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Objective: This double-blind, placebo-controled randomized study was designed to compare the antihypertensive effect and tolerability of extended-release felodipine and slow-release nifedipine retard in elderly hypertensive patients. Methods: Thirty patients of both sexes (mean age 71 years) with mild to moderate essential hypertension were recruited from our hypertension outpatient clinic. After a 2-week placebo period, felodipine extended-release (felodipine ER), 10 mg once daily, nifedipine slow-release retard (nifedipine SR), 20 mg twice daily or placebo were administered to each patient for 2 weeks according to a 3 × 3 latin-square design. At the end of each treatment period, the patients underwent 24-h noninvasive blood pressure monitoring. Results: All of the patients completed the trial and no serious adverse experience was reported. In comparison with placebo, felodipine and nifedipine decreased mean 24-h diastolic blood pressure by 6.7 and 4.3 mmHg, respectively, with no significant difference between the two drugs. Mean 24-h systolic blood pressure also decreased after felodipine and nifedipine, with no difference between the two drugs. Both drugs reduced blood pressure variability, lowering the 24-h mean standard deviation of mean hourly blood pressure values. The trough:peak ratio for felodipine was 80% for systolic and 75% for diastolic blood pressure. Conclusion: Felodipine ER once daily lowers blood pressure in elderly hypertensives and is as effective as nifedipine SR twice daily. The high trough:peak ratio suggests that the dose and the between-dose interval of felodipine provides adequate therapeutic coverage.

Melatonin (N-acetyl-5-methoxytryptamine), the principal hormone of the vertebral pineal gland, elicits several neurobiological effects. However, the effects of melatonin on cardiac muscle are still unknown. The first goal of the study was to investigate the role of melatonin on myocardial contractility in isolated rat papillary muscle using dose-response curves to melatonin, to isoproterenol and calcium either in the presence or in the absence of melatonin (0.3 nM). Response curves to isoproterenol were additionally performed in the presence of melatonin plus the specific receptor antagonist N-acetyltryptamine (10 microM); the adenylate-cyclase stimulator forskolin (10 microM) was also used. Melatonin has no direct inotropic effect in isolated rat papillary muscle but counteracts isoproterenol but not [Ca2+] effects. In fact, the EC50 for isoproterenol was significantly higher in the presence than in the absence of melatonin (p < 0.001). This anti-adrenergic action occurs through an interaction to a specific cardiac receptor. Forskolin-stimulated adenylate cyclase induced an increase of contractile force (+118 +/- 25%) which was reduced in the presence of melatonin (+26 +/- 10%; p < 0.01). In conclusion, we found that melatonin possess anti-adrenergic effect in isolated rat papillary muscle. This phenomenon was abolished in the presence of its receptor antagonist N-acetyl-tryptamine demonstrating that melatonin operates through a specific cardiac receptor. The reduction of contractility increase, induced by forskolin-stimulated adenylate cyclase, shows that melatonin may act through a reduction of cyclic AMP accumulation.

BACKGROUND Oxidative modification of low-density lipoprotein (LDL) appears to play a pivotal role in atherogenesis. The specific role played by LDL peroxidation in aging is not known. Since estrogens may protect LDL from peroxidation in vitro and in vivo, we chose to investigate only men of various ages. OBJECTIVE To determine whether LDL from healthy elderly men was differently susceptible to peroxidation than LDL of young and adult men. SUBJECTS AND METHODS LDL was isolated from 15 normolipidemic young (aged 19-23 years), 17 adult (aged 35-55 years), and 16 elderly (aged 77-90 years) healthy men. None of the men included in the study was a smoker or a hypertensive. LDL peroxidation was achieved by exposure to 5 mumol/l copper sulfate for 18 h at 37 degrees C, and some markers of lipid peroxidation (estimating various levels of peroxidation) were evaluated. RESULTS The levels of lipid peroxides in LDL from our elderly men were already higher under basal conditions than were those both of adult and of young men. LDL from elderly men was more susceptible to peroxidation than was that of adult and young men. Furthermore, the lag time correlated inversely to age (r = -0.68, P < 0.01), whereas lipid peroxide and malonyldialdehyde levels correlated highly to age (r = 0.79 and r = 0.77, P < 0.0002 and P < 0.0012, respectively). With aging the vitamin E content in LDL decreased whereas the arachidonic fatty acid content increased. More importantly, the relationship between the vitamin E content and the lag time made evident the parallel increase in lag time and in vitamin E level with aging. The vitamin E concentration also correlated inversely to levels of thiobarbituric acid-reactive substances in LDL from elderly patients (r = -0.61, P < 0.05). CONCLUSIONS The present study shows that LDL peroxidation increases with age. This phenomenon may favor the progression of atherosclerosis in elderly men.

OBJECTIVES: The present study examined whether angina 48 h before myocardial infarction provides protection in adult and elderly patients. BACKGROUND: The mortality rate for coronary artery disease is greater in elderly than in young patients. In experimental studies, ischemic preconditioning affords an endogenous form of protection against ischemia-reperfusion injury in adult but not in senescent hearts. Angina before myocardial infarction, a clinical equivalent of experimental ischemic preconditioning, has a protective effect in adult patients. It is not known whether angina before myocardial infarction is also protective in aged patients. METHODS: We retrospectively verified whether antecedent angina within 48 h of myocardial infarction exerts a beneficial effect on in-hospital outcomes in adult (< 65 years old, n = 293) and elderly (> or = 65 years old, n = 210) patients. RESULTS: In-hospital death was more frequent in adult patients without than in those with previous angina (10% vs. 2.6%, p < 0.01), as were congestive heart failure or shock (10.7% vs. 3.3%, p < 0.02) and the combined end points (in-hospital death and congestive heart failure or shock) (20.7% vs. 5.9%, p < 0.0003). In contrast, the presence or absence of previous angina before acute myocardial infarction in elderly patients seems not to influence the incidence of in-hospital death (14.4% vs. 15.2%, p = 0.97), congestive heart failure or shock (11.0% vs. 11.9%, p = 0.99) and the combined end points (25.4% vs. 27.1%, p = 0.89). Logistic regression analysis models for in-hospital end points show that previous angina is a positive predictor in adult but not in elderly patients. CONCLUSIONS: The presence of angina before acute myocardial infarction seems to confer protection against in-hospital outcomes in adults; this effect seemed to be less obvious in elderly patients. This study suggests that the protection afforded by angina in adult patients may involve the occurrence of ischemic preconditioning, which seems to be lost in senescent patients

