Protective effect of nisoldipine on dipyridamole-induced myocardial ischemia: correlation with exercise electrocardiography.

BACKGROUND: Nisoldipine, a dihydropyridine calcium channel blocker with strong coronary dilatative action, is commonly used in the treatment of myocardial ischaemia; its beneficial effect on effort angina has been demonstrated by several previous reports. Infusion of dipyridamole in doses sufficient to provoke myocardial ischaemia in patients with significant coronary artery disease is used safely in imaging studies for diagnostic purposes. OBJECTIVE: To evaluate the potential effect of nisoldipine on dipyridamole-induced ischaemia and to compare the results with the effect of nisoldipine on exercise-induced ischaemia. METHOD: Twelve patients (10 men and two women, mean age 62 +/- 8 years) with significant coronary artery disease (at least 70% lumen reduction in at least one major coronary vessel) were selected for inclusion in the study. In accordance with the inclusion criteria, the patients exhibited an ischaemic diagnostic response to a multistage exercise electrocardiography stress test (> 0.15 mV ST segment depression compared with the resting electrocardiographic tracing) and to a dipyridamole-echocardiography test (transient left ventricular dyssynergy of contraction during infusion of dipyridamole up to 0.84 mg/kg over 10 min), after 3 days' cessation of antianginal treatment. After treatment with oral nisoldipine (10 mg twice daily) was introduced, the patients repeated the two tests, within 18 days of the first evaluation. RESULTS: The dipyridamole-echocardiography test was positive for ischaemia in 12 patients who were not receiving nisoldipine and in eight patients who were receiving the drug (100% and 67% respectively, P < 0.05). In the eight patients who gave positive dipyridamole-echocardiography tests both with and without treatment, dipyridamole time (time to onset of dyssynergy during the test) increased from 7.9 +/- 2.9 min to 10.2 +/- 3.1 min (P < 0.01). In these patients, no significant changes were observed, at ischaemia, in the severity and extent of induced dyssynergy, evaluated as wall motion score index (each of 16 left ventricular segments scored from 1 = normal to 4 = dyskinetic) after treatment (score variations from baseline to ischaemia: 0.20 +/- 0.11 without nisoldipine and 0.16 +/- 0.06 with nisoldipine; NS). Variations in dipyridamole time (arbitrarily considered to be 15 min in the negative dipyridamole-echocardiography test) were significantly correlated with variations in exercise time (duration of exercise to exhaustion or diagnostic positive response on the electrocardiogram): r = 0.75 (P < 0.01). No significant differences were recorded in rate-pressure product (beats/min x mmHg x 100) at peak ischaemia between patients who were or were not receiving nisoldipine, during either the exercise electrocardiography stress test (233 +/- 36 with nisoldipine and 244 +/- 39 without nisoldipine; NS) or the dipyridamole-echocardiography test (147 +/- 21 with nisoldipine and 133 +/- 30 without nisoldipine; NS). CONCLUSION: Nisoldipine treatment can protect from dipyridamole-induced ischaemia, being associated with a longer stress time, and completely preventing the development of ischaemia in some patients. The therapy-induced changes in ischaemic threshold during the dipyridamole-echocardiography test correlate with variations in exercise tolerance.

Increased myocardial ultrasonic reflectivity is associated with extreme hypertensive left ventricular hypertrophy: a tissue characterization study in humans.

We assessed myocardial reflectivity pattern in a large spectrum of left ventricular mass values, covering the extremes from absent to severe myocardial hypertensive hypertrophy. Quantitatively assessed ultrasonic backscatter is an index of ultrasonic tissue characterization directly related to the morphometrically evaluated collagen content in humans. We enrolled 88 essential hypertensives. With an echo prototype implemented in our Institute, integrated values of the radiofrequency signal of myocardial walls were obtained and normalized for those of the pericardium (Integrated Backscatter Index, IBI, %). Left ventricular mass index (LVMI) was measured by Devereux formula. There was a weak correlation between septal IBI and LVMI (r = 0.35; P < .001). On the basis of LVMI values, three groups of hypertensives were identified, with absent (Group I, n = 23; LVMI < 125 g/m2), mild to moderate (Group II, n = 44; LVMI from 125 to 174 g/m2), or severe (Group III, n = 21; LVMI > 175 g/m2) left ventricular hypertrophy. The Integrated Backscatter Index in the septum was lower in patients of Group I (IBI = 23.3% +/- 3.6%) and II (IBI = 26.5 +/- 7.6; P = NS v Group I), in comparison with patients of Group III (IBI = 31.1 +/- 5.9; P < .02 v II; P < .0001 v I). An increased myocardial wall reflectivity is detectable only in the presence of extreme forms of hypertensive left ventricular hypertrophy.

