An update on atrial fibrillation in 2014: From pathophysiology to treatment.

Atrial fibrillation (AF) is the most frequently encountered cardiac arrhythmia. The trigger for initiation of AF is generally an enhanced vulnerability of pulmonary vein cardiomyocyte sleeves to either focal or re-entrant activity. The maintenance of AF is based on a "driver" mechanism in a vulnerable substrate. Cardiac mapping technology is providing further insight into these extremely dynamic processes. AF can lead to electrophysiological and structural remodelling, thereby promoting the condition. The management includes prevention of stroke by oral anticoagulation or left atrial appendage (LAA) occlusion, upstream therapy of concomitant conditions, and symptomatic improvement using rate control and/or rhythm control. Nonpharmacological strategies include electrical cardioversion and catheter ablation. There are substantial geographical variations in the management of AF, though European data indicate that 80% of patients receive adequate anticoagulation and 79% adequate rate control. High rates of morbidity and mortality weigh against perceived difficulties in management. Clinical research and growing experience are helping refine clinical indications and provide better technical approaches. Active research in cardiac electrophysiology is producing new antiarrhythmic agents that are reaching the experimental clinical arena, inhibiting novel ion channels. Future research should give better understanding of the underlying aetiology of AF and identification of drug targets, to help the move toward patient-specific therapy.

[Clinical study on the pharmacological treatment of hemorrhoids with 0.25% oxethacaine chlorhydrate]. / Nota clinica sul trattamento farmacologico della malattia emorroidaria con "Oxetacaina Cloridrato" allo 0.25%.

In this clinical study, the authors refer to a thirty-six month treatment of Grades I and II haemorrhoids (pharmacological treatment) with a group of 75 patients (45 females and 30 males) and treatment for Grades III and IV haemorrhoids (Pharmacological and surgical treatment) on a second group of 23 patients for a total of 98 patients treated and observed. For the pharmacological treatment, a rectal cream containing 0.25% Oxethacaine chlorhydrate (Emoren, produced by Novasorel, srl) was used on all patients. The cream was applied intra-anally and on the external orifice twice a day, morning and evening, for ten days. In order to evaluate the therapeuctic effect, the following symptoms were monitored: pruritus, ematochezia, burning, tenesmus, and pain. The following results were demonstrated: a) in all patients: A reduction in pruritus, pain, blood and mucous loss, Elimination of tenesmus, Absence of peri-anal eczema, b) in 15 patients, haemorrhoids were reduced for 11 months. Therefore the results obtained reconfirm that local treatment with EMOREN demonstrated to be clinically efficient in the treatment of Grades I and II haemorrhoids as well as in post surgical treatment both for the attenuation and elimination of pain and the clinical objectives of the pathology in question.

Atrial electroanatomic remodeling after circumferential radiofrequency pulmonary vein ablation: efficacy of an anatomic approach in a large cohort of patients with atrial fibrillation.

BACKGROUND: Circumferential radiofrequency ablation around pulmonary vein (PV) ostia has recently been described as a new anatomic approach for atrial fibrillation (AF). METHODS AND RESULTS: We treated 251 consecutive patients with paroxysmal (n=179) or permanent (n=72) AF. Circular PV lesions were deployed transseptally during sinus rhythm (n=124) or AF (n=127) using 3D electroanatomic guidance. Procedures lasted 148+/-26 minutes. Among 980 lesions surrounding individual PVs (n=956) or 2 ipsilateral veins with close openings or common ostium (n=24), 75% were defined as complete by a bipolar electrogram amplitude <0.1 mV inside the lesion and a delay >30 ms across the line. The amount of low-voltage encircled area was 3594+/-449 mm(2), which accounted for 23+/-9% of the total left atrial (LA) map surface. Major complications (cardiac tamponade) occurred in 2 patients (0.8%). No PV stenoses were detected by transesophageal echocardiography. After 10.4+/-4.5 months, 152 patients with paroxysmal AF (85%) and 49 with permanent AF (68%) were AF-free. Patients with and without AF recurrence did not differ in age, AF duration, prevalence of heart disease, or ejection fraction, but the LA diameter was significantly higher (P<0.001) in permanent AF patients with recurrence. The proportion of PVs with complete lesions was similar between patients with and without recurrence, but the latter had larger low-voltage encircled areas after radiofrequency (expressed as percent of LA surface area; P<0.001). CONCLUSIONS: Circumferential PV ablation is a safe and effective treatment for AF. Its success is likely due to both PV trigger isolation and electroanatomic remodeling of the area encompassing the PV ostia.

