The many ways to myocardial perfusion imaging.

Myocardial perfusion imaging (MPI) is important for the management of patients with suspected or known coronary artery disease (CAD). Nuclear cardiology is the most widely used noninvasive approach for the assessment of myocardial perfusion. The available single-photon emission computed tomography (SPECT) flow agents are characterized by a rapid myocardial extraction and by a cardiac uptake proportional to blood flow. In addition, different positron emission tomography (PET) tracers may be used for the quantitative measurement of myocardial blood flow and coronary flow reserve. The decrease in blood flow, determined by coronary artery stenosis, produces myocardial ischemia leading to perfusion abnormalities detectable by SPECT or PET in the early phase of ischemia. Other imaging techniques, such as contrast echocardiography and magnetic resonance imaging (MRI) have been more recently proposed as alternative methods for the evaluation of myocardial perfusion. Although several technical aspects have to be better defined to use contrast echocardiography in clinical practice, this approach appears promising for the evaluation of myocardial perfusion. MRI has also been proposed for the assessment of myocardial perfusion by measuring the alteration of regional myocardial magnetic properties after the intravenous injection of contrast agents. Due to the high contrast and spatial resolution of the technique, MRI allows differentiating sub-endocardial and sub-epicardial perfusion, emerging as a potential alternative non-ionizing technique to evaluate myocardial perfusion. This review illustrates the noninvasive imaging modalities for the evaluation of myocardial perfusion, underlying advantages and disadvantages of each technique.

A common variant of endothelial nitric oxide synthase (Glu298Asp) is an independent risk factor for carotid atherosclerosis.

BACKGROUND AND PURPOSE: Endothelium-derived NO is formed from L-arginine by endothelial NO synthase (eNOS) encoded by the NOS 3 gene on chromosome 7. Because several studies have indicated that NO plays a key role in the development of the atherosclerotic process, we investigated whether common variants in the eNOS gene are associated with an increased risk of plaque on carotid arteries. METHODS: We studied 375 subjects attending the hypertension center of our institution to be screened for arterial hypertension. The examined subjects were classified according to the presence of carotid plaques (intima-media thickness >/=1.5 mm), and 2 intronic (CA and 27-bp repeats) polymorphisms and 1 exonic (Glu298Asp) polymorphism of the eNOS gene were explored. RESULTS: Only the Glu298Asp polymorphism of eNOS was associated with the presence of carotid plaques (P:<0.05). In particular, there was an excess of homozygotes for the Asp298 variant among subjects with carotid plaques, whereas the number of subjects who had the Glu298 allele in exon 7 of the eNOS gene was equally distributed in both study groups. Interestingly, the risk of having carotid plaques was increased approximately 3 times in subjects who were homozygotic for the Asp298 variant compared with subjects who were homozygotic for the Glu298 variant and was independent of the other common risk factors (age, blood pressure, and smoking). CONCLUSIONS: Homozygosity for Asp298, a common variant of the eNOS gene, is an independent risk factor for carotid atherosclerosis in this study population.

Haemodynamic and metabolic effects of rilmenidine in hypertensive patients with metabolic syndrome X. A double-blind parallel study versus amlodipine.