Hyperkinetic ventricular arrhythmias in very elderly people with and without cardiac disease. Correlation with left ventricular echocardiographic parameters.

BACKGROUND: Morphological and functional changes induced by aging can hamper a clear distinction between pathological or paraphysiological phenomena in very old people. The incidence of hyperkinetic ventricular arrhythmias, for example, progressively increases in the elderly, even in the absence of overt cardiac disease. METHODS: One-hundred fifty-two clinically stable patients older than 80 years, submitted within 15 days to clinical evaluation, 24-hour continuous ambulatory ECG monitoring and echo Doppler examination, in the absence of antiarrhythmic treatment, were retrospectively selected in order to evaluate the incidence of ventricular arrhythmias, in patients with and without significant heart disease. The further aim of the study was to correlate the number of arrhythmias with left ventricular morphological and functional parameters, echocardiographically assessed. From the initial population, 80 patients (41 males, age 83 +/- 3 years) had significant heart disease (ischemic, hypertensive or valvular): Group I. Seventy-two patients (30 males, age 83 +/- 3 years) had no clinical or instrumental signs of heart disease: Group II. RESULTS: Considering echocardiographic data, Group I patients had a significantly higher left ventricular end-diastolic diameter (52 +/- 6 mm vs 47 +/- 4 mm, p < 0.01), lower ejection fraction (57 +/- 10% vs 64 +/- 6%, p < 0.01) and higher mass (275 +/- 84 g vs 208 +/- 46 g, p < 0.01), when compared with Group II. From ECG monitoring data, significant differences between the two groups were recorded in the incidence of premature ventricular beats per hour (79 +/- 163 vs 15 +/- 34, Group I vs Group II, p < 0.01) and presence of complex phenomena (couplets, triplets and runs: 51% vs 22%, p < 0.01). In old patients with documented cardiac disease a significant correlation was present between premature ventricular beats incidence and left ventricular end diastolic diameter (r = 0.39, p < 0.05) and left ventricular ejection fraction (r = 0.40, p < 0.05), while in patients without heart disease, no significant correlation was found between incidence of premature ventricular beats and echocardiographic morpho-functional parameters. CONCLUSIONS: In conclusion, hyperkinetic ventricular arrhythmias are globally frequent in old persons of very advanced age (more than 80 years), but, also in this subset, a significant distinction in terms of incidence and severity of arrhythmias is present between subjects with and without cardiac disease. A significant correlation between incidence of premature beats and non-invasive morpho-functional left ventricular parameters is present only for patients with overt heart disease.

The atropine factor in pharmacologic stress echocardiography. Echo Persantine (EPIC) and Echo Dobutamine International Cooperative (EDIC) Study Groups.

OBJECTIVES: This study sought to compare, head to head, the two most popular pharmacologic stress echocardiographic tests--dipyridamole and dobutamine--with state of the art protocols in a large multicenter prospective study. BACKGROUND: In the continuing quest for ideal diagnostic accuracy, pharmacologic stress echocardiography has quickly moved over the years from low to high dose regimens and is currently performed with atropine coadministration. METHODS: Dobutamine (up to 40 microgram/kg body weight per min) plus atropine (up to 1 mg over 4 h) and dipyridamole (up to 0.84 mg/kg per min over 10 h) plus atropine (up to 1 mg over 4 h) stress echocardiography was performed on different days, in random order and within 1 week in 360 patients with chest pain syndrome. Thirteen different echocardiographic laboratories, all fulfilling quality control criteria for stress echocardiographic reading, contributed to the study. RESULTS: No major complications occurred during either test. The test was interrupted before achievement of predetermined end points for limiting side effects in 37 dobutamine-atropine and 7 dipyridamole-atropine stress echocardiographic studies (feasibility 90% vs. 98%, p < 0.01). Diagnostic accuracy was assessed in a subset of 110 patients with no obvious rest dyssynergy (akinesia or dyskinesia) who underwent coronary angiography independently of test results and within 1 week of testing. Significant coronary artery disease (> or = 50% diameter reduction in at least one major coronary vessel by quantitative coronary angiography) was found in 92 patients. Sensitivity for detection of coronary artery disease was 84% (77 of 92) for dobutamine-atropine and 82% (75 of 92) for dipyridamole-atropine stress echocardiography (p = NS), with a specificity of 89% (16 of 18) for dobutamine-atropine and 94% (17 of 18) for dipyridamole-atropine stress echocardiography (p = NS). A significant correlation was present between peak wall motion score index during dipyridamole-atropine and dobutamine-atropine stress echocardiography (r = 0.83, p < 0.0001). CONCLUSIONS: Dobutamine-atropine and dipyridamole-atropine stress echocardiography are safe and feasible, although submaximal studies are more frequent with dobutamine. The two stresses have comparable accuracy in the detection of angiographically assessed coronary artery disease, although dobutamine is marginally more sensitive and dipyridamole marginally more specific. Stratification of the ischemic response in the space domain is also comparable with the two stresses.

