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Ten patients with congestive heart failure (CHF), in III and IV NYHA Class, were treated orally with a single dose of ibopamine ranging from 1.2-3.3 mg/kg, and were studied using the Swan-Ganz catheter and thermodilution technique. Cardiac index (CI) and stroke volume index (SVI) were increased, and mean pulmonary pressure (PAP), systemic vascular resistances (SVR) were lowered. Ibopamine increased CI (+33%) and SVI (+26%), and decreased PAP (-17%) and SVR (-24%). All changes were statistically significant. The maximum haemodynamic effect occurred 180 min after ibopamine administration. Blood pressure and heart rate were unaffected. Tolerability was good. This study shows that ibopamine when orally administered to human subjects improves cardiac performance and further investigations on its use as a therapeutic agent in the long term treatment of CHF are recommended. [ABSTRACT FROM AUTHOR]

Background: The outcome of percutaneous coronary intervention (PCI) is apparently worse in patients receiving a prior thrombolytic therapy ('facilitated PCI'). Recombinant tissue-type plasminogen activator (rt-PA) can degrade circulating high-density lipoproteins (HDL) bound apolipoprotein A-I (apoA-I), thus possibly reducing the vascular protective activity. There have never been reports of the detection of apolipoprotein breakdown products in the circulation., Aim: We studied the potential interactions between the protein components of HDL and tenecteplase, infused as thrombolytic therapy., Methods: Sera from a total of 40 patients with acute myocardial infarction (AMI), unstable angina (UA), and dilative cardiomyopathy (controls) were investigated. AMI patients underwent either immediate PCI or were treated with tenecteplase thrombolysis., Results: Products of extensive proteolysis of apoA-I were found in many acute coronary patients treated with tenecteplase, and in some AMI patients before starting the treatment (time 0). These were not detected in controls, UA patients as well as AMI patients undergoing immediate PCI. Small pre-beta-HDLs were selectively degraded., Conclusion: Significant apoA-I degradation occurs in AMI patients after thrombolytic treatment. This finding may provide a potential mechanism for the apparent reduction of benefit of facilitated versus nonfacilitated PCI.

Mitral annular calcification (MAC) is a common echocardiographic finding. Caseous calcification is a rare variant appearing as a round, tumor-like mass with central echolucent area located in the periannular region. Although occasionally misdiagnosed as a tumor and submitted to exploratory cardiotomy, this lesion appears to carry a benign prognosis. The true significance of caseous calcification is unknown; it might be an early and reversible stage of MAC or an atheroma-like lesion. We describe a case of caseous calcification with spontaneous resolution in a 60-year-old woman-such a finding should be considered in the differential diagnosis of intracardiac masses.

Probucol treatment has been evaluated in 140 patients with hypercholesterolemia attending a single Lipid Clinic, in an attempt to identify the relations between lipid/lipoprotein responses and patient characteristics. Probucol was administered as a single drug at the standard dose (0.5 g tablets b.i.d.) for at least 6 months. One-hundred (71%) patients displayed a reduction of low-density lipoprotein cholesterol (LDL-C), which was significantly correlated with the baseline LDL-C level (r = 0.64; p < 0.0001). Most of the patients (90%) also responded with a reduction of high-density lipoprotein cholesterol (HDL-C); the HDL-C reduction was also directly related to baseline HDL cholesterolemia (r = 0.67, p < 0.0001). A highly significant correlation was found between the individual LDL-C and HDL-C responses. Eleven patients who continued with probucol treatment had a B-mode ultrasonographic investigation performed at baseline and after 24 months. No changes in carotid mean and maximal intimal-medial thickness were recorded, in contrast to an increase (i.e., indicative of atherosclerosis progression) in matched patients with hypercholesterolemia receiving other lipid-lowering regimens. Our report underlines that probucol can still provide a valuable option for the treatment for hypercholesterolemia, being particularly effective in patients with a combined increase of LDL-C and HDL-C levels.