OBJECTIVE: To compare the effects of rilmenidine with those of amlodipine on blood pressure, glucose metabolism, plasma lipid concentration and fibrinolysis parameters. DESIGN: A four-month randomized double-blind, parallel group study. PATIENTS AND METHODS: Obese hypertensive patients with hypertriglyceridaemia (> or = 2.3 mmol/l) and impaired glucose tolerance (OMS-ADA) were included (n = 52). A placebo run-in period of 2 weeks was followed by 4 months of double-blind treatment with either rilmenidine or amlodipine. Blood pressure was recorded using a mercury sphygmomanometer. Glucose metabolism was evaluated by an oral glucose tolerance test RESULTS: Of the 52 patients recruited, 47 (21 rilmenidine and 26 amlodipine) completed the 4-month treatment period. The intention-to-treat analysis showed a comparable reduction in systolic and diastolic blood pressure (SBP, DBP) with the two anti-hypertensive treatments (rilmenidine -13.9/-13.5 mmHg; amlodipine - 17.6/-15.0 mmHg). Insulin concentrations under basal conditions and 2 h after a standard oral glucose load did not change significantly after treatment in both groups. Plasma glucose under basal conditions and 2 h after a standard oral glucose load as well as the area under the plasma glucose concentration curve tended to decrease in the rilmenidine group and to increase in the amlodipine group so that the changes in these parameters were significantly different between the two study groups (P= 0.041, P = 0.042 and P = 0.015, respectively). Plasminogen activator inhibitor type 1 (PAI-1) antigen and PAI-1 activity were only decreased in the rilmenidine group (not statistically significant). CONCLUSION: Our results demonstrate that rilmenidine and amlodipine have a comparable anti-hypertensive effect but only rilmenidine is able to improve glucose metabolism.

Effect of alpha-phenyl-N-tert-butylnitrone on diabetes and lipid peroxidation in BB rats.

Oxygen free radicals have been shown to interfere with pancreatic islet beta cell function and integrity, and have been implicated in autoimmune type 1 diabetes. We hypothesized that the spontaneous autoimmune type 1 diabetes of the BB rat would be prevented by in vivo administration of a free-radical spin trap, alpha-phenyl-N-tert-butylnitrone (PBN). Twenty-eight diabetes-prone (BBdp) and 13 non-diabetes-prone (BBn) rats received PBN (10 mg/kg) subcutaneously twice daily, and 27 BBdp and 12 BBn rats received saline as controls. Rats were treated from age 47 +/- 6 days until diabetes onset or age 118 +/- 7 days. PBN caused no growth, biochemical, or hematological side effects. Sixteen control BBdp rats became diabetic (BBd, mean age 77 +/- 6 days) and six demonstrated impaired glucose tolerance (IGT rats). The incidence of diabetes and IGT was not different in PBN-treated BBdp rats. Saline-treated rats showed no differences in pancreatic malondialdehyde (MDA) contents of BBd, IGT rats, and the BBdp that did not develop diabetes, versus BBn rats (2.38 +/- 0.35 nmoL/g). Among rats receiving PBN, BBn had lower pancreatic MDA than BBd and IGT rats (1.38 +/- 0.15 vs. 1.88 +/- 0.15 and 2.02 +/- 0.24 nmoL/g, p < 0.05), but not than BBdp rats (1.78 +/- 0.12 nmoL/g, ns). BBn rats receiving PBN also had lower pancreatic MDA than the saline controls (p < 0.05). Thus, PBN is remarkably nontoxic and is able to decrease MDA in the absence of the autoimmune process, but does not prevent diabetes. A combination of PBN with other complementary antioxidant agents may hold better promise for disease prevention.

Effects of valsartan on left ventricular diastolic function in patients with mild or moderate essential hypertension: comparison with enalapril.