Regression of hypertensive myocardial hypertrophy does not affect ultrasonic myocardial reflectivity: a tissue characterization study.

OBJECTIVE: Ultrasonic backscatter from the myocardial walls is directly related to the morphometrically or biochemically evaluated collagen content in man, and shows a normal pattern of quantitatively assessed ultrasonic backscatter in hypertensive patients, even in the presence of left ventricular hypertrophy. Whether the pharmacologically induced regression of left ventricular hypertrophy in hypertensive patients is accompanied by a disproportionate increase in relative connective tissue content is not yet known. The objective of the present study was to assess the effects of regression of left ventricular hypertrophy on the quantitatively evaluated myocardial reflectivity in essential hypertensives. DESIGN: We evaluated 19 mild-to-moderate essential hypertensives with echocardiographically assessed left ventricular hypertrophy, before and after 8 months' effective antihypertensive therapy with 20-40 mg enalapril once a day, associated with diuretics or calcium antagonists, or both, in six patients to achieve optimal blood pressure control. Using a modified echo machine developed in the Institute of Clinical Physiology, Pisa, an on-line radio-frequency analysis was performed to obtain quantitative operator-independent measurements of the integrated backscatter signal of the ventricular septum and the posterior wall. The integrated values of the radio-frequency signal from the myocardial walls were normalized for those from the pericardial interface and were expressed as percentages (integrated backscatter index). RESULTS: In comparison with baseline, the treated hypertensives showed significant decreases in mean blood pressure, left ventricular mass index, and septal and posterior wall thickness. However, integrated backscatter index values were similar at baseline and after therapy for both the septum and the posterior wall. CONCLUSION: Antihypertensive therapy with enalapril does not increase myocardial reflectivity, although it does induce regression of left ventricular hypertrophy. This suggests that, in accord with experimental data, regression of hypertrophy is achieved by enalapril through a proportionate regression of the myocyte and connective tissue components of the myocardium.

Normal ultrasonic myocardial reflectivity in hypertensive patients. A tissue characterization study.

Ultrasonic backscatter of myocardial walls is directly related to the morphometrically evaluated collagen content in humans. The integrated backscatter is also increased in hypertrophic cardiomyopathy, whereas it gives normal values in the physiological hypertrophy of elite athletes. We assessed the quantitatively evaluated myocardial reflectivity in 46 mild to moderate, clinically uncomplicated essential hypertensive patients, with echocardiographically assessed normal regional and global left ventricular function, and 22 age- and sex-matched normotensive control subjects. With an echo prototype implemented in our institute, we performed an on-line radiofrequency analysis to obtain quantitative operator-independent measurements of the integrated backscatter signal of the ventricular septum and posterior wall. The integrated values of the radiofrequency signal of myocardial walls were normalized for those of the pericardial interface and expressed as a percent (integrated backscatter index). Hypertensive patients and control subjects differed in mean blood pressure (119 +/- 11 versus 95 +/- 5 mm Hg, p < 0.001) and left ventricular mass index (134 +/- 31 versus 105 +/- 21 g/m2, p < 0.001). However, integrated backscatter index overlapped for both the septum (28 +/- 17% versus 25 +/- 6%, p = NS) and the posterior wall (13 +/- 7% versus 13 +/- 4%, p = NS). In the hypertensive group, there was no detectable correlation between septal integrated backscatter index and either septal thickness (r = -0.26, p = NS) or mean arterial pressure (r = -0.14, p = NS). Hypertensive patients showed a normal pattern of quantitatively assessed ultrasonic backscatter, even in the presence of left ventricular hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Activation of sympathetic tone during dipyridamole test.