Congestive heart failure (CHF) is an insulin-resistant state which constitutes the main risk factor for the development of non-insulin-dependent diabetes mellitus (NIDDM). Our study investigated the predictive role of CHF on the development of NIDDM in 1,339 elderly subjects with a mean ( +/- SD) age of 74.2 +/- 6.4 years. CHF had a 9.5% prevalence, and 14.7% of the subjects had NIDDM. After stratification by age, subjects between 80 and 84 years had the highest prevalence of CHF and a total of 29.6% of CHF patients had NIDDM. In multiple logistic regression analysis, CHF was associated with NIDDM [odds ration (OR) = 2.0, 95% confidence interval (CI) - 1.6-2.5] independent of age, sex, family history of diabetes, body mass index, (BMI), waist/hip ratio, and diastolic blood pressure. When only untreated CHF patients were taken into account, the association between CHF and NIDDM was even stronger (OR = 4.0, 95% CI = 3.4-5.8). When untreated CHF patients were grouped into those with low (I and II) and high (III and IV) New York Heart Association (NYHA) classes, the association of CHF and NIDDM was stronger with the worsening of CHF. In a longitudinal study, CHF predicted NIDDM independently of age, sex, family history of diabetes, BMI, waist/hip ratio, systolic and diastolic blood pressure, and therapy for CHF (OR = 1.4, 95% CI = 1.1-1.8). CHF was associated with a higher prevalence of NIDDM and was a risk factor for its development. Elevated FFA concentrations may play a pivotal role.

OBJECTIVES: This study was performed to investigate the effect of single or multiple brief periods of ischemia and the administration of exogenous norepinephrine before a more prolonged ischemic period and after reperfusion in adult and senescent isolated and perfused rat hearts. BACKGROUND: The mortality rate for coronary artery disease is greater in the elderly. Ischemic preconditioning has been proposed as an endogenous form of protection against ischemia-reperfusion injury. However, the role of preconditioning in aging heart is unknown. METHODS: We compared the protective effect of preconditioning transient ischemic and norepinephrine stimuli against 20 min of global normothermic ischemia and 40 min of reperfusion in isolated perfused hearts of adult (6 months old) and senescent (24 months old) rats. Norepinephrine release in coronary effluent was determined by high performance liquid chromatography. RESULTS: Final recovery of percent developed pressure was improved after single preconditioning transient ischemic and norepinephrine stimuli in adult hearts (87.7 +/- 9% and 82.3 +/- 8.7%) versus unconditioned control hearts (50.6 +/- 4.8%, p < 0.01 [mean +/-SD]). The effect of preconditioning on developed pressure recovery was not present in senescent hearts after transient ischemic stimulus (39.8 +/- 4.9% vs. 41.6 +/- 5.8%, p = NS) but was present after norepinephrine stimulus (74.3 +/- 10.5, p < 0.01). Norepinephrine release significantly increased after preconditioning transient ischemic stimulus in adult but not in senescent hearts (p < 0.01 vs. adult). Transient ischemic- and norepinephrine-induced preconditioning was blocked by alpha-adrenergic receptor antagonists in both adult and senescent hearts. Multiple transient ischemic stimuli were able to reduce postischemic dysfunction in adult but not in senescent hearts. CONCLUSIONS: Preconditioning transient ischemic stimulus significantly reduces postischemic dysfunction in adult but not in senescent hearts, whereas exogenous norepinephrine is able to mimic preconditioning in both adult and senescent hearts. Ischemic preconditioning induces an increase in norepinephrine release in adult but not in senescent hearts. Preconditioning induced by transient ischemic stimulus and norepinephrine was abolished by alpha-adrenergic receptor blockade in both adult and senescent hearts. Thus, our data demonstrate that preconditioning is absent in aging heart and is probably related to the reduction of norepinephrine release and alpha-adrenergic receptor stimulation in response to ischemic preconditioning.

BACKGROUND Sarcolemmal Na(+)-Ca2+ exchange system is believed to be fundamental to the control of cardiac contractility. However, the relation between Na(+)-Ca2+ exchange and the control of contractile force has not been studied in senescent myocardium. METHODS The role of Na(+)-Ca2+ exchange in the regulation of the cardiac muscle's contractile force was studied in adult and senescent papillary muscles by simultaneously measuring intracellular sodium activity (aNai), action potential, and contractile force while varying extracellular concentration of sodium and/or calcium. RESULTS Reduction of [Na+]o decreased aNai from 8.0 +/- 1.8 to 4.1 +/- 0.8 in adult (-3.9 mM) and from 8.7 +/- 1.9 to 4.7 +/- 0.9 in senescent (-4.0 mM) papillary muscles, while developed tension (DT) increased by 80.2% in adult and by 135.6% in senescent papillary muscles (p < .01 vs adult). During low [Ca2+]o and high [Na+]o, aNai and DT modifications were similar both in adult and senescent papillary muscles. During high [Ca2+]o, aNai decreased to a similar extent in both adult and senescent papillary muscles, while DT increased by 37.8% in adult and by 67.8% in senescent (p < .05 vs adult). Simultaneous reduction of [Na+]o and [Ca2+]o decreased aNai from 8.1 +/- 1.2 to 6.8 +/- 1.1 mM in adult (-1.3 mM), and from 8.4 +/- 1.0 to 7.2 +/- 1.0 mM in senescent (-1.2 mM) papillary muscles while DT decreased by 22.1% in adult and by only 12.0% in senescent (p < .01 vs adult) papillary muscles. Simultaneous increase of [Na+]o and [Ca2+]o similarly increased aNai in both adult senescent papillary muscles, but decreased DT by 28.5% in adult and by 11.7% in senescent (p < .01 vs adult). After [Na+]o modifications, the equilibration time for the ratio of external and internal sodium ion activities was slowed in senescent papillary muscles (i.e., in low [Na+]o solution the equilibration time was 4.6 +/- 0.9 min in adult and 6.3 +/- 1.2 min in senescent papillary muscles, p < .001). CONCLUSIONS Similar changes of aNai during transmembrane Na+ and Ca2+ gradients modifications associated to changes in contractile force seem to demonstrate that Na(+)-Ca2+ exchange is probably not modified by the aging process. However, the slow equilibration time for the ratio of Na+ activities might reflect an age-related reduction of the Na(+)-K+ pump activity.

Background Hypertrophic cardiomyopathy (HCM) has different clinical and prognostic aspects in young than in adult patients. This study was undertaken to determine whether these reported differences are reflected by changes in ultrasonic backscatter parameters and whether oral treatment with verapamil modifies backscatter variables in children with HCM. Methods and Results Sixty-eight subjects underwent backscatter analysis to assess the ultrasonic myocardial reflectivity and the amplitude of the cardiac cycle–dependent variation of the backscatter power curve. Subjects were divided into four groups: 10 HCM and 23 normal subjects Conclusions These data demonstrate that in young HCM patients, the ultrasonic myocardial reflectivity is normal, in contrast to the significant increase observed in adult patients affected by the same disease. This observation is in accord with the different clinical manifestations reported in young HCM patients and indicates an age-dependent difference in the echogenic structure of the hypertrophied myocardium in HCM.