[Prospects of the treatment of atrial fibrillation. Circumferential radiofrequency ablation of pulmonary vein ostia]. / Prospettive nel trattamento della fibrillazione atriale. L'ablazione circonferenziale in radiofrequenza degli osti delle vene polmonari.

The dominance of the left atrium (LA) in the pulmonary vein (PV) regions for triggering and maintaining atrial fibrillation (AF) is now widely recognized. Radiofrequency (RF) PV isolation with electroanatomical guidance has recently emerged as a promising approach for AF treatment. We report the clinical outcome of the procedure in 251 consecutive patients with paroxysmal (n = 179) or permanent (n = 72) AF. Circular RF lesions were deployed transseptally during sinus rhythm or AF at 5 mm from PV ostia. Procedural and mapping times were 112 +/- 32 min and 75 +/- 27 min, respectively, with 29 +/- 11 min of fluoroscopy. Complete lesions (peak-to-peak bipolar electrogram amplitude < 0.1 mV inside the line and no double potentials) were achieved in 85% of the veins treated. Sinus rhythm was restored during RF delivery in 52% and by DC shock in the remaining. Major complications (cardiac tamponade) occurred in 3%. Extent of ablated area was 4.9 +/- 0.5 cm2, accounting for 28 +/- 9% of the total LA map surface. After 11 +/- 5 months, procedure success rates (freedom from AF without antiarrhythmic drugs) were 85% for paroxysmal and 68% for permanent AF. No PV stenoses were detected. By univariate analysis, an increased risk of recurrence was predicted by LA dilation (diameter > 50 mm), AF duration, and a low ablated area (< 15% of total LA surface). After adjustment, only the latter variable continued to be significant (odds ratio 3.5, 95% confidence interval, 1.6-5.8). In conclusion, RF PV isolation is safe and effective in either paroxysmal or permanent AF. Patients with enlarged left atrium may require wider lesions to achieve AF suppression.

Electrical modulation of cardiac contractility: clinical aspects in congestive heart failure.

Heart failure is a highly prevalent disease in western society. Drug therapies aimed at increasing myocardial contractility have been associated with decreased survival. Several short and mid term clinical studies have suggested adjuvant or alternative therapies to congestive heart failure using modified pacing techniques that were aimed to increase contractility (e.g. Paired pacing) or restore synchrony of contraction (biventricular pacing). While delivery of paired pacing was abandoned during the early 70's, biventricular pacing has recently emerged as an adjuvant treatment to limited group of congestive heart failure patients with aberrant left ventricular conduction. In this brief review, we describe our initial safety and efficacy experience in patients with heart failure using a novel non-stimulatory electrical approach to the delivery of positive inotropic therapy to the failing myocardium. The study suggests that unlike modified pacing techniques, delivery of the signal to the left ventricle during the refractory period resulted in a rapid increase in myocardial contractility and improved hemodynamic performance. The near instantaneous contractility improvement achieved by this type of stimulus was shown to be safe and effective independently of the primary cause of heart failure or the function of the conduction system. Unlike pharmacologic treatments, which have a relatively constant effect, use of electrical stimuli may prove useful as a new therapeutic modality in the treatment of heart failure with which contractility can be improved when and as needed.

Circumferential radiofrequency ablation of pulmonary vein ostia: A new anatomic approach for curing atrial fibrillation.

BACKGROUND: The pulmonary veins (PVs) and surrounding ostial areas frequently house focal triggers or reentrant circuits critical to the genesis of atrial fibrillation (AF). We developed an anatomic approach aimed at isolating each PV from the left atrium (LA) by circumferential radiofrequency (RF) lesions around their ostia. METHODS AND RESULTS: We selected 26 patients with resistant AF, either paroxysmal (n=14) or permanent (n=12). A nonfluoroscopic mapping system was used to generate 3D electroanatomic LA maps and deliver RF energy. Two maps were acquired during coronary sinus and right atrial pacing to validate the lateral and septal PV lesions, respectively. Patients were followed up closely for >/=6 months. Procedures lasted 290+/-58 minutes, including 80+/-22 minutes for acquisition of all maps, and 118+/-16 RF pulses were deployed. Among 14 patients in AF at the beginning of the procedure, 64% had sinus rhythm restoration during ablation. PV isolation was demonstrated in 76% of 104 PVs treated by low peak-to-peak electrogram amplitude (0. 08+/-0.02 mV) inside the circular line and by disparity in activation times (58+/-11 ms) across the lesion. After 9+/-3 months, 22 patients (85%) were AF-free, including 62% not taking and 23% taking antiarrhythmic drugs, with no difference (P:=NS) between paroxysmal and permanent AF. No thromboembolic events or PV stenoses were observed by transesophageal echocardiography. CONCLUSIONS: Radiofrequency PV isolation with electroanatomic guidance is safe and effective in either paroxysmal or permanent AF.