Cardiac imaging with dipyridamole infusion has been proposed as an exercise-independent tool for the diagnosis of coronary artery disease. Dipyridamole acts through the accumulation of adenosine, which reduces sympathetic tone in vasomotor nuclei of the brainstem and inhibits norepinephrine release in noradrenergic neurons but also activates arterial chemoreceptors. The aim of this study was to assess whether dipyridamole administration (up to 0.84 mg/kg over 10 minutes, a dosage commonly employed for diagnostic testing) may modulate sympathetic activity either directly or indirectly through blood pressure reduction or myocardial ischemia, which may be evoked by dipyridamole infusion and represent two recognized sympathetic stimuli. Twenty patients were studied with infusion combined with two-dimensional echocardiography and 12-lead ECG monitoring. Blood pressure was recorded each minute by a cuff sphygmomanometer. In all patients, we obtained venous blood samples for epinephrine (an index of adrenomedullary catecholamine release) and norepinephrine (an index of neuronal activity) both in resting conditions and at peak dipyridamole, ie, at the first minute after termination of dipyridamole infusion in negative cases or in the presence of obvious ischemia in positive cases (ie, as soon as a regional ventricular dyssynergy or an ST segment depression greater than 0.1 mV appeared). Epinephrine and norepinephrine determinations were made by a high performance liquid chromatography (HPLC) method. After dipyridamole, there was a significant rise in norepinephrine, while epinephrine did not change significantly. Dipyridamole-induced percentage variations of norepinephrine from baseline were not significantly correlated with mean blood pressure changes (r = .1, p = ns) and were of a similar extent in patients with (n = 10) and without (n = 10) dipyridamole-induced ischemia (+68 vs +73 percent, p = ns). Dipyridamole administration provokes an activation of sympathetic tone which can be detected even in the absence of myocardial ischemia and is not related to blood pressure changes. The increased catecholamine release appears to be of neuronal rather than adrenomedullary origin.

Atrial natriuretic factor in essential hypertension: echocardiographic and humoral correlates.

Aim of this study was to assess the relationship between plasma concentration of atrial natriuretic factor (ANF) and its two-dimensional echocardiographic (left ventricular mass, left atrium diameter) and humoral (plasma renin and aldosterone) variables in essential hypertension (EH). We evaluated 32 patients with uncomplicated mild to moderate EH and 10 controls. They were studied in the supine position after 7 days of constant dietary sodium intake and were off therapy since at least 3 weeks. ANF values overlapped between EH patients and controls (27.8 +/- 11.5 vs. 19.5 +/- 7.4 pg/ml, p = NS). In EH, no significant correlation was found between ANF values and left ventricular mass (r = 0.29), left atrial diameter (r = 0.04), mean arterial blood pressure (r = 0.26), plasma renin activity (r = 0.00), and aldosterone (r = 0.26). In EH, ANF values overlapped between the 15 patients with hypertrophy and the 17 patients with normal ventricular mass: 30.3 +/- 17 vs. 25.6 +/- 10.6 pg/ms (p = NS). We conclude that there is a substantial overlap in plasma ANF values between mild to moderate uncomplicated EH and controls, and left ventricular hypertrophy is not a major independent stimulus to ANF release in EH.

Coronary microvascular disease in hypertensives.

Arterial hypertension can badly affect coronary circulation through several mechanisms that are not mutually exclusive, namely, coronary artery disease, left ventricular hypertrophy, and microvascular disease. Theoretical and experimental data suggest that coronary microvascular disease may exist in hypertensives, in whom it can cause both a reduction of coronary flow reserve and a shift to the right of the coronary flow autoregulation curve. To address this issue, we used dipyridamole- echocardiography test, which causes ischemic-like ST segment depression with no detectable changes in left ventricular function in different subsets of patients with microvascular disease (Syndrome X; Hypertrophic cardiomyopathy; acute heart rejection). We found that dipyridamole infusion can cause a similar pattern of response (i.e., echocardiographically silent ST segment depression) in mild-moderate essential hypertensives with normal epicardial coronary arteries, without left ventricular hypertrophy, with increased forearm minimal vascular resistances and with a reduced coronary reserve. This pattern of response identifies hypertensives with higher risk of ventricular arrhythmias, is amplified by acute reduction of diastolic blood pressure and can be reversed, together with the reduction of forearm vascular resistances by chronic antihypertensive treatment. Taken together these findings suggest that microvascular coronary disease can exist in hypertensives with two adverse consequences, consistent with the experimental background: the reduction of coronary flow reserve as well as a shift to the right of the coronary flow autoregulation curve.