Previous studies have shown that acute exogenous administration of coenzyme ubiquinone (C0Q10) can protect the heart against oxidant-mediated injury. The aim of this study was to investigate whether protection against cardiac oxidative stress could be obtained by increasing tissue levels of CoQ10, as achieved by chronic CoQ10 supplementation.Wistar rats were randomly divided into two groups: a control group given standard diet and a test group receiving diet supplemented with CoQ10 (5 mg/kg/day) for 4 weeks. Functional and metabolic changes induced by oxidative stress were investigated in isolated perfused hearts and in papillary muscles. Tissue concentrations of ubiquinones were significantly higher in the left yentricle of treated rats than in controls. H202 infusion (60 ıtM for 60 mm) induced marked alterations of both developed pressure, which decreased to -58.8 ± 16.8% of base line and end-diastolic pressure which increased almost 13-fold. These effects were reduced significantly (P < .05) in hearts from CoQ10-supplemented rats (-13.8 ± 2.3 and +375.0 ± 42.5%, respectively). In the same hearts, cumulative release of oxidized glutathione (a specific marker of oxidative stress) was 450.2 ± 69.2 nmol/g of wet weight in the control group and only 89.6 ±22.3 nmol/g of wet weight in treated hearts (P < .01). In papillary muscles, after 60 mm of perfusion with H202, active tension decreased, largely in controls whereas it was almost unchanged in the treated group (-34.4 ± 7.5% of baseline vs. -0.1 ± 0.05%, P < .05). Resting tension also showed a remarkable increase in papillary muscles of the control group withrespect to treated ones (+600.5 ± 72.7% vs.+20.3 ± 6.7%, P< .005). Action potential duration was reduced in control with respect to treated hearts, reaching a maximum difference at 60 mm (-51 .4 ± 8.4% of baseline and -0.1 ± 0.03, P < .05), whereas amplitude showed a progressive reduction in control with respect to treated papillary muscles (-5.6 ± 1 .3% and -0.1 ± 0.02; P < .05). These effects were a specific consequence on oxidant injury, because inotropic and chronotropic responses to isoproterenol were not different between control and CoQ10-pretreated rats. Thus, our data demonstrate that chronic dietary supplementation of CoQ10 reduces cardiac injury produced by H202, as assessed by several indices. The marked reduction observed in oxidized glutathione release suggests that this protective action may occur via an antioxidant effect of increased tissue concentrations of ubiquinone.

To evaluate the safety and efficacy of delapril versus enalapril in patients with congestive heart failure (CHF), New York Heart Association (NYHA) class II and III, 198 patients were enrolled in a study in 13 centers involving a double-blind parallel group design. After completing a 2-week run-in period on placebo, patients were randomized to receive delapril 7.5 mg twice daily or enalapril 2.5 mg twice daily for 2 weeks. The dose was then doubled for the remaining 6 weeks. In this phase, 1 patient in each group experienced orthostatic hypotension; the dose was then reduced to the initial dose for study completion. A total of 195 patients received active treatment (96 delapril, 99 enalapril). After 8 weeks' treatment, bicycle ergometry demonstrated a significant increase in exercise duration (p0.01) and workload (p0.01). Echo Doppler investigations showed a significant reduction (p0.01) in left ventricular end-systolic volume associated with a significant increase (p0.01) in ejection fraction and cardiac output. No clinically significant changes in blood pressure, heart rate, electrocardiogram, or biochemical and hematologic tests were found. There were no significant differences between treatment groups. Three patients in each group experienced adverse reactions requiring withdrawal of 1 patient in each group. Delapril 15 mg twice daily, like enalapril 5 mg twice daily, was effective in improving signs and symptoms of CHF and was well tolerated.

We evaluated the efficacy and safety of gallopamil 150 mg daily in middle-aged and elderly patients with stable exertional ischemia, using a medium-term randomized double-blind cross-over placebo-controlled trial. Twenty middle-aged patients (52.8 +/- 6 years; range 38-61 years) and 14 elderly patients (67.4 +/- 2.8 years; range 65-73 years) with stable exertional ischemia underwent a bicycle exercise test. After a run-in period, both groups received treatment with either placebo or gallopamil 50 mg tid for 28 days. At the end of this time, each patient crossed over to the alternate regimen. Gallopamil significantly reduced heart rate, blood pressure and rate pressure product (from 15.37 +/- 2.7 to 13.65 +/- 4.16 U x 10(-3); p < 0.01) in elderly patients at submaximal exercise, but had no effect in middle-aged patients (from 14.52 +/- 4.45 to 13.49 +/- 3.77 U x 10(-3); p = NS). At peak exercise, none of the hemodynamic parameters was modified with gallopamil in either group. At peak exercise, both middle-aged and elderly patients achieved rate-pressure products similar to those reached during placebo at higher work loads. Exercise duration and maximal work load significantly increased in both groups. Electrocardiographic signs of ischemia were favorably influenced by gallopamil in both groups (from 1.39 +/- 0.5 mm to 0.76 +/- 0.73 mm; p < 0.001 in the middle-aged patients and from 1.5 +/- 0.34 mm to 1 +/- 0.76 mm; p < 0.01 in the elderly patients).(ABSTRACT TRUNCATED AT 250 WORDS)

Congestive heart failure (CHF) represents the most frequent cause of death and disability in the elderly. The prevalence of impairment of cognitive abilities is very high in aging and several clinical studies have demonstrated high association between cardiovascular diseases (in particular CHF) and cognitive deterioration. However, little attention has been paid to the decline of cognitive functioning during congestive heart failure in elderly patients. In this paper an overview of studies investigating this association is offered, suggesting that hemodynamic alterations due to heart failure and cognitive deteriorations are very frequently associated in aging, increasing morbidity and mortality risks. Moreover, preliminary results of a prospective study on hospitalized elderly patients with heart disease are reported (CHF Italian Study). These data show that some psychosocial variables (illiteracy, depression, and particularly cognitive deterioration) determine a significant increase of the risk to develop heart failure. This paper confirms that a multidimensional approach is necessary to better characterize and treat elderly patients, in particular those with CHF. More attention should be paid to encourage mild physical activity, to provide emotional support to patients and also to assess their general cognitive abilities. Studies on large populations of patients with heart disease have to be designed to investigate psychosocial and cognitive status in these patients.