Cardiac pacing in heart failure patients with left bundle branch block: impact of pacing site for optimizing left ventricular resynchronization.

BACKGROUND: Acute left ventricular pacing has been associated with hemodynamic improvement in patients with congestive heart failure and wide QRS complex. We hypothesized that pacing two left ventricular sites simultaneously would produce faster activation and better systolic function than single-site pacing. METHODS: We selected 14 heart failure patients (NYHA functional class III or IV) in normal sinus rhythm with left bundle branch block and QRS > 150 ms. An 8F dual micromanometer catheter was placed in the aorta for measuring +dP/dt (mmHg/s), aortic pulse pressure (mmHg), and end-diastolic pressure (mmHg). Pacing leads were positioned via coronary veins at the posterior base and lateral wall. Patients were acutely paced VDD at the posterior base, lateral wall, and both sites (dual-site) with 5 atrioventricular delays (from 8 ms to PR -30 ms). Pacing sequences were executed in randomized order using a custom external computer (FlexStim, Guidant CRM). RESULTS: Dual-site pacing increased peak +dP/dt significantly more than posterior base and lateral wall pacing. Dual-site and posterior base pacing raised aortic pulse pressure significantly more than lateral wall pacing. Dual-site pacing shortened QRS duration by 22 %, whereas posterior base and lateral wall pacing increased it by 2 and 12%, respectively (p = 0.006). CONCLUSIONS: In heart failure patients with left bundle branch block, dual-site pacing improves systolic function more than single-site stimulation. Improved ventricular activation synchrony, expressed by paced QRS narrowing, may account for the additional benefit of dual- vs single-site pacing in enhancing contractility. This novel approach deserves consideration for future heart failure pacing studies.

Catheter ablation of paroxysmal atrial fibrillation using a 3D mapping system.

BACKGROUND: We treated paroxysmal recurrent atrial fibrillation (AF) with radiofrequency (RF) catheter ablation by creating long linear lesions in the atria. To achieve line continuity, a 3D electroanatomic nonfluoroscopic mapping system was used. METHODS AND RESULTS: In 27 patients with recurrent AF, a catheter incorporating a passive magnetic field sensor was navigated in both atria to construct a 3D activation map. RF energy was delivered to create continuous linear lesions: 3 lines (intercaval, isthmic, and anteroseptal) in the right atrium and a long line encircling the pulmonary veins in the left atrium. After RF application, the atria were remapped to validate completeness of the block lines, demonstrated by late activation of the areas circumscribed by the lines. The mean procedure duration was 312+/-103 minutes (range, 187 to 495), with mean fluoroscopy time of 107+/-44 minutes (range, 32 to 185 minutes). No acute complications occurred, but 1 patient experienced early prolonged sinus pauses and received a pacemaker. During the first day, 17 patients (63%) had AF episodes, but at discharge, 25 patients were in sinus rhythm. After a follow-up of 6. 0 to 15.3 months (average, 10.5+/-3.0 months), 16 patients are asymptomatic, 3 have an almost complete disappearance of symptoms, 1 patient is improved, and 7 patients have their AF attacks unchanged. CONCLUSIONS: Paroxysmal recurrent drug-refractory AF can be treated by RF catheter ablation. Creation of long continuous linear lesions necessary to compartmentalize the atria is facilitated by a nonfluoroscopic electroanatomic mapping system.

[The Registry for Angioplasty in Infarction (RAI): brief preliminary report on the main indicators and process of acute outcome]. / Registro per l'Angioplastica nell'Infarto (RAI): breve report preliminare dei principali indicatori di processo e di esito acuto. Conto di Tutti i Ricercatori del RAI.

BACKGROUND: Emergency coronary angioplasty can be the treatment of choice in selected patients with acute myocardial infarction in centers with adequate facilities and organization. METHODS: A multicenter observational study in patients with high-risk acute myocardial infarction was conducted to evaluate the quality of emergency angioplasty treatment according to process, acute and long-term outcome, and use of resources. RESULTS: The RAI registry included 345 patients with high-risk acute myocardial infarction who were admitted to six participating centers over a thirteen-month period. Emergency coronary angiography was performed in 261 patients (76%) and was followed by immediate angioplasty in 236 of them (68%). Mean door-to-procedure time was 58 +/- 47 min. Severe left ventricular failure was present at admission in 35 (13%) of the 261 patients with emergency coronary angiography; and 29 of them were in cardiogenic shock (11%). Overall, in-hospital mortality for patients with angioplasty was 7.6%; i.e., 43% and 3.7% for patients with and without shock, respectively. CONCLUSIONS: Despite logistical limitation, in centers with emergency angioplasty programs this treatment can be performed with favorable process and acute outcome characteristics in patients with high-risk myocardial infarction.