Lack of correlation between cardiac mass and arteriolar structural changes in mild-to-moderate hypertension.

A morphological restructuring of cardiac and arteriolar tissue is common in hypertension. The parallel evolution of these two processes as a compensatory response to pressure overload is a frequently assumed but unsubstantiated hypothesis. To evaluate this possibility, we have concomitantly measured left ventricular mass (LVM; two-dimensional echo) and minimal forearm vascular resistance (FVR; derived from the ratio of intra-arterial blood pressure: forearm blood flow by venous plethysmography) at maximal postischemic (13 min ischemia + 1 min hand exercise) reactive hyperemia. The study was performed on 29 essential hypertensive patients (15 males, 14 females, aged 50 +/- 10 years) who had not been undergoing treatment for hypertension for at least 15 days at the time of study. Minimum FVR was taken as a hemodynamic index of the integrated arteriolar lumen at the forearm level. LVM index and minimum FVR ranged from normal to clearly altered values. In spite of a wide spread of values, no correlation existed between the individual values of the two variables. Systemic mean blood pressure correlated with minimum FVR and tended to correlate with LVMI. Thus, morphological restructing of cardiac and arteriolar tissue does not seem to evolve in parallel in human hypertension. Pressure overload may contribute to cardiovascular hypertrophy, but other unrelated mechanisms may also underlie the development of cardiac and arteriolar abnormalities of human hypertension.

Increased prevalence of ventricular arrhythmias in essential hypertensives with dipyridamole-induced ischemic-like S-T segment changes.

Essential hypertensives are at greater risk for ventricular arrhythmias than normotensive controls. A reduction in coronary flow reserve may be one of the mechanisms underlying this increased prevalence of ventricular dysrhythmias in hypertensives. It has previously been shown that dipyridamole infusion may provoke ischemic-like S-T segment depression in essential hypertensives with angiographically normal coronary arteries and reduced flow reserve. The aim of the present study was to assess whether electrocardiographic positivity (S-T segment depression greater than 0.1 mV from baseline) during dipyridamole testing (12-lead electrocardiogram and two-dimensional echomonitoring, with the infusion of 0.84 mg/kg dipyridamole over 10 min) might identify hypertensives at greater risk for ventricular dysrhythmias. We therefore studied 51 mild-to-moderate essential hypertensives by dipyridamole testing and 48-h Holter monitoring. All patients were off therapy for at least 2 weeks before testing and Holter evaluation. Left ventricular mass (by Penn convention) and ejection fraction (by Teichholtz rule) were evaluated by two-dimensional echocardiography. Lown classes 0-1 were found in 31 patients (Group 1) and Lown classes II-IV in 20 (Group 2). The two groups overlapped for mean blood pressure (121 +/- 9 versus 124 +/- 8 mmHg), left ventricular mass index (120 +/- 27 versus 141 +/- 42 g/m2) and left ventricular ejection fraction (54 +/- 6 versus 52 +/- 6). An electrocardiographically-positive dipyridamole test was found in seven of Group I and 16 of Group II patients (23 versus 80%, P less than 0.01). No patient showed a transient, either regional or global, systolic dysfunction during dipyridamole testing.(ABSTRACT TRUNCATED AT 250 WORDS)

Dipyridamole-induced myocardial ischaemia increases ANF release in man.