Left ventricular diastolic filling by Doppler echocardiography was investigated in 84 diabetic patients without evidence of heart disease and in 84 normotensive nondiabetic age- and sex-matched control subjects. Diabetic patients were subdivided into two groups on the basis of the presence of arterial hypertension. Group 1 comprised 41 normotensive diabetic patients (19 men, 22 women, mean age 63.7 ± 9.1 years); Group 2 comprised 43 hypertensive diabetics (15 men, 28 women, mean age 65.6 ± 9.6 years). Doppler measures of diastolic filling were significantly altered in the two groups as compared with control subjects. Peak atrial flow velocity, velocity integral for the atrial filling period, and atrial filling fraction were increased, whereas the ratio of peak early to peak atrial flow velocity and the ratio of flow velocity integrals were decreased, especially in Group 2 patients. Thirteen patients in Group 1 (32%) and 17 in Group 2 (40%) had evidence of diastolic dysfunction, as assessed by the presence of at least two independent abnormal indices (outside age-corrected 95% confidence interval). In each group, patients with altered diastolic filling differed slightly from diabetic patients with normal Doppler indices, tending to increased wall thickness and left ventricular mass. In conclusion, diastolic filling of the left ventricle is frequently altered in diabetic patients and is adversely affected by arterial hypertension whose coexistence further impairs left ventricular relaxation.

Background: Higher neurohormonal activation levels are known markers of severity and adverse prognosis in heart failure (HF) patients. Classical linear indexes of heart rate variability (HRV) have been shown to be associated with neurohormonal activation.Whether and to what extent nonlinear Poincaré plot indexes (PPI) of HRV reflect similar relationship is not known. The purpose of the study was to assess the association of PPI with plasma norepinephrine (NPE) levels as compared with classical linear indexes of HRV. Methods: Ninety-nine stable mild-to-moderate HF patients in sinus rhythm (age: 51 ± 8 years, NYHA class II-III 88%, LVEF 24% ± 6%, VO2max during exercise tests 14 ± 4 mL/kg per minute) were studied. Each patient had a 24-hour Holter recording and, beside standard clinical and laboratory examinations, underwent plasma NPE assay within 1 week. The SDNN and the power in the low-frequency band (LFP; 0.04-0.15 Hz) were computed on consecutive 5-minute RR sequences; these linear indexes have been shown to have the highest prognostic value in HF patients. Poincaré plot indexes were obtained by automated quantification of the bidimensional length (L) and tridimensional (peak's number Np, radii of the semi-ellipse of inertia Px, Py, Pz) morphologic characteristics, with a technique whose good reproducibility has been previously shown by the authors. The association between HRV and neurohormonal indexes was assessed by Spearman correlation coefficient. Results: Norepinephrine, LFP, and SDNN were, respectively, (mean ± SD) 363 ± 210 pg/L, 162 ± 171 ms2, and 36 ± 15 milliseconds. Poincaré plot indexes were as follows: L = 576.5 ± 189.9 milliseconds; Np = 28.01 ± 19.38; Px = 56.36 ± 21.31 milliseconds; Py = 113.1 ± 29.44 milliseconds; and Pz =101.6 ± 43.36 milliseconds. Both SDNN and LFP showed a moderate but significant negative correlation with NPE levels (r = ???0.37 and ???0.44, respectively; P b .0001), whereas a weaker association was found for L, Np, and Py ranging from r = ???0.33 to ???0.25 (P although patterns of beat-to-beat variability quantified by PPI provide useful information in the assessment of cardiac autonomic control impairments, the power in the low-frequency band appears to reflect more closely the level of adrenergic activation of HF patients.

We evaluated the acute therapeutic effects of the oral administration of nifedipine (10 mg) and diltiazem (120 mg) alone and in combination in 16 patients with effort angina. The 16 patients (13 men and three women; mean age 59 +/- 7 years) performed a symptom-limited bicycle exercise stress test 3 h after placebo or active substance administration. Maximal work load, exercise duration and time to 1 mm ST segment depression were significantly increased and ST depression at peak exercise was significantly decreased by the combination of drugs. Nifedipine and diltiazem alone similarly improved exercise duration as markedly as their combination. One patient stopped the test after all three treatments for angina associated with ST depression2 mm. The combination of drugs yielded the best symptomatic effect: only four patients complained of angina in comparison to eight and seven patients after diltiazem and nifedipine, respectively. Nifedipine and diltiazem are effective and safe antianginal drugs. Some patients respond better to one drug than to the other. Patients who remain symptomatic in spite of maximal doses of a single drug may derive some benefit from combination therapy.

Objective: To evaluate the effects of mild to moderate hypertension and of LVH on diastolic filling and other Doppler indices in the elderly. Design: Survey with a control group. Subjects: Seventy-one hypertensives (34 men, 37 women) referred for echocardiograms and 32 age- and sex-matched normotensive volunteers. Thirty-six of the hypertensives had LVH; 34 did not. Setting: Echocardiography laboratory. Measurements: M-mode, two-dimensional, and pulsed Doppler echocardiograms. A wide variety of Doppler-derived indices of diastolic function were assessed. Results: All Doppler derived indices of left ventricular diastolic filling (peak E, peak A, their ratio, EF slope, time-velocity integrals, atrial filling fraction, and isovolumic relaxation time) were similar among the three groups. Conclusion: Elderly mild to moderate hypertensives with or without LVH have LV diastolic filling that is normal for age. The identification of pathological diastolic dysfunction requires comparison to age-matched controls, since aging, a major factor influencing diastolic filling, can mask the effect of hypertension.

A double-blind phase II study of propionyl-L-carnitine (CAS 17298-37-2) versus placebo was carried out on a group of 60 patients with mild to moderate (II and III NYHA class) congestive heart failure. The group was made up of men and women aged between 48 and 73 years in chronic treatment with digitalis and diuretics for at least 3 months and who still displayed symptoms. Thirty of these patients were chosen randomly and for 180 days, 500 mg of propionyl-L-carnitine was orally administered, 3 times a day in addition to their usual treatment. At basal conditions and after 30, 90 and 180 days the maximum exercise time was evaluated using an exercise tolerance test performed on an ergometer bicycle and the left ventricular ejection fraction was tested by means of bidimensional echocardiography. After one month of treatment, the patients treated with propionyl-L-carnitine, compared to the control group, showed significant increases in the values of both tests, increases which became even more evident after 90 and 180 days. At the stated times the increases in the maximum exercise time were 16.4%, 22.9%, and 25.9%, respectively. The ventricular ejection fraction increased by 8.4%, 11.6% and 13.6%, respectively. On the basis of these results, having studied the particular mechanism of action of propionyl-L-carnitine the authors conclude that it represents a drug of undoubted therapeutic interest in patients with congestive heart failure, in whom it could be efficaciously administered along with a standard pharmacological therapy.

The treatment of symptomatic chronic obstructive peripheral arteriopathies is a difficult task since it requires the prolonged administration of drugs which are often unable to correct the various pathogenetic factors reponsible for the disability. The authors, on the basis of recent studies demonstrating the rheological and vasoactive as well as metabolic activities of levocarnitine propionyl, have decided to use this substance in the treatment of arteriopathics affected by intermittent claudication. Levocarnitine propionyl administered orally to 142 arteriopathics affected by intermittent claudication was responsible for a marked increase in initial as well as absolute walking distances. It is particularly important to note that these clinical results were obtained primarily due to the metabolic activities of levocarnitine propionyl.