OBJECTIVE: This study compares the effects of an AT1 angiotensin II receptor antagonist (valsartan) with those of an ACE inhibitor (enalapril) on left ventricular (LV) diastolic function in patients with mild or moderate essential hypertension and no evidence of LV hypertrophy at echocardiography. METHODS: A total of 24 patients (16 men, mean age 47 +/- 8 years) underwent radionuclide ambulatory monitoring (Vest) of LV function at rest and during upright bicycle exercise testing before and after two 4-week treatment periods with valsartan (80-160 mg/day orally) and enalapril (20-40 mg/day orally) according to a double-blind, crossover randomization scheme. RESULTS: In the overall population no differences between the two treatments were found in LV peak filling rate (PFR) either at rest or at peak exercise. In a subgroup analysis it was found that baseline PFR was normal (= 2.5 EDV/sec) in 12 patients (subgroup A) and impaired (< 2.5 EDV/sec) in the remaining 12 (subgroup B). In both subgroups, valsartan and enalapril induced a significant and comparable reduction of systolic and diastolic blood pressure. In subgroup A, valsartan and enalapril did not induce significant changes in PFR. In subgroup B, valsartan increased PFR both at rest (from 2.0 +/- 0.3 to 2.4 +/- 0.3 EDV/sec, P < 0.01) and at peak exercise (from 4.1 +/- 1.1 to 4.4 +/- 1.0 EDV/s, P < 0.05), whereas enalapril did not change PFR either at rest (2.0 +/- 0.4 EDV/s, P < 0.01 versus valsartan) or at peak exercise (3.7 +/- 1.1 EDV/sec, P < 0.05 versus valsartan). CONCLUSIONS: Valsartan-induced renin-angiotensin system blockade is able to improve LV filling in patients with mild or moderate essential hypertension and impaired diastolic function. These findings support the hypothesis of a contribution of the renin-angiotensin system in the control of LV diastolic function in these patients.

Distinct vasodilation, without reflex neurohormonal activation, induced by barnidipine in hypertensive patients.

Barnidipine is a new 1,4-dihydropyridine calcium antagonist with a strong and long-lasting vasodilatory effect. In order to assess the haemodynamic profile of the antihypertensive effect of barnidipine, a randomized, double-blind study of barnidipine vs nitrendipine was performed in 24 patients with mild to moderate essential hypertension. Following an initial 4-week placebo period, patients whose sitting diastolic blood pressure (SiDBP) was between 95 and 114 mm Hg, and whose sitting systolic blood pressure was between 150 and 219 mm Hg, were randomized (2:1 ratio) to receive either barnidipine (10 mg) or nitrendipine (10 mg) once daily, for a 6-week double-blind period. Subsequently, patients with an SiDBP of less than 90 mm Hg continued for a second 6-week period with the same monotherapy, while patients with an SiDBP of 90 mm Hg or above received double the dose of antihypertensive treatment for the next 6 weeks. Two-dimensional M- and B-mode echocardiography with Doppler flowmetry was performed at the end of both the placebo and active treatment phases. Barnidipine and nitrendipine reduced blood pressure by the same degree (barnidipine: from 165 +/- 2/100 +/- 1 to 145 +/- 2/89 +/- 1 mm Hg, p < 0.01; nitrendipine: from 163 +/- 3/100 +/- 2 to 143 +/- 7/90 +/- 3 mm Hg, p < 0.01) as a result of peripheral vasodilation. This was not accompanied by reflex neurohormonal activation. Moreover, only in the group receiving barnidipine was a significant decrease in plasma noradrenaline observed, both when the patients were in the supine position (from 298 +/- 27 to 214 +/- 21 pg/ml, p < 0.05) and when they were upright (from 472 +/- 37 to 348 +/- 38 pg/ml, p < 0.05).

Influence of left ventricular hypertrophy on heart period variability in patients with essential hypertension.

OBJECTIVE: To evaluate whether left ventricular hypertrophy in hypertensive patients is associated with a greater impairment of sympathovagal balance assessed by means of heart period variability. DESIGN AND METHODS: Forty hypertensive patients, 20 with echocardiographic evidence of left ventricular hypertrophy and 20 without, and 20 control subjects, were subjected to 24 h blood pressure monitoring and Holter recording on 2 consecutive days. Power spectrum analyses of heart period variability were performed utilizing the fast Fourier transform algorithm. RESULTS: No difference was detectable in 24 h, daytime and night-time blood pressure values between hypertensive patients with and without left ventricular hypertrophy. Low- and high-frequency powers were higher in controls than in hypertensives; in particular, low-frequency power showed a progressive decrease through control subjects and hypertensives without and with left ventricular hypertrophy. Furthermore, significant negative correlations were found between left ventricular mass index and low- and high-frequency power. No difference was detectable in ultra-low- and very low-frequency power. During daytime low- and high-frequency power were higher in controls than in hypertensives; during night-time, low- and high-frequency power increased significantly in all groups and low-frequency power was still higher in control subjects. CONCLUSIONS: Considering that, when analysed over 24 h Holter recording, low- and high-frequency power both reflected the parasympathetic modulation of heart rate, the present results demonstrate a parasympathetic withdrawal in hypertension; this sympathovagal imbalance is greater in patients with cardiac hypertrophy and is related to the increase in left ventricular mass.