[Immediate and long-term clinical and angiographic results of the Wiktor stent in the treatment of chronic coronary occlusions]. / Risultati clinici ed angiografici immediati ed a lungo termine dello stent Wiktor nel trattamento delle occlusioni coronariche croniche.

BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) of chronic total coronary artery occlusions is associated with very high restenosis and reocclusion rates. Coronary stenting has been proposed as a means of improving outcome. However, the Wiktor device for chronic coronary occlusion has never been tested in a large patient sample. This study reports the first multicenter experience with the Wiktor stent for treatment of chronic occlusions. METHODS: From January 1993 to December 1996, 89 consecutive patients with 91 chronic occlusions underwent Wiktor stent implantation after successful PTCA. Post-stenting regimen consisted of coumadin plus aspirin in the first 49 (55%) patients and aspirin plus ticlopidine in the following 40 (45%). RESULTS: Stenting was successful in 87 (98%) patients. At 1 month, 6% of patients had subacute stent thrombosis, 1% access-site complications and 3% major bleeding events. Stent thrombosis showed a univariate association with coumadin therapy (p = 0.009). Angiographic follow-up was obtained in 93% of 82 eligible patients. Restenosis rate was 32%, including 4% reocclusions. Through multiple logistic regression analysis, restenosis was independently associated with multiple stents (odds ratio-OR = 27.67, 95% confidence interval-CI = 4.25 to 79.95, p = 0.0008) and increasing values of occlusion length (OR = 1.23, 95% CI = 1.09 to 1.39, p = 0.001). Freedom from death, myocardial infarction or stented vessel revascularization was 87 and 72% at one and three years, respectively. CONCLUSIONS: Short- and long-term clinical and angiographic outcomes are favorable in patients undergoing Wiktor stent implantation for chronic coronary occlusion. Further technical refinements are needed to reduce restenosis rate in patients with long lesions and multiple stents.

Exercise-induced ischemic arrhythmias in patients with previous myocardial infarction: role of perfusion and tissue viability.

OBJECTIVES: This study sought to investigate whether residual viability of infarcted myocardium may play a role in the pathogenesis of exercise-induced ventricular arrhythmias. BACKGROUND: We previously showed that transient ischemia within partially infarcted areas often precipitates ventricular arrhythmias during exercise that are consistently obliterated by intravenous nitrates. METHODS: We studied 60 patients with chronic stable angina and a previous myocardial infarction. All underwent at least two consecutive exercise stress tests, coronary angiography and stress/rest myocardial perfusion tomography by Tc-99m 2-methoxy isobutyl isonitrile (MIBI). In the last 26 consecutive patients, residual viability was assessed by single-photon emission computed tomography (SPECT) using fluorine (F)-18 fluorodeoxyglucose. Perfusion and metabolic data were evaluated qualitatively by three independent observers in blinded manner. RESULTS: With exercise, 30 patients (group A) consistently developed ventricular arrhythmias (> 10 ventricular ectopic beats/min, couplets, nonsustained ventricular tachycardia); the remaining 30 patients (group B) did not. The severity of coronary artery disease (Gensini score) was similar in the two groups. Postexercise SPECT showed partial reperfusion of an infarcted area in 28 of 30 patients of group A but in only 9 of 30 of group B (p < 0.0001). Uptake of F-18 fluorodeoxyglucose was observed within the infarcted zone in 10 of 13 and 1 of 13 patients in groups A and B, respectively (p = 0.0003). CONCLUSIONS: In patients with myocardial infarction, exercise-induced ventricular arrhythmias appear to be triggered by transient ischemia occurring within a partially necrotic area containing large amounts of viable myocardium. Therefore, occurrence of arrhythmias during exercise may represent a clue to the presence of residual viability within a previously infarcted area.

Intravenous nitroglycerin suppresses exercise-induced arrhythmias in patients with ischaemic heart disease: implications for long-term treatment.