The response of coronary hemodynamics to the intracoronary (i.c.) bolus administration of gallopamil, 1.5 and 3.0 micrograms/kg, was evaluated in 14 patients with normal coronary arteries. Gallopamil, 3.0 micrograms/kg, induced a small and transient decrease in systolic and mean arterial pressure and a small increase in the preejection period. Coronary sinus blood flow increased significantly at 30 s (p less than 0.01) and returned to baseline 10 min after gallopamil administration. Coronary vascular resistance was still reduced at 10 min and returned to baseline at 15 min. Myocardial O2 consumption and extraction decreased significantly (p less than 0.01) at 30 s. While myocardial O2 consumption returned to baseline 15 min after gallopamil administration, myocardial O2 extraction was still significantly reduced at this time. Milder and more transient changes were observed after i.c. administration of the lower dose (1.5 micrograms/kg), and no significant changes were found after i.c. administration of saline. These data show that i.c. gallopamil, in patients with normal coronary arteries, induces direct, transient, and dose-related peripheral coronary vasodilation. The reduction of myocardial O2 consumption and extraction suggests a direct negative inotropic and metabolic effect of gallopamil.

We studied 40 subjects, 20 under 60 yrs old (10 normotensive and 10 hypertensive) and 20 over 60 yrs old (10 normotensive and 10 hypertensive). Each patient underwent a 24-hour ambulatory blood pressure monitoring (8:00 a.m. to 8:00 a.m.), by a noninvasive method using an ICR 5300 apparatus. Systolic blood pressure was significantly higher on random measurement and during the daytime in the older patients. Although comparison of the other parameters did not reveal significant differences, we noted a tendency to higher systolic values among the older group, and higher diastolic values in the younger one. The variability of the values was slightly higher, although not significantly, among the older patients. In both groups random systolic measurements, and in the younger group diastolic values as well, were significantly higher than mean 24 hour values. The incidence of abnormal systolic BP values ranged from 18.8% to 100% (mean 60.2% +/- 28.9) in younger hypertensives, and from 54% to 100% (mean 76.5% +/- 14.4) in older patients. The incidence of abnormal diastolic BP values ranged from 64.5% to 100% (mean 80.4% +/- 15.6) in younger patients and from 47.2% to 96% (mean 67.8% +/- 15.8) in older patients. The correlation between mean systolic and diastolic values recorded from 8:00 to 10:00 a.m., and mean 24-hour values was significant in young hypertensives, while in the older group there was a significant correlation only for diastolic BP. The lack of significance for systolic values is probably due to a greater variability in systolic pressure in elderly subjects during the morning.

Summary We studied the influence of exercise level, severity of coronary artery disease (CAD), presence of previous myocardial infarction (MI), anterior or diaphragmatic, on the clinical value of exertional Q wave changes (Delta-Q). We retrospectively evaluated the exercise electrocardiograms of 62 patients without angiographic evidence of CAD and 133 patients with CAD; 28 of them had single (SVD) and 105 multivessel disease (MVD). Forty-one patients had a previous diaphragmatic MI and 23 anterior. The sensitivity specificity and predictive value of Delta-Q were compared to the ST criterion. The exercise level affected Delta-Q. ST and Delta-Q had similar specificity and predictive values. The extent of CAD did not affect the sensitivity of Delta-Q and this method was better than ST to detect SVD patients. The Delta-Q criterion was equally as efficient as ST in MVD patients without MI and with diaphragmatic MI. The loss of septal forces on resting electrocardiograms made useless Delta-Q analysis on patients with anterior MI. The improvement of sensitivity in SVD patients by Delta-Q might be of clinical value since these latter are frequently not diagnosed by the ST criterion.

These experiments have been designed to study the influence of alanine infusion on glucose dynamics in the dog and to further elucidate the role of pancreatic hormones in the interaction of alanine with glucose homeostasis. The primed constant infusion of glucose-2-t was used in order to quanti ta te the rates of glucose production by the liver (Ra) and glucose utilization (Rd). In a first group of experiments, the intravenous infusion of alanine at the rate of 2 mg./kg./min. produced a moderate enhancement of plasma insulin (IRI), while pancreatic glucagon (IRG) increased more consistently. This different pattern of IRI and IRG response caused the insulin/glucagon molar ratio to decline progressively throughout the experiment. Both rates of glucose turnover increased significantly during alanine infusion. Since Ra rose more rapidly than Rd did initially, hyperglycemia developed. Later, glucose production slowly decreased and, in spite of the sustained hyperglucagonemia, reached levels very close to the baseline in the second part of the experiment. A significant direct correlation between Ra and IRG was found, while the changes in Ra correlated inversely with those in I/G molar ratio. In a second group of experiments, alanine was infused at the same dose together with 0.4 /mg./kg./min. of cyclic somatostatin. In the First part of the infusion, IRG fell more than IRI did, so that I/G ratio increased. Later, IRI levels maintained at low values while IRG returned slowly to the baseline and consequently I/G ratio significantly decreased. Glucose production fell rapidly soon after the beginning of the infusion, and therefore hypoglycemia developed. Later, Ra increased progressively to levels above baseline and plasma glucose returned to the preinfusion levels. As in the first group of experiments, a significant direct correlation between Ra and IRG and an inverse correlation between the changes in Ra and I/G ratio were observed. These experiments demonstrate that alanine infusion produces an acceleration of glucose turnover and that a clear interrelationship between the release of glucose by the liver and the mobilization of pancreatic hormones exists. Finally, the experiments with somatostatin indicate that hyperglucagonemia is one of the mechanisms underlying the stimulatory effect of alanine on glucose production.

In most arteriopathic patients, the release of a transitory ischemia in the affected limb reduces blood flow, instead of increasing it as in normal subjects. In this study the effects of propranolol administration on this paradoxical response have been investigated. After rheographic tracings were recorded in 14 arteriopathic patients in the basal condition and in the postischemic period, 10 mg of propranolol was administered IV and the protocol was then repeated. The blood flow in the affected area, measured as Jantsch's index of the rheographic tracings, was 0.63 ± 0.04 in the basal condition and was reduced to 0.51 ± 0.05 (P < 0.001) in the postischemic period. When the ischemia was repeated after propranolol administration, Jantsch's index rose from 0.57 ± 0.04 to 0.85 ± 0.09 (P < 0.01). The reversion of the paradoxical response to the ischemia induced by pro pranolol administration suggests that the beta-adrenergic blockade can increase blood flow to the ischemic area, probably through a constrictive action on arterovenous connections.