Atrial natriuretic factor (ANF) release is modulated by several haemodynamic factors, including ventricular and atrial wall stretch. Dipyridamole infusion, which is commonly used as a pharmacological stressor in patients with coronary artery disease, can acutely increase ventricular and atrial pressure via myocardial ischaemia. The aim of this study was to assess whether dipyridamole infusion (up to 0.84 mg kg-1 over 10') can affect ANF release in man. Nineteen patients (13 men, 6 women) with a history of chest pain were studied. Their drug regimen was interrupted and instead they were administered a dipyridamole infusion, combined with two-dimensional echocardiography and 12-lead ECG monitoring. Plasma ANF was measured by RIA while the patients rested, and after dipyridamole infusion. Eight patients had no evidence of myocardial ischaemia, as measured by electrocardiographic and/or echocardiographic criteria, during dipyridamole infusion: among them, ANF values were similar while they were at rest and at peak dipyridamole administration (23.9 +/- 9.5 vs 23.4 +/- 6.9 pg ml-1, P = ns). Eleven patients had dipyridamole-induced transient ischaemia (regional ventricular dyssynergy and/or ST segment depression): among them, ANF values rose significantly at peak dipyridamole administration (31.8 +/- 13.8 vs 65.5 +/- 36.4, P less than 0.01). We conclude that dipyridamole infusion does not increase ANF release in man in the absence of ischaemia. The induction of myocardial ischaemia acutely increases ANF release, probably through a rise in ventricular and atrial wall stress.

Dipyridamole echocardiography stress testing in hypertensive patients. Targets and tools.

Arterial hypertension can provoke a reduction in coronary flow reserve through several mechanisms that are not mutually exclusive, namely, coronary artery disease, left ventricular hypertrophy, and microvascular disease. These different targets of arterial hypertension should be explored with different diagnostic markers. The transient dyssynergy detected by two-dimensional echocardiography and evoked during dipyridamole infusion is a marker of coronary disease that is equally reliable in normotensive and hypertensive individuals. On the contrary, dipyridamole-induced ST segment depression is frequently elicited in hypertensive patients when angiographically assessed coronary disease is absent. This ischemiclike electrocardiographic response can be found in echocardiographically assessed left ventricular hypertrophy. However, even when left ventricular mass is normal, dipyridamole-induced ST segment depression is associated with an impaired coronary flow response to pacing, which is consistent with microvascular disease. Whether echocardiographically silent electrocardiographic changes are simply diagnostic noises transmitting a misleading false positive response or a potentially important clinical marker of early myocardial damage remains a pivotal though still unanswered question.

[Humoral and hemodynamic (systemic and renal) effects of ketanserin in patients with essential hypertension: what is the role of prostaglandins?]. / Effetti umorali ed emodinamici, sistemici e renali della ketanserina negli ipertesi essenziali: quale ruolo per le prostaglandine?

We have studied the hemodynamic and humoral effects of ketanserin, an S2 antagonist, and whether PG synthesis blockade, induced by indomethacin, might modify its effects. Eight patients with uncomplicated essential hypertension were submitted to a treatment for three days with indomethacin (50 mg/b.i.d.) and for 3 days with placebo. At the end of each period, saline and ketanserin (10 mg i.v.) were given. The effects of placebo and of ketanserin were assessed for one hour by measuring the following parameters: blood pressure (BP), heart rate (HR), renal plasma flow (RPF), glomerular filtration rate (GFR), renal vascular resistance (RVR), PRA, aldosterone, noradrenaline (NA) serum and urinary thromboxane, urinary 6-keto-PGF1 alpha. Under placebo and as compared in saline, ketanserin significantly reduced BP aldosterone and RVR and increased HR, GFR, PRA, NA, serum and urinary thromboxane and urinary 6-keto-PGF1 alpha without modifying RPF. Pretreatment with indomethacin which significantly reduced serum thromboxane and urinary thromboxane and 6-keto-PGF 1 alpha prevented the renin stimulating effect and the increase in GFR induced by ketanserin without changing the other actions of this drug. Taken together, these findings indicate that PG do not play a relevant role in the antihypertensive effect of ketanserin, but mediate the GFR increase induced by this drug.

ST segment depression elicited by dipyridamole infusion in asymptomatic hypertensive patients.