The result of this study showed that echocardiographic and Doppler parameters in patients with mild to moderate mitral stenosis did not undergo any major changes over a relatively long observation period, reflecting the substantial stability of the valve disease process. Thus, unless such patients experience clinical deterioration, a yearly echocardiographic examination appears to be unjustified.

Objectives: This study was conducted to assess the efficacy of sulodexide, a glycosaminoglycan compound with antithrombotic properties, in preventing death and thromboembolic events after acute myocardial infarction., Background: Antithrombotic therapy has been found to play an important role in the prevention of cardiovascular events and death after acute myocardial infarction. Glycosaminoglycan-containing compounds, including sulodexide, show profibrinolytic and antithrombotic properties that render them suitable for use in patients after infarction., Methods: A total of 3,986 patients who had recovered from acute myocardial infarction were randomized to receive either the standard therapy routinely administered at each study center, excluding antiplatelet and anticoagulant drugs (control group, 1,970 patients), or the standard therapy plus sulodexide (treated group, 2,016 patients). Between 7 and 10 days after the episode of acute myocardial infarction, sulodexide was administered as a single daily 600-lipoprotein-lipase-releasing unit (LRU) intramuscular injection for the 1st month, followed by oral capsules of 500 LRU twice daily. Patients were evaluated for > or = 12 months., Results: At the end of the study, 140 deaths (7.1%) were recorded in the control group and 97 (4.8%) in the sulodexide group (32% risk reduction, p = 0.0022, chi-square test). A total of 90 patients (4.6%) in the control group had a further infarction, compared with 66 (3.3%) in the sulodexide group (28% risk reduction, p = 0.035). Furthermore, a reduction in left ventricular thrombus formation (evaluated by echocardiography) was observed in the sulodexide group (n = 12; 0.6%), compared with values in the control group (n = 25; 1.3%) (53% risk reduction, p = 0.027). Sulodexide was well tolerated and devoid of significant adverse events. All significant results were confirmed by "actual treatment" analyses., Conclusions: The study provides evidence that long-term therapy with sulodexide started early after an episode of acute myocardial infarction is associated with reductions in total mortality, rate of reinfarction and mural thrombus formation.

Acute clinical tolerance to N-methyl-N-(beta-hydroxyethyl) guanidine O-phosphate (creatinol O-phosphate, COP) was investigated in volunteer human subjects without heart or renal disease and without other serious illness. COP was administered i.v. at three different dosages, 1020 mg (group A), 2040 mg (group B) and 3060 mg (group C), in comparison with a placebo (group D). Arterial pressure, heart rate, ECG pattern and a complete blood analysis showed no change at any COP dosage, with the exception of blood phosphate, which increased in groups B and C. Cumulative urinary excretion of phosphate and creatinine and diuresis increased, whereas other urine parameters did not change. The phosphate and creatinine increases derived from the COP molecule and the increase in diuresis from a simple osmotic process required to dilute the phosphate in the tubular fluid. All these alterations were statistically significant and dose-related with COP and had been expected. COP proved to be a very well tolerated drug without any evident side effect.

A revision of 1300 echocardiograms of adults showed 14 patients whose echocardiographic diagnosis of aortic root dissecting aneurism (D.A.). Of these, 8 didn't have any anamnestic, clinical or instrumental evidence of D.A. In the other 6, admitted to our department with a suspected D.A., echocardiography proved to be useful in confirming such diagnosis in 4, in excluding it in 1, but gave a false positive diagnosis of D.A. in the sixth, affected by a diffuse carcinomatosis with pleuropericardial blood effusion. From the examination of the present experience, the Authors deem echocardiography is a useful diagnostic tool in the screening of D.A. when the following conditions are fulfilled: 1) presence of all the major criteria of Nanda and Gramiak, especially the aortic root anterior wall dilatation beyond 16 mm; 2) an almost suggestive story and clinical evidence of D.A. The usefulness of an echocardiographic pattern recently described as diagnostic of D.A. (loss of continuity between the borders of the anterior aortic wall with interventricular septum, and/or posterior aortic wall with mitral anulus) was confirmed: it was detected in 3 of the 4 D.A. patients but in none of the others. The presence of a false positive and the possibility of technical artifacts nevertheless induce caution in the interpretation of the echocardiographic pattern alone.