Hypoxia is the most effective and consistent stimulus to pulmonary hypertension in all species; however, the genesis of this phenomenon is still unclear. Histamine has been proposed as the possible mediator of this response and extensively studied. However, there remain doubts as to its behaviour in the different vascular districts during hypoxia. Accordingly, in seven dogs, histamine content was measured in the distal vena cava, hepatic vein, pulmonary artery and aorta; pulmonary artery pressure and systemic arterial pressure were also recorded. All measurements were repeated after 5 min of breathing a mixture containing 8% oxygen. Histamine content in the pulmonary artery blood was significantly increased during hypoxia (from 29 ± 3 to 36 ± 3 ng·cm−3 P

These experiments were carried out to study the influence of prostaglandin A1 (PGA1) on basal and glucose—stimulated insulin secretion in anesthetized dogs. During intravenous PGA1 infusion (0.25 μg/kg/ min), no changes in basal insulin levels occurred, in spite of the significant increase in plasma glucose and free fatty acids (FFA). Following iv glucose tolerance test (0.33 gAg), PGA1 treated dogs exhibited significantly higher plasma glucose and FFA levels and lower mean glucose disappearance rate than controls. An impaired insulin response to glucose loading was observed in dogs receiving PGA1 as shown by the plasma insulin concentrations and by the mean integrated insulin areas and insulinogenic index. The PGA1 infusion rate did not cause any modifications of the blood flow in splanchnic area, while it significantly reduced the systemic arterial pressure. These findings allow us to exclude that a modified pancreatic perfusion may be responsible for the inhibition of insulin secretory response.(Endocr...

OBJECTIVESTo investigate the effects of ischemic preconditioning in hearts from adult and both sedentary and trained senescent rats.BACKGROUNDIschemic preconditioning does not prevent postischemic dysfunction in the aging heart, probably because of reduction of cardiac norepinephrine release. Exercise training can reverse the age-related decrease of norepinephrine production.METHODSWe investigated the effects on mechanical parameters of ischemic preconditioning against 20 min of global ischemia followed by 40 min of reperfusion in isolated perfused hearts from adult (six months) and sedentary or trained (six weeks of graduated swim training) senescent (24 months) rats. Norepinephrine release in coronary effluent was determined by high-performance liquid cromatography.RESULTSFinal recovery of percent-developed pressure was significantly improved after preconditioning in adult hearts (91.6 ± 9.6%) versus unconditioned controls (54.2 ± 5.1%, p < 0.01). The effect of preconditioning on developed pressure recovery was absent in sedentary but present in trained senescent hearts (39.6 ± 4.1% vs. 64.3 ± 7.1%, p < 0.05). Norepinephrine release significantly increased after preconditioning in adult and in trained but not in sedentary senescent hearts. The depletion of myocardial norepinephrine stores by reserpine abolished preconditioning effects in adult and trained senescent hearts.CONCLUSIONSIn adult and trained but not in sedentary senescent hearts, preconditioning reduces postischemic dysfunction and is associated with an increase in norepinephrine release. Preconditioning was blocked by reserpine in both adult and trained senescent hearts. Thus, exercise training may restore preconditioning in the senescent heart through an increase of norepinephrine release.

SummaryThe effectiveness of a new potent diuretic, xipamide, was evaluated in the treatment of patients with mild to moderate essential hypertension. The effects of daily doses of 40 mg xipamide were compared with those of 100 mg chlorthalidone with respect to systolic and diastolic blood pressure, using a double-blind crossover design. Patients received each drug for 6 weeks, the order of treatments being at random and the periods being separated by a ‘washout’ period of 7 days. The results showed that xipamide was as effective as chlorthalidone in controlling blood pressure, both in the upright and supine positions, and when administered after chlorthalidone produced a further reduction. No such further reduction occurred when chlorthalidone was given after xipamide. Serum electrolyte changes induced by the two diuretics were comparable. Both drugs were well tolerated and caused few side-effects.

In order to evaluate whether the changes in the electrical systole/electromechanical systole ratio (QT/QS2) may reflect the effects of beta-adrenergic stimulation on the heart, we studied the variations of this ratio induced by active standing. We studied 45 healthy volunteers aged 15 to 82 years, subdivided into three groups; Group 1 (mean age 22 +/- 4 years), Group 2 (mean age 44 +/- 6 years), and Group 3 (mean age 74 +/- 6 years). Fifteen subjects repeated the test after propranolol administration (0.1 mg/kg iv). Resting QT/QS2 ratio increased slightly, but not significantly, with age. Upright position significantly increased QT/QS2 ratio in all groups. Changes in heart rate (r = -.43), electromechanical systole (r = .55) and QT/QS2 were significantly correlated with age. Propranolol prevented the increase in QT/QS2 ratio induced by active standing. Therefore, QT/QS2 changes induced by standing are correlated with age and are inhibited or reduced by beta-blockade. QT/QS2 changes can be used to monitor adrenergic activity, even if their value is limited by the overlapping responses of the individual cases.

It has been previously shown that among patients with premature ventricular contractions (PVCs) there is a high risk of sudden death (SD). This study was designed to assess whether any electrocardiographic pattern of PVCs was associated with an increased risk of SD. Moreover, among patients with PVCs the influence of the different coronary risk factors on the incidence of SD was also studied.Two-hundred and thirty-two patients admitted to our hospital during a period of 3 years, who presented PVCs in the electrocardiogram on admission were followed for at least 30 months. Among these patients there were 47 SD. A higher incidence of SD has been found among patients with RR' of less than 360 msec (35.7% as compared with 18%, p

One-hundred and seven exercise stress tests and coronary angiograms were reviewed retrospectively, in order to evaluate the usefulness of R wave amplitude changes (ΔR) during exercise compared with ST segment depression in the screening of patients with coronary artery disease (CAD). We also attempted to correlate ΔR with the severity of CAD as expressed by coronary arteriography and left ventriculography. Thirty-six patients showed no coronary artery narrowing (0-V); the remaining 71 patients with stenosis of 70% of at least one of the major coronary arteries were divided into three groups. Sixteen patients had single vessel disease (1-V); five (31%) in this group showed abnormal left ventricular wall motion. Thirty-one patients had two-vessel disease (2-V); 22 (71%) of the 31 demonstrated abnormal left ventricular wall motion. Twenty-four patients had three-vessel disease (3-V); 20 (83%) of the 24 showed abnormal left ventricular wall motion. We considered ΔR values ≥ 0 and ST segment depression ≥ 1 mm. significant for diagnosis of CAD. The sensitivity of the ΔR method in predicting CAD was superior to the method based upon ST segment depression; however, the latter was significantly (P We found ΔR values ≥ 0 more frequently in the 2-V and 3-V groups as compared with the 1-V group. Patients of the 2-V and 3-V groups had a significantly higher incidence of abnormal left ventricular wall motion (P Even though the accuracy of the ΔR method was greater in more severe CAD, it seems to be offset by a concomitant decrease in specificity.