In asymptomatic patients with essential hypertension, electrocardiographic changes suggestive of myocardial ischemia can be elicited by rapid pressure lowering or by pronounced coronary arteriolar dilation. The aim of this study was to assess whether dipyridamole infusion might induce ischemic-like electrocardiographic changes in asymptomatic essential hypertensive patients and to describe the clinical and echocardiographic correlates possibly associated with this response. We therefore studied a control group of 20 normotensive individuals and a group of 28 asymptomatic patients with mild-to-moderate essential hypertension. All underwent dipyridamole-echocardiography testing (12-lead electrocardiogram and two-dimensional echocardiographic monitoring with dipyridamole infusion, 0.84 mg/kg over 10'). No patient showed transient regional dyssynergy during dipyridamole infusion. None of the normotensive and 10 of 28 of the hypertensive participants had horizontal or downsloping ST segment depression more than 0.1 mV during dipyridamole (0% versus 36%, p less than 0.01). Hypertensive patients with ("responders") (n = 10) and without ("nonresponders") (n = 18) ST segment depression showed similar values of percent fractional shortening in baseline conditions (32 +/- 5 versus 33 +/- 6, p = NS) and at peak dipyridamole infusion (45 +/- 8 versus 43 +/- 5, p = NS). The peak early to peak late velocity ratio values (evaluated from transmitral flow tracings by Doppler technique) were also similar in baseline conditions (0.86 +/- 0.14 versus 0.94 +/- 0.30, p = NS) and at peak dipyridamole (0.72 +/- 0.15 versus 0.78 +/- 0.32, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of dopamine-1 receptor blockade on the humoral and renal effects of low-dose atrial natriuretic factor in human hypertensives.

To test whether dopaminergic mechanisms can modulate the humoral and renal effects of atrial natriuretic factor (ANF), seven untreated, mildly hypertensive patients without complications were given a placebo (saline for 60 min) followed by a low dose of ANF (0.005 microgram/kg per min), or D-sulpiride (0.05 mg/kg per min), a specific dopamine-1 antagonist, or ANF + D-sulpiride at the same doses, for 60 min. The sequence of the three treatments was random, with a 72-h interval between treatments. The ANF infusion, which increased plasma ANF within the physiological range, significantly increased urinary sodium excretion, fractional sodium excretion and haematocrit; it reduced plasma aldosterone and tended to reduce plasma renin activity without changing blood pressure, the heart rate, renal plasma flow or the glomerular filtration rate. D-Sulpiride, when given alone, significantly increased mean blood pressure and reduced absolute and fractional sodium excretion without changing the heart rate, glomerular filtration rate, renal plasma flow, haematocrit, plasma renin activity or plasma aldosterone. When infused with D-sulpiride, ANF did not change absolute or fractional sodium excretion or haematocrit. This study provides evidence that dopaminergic mechanisms play a role in the natriuretic and plasma volume effects of a synthetic human ANF analogue infused at a low dose in patients with essential hypertension.

Naloxone does not antagonize the antihypertensive effect of chronic captopril therapy in hypertensive patients.

It has been reported that naloxone, an opiate receptor antagonist, blunts the hypotensive effect of captopril in normotensives. However, our previous data did not show any interaction between captopril given acutely and naloxone (0.1 mg/kg) in hypertensives. To test whether a greater naloxone dose could interfere with the hemodynamic effect of chronically administered captopril, 12 male hypertensives were studied: Six of them had been under captopril treatment (50 mg tid) for at least 1 month, whereas the others had been drug free for the same time. Both groups randomly received a saline or naloxone (0.2 mg/kg) infusion for 1 hour, and blood pressure, heart rate, PRA, plasma aldosterone, adrenaline, and noradrenaline were measured at regular intervals before, during, and after naloxone infusion. In drug-free hypertensives, naloxone tended to reduce blood pressure slightly and did not modify heart rate, PRA, plasma aldosterone, adrenaline, or noradrenaline. In captopril-treated hypertensives, naloxone did not blunt the hypotensive effect of captopril, but rather enhanced it, without changing the heart rate, adrenaline, and noradrenaline. Moreover, naloxone increased the renin-stimulating action and did not modify the aldosterone-inhibiting effect of captopril. Our results show that the hemodynamic action of captopril given chronically is not influenced by opioid receptor blockade and therefore that the antihypertensive effect of this drug seems to be unrelated to the activation of the opioidergic system.

[The dipyridamole-echo-ECG test in hypertensives with microvascular angina]. / Il test ECG-eco-dipiridamolo negli ipertesi con angina microvascolare.