50 patients with congestive heart failure underwent monitored long-term treatment aimed at evaluating the effect of ibopamine (SB-7505), the 3,4-diisobutyryl ester of N-methyldopamine, on their condition. Ibopamine was administered alone or in combination with traditional therapy mainly at a dose of 100 mg t.i.d. Clinical scores and NYHA (New York Heart Association) functional classes improved. Biochemical parameters showed no adverse modifications. Mild transient side-effects probably related to ibopamine occurred in two patients.

Results about an echocardiographic study of 20 patients with Ebstein's anomaly diagnosed by cardiac catheterization and angiography, are referred. In 8 patients an echocardiogram and phonocardiogram were recorded and in five patients an echocontrast examination was performed. The echocardiographic features constantly recorded in Ebstein's anomaly are represented by anterior chamber dilatation, interventricular septum paradoxical movement, anterior tricuspid leaflet wide excursion, decreased diastolic closure rate and delayed closure of tricuspid valve compared to mitral valve. The reduced left ventricular dimension and frequent incidence of "hammock-like" shape of mitral valve during systole and reduced diastolic closure rate of anterior mitral leaflet are pointed out. Possible causes of anterior chamber dilatation, of interventricular septum paradoxical motion and delayed tricuspid closure are discussed. According to the previous study no echocardiographic pattern is surely diagnostic of the disease by itself; a delayed tricuspidal closure (more than 70 msec) when associated to an anterior tricuspid leaflet wide excursion and decreased E-F slope, is of particular value for diagnosis.

The pharmacokinetics of Deslanatoside C-3H, a short-acting polar cardiac glycoside, were investigated in the guinea-pig, rabbit and dog, after parenteral administration. Deslanatoside C was on average 20% plasma protein-bound and had a red blood celle/plasma partition ratio of 1/9. Tissue uptake of Deslanatoside C observed in the guinea-pig seems on average to be higher than in rabbits. Among the various organs and fluids tested, the highest levels were encountered in the urine, bile and kidneys of both the guinea-pig and rabbit. The main excretory route of this glycoside was via the urine, although significant amounts were excreted via the bile in all the three species tested. Cumulative urinary excretion 24 hr after i.v. injection was 50% (75% of which in unchanged form) in the guinea-pig, 46.5% (86% of which in unchanged form) in the rabbit, and 42.9%(84% of which in unchanged form) in the dog. Among the cardiac glycosides, Deslantoside C seems to possess the highest urinary excretion rate, which has in fact also recently been confirmed in human subjects.

Eight patients with NYHA Class II congestive heart failure were studied before and after captopril with right heart catheterization, cycloergometric stress tests and radionuclide 99Tc cineventriculography. Acute administration of captopril increased stroke volume and cardiac index and reduced left ventricular filling pressure. Similar changes though less marked were seen after 30 days of captopril therapy. Functional aerobic capacity and left ventricular performance improved over 15 and 30 days of captopril respectively. We therefore suggest that captopril can be effective also in patients with moderate congestive heart failure.

100 patients with endocardial cushion defect of the partial type underwent surgical correction between the years 1957-1975. The age of patients ranged from 3 to 57 years with a mean of 18 years. In 89 patients there was a mitral insufficiency. The repair of the mitral valve was performed in 78 patients; in 21 was repaired also the tricuspidal valve. The hospital mortality was of 8 patients. The mortality was correlated with the age of the patients, the pulmonary pressure and with the presence of malformations of the tricuspid valve. A major complication was represented by a complete atrioventricular block that occurred in 8 patients, in 5 of these the block disappeared before the dimission from the hospital. 86 patients have been followed for a period variable from 2 to 228 months and an average of 61 months. The late mortality was of 4 patients. Two patients have been reoperated of mitral valve replacement because of residual important mitral insufficiency. The phonocardiographic study, done in 50 patients, showed a presence of a holosystolic murmur in 20. The standard X-ray chest and electrocardiogram iid not show important changes between the pre and post operative examination.