This study was performed to determine if QT prolongation before and during early exercise is related to the occurrence of exercise-induced ventricular arrhythmias (EIVA). EIVA occurred in 47 of 142 patients with angiographic evidence of coronary artery disease (CAD); no EIVA occurred among the 22 patients without CAD (OV). Resting QTc and QT intervals during early exercise were similar in patients without EIVA, irrespective of the presence or absence of CAD; however resting QTc was significantly longer in CAD patients who showed EIVA (443 +/- 40 ms; P less than 0.01) than in CAD patients without EIVA (424 +/- 37 ms) and in OV patients (421 +/- 32 ms). During early exercise, the QT interval remained significantly longer in patients with than in those without EIVA. There was a trend toward increasing resting QTc in patients who exhibited EIVA more severe than grade 3. When resting QTc was longer than 440 ms, subsequent EIVA were correctly predicted in CAD patients with a sensitivity of 43%, a specificity of 72% and a predictive accuracy of 63%. Thus, a trend toward longer resting QTc values exists in CAD patients who develop EIVA; however, a long resting QTc (greater than 440 ms) appears to be only a weak predictor of subsequent EIVA.

The vascular steal phenomenow, that is, the shunting of blood from ischemic to normally perfused areas, is commonly observed during exercise in the affected limbs of patients with peripheral arterial insufficiency. Propranolol was administered to 18 arteriopathic patients before the exercise to ascertain whether the reverse situation can be induced. The results indicate that before propranolol administration, Jantsch's index (used to quantify the plethysmographic waves) decreased from 0.53 +/- 0.05 to 0.33 +/- 0.04 (P less than 0.001) at 1 minute, and to 0.38 +/- 0.04 (P less than 0.001) at 5 minutes after the end of the exercise. When the exercise was repeated after propranolol, Jantsch's index did not change. These findings indicate that propranolol can inhibit exercise-induced vascular steal.

1. The reflex control of arginine-vasopressin release was studied in 12 essential established hypertensive patients and in 12 age-matched normal subjects by comparing the effects of head-up tilt and a variable-pressure neck-chamber. 2. After 45 min 85° head-up tilt, normal subjects showed an increase in plasma arginine-vasopressin and in plasma renin activity, while plasma volume decreased. In hypertensive patients, plasma arginine-vasopressin showed changes after tilt opposite to those of controls, while the changes in plasma renin activity and plasma volume were similar to those observed in the normal group. In both groups the changes in systolic and diastolic blood pressure were not statistically significant. A reduction in carotid sinus transmural pressure obtained by increasing neck-tissue pressure (+ 50 mmHg) by means of a neck-chamber, evoked different responses in mean blood pressure in the two groups, but failed to induce any significant change in plasma arginine-vasopressin concentration both in the normal and in the hypertensive subjects. 3. These results seem to suggest that carotid sinus baroreceptors, though active in blood pressure control, do not play a direct role in arginine-vasopressin release and, therefore, the opposite response of arginine-vasopressin observed after tilt in the two groups of subjects should be ascribed to more complex mechanisms.

The intravenous infusion of prostaglandin (PG) E1, E2, and A1 into normal rats at a dose of 2 μg/min significantly lowered plasma insulin levels with a tendency to recovery in the post-infusion period. Whereas PGA1 infusion resulted in a moderate but significant hypoglycaemia, the administration of E-series PGs always produced a hyperglycaemic effect. The interference of PGE1 on insulin response to classical insulinogogues (glucagon, aminophylline, and tolbutamide) was also investigated. The results of these experiments demonstrate that PGE1 exerts an inhibitory action on insulin response to all insulin releasing agents investigated. As regards the haemodynamic effects of PGs, PGE1 and PGE2 lowered the arterial blood pressure by about 20%, while PGA1 was almost completely ineffective. On the other hand, the lowering effect of PGE1 on circulating insulin levels remained unchanged in rats treated with reserpine. These findings thus rule out a sympathetic over-activity secondary to the lowered arterial blood pressure as the mechanism of action of PGE1. A possible direct interference with the adrenergic receptor system of the pancreatic islets was also ruled out since the inhibitory effect of PGE1 was not overcome by phentolamine pre-treatment.

We evaluated the changes in regional coronary hemodynamics induced by diltiazem, 0.25 mg/kg intravenously, in nine patients with 75% to 90% diameter stenosis of the left anterior descending coronary artery (LAD) (group 1) and in 10 patients with 100% occlusion of the LAD and collaterals to the distal LAD (group 2). Although diltiazem induced similar changes in systemic hemodynamics in the two groups, a decrease in anterior coronary vascular resistance (ACVR) and an increase in great cardiac vein flow (GCVF) were observed after administration of diltiazem in all patients in group 1 but in only 6 of 10 patients in group 2 (subgroup 2B). ACVR increased and GCVF decreased after administration of diltiazem in 4 of 10 patients in group 2 (subgroup 2A). Clinico-angiographic characteristics, origin of collaterals, and diltiazem-induced changes in systemic hemodynamics were similar in subgroups 2A and 2B. Thus diltiazem increases coronary flow distal to a stenotic coronary artery but can decrease regional coronary flow and increase regional coronary resistance in a minority of patients with an occluded coronary artery supplied by collaterals, probably through a steal mechanism.

To characterize further the role of glucagon in the glucoregulatory response to hypoglycemia, the changes in the hepatic glucose production (Ra) and tissue uptake (Rd) after the injection of insulin (100 mU, i.v.) were measured in control and somatostatin-treated rats by using the primed constant infusion of glucose-2-3H. The physiologic glucagon hypersecretion due to hypoglycemia observed in controls was completely abolished by somatostatin. Hypoglycemia was slightly more pronounced in SRIF-treated rats than in controls; however, a clear tendency to recovery was recorded in both groups. Although the morphology of Ra response-curves was similar, the values of Ra were significantly lower in SRIF-treated rats throughout the experimental period. Glucose uptake showed in rats receiving somatostatin an initial increase of the same magnitude as in controls, but later it decreased more consistently. If the tissue sensitivity to insulin effect was expressed as metabolic clearance rate, no appreciable difference was recorded. These studies provide direct evidence that glucagon is involved in the metabolic reaction to insulin-induced hypoglycemia. However, the tendency to recovery from hypoglycemia shown by glucagon-deficient rats suggests that factors other than glucagon must play a more prominent role in the maintenance of glucose homeostasis in emergency situations such as represented by hypoglycemia induced by a large dose of exogenous insulin.