Microvascular angina - chest pain syndrome in the presence of angiographically normal epicardial coronary arteries and reduced flow reserve - has been also described in patients with essential hypertension and it has been linked to the development of left ventricular hypertrophy. Dipyridamole-Echocardiography Test (DET: 2D-echo and 12 lead ECG monitoring with dipyridamole infusion, up to 0.84 mg/kg over 10') was performed in 28 essential hypertensives meeting the following inclusion criteria; 1) history of chest pain; 2) angiographically normal coronary arteries; 3) normal resting regional and global left ventricular function. A group of 12 (age and sex matched) normotensives with the same inclusion criteria, as well as with negative exercise stress test, was also evaluated. During DET, none, either in essential hypertensives or in control group, developed a regional dyssynergy of contraction; 15 in essential hypertensives, and 2 in control group had a diagnostic (greater than 0.1 mVolt from baseline) ST segment depression on ECG tracing (54 vs 17% p less than 0.01); 16 in essential hypertensives and 2 in control group had chest pain (57 vs 17%, p less than 0.01). None of the control group and 9 of the essential hypertensives had echocardiographically assessed left ventricular hypertrophy. In the essential hypertensives group, ventricular hypertrophy was present in 7/20 patients with and in 2/8 patients without dipyridamole induced chest pain and/or ST segment depression (35 vs 25%, p = ns). In conclusion, essential hypertensives patients with chest pain and angiographically normal coronary arteries frequently show "echocardiographically silent" angina and/or ST segment depression during DET. The presence of ventricular hypertrophy does not appear to be a prerequisite for the induction of angina in these patients.

Dipyridamole-echocardiography test in essential hypertensives with chest pain and angiographically normal coronary arteries.

Microvascular angina--chest pain syndrome in the presence of angiographically normal epicardial coronary arteries and reduced flow reserve--has been described in patients with essential hypertension (EH) and linked to the development of left ventricular hypertrophy (LVH). We performed a dipyridamole-echocardiography test (DET: 2D-echo and 12 lead ECG monitoring with dipyridamole infusion, up to 0.84 mg/kg over ten minutes) in 28 essential hypertensives meeting the following inclusion criteria: (1) history of chest pain; (2) angiographically normal coronary arteries; (3) normal resting regional and global left ventricular function. A group of 12 (age- and sex-matched) normotensives with the same inclusion criteria, as well as with negative exercise stress test, was also evaluated. During DET, none of the essential hypertensives or the control group developed a regional dyssynergy of contraction. Fifteen essential hypertensives and two in the control group had a diagnostic (greater than 0.1 mV from baseline) ST segment depression on ECG tracing (54 v 17%, P less than .01); 16 essential hypertensives and two in the control group had chest pain (57 v 17%, P less than .01). None of the control group and nine of the essential hypertensives had echocardiographically assessed LVH. In the essential hypertensive group ventricular hypertrophy was present in seven of 20 patients with and in two of eight patients without dipyridamole induced chest pain and/or ST segment depression (35% v 25%, P = NS). In conclusion, essential hypertensive patients with chest pain and angiographically normal coronary arteries frequently show echocardiographically silent angina and/or ST segment depression during DET.(ABSTRACT TRUNCATED AT 250 WORDS)

Humoral effects of metoclopramide and domperidone in normal subjects and in hypertensive patients.

To evaluate whether, in humans, metoclopramide (MCP), a DA2 antagonist which readily crosses the brain-blood barrier, can stimulate plasma aldosterone (ALD) through hypophyseal-adrenal axis activation in addition to its direct adrenal antidopaminergic activity, we have investigated the effects of MCP and domperidone (DMP), a specific antagonist of peripheral DA2 receptors, on plasma ALD, adrenocorticotropin (ACTH), cortisol and prolactin (PRL) in 15 subjects. Ten controls and 5 uncomplicated essential hypertensive patients, in whom the dopaminergic tone is hypothesized to be reduced, received, according to a single-blind randomized procedure, MCP (10 mg iv) or DMP (10 mg iv) and, after an interval of at least 1 week, the reverse treatment. MCP and DMP similarly increased PRL (p less than 0.001), while only MCP significantly increased plasma ALD (p less than 0.01), ACTH (p less than 0.02) and cortisol (p less than 0.02) both in normotensives and in hypertensives, without any difference between them. These data confirm that, in spite of similar DA2 antagonistic potency of the two drugs, only MCP is able to increase plasma ALD. Since MCP significantly increased also ACTH levels we cannot exclude an involvement of this hormone on MCP-induced ALD release. Finally, the similar PRL and ALD response in normotensives and hypertensives does not support the hypothesis of a reduced dopaminergic system activity in essential hypertensives.