Experiments were performed on 19 anaesthetized open-chest dog instrumented with polyethylene catheters inserted: into the aorta, in pulmonary artery and in left atrium and with an electromagnetic flow-transducer placed around the ascending aorta in order to record : systemic arterial and pulmonary pressures, mean left auricular pressure and phasic aortic flow. Heart rate, stroke volume, total systemic and pulmonary resistance, cardiac work were moreover calculated. Each dog was given intravenously by slow infusione : Dopamine (micrograms 5--10--20/kg/min/ 5 min), Isoproterenol (microgram 0.125--0.25--0.5/kg/min/5 min) and Norepinephrine (microgram 0.25--0.5--1 /kg/min/5 min). Results obtained on systemic hemodynamics agree with those reported by many other investigators. On pulmonary circulation : Isoproterenol, at the tested doses, elicited vasodilator effects, Norepinephrine increased total pulmonary resistance but not pulmonary vascular resistance, while Dopamine did not modify or slightly reduced vascular pulmonary tone.

This study compares the effects of digoxin, placebo and ibopamine (SB-7505), the orally active 3,4-diisobutyryl ester of N-methyl-dopamine, on exercise tolerance and cardiac rhythm of 14 patients whose left ventricular heart failure (end-diastolic pressure, 26.3 +/- 5.9 mmHg; ejection fraction, 0.42 +/- 0.10%) depended on a previous myocardial infarction. Patients were admitted to the study while on chronic oral digoxin treatment (serum levels between 1.1 and 1.9 ng/ml). Placebo instead of digoxin was given for the following month. Thereafter ibopamine 50 mg t.i.d. for one month was given. A sequence of one-month treatments with digoxin, placebo and ibopamine was repeated, then ibopamine was administered continuously for the next two months. The concurrent treatment (diuretics in all patients, nitroderivates in twelve, calcium antagonists in two) remained unchanged during the observation period. Symptoms-limited exercise tests and 24-h Holter recordings were obtained at admission, at the end of each one-month treatment and at the end of the observation period. Two patients developed unstable angina without increase of serum creatine phosphokinase while on ibopamine and were withdrawn. Out of the 12 patients that concluded the trial, one required supplementary doses of diuretic at the end of the second period on placebo. The results obtained during the trial suggest that: a) therapeutic plasma levels of digoxin have no deleterious effect on cardiac rhythm nor significantly increase exercise tolerance as compared with placebo; b) diuretics and nitrates appear to sustain the clinical stability of these patients as a group.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of a new orally effective dopamine-like derivative, ibopamine (SB-7505), the 3,4-diisobutyryl ester of N-methyldopamine, on the cardiovascular system were investigated in anesthetized dogs. Ibopamine increased dose-dependently stroke volume index, cardiac index, left ventricular pressure, its first derivative: dP/dt, peak velocity left ventricular ejection and renal blood flow. After beta-blockade the positive inotropic effect of ibopamine is inhibited. Total peripheral resistance and renal vascular resistance decreased after ibopamine. Urine output was increased dose-dependently, reaching 115% after ibopamine 8 mg/kg intraduodenally. Coronary and femoral flows and resistance did not change after administration of 4 and 8 mg/kg. Only very high doses (24 mg/kg) caused an increase in flow and resistance. Mesenteric flow decreased transiently and then returned to the previous level or increased considerably over the basal figures when a high dose was used. No significant changes or fall in heart rate were observed with doses up to 16 mg/kg and no significant changes in pulmonary resistance were noted. The data obtained from the present investigation show, however, that oral ibopamine is capable of producing most of the effects induced by intravenously given dopamine in anesthetized dogs. Ibopamine's cardiac and renal effects may open new prospects for the long-term treatment of chronic heart failure in human subjects.