We correlated the incidence and degree of exercise induced ventricular arrhythmias (EIVA) with the angiographic severity of coronary artery disease (CAD) in 162 patients with a history of stable effort angina, all showing a positive exercise stress test for myocardial ischemia and a greater than or equal to 70% stenosis of a major coronary artery. Patients were grouped according to the following criteria: presence of electrocardiographic evidence of old transmural myocardial infarction (MI), number of significant coronary stenoses and number of left ventricular (LV) areas showing abnormal segmental wall motion (ASWM). The incidence of EIVA in patients with multivessel CAD was higher than in patients with single vessel CAD, but this difference was not statistically significant. The number of LV areas with ASWM was better correlated with the frequency of EIVA, which was 20.0% in patients with normal LV wall motion, 31.2% in patients with 1 area of ASWM, 54.0% in patients with 2 areas of ASWM (p less than 0.005 vs normal LV wall motion), 74.1% in patients with 3 or more areas of ASWM (p less than 0.001 vs normal LV wall motion and 1 area of ASWM), and 81.8% in patients with LV aneurysm (p less than 0.001 vs normal LV wall motion and 1 area of ASWM, p less than 0.005 vs 2 areas of ASWM). Patients with old MI showed a significantly higher incidence of EIVA than those without MI (p less than 0.001), but this difference was due to the more severe LV asynergy in the MI group. In conclusion, our results show that, in a selected population of patients with CAD, the incidence of EIVA correlates better with the extent of LV segmental wall motion abnormalities than with the number of diseased coronary arteries or the presence of an old transmural MI.

In order to evaluate the clinical implications of QT/QS2 ratio during manoeuvres of sympathetic stimulation we studied the effects of handgrip (75% of maximal voluntary contraction) in 18 middle-aged normal subjects and in 16 patients with previous myocardial infarction. We also evaluated the effects of propranolol (0.1 mg/kg i.v.) in all normal subjects and in 10 of the 16 patients with coronary artery disease. At rest the two groups had similar heart rate, blood pressure, QT, QS2 and QT/QS2 ratio values. A significant increase in heart rate and systolic blood pressure was recorded during handgrip both in normal subjects and in patients with coronary artery disease; QT/QS2 significantly increased in normal subjects but did not show significant variations in patients with coronary artery disease, with significant differences between the two groups at peak exercise. Handgrip-induced QT/QS2 changes showed a marked variability both in normal and diseased subjects. After propranolol, QT/QS2 showed no significant difference at peak exercise in the two groups. The variability of ratio changes was nullified by the administration of the drug. These findings suggest that handgrip-induced QT/QS2 changes might be an expression of beta-adrenergic discharge. The clinical value of handgrip-induced QT/QS2 changes in detecting patients with coronary artery disease is limited by the variability of the response of the ratio observed in the two groups.

The primed constant infusion of glucose-2−3H was used to study the influence of prostaglandins (PGs) infusion (2μg./min.) on glucose turnover in intact rats in the postabsorptive state. While PGA1 did not exert any appreciable effect on glucose production by the liver and on plasma glucose levels, prostaglandins of E-series significantly increased hepatic glucose output and consequently plasma glucose levels. In this regard, PGE1 appeared more effective than PGE2. In some experiments PGE1 was infused for two hours at the dose of 1.5μg./xmin.: glucose concentration rose to a maximum of 127 per cent above the control values and glucose production reached during the second hour of the infusion a level twice the base line (from 8.1 ±0.5 to 16.9±0.5 mg./kg. body weight/min.). These changes were paralleled by a proportional increase in glucose uptake by peripheral tissues which reached a level very near to that of hepatic output toward the end of the infusion.

The antianginal effects of 360 mg/day of diltiazem were evaluated, using intrapatient comparisons, in a double/blind, randomized, placebo/controlled trial in 24 young patients (50 +/- 7 years) and in 16 elderly patients (67 +/- 3 years) with stable effort angina. All patients had angiographic documentation of significant coronary artery disease. An open-labelled, randomized, crossover design was employed. For 1 week prior to beginning the study, the patient was on no medication except sublingual nitrates. The study consisted of an initial 2-week single-blind placebo run-in period followed by a 4-week randomized double-blind crossover between diltiazem, 120 mg t.i.d., and placebo. A diary of chest pain and nitroglycerin usage was kept during this period and run-in. Exercise tests were carried out during the run-in period (2 tests) and at the end of the 4-week treatment. After diltiazem 12 of the 24 young patients stopped the exercise test because of angina. A similar number (9/16) of elderly patients stopped the exercise test because of angina. During diltiazem treatment, weekly angina frequency was significantly reduced in the young patients (1.25 +/- 0.67 vs 3.87 +/- 1.19-run-in, 4.08 +/- 1.24-placebo; p less than 0.01) and in the elderly patients (0.87 +/- 0.71 vs 4.06 +/- 1.48-run-in, 4.12 +/- 1.5-placebo; p less than 0.01). Weekly TNT consumption significantly decreased in both groups of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial asynergies detected by two-dimensional echocardiography during intravenous administration of Dipyridamole (0.75 mg/kg) were evaluated in 54 patients referred for angiographic evaluation of chest pain. Technically adequate two-dimensional echocardiograms suitable for analysis were recorded in 42 of 54 (77.7%) patients studied. Thallium-201 myocardial perfusion scintigraphy, during dipyridamole test was performed in the same patients. Thirty of the 42 patients studied showed significant coronary narrowing at cardiac catheterization. Dipyridamole-induced wall motion abnormalities and myocardial perfusion defects were detected, respectively, in 19 (63.3%) and 21 (70%) of 30 patients with significant coronary artery disease. Wall by wall comparison of the distribution of dipyridamole-induced echocardiographic asynergy with reversible thallium-201 (/sup 201/Tl) perfusion defects demonstrated complete correlation in 42 segments examined. Three segments with perfusion defects at thallium scanning did not show asynergy during the test while two segments showing wall motion abnormalities during dipyridamole infusion did not manifest perfusion defects. Our study demonstrates that two-dimensional echocardiography during dipyridamole testing is useful in detecting patients with coronary artery disease. Furthermore, ventricular asynergies detected during the test show a high correspondence with site of myocardial perfusion defects at thallium scanning.

This study was designed to evaluate the usefulness of non-invasive parameters in the follow-up of cardiopathic patients without valvular cardiac diseases. In 49 patients suffering from heart disease we have studied the changes of radiologic cardiac measurements and systolic time intervals (STI) in the 4 functional classes of the NYHA classification, investigating also the existence of any relationship between these different parameters. Only the patients in the 3rd and the 4th functional classes showed significant changes in STI and radiologic measurements, as compared with the control group. Moreover, significant negative correlations have been observed between relative heart volume and LVET (r = 0.69, P less than 0.001) and LVETc (r = 0.82, P less than 0.001) and positive correlations between relative heart volume and PEP (r = 0.59, P less than 0.01) and PEP/LVET ratio (r = 0.75, P less than 0.001). These results, while confirming the close correlation between STI and cardiac performance, seem to demonstrate that relative heart volumetry is a fairly accurate index of the cardiac conditions in non-valvular heart diseases.