional hemodynamic responses to bilateral lesions of the nucleus tractus solitarii (NTS) were studied in alpha-chloralose-urethane anesthetized American Wistar rats (NR), Wistar-Kyoto rats (WKY), and spontaneously hypertensive rats (SHR) by microsphere methods. After NTS lesions, arterial pressure rose by virtue of increased total peripheral resistance in each strain. Cardiac output was lower in NR and WKY, but not in SHR. In all strains, vasoconstriction was nonuniformly distributed among the systemic vasculatures: hepatosplanchnic, renal, and carcass (i.e. skin, skeletal muscle, bone, fat) vascular resistances were higher, but cerebral and coronary vascular resistance remained unchanged. There were some differences, however, in regional vascular responses to NTS lesions among these strains: carcass vasoconstriction was predominant in NR; it was less evident in SHR; and the WKY responses were intermediate. These results indicate that, although systemic hemodynamic responses were similar in these strains, and the reflex inhibition of central sympathetic outflow is not evidently deteriorated in SHR, the regional hemodynamics (i.e., hepatosplanchnic and renal vasculatures) in the SHR demonstrated greater arteriolar constriction.

Disparate effects of methyldopa and clonidine on cardiac mass and haemodynamics in rats.

1. Wistar-Kyoto and spontaneously hypertensive rats were given either methyldopa (400 mg day-1 kg-1) or clonidine (0.1 or 0.3 mg day-1 kg-1) for 3 weeks commencing at 20 weeks of age. 2. Both drugs significantly decreased mean arterial pressure in spontaneously hypertensive but not Wistar-Kyoto rats. Heart rate was significantly increased in spontaneously hypertensive rats by methyldopa, whereas clonidine significantly decreased heart rate. The higher dose of clonidine also decreased heart rate in Wistar-Kyoto rats. Both cardiac output and total peripheral resistance decreased slightly, but not significantly, with both agents. 3. Methyldopa, but not the lower equipotent depressor dose of clonidine, reduced left ventricular hypertrophy in spontaneously hypertensive rats. However, the higher dose of clonidine also significantly decreased the heart to body weight ratio despite an increased total peripheral resistance presumably due to the alpha-adrenergic agonist effect. 4. Minimal changes in organ blood flows were noted with both drugs. 5. These results suggest that neither systemic haemodynamics nor central inhibition of adrenergic drive are primary factors responsible for the regression of hypertrophy.

Reference sample microsphere method: cardiac output and blood flows in conscious rat.

Validation of the reference sample method (RSM) in the rat was accomplished by: 1) simultaneous measurement of cardiac output (CO) by the RSM and electromagnetic flowmetry method in ether-anesthetized open-chest Wistar rats, and 2) determination of systemic and regional hemodynamic reproducibility in conscious rats following three serial injections of microspheres. The optimal sampling time and sampling rate were determined in several CO states. The results indicate that: 1) 200 or more microspheres contained in the reference sample result in an accurate determination of CO, 2) almost 100% of the microspheres are trapped by tissues with in 20 s of cessation of the microsphere injection, 3) the hemodynamic steady state is affected only under low cardiac output conditions at a high sampling rate (1.211 ml/min), 4) three repeated injections of microspheres in conscious animals do not alter systemic hemodynamis, and 5) the reproducibility of regional blood flow distribution is good in all organs except the liver, stomach, spleen, and skin (third application). These data indicate that the RSM is reliable, providing reasonable accuracy and reproducibility of systemic and regional hemodynamics in the rat.

[Plasma renin activity response to isometric handgrip exercise in normotensive and hypertensive patients (author's transl)].

1) Plasma renin activity (PRA) response to isometric exercise was studied before and after the intravenous administration of 0.2 mg/kg of propranolol in 8 normotensive and 10 normal renin hypertensive patients. 2) Handgrip exercise at the 30% level of maximal voluntary contraction (MVC) for four minutes induced a significant increase in PRA in either normotensive or normal renin hypertensive patients, while the increase in PRA in normal renin hypertensive patients was significantly higher than that in normotensive patients. 3) Pretreatment with the administration of propranolol inhibited an increase in PRA after handgrip exercise in either normotensive or normal renin hypertensive patients. 4) The results suggest that isometric handgrip exercise can induce an augmentation in renin release mainly by stimulation of the sympathetic nervous system in either normotensive or normal renin hypertensive patients. The possible mechanism of the exaggerated response in PRA to handgrip exercise in normal renin hypertensive patients has been discussed.