Although Lown grading system of ventricular premature complexes (VPCs) has important conceptual shortcomings and has shown severe limitations in either cross-sectional or longitudinal studies, this classification is still the most well-known and used method to characterize the arrhythmologic ventricular pattern of the individual patient. We have looked at a modification of VPCs Lown grading scheme to correct the defects and to make the use of the classification more accurate. Our proposal is based on maintenance of 5 classes--similar to those of Lown original classification--to which we have assigned a score from 0 to 60. We have also introduced many sub-classes, each with a definite score, to better characterize the type of arrhythmic event. The sum of the score of the highest class and the score of every subclass furnishes the final score. This score is a direct index of the importance of the ventricular arrhythmias and seems to be useful for statistical evaluation of the anti-arrhythmic therapy and for follow-up studies, as confirmed by preliminary clinical results obtained through the use of this new VPCs classification.

Latero-lateral femoro-femoral arteriovenous fistulae (AVFs) were surgically created in mongrel dogs. After 7-9 months during which the dogs were trained on a treadmill, devices suitable for recording arterial pressure and aortic and coronary flow were chronically implanted. Haemodynamic parameters of the dogs were controlled either at rest or after effort, keeping AVFs open or manually closed. The results, when statistically processed, showed that haemodynamic changes induced by occlusion of AVFs at rest and under effort are similar from a qualitative point of view, but considerably more marked after muscular exercise. Under effort the shunt index calculated rose to a higher extent than cardiac output. The decrease in heart rate after AVFs occlusion was significantly correlated with flow in the fistulae. However, the Nicoladoni-Branham phenomenon ought to be used for indirect evaluation of the shunt flow.

100 patients with mitral prolapse syndrome (MPS) were studied with electrocardiogram, phonocardiogram, thorax radiography and echocardiogram. In 44 of the patients, the effort test and dynamic electrocardiogram were performed; 25 underwent hemodynamic examination, and 10 underwent selective coronarography. The most frequent symptomatologies were palpitations and vertigo; the most-registered electrocardiographic alterations were ventricular extrasystoles and altered electrical repolarization in the inferior seat. The symptomatic patients with rhythm disturbances showed reduced work capacity (RWC) with aggravation of the effort arrhythmias. The phonocardiogram showed variability of the phonoauscultatory reports, not only from patient to patient, but also in the same patient. The apicocardiogram presented a characteristic systolic re-entry which coincided with the non-ejective click. In all cases, the echocardiogram demonstrated a systolic movement backwards from the mitralic strips with different aspects. The endocavitary pressures in the studied cases were normal or only slightly altered. The left ventriculography frequently demonstrated assynergic areas, and constantly, eversion of the posterior mitralic strips in the left atrium. In most of the cases, the selective coronarography showed the absence of the ventricular atrial tract of the circumflex. The sustained role of the mixomatous degeneration in the pathogenetic mechanism of the MPS must be emphasized. The beta-blockers were the most effective drugs against arrhythmias, which in some cases showed themselves impervious to any medicinal treatment. MPS is considered a very diffuse disease which can run its course without detection or which can be accompanied by serious rhythm disturbances that can threaten the patient's life. The importance of echocardiography in the diagnosis of MPS is emphasized. The SPM patient showed undergo a series of wave tests which reveal malignant potentialities, so that the best therapeutic principles, both for the treatment and prevention of the arrhythmias, can be applied.

Numerous authors reported a significant deterioration of heart function induced by aortic cross-clamping. Nevertheless, the aorta has been clamped during various surgical procedures without any complication. We studied the hemodynamic and metabolic variations induced by 20 min thoracic aorta cross-clamping in 6 open-chest dogs. During clamping the most striking modifications were an increase in coronary blood flow of over 65%, an increase in cardiac work of over 77% and an increase in total peripheral resistances of over 68% compared to base values. No significant variations were found in the heart rate and cardiac index. Metabolic parameters, such as O2 consumption and lactate consumption increased significantly during the clamping period. The increase in lactate consumption and the progressive and continuous improvement in oxygenation indexes (lactate/pyruvate, redox potential, excess of lactate) proved the absence of any myocardial anoxia during this period. Within 15--30 min after declamping all hemodynamic and metabolic parameters reverted to values close to basal values. These data strongly suggest that the mammalian heart can tolerate this procedure satisfactorily for a limited period of time. In clinical settings, one should consider the base conditions of the cardiovascular system before transposing these conclusions.