Rilmenidine in patients with left ventricular hypertrophy: beyond the reduction of left ventricular mass.

It is generally accepted that the development of left ventricular hypertrophy (LVH) represents a multifactorial phenomenon that also involves neurohormonal mechanisms. This finding may account for the ability of angiotensin-converting enzyme inhibitors to induce faster and more complete reversal of LVH than that observed with other antihypertensive treatments. The sympathetic system is also involved in the genesis of hypertension-induced LVH. We assessed the effects of satisfactory long-term treatment with rilmenidine, a new oxazoline with a potent antihypertensive action, on cardiovascular structural abnormalities and cardiac endocrine function in hypertensive patients with left ventricular hypertrophy. Eleven patients underwent M-mode and two-dimensional Doppler echocardiography, peripheral pulsed Doppler flowmetry, determination of plasma atrial natriuretic factor [(ANF) pg/ml] and renin activity, and 24-h urine electrolyte excretion under control conditions, after 4 weeks of blood pressure normalization, after 1 year of satisfactory antihypertensive treatment and, finally, 4 weeks after therapy withdrawal. I.VH (g/m2 body surface area) was reversed after 1-year treatment (from 152 +/- 5 to 131 +/- 4, p < 0.05). One-year treatment induced an improvement in brachial artery compliance (cm4/dyne.10(7)) (from 0.92 +/- 0.06 to 1.16 +/- 0.08, p < 0.05) that persisted after withdrawal of treatment (1.17 +/- 0.06, p < 0.05). Plasma renin activity and urinary electrolyte excretion did not change throughout the study, whereas ANF remained unchanged after blood pressure normalization (48.4 +/- 6.2 versus 44.7 +/- 2.9, NS), fell after reversal of LVH (28.6 +/- 3.4, p < 0.05), and remained significantly lower than under control conditions after therapy withdrawal (27.5 +/- 2.9, p < 0.05). These results demonstrate that a satisfactory long-term antihypertensive treatment with rilmenidine is able to reverse cardiovascular structural changes and to restore cardiac endocrine function.

[Non-hemodynamic mechanisms of cardiovascular risk in the hypertensive patient: insulin resistance]. / Rischio cardiovascolare nel paziente iperteso, i meccanismi non emodinamici: l'insulino-resistenza.

Insulin resistance is a condition which is present in many different diseases all characterized by an increased risk of cardiovascular morbidity and mortality. Generally, the contribution of insulin resistance to the development of cardiovascular pathology is considered to be due to its metabolic consequences. However, recent findings suggest alternative mechanisms by which insulin resistance could exert its role of cardiovascular risk factor. In fact, it has been demonstrated that insulin resistant hypertensive patients have a sympathetic response to euglycemic hyperinsulinemia which is three-fold greater than in normal subjects. This phenomenon could represent an important link between sympathetic nervous system and arterial hypertension. Furthermore, in normal subjects it has been demonstrated that hyperinsulinemia modulates the sympathetic induced vascular response and that this effect is lost in insulin resistant hypertensives. This latter phenomenon could further worsen the consequences of sympathetic overactivity.

[Carotid vascular structural changes and left ventricular hypertrophy]. / Alterazioni strutturali vascolari carotidee ed ipertrofia ventricolare sinistra.