The effects of ibopamine (SB-7505, Ib), a new orally active 3,4-diisobutyryl ester of N-methyldopamine, were studied in 8 patients aged between 34-56 years with idiopathic dilatative cardiomyopathy (II-III New York Heart Association Class) diagnosed by means of right and left heart catheterization and selective coronary angiography. Equilibrium radionuclide ventriculography (RVG) was performed in baseline conditions and 1, 2, and 3 h after the administration of a single oral dose of 200-300 mg of Ib. After 2 h Ib increased cardiac output (CO) (+16%, p less than 0.05), stroke volume (SV) (+12%, p less than 0.05) and ejection fraction (EF) (+10%, p less than 0.01). Patients were then randomly treated with placebo or Ib 100 mg t.i.d. according to a double-blind cross-over design for two periods of 15 days each. At the end of each period a RVG was repeated in baseline conditions and 1, 2, and 3 h thereafter. The mean values of the four determinations where higher after Ib than after placebo (CO: +10.1%, p less than 0.01; SV: +14.1%, p less than 0.01; EF: +10.8%, p less than 0.05). Patients subsequently started a long-term treatment with Ib 100 mg t.i.d.; after 6 months patients underwent RVG 3 h after the last dose of Ib: compared with the values recorded at the same time after the short-term treatment. CO further increased by 17% (NS), SV by 22% (p less than 0.05) and EF by 24% (p less than 0.05). The treatment was well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of Ibopamine, a new orally active dopaminergic agent, on cardiac performance were studied both in a group of healthy volunteers and in a group of patients with congestive heart failure (CHF), using non-invasive methods, such as echocardiography and polygraphy. Randomly, and in double-blind fashion, the healthy volunteers received single doses of Ibopamine 50, 100 and 150 mg orally every 3 days. The CHF patients, also randomly and in double-blind fashion, were given single doses of either placebo or Ibopamine 100 or 150 mg every 2 days. Echocardiographic and polygraphic data were recorded in baseline conditions and 3, 6 and 8 hours after the drug administration. The heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured at the same time. The following parameters were considered: echocardiography: left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), interventricular septum excursion (IVSE), left ventricular posterior wall excursion (LVPWE), per cent fractional fiber shortening (%FS); polygraphy: electromechanical systole (Q-A2), total ejection time (ET), pre-ejection period (PEP), ET/PEP ratio. In CHF patients, body weight and 24-h diuresis were also measured daily. Neither of the two groups showed significant changes in HR, SBP and DBP with any drug dose. A shortening of ET (-2.2%, p less than 0.01) and Q-A2 (-2.8%, p less than 0.001) was found in the group of normal subjects with a dose of 50 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

Holter monitoring may be effected during hospitalization either for clinical research or for high-risk patients or after surgical treatments. In the other cases, if possible, it should be better to effect ambulatory electrocardiographic monitoring in patients engaged in their normal daily activity nevertheless reducing hospital costs. Last year, in our department we effected 2420 Holter monitoring, of which 44% for patients hospitalized in our department, 11% hospitalized in other divisions, 44% for ambulatory patients. Holter monitoring was effected in the 35% of patients to detect arrhythmias, in the 29% for the evaluation of the effect of antiarrhythmic therapy; the 28% of Holter monitoring was recorded for patients recovering from acute infarction. Holter monitoring, associated to the other cardiological screening tests, has a very important rule for diagnosis of arrhythmias or myocardial ischemia, prognostic evaluation of cardiopathic patients (ischemic heart disease, cardiomyopathies, valvular and congenital heart disease), verification of the effects of therapy (PTCA, surgical and antiarrhythmic treatment).