In the literature there are few studies evaluating carotid vascular atherosclerotic involvement in patients with essential arterial hypertension. Nowadays with new non-invasive methodological methods, such as Doppler-echotomography, it is possible to evaluate accurately structural vascular and cardiac changes. In this study we evaluated the relationship between carotid vascular structural changes and cardiac left ventricular mass index in 15 normotensive subjects and in 15 patients with essential hypertension. We performed a B-mode echotomography (7.5 MHz) of a common carotid in order to measure the diameter of the vessel and intima-media wall thickness. In the same subjects we determined echocardiographic left ventricular mass index and we measured arterial pressure by sphygmomanometric method. There was no statistical significant difference in the two groups except that in systolic, diastolic and mean arterial pressure (96 +/- 2 vs 123 +/- 2 mmHg, p < 0.01), left ventricular mass index (102 +/- 3 vs 118 +/- 3 g/m2, p < 0.01) and in the common carotid intima media wall thickness (0.91 +/- 0.01 vs 2.23 +/- 0.02 mm). In the normotensive subject mean arterial pressure correlated significantly with age (r = 0.699) and with common carotid arterial diameter (r = 0.523) (both p < 0.05). In hypertensive patients, on the contrary, mean arterial pressure correlated with left ventricular mass index (r = 0.523), carotid arterial diameter (r = 0.627) and common carotid intima media wall thickness (r = 0.847). These results demonstrate that in hypertensive patients cardiac abnormalities accompanied vascular structural changes.

[Effects of antihypertensive treatment on carotid vascular changes]. / Effetti del trattamento antipertensivo sulle alterazioni vascolari del distretto carotideo.

The carotid artery is one of the most important sites in the progression of atherosclerotic lesions. Atherosclerosis is known to be determined by a variety of factors, among which arterial hypertension is one of the most important. Blood pressure control by antihypertensive treatment is thus of great benefit in management of atherosclerosis, particularly in view of the direct action of some classes of antihypertensive agents on atheromatous lesions. Today, modern diagnostic technique allow a non-invasive examination of the artery wall (B-mode ultrasound and pulsed-Doppler), so that early detection of structural and functional alterations is possible. In order to evaluate the efficacy of the long term blood pressure reduction in the progression and/or in the regression of cardiovascular structural abnormalities, we studied intima-media thickness and arterial compliance during one-year antihypertensive treatment with a new calcium-antagonist, lacidipine, or a diuretic hydrochlorothiazide. In both groups we observed a comparable blood pressure reduction (lacidipine: from 166 +/- 5/100 +/- 1 to 142 +/- 4/88 +/- 2 mmHg; hydrochlorothiazide: from 154 +/- 5/102 +/- 2 to 140 +/- 4/88 +/- mmHg; both p < 0.01). On the contrary, only in patients treated with lacidipine did we obtain a significant improvement in carotid blood flow (383 +/- 16 vs 411 +/- 16 ml/min p <) and in arterial compliance (0.8 +/- 0.1 vs 1.2 +/- 0.2 cm/dyne p < 0.01). Indeed, we observed a different behaviour of the intima-media thickness in the two groups (lacidipine: 1.11 +/- 1.4 vs 1.13 +/- 1.5 mm n.s.; hydrochlorothiazide: 1.15 +/- 0.15 vs 1.21 +/- 0.17 mm p < 0.06). Our results demonstrate that an effective antihypertensive treatment with calcium antagonists may influence the progression of carotid vascular abnormalities.

[The effects of plasma cholesterol reduction on vasoconstriction due to sympathetic activation in patients with moderate primary hypercholesterolemia]. / Effetti della riduzione del colesterolo plasmatico sulla vasoconstrizione da attivazione simpatica in pazienti con ipercolesterolemia primaria moderata.

Recent studies have demonstrated that hypercholesterolemia is one of the major factor involved in the progression of coronary heart disease and that the reduction in plasma cholesterol reduces mortality for cardiovascular events. Indeed, recent experimental studies have demonstrated alterations in vascular reactivity in atherosclerosis. The aim of this study was to evaluate in patients with primary hypercholesterolemia the consequences of an effective of chronic treatment with inhibitor of HMG-CoA reductase on vascular responsiveness to cold pressure test. We observed a significant reduction in total plasma cholesterol during the study that was accompanied by a significant decrease in the response of peripheral vascular resistances to cold pressure test (55 +/- 4% vs 73 +/- 5% p < 0.01). There was also a significant relationship between the reduction of total cholesterol and the response of vascular resistance to the cold pressure test (r = 0.853, p < 0.05). Our results demonstrate that the reduction in total plasma cholesterol may influence the haemodynamic response induced by the activation of the sympathetic system.

Site of myocardial ischemia as a determinant of postexercise blood pressure and heart rate response in coronary artery disease.

Forty patients with coronary artery disease and 15 normal subjects (group C) were studied to assess the influence of the site of stress-induced myocardial ischemia on cardiovascular response after exercise. Patients were divided in 2 groups according to myocardial thallium-201 scintigraphy: those with an anteroseptal reversible perfusion defect (group A; n = 24), and those with an inferoposterior reversible perfusion defect (group I; n = 16). All patients underwent serial bicycle exercise stress tests. The first 2 stress tests were interrupted when 0.1 mV of ST-segment depression was achieved (2,000 to 2,500 kg-m); a third test was stopped before the onset of ischemia (1,500 kg-m). Normal subjects performed stress tests at comparable work loads. At ischemic threshold, there was no difference in ejection fraction between groups A (65.5%) and I (67.3%). Mean values and recovery ratios of heart rate and systolic blood pressure were significantly higher in group A than in C and I during the recovery period of the 2,000 to 2,500 kg-m stress test. In contrast, no significant difference was observed among the groups in the 1,500 kg-m stress test, and between groups I and C in any stress test. The data show that in patients with the same degree of stress-induced impairment of ventricular function, the anterior site of ischemia leads to persistently higher values of heart rate and blood pressure after exercise, which are likely due to an enhanced adrenergic discharge.

Diastolic perfusion time and exercise posture in coronary artery disease patients: correlation with ST segment changes.

The relationship between either heart rate or diastolic time and ST segment depression has been evaluated during supine and upright exercise in 16 coronary artery disease patients. Diastolic perfusion time and ST segment depression were related by a linear regression, which was independent of exercise posture. The entity of ST segment depression was greater during supine than in upright exercise for the same heart rate. The assessment of the relationship between heart rate and diastolic perfusion time during two exercises showed that at the same heart rate, diastolic perfusion time was shorter in supine posture. In conclusion, the greater entity of ST segment depression induced by supine rather than upright exercise might be explained by the effect of supine posture on diastolic perfusion time.

[The smooth muscle autograft in continent colostomies. Experimental research on rabbits]. / L'autotrapianto di muscolatura liscia nelle colostomie continenti. Ricerca sperimentale nel coniglio.

The authors stop onto make use of the colon smooth musculature to resolve the question of medical and surgical methods used until now to improve the continence of colostomies. Owing to the experiences and co-operating with some other research centers, the authors refer about the experiment performed on the rabbit, where a small leaf of intestine serous-muscular tissue was employed to perform a continence system on colostomy. The analysis of manometric results obtained from check animals in different post-operatory periods (3-7-14-21 days) pointed out a moderate reaction of neosphincterial function, while the histological results prove a favorable histological development without to change the muscular tunica fibrous tissue. The easy application, harmless of employed methods and undoubted comfort for the patient stand for valid indications in the development to come of this method.

[Behavior of the electrocardiographic and spirographic parameters in athletes practicing rowing who have at the same time taken an anti-inflammatory drug]. / Comportamento dei parametri elettrocardiografici e spirografici in atleti praticanti canottaggio e che hanno contemporaneamente assunto un farmaco antiflammatorio.

The AA. studied the effects of a new anti-inflammatory drug on some spirographic and electrocardiographic parameters in a group of oarsmen. The results show a not significant changes of these parameters after drug engagement. The variations found are to be ascribed to the training.