We studied 20 patients with ischaemic heart disease, who consistently developed complex ventricular arrhythmias during exercise testing. Treadmill exercise was performed twice, both during the placebo infusion and then during intravenous administration of nitroglycerin, titrated to reduce systolic blood pressure by 10 mmHg. Exercise duration in those administered placebo was 7.8 +/- 1.7 and 7.9 +/- 1.5 min, respectively (ns); angina developed in five patients and ischaemic ST changes in 10. In those administered nitroglycerin, exercise duration increased to 8.4 +/- 2 min (P less than 0.05). Diagnostic ST segment depression was observed in only two patients and only one had angina. Ventricular arrhythmias, consistently present during both tests on those administered placebo, were dramatically reduced by nitroglycerin in all 20 patients. There were 455 (mean 35.8 +/- 16.8) and 418 (mean 34.4 +/- 11.1) ventricular ectopic beats in the two exercise tests on those administered placebo and 11 in those receiving the nitroglycerin infusion (mean 0.6 +/- 0.1) (P less than 0.001). There were 28 and 29 couplets in those receiving placebo (ns) and none in those receiving nitroglycerin (P less than 0.001). Ventricular tachycardia was present in six and eight patients who received placebo but in none in those administered nitroglycerin (P less than 0.001). Abolition of exercise-induced arrhythmias was maintained during chronic treatment with oral coronary vasodilators. Prevention of exercise-related arrhythmias by nitroglycerin appears a good indicator of their ischaemic origin and may provide valuable information for long-term prophylaxis with oral vasodilators, thus avoiding antiarrhythmic agents with their potential side effects.

Proarrhythmic activity of intracoronary endothelin in dogs: relation to the site of administration and to changes in regional flow.

The endothelium-derived peptide, endothelin, has been shown to exert powerful constrictor activity in both isolated and in situ coronary arteries. Recent in vitro data on isolated cardiac myocytes suggest that the substance might also possess electrophysiologic properties. We investigated the possibility that endothelin (ET-1) may exert proarrhythmic effects when infused selectively in the coronary circulation of open-chest-anesthetized dogs. Animals were instrumented for the measurement of left anterior descending (LAD) or left circumflex (LCX) coronary artery blood flow, left systolic ventricular pressure (LSVP), dP/dtmax, mean arterial pressure (MAP), and epicardial electrocardiogram (ECG; three leads). Data were recorded during infusion (2 min) of saline (n = 5) or increasing doses of endothelin (5-80 pmol/kg) given selectively in either the LCX (n = 10) or the LAD (n = 10). When infused into the LCX, endothelin produced a dose-dependent decrease in flow (40 +/- 23% at 80 pmol/kg, mean +/- SD, p less than 0.01) with a concomitant increase in coronary resistance and a decrease in dP/dtmax and MAP. ECG changes typical of myocardial ischemia paralleled the decrease in flow and culminated in ventricular fibrillation at the highest dose (80% of dogs). Endothelin caused similar hemodynamic effects when infused in the LAD, but fatal arrhythmias occurred for lower doses and for little or no change in coronary blood flow. Thirty percent of the animals died at 10 and 60% died at 20 pmol/kg, doses that induced only a moderate decrease (8 +/- 7 and 21 +/- 12%, respectively) in LAD total blood flow. Ventricular tachycardia always preceded ventricular fibrillation and death.(ABSTRACT TRUNCATED AT 250 WORDS)

[Left atrial enlargement during the exercise test: a new electrocardiographic sign of transitory ischemia]. / Impegno atriale sinistro durante test da sforzo: un nuovo segno elettrocardiografico di ischemia transitoria.

In patients with coronary artery disease, electrocardiographic signs of left atrial enlargement (LAE-negative P wave deflection greater than or equal to 1 mm2 in lead V1) are associated with increased left ventricular end diastolic pressure (LVEDP). We investigated the possibility that transient LAE could represent an additional criterion for diagnosing myocardial ischemia during exercise testing (EST). We studied 48 consecutive patients with chronic stable angina, positive EST and 201 Tl scintigraphy, and angiographically proven CAD; 200 other consecutive patients with atypical chest pain and normal stress/rest 201 Tl scintigraphy served as controls. During EST, transient LAE developed in 34/48 patients with CAD but in only 1/200 controls (p less than 0.001). When present, LAE preceded ST changes (6.1 +/- 1 min vs 8.2 +/- 2 min) and recovered earlier (4.7 +/- 4 min vs 5.8 +/- 3 min). The prevalence of 2-3 vessel CAD was significantly higher in patients with EST-induced LAE (54% vs 34%, p less than 0.05). In conclusion, transient ECG signs of LAE during EST represent a highly specific sign of reversible ischemia and are frequently associated with multivessel CAD. Although less sensitive than classical ST criteria, this sign may prove useful in patients exhibiting equivocal ST changes and in the presence of ventricular conduction disturbances.

[Intravenous nitroglycerin infusion suppresses exercise-induced arrhythmia in patients with ischemic cardiopathy: indications for chronic treatment ]. / L'infusione endovenosa di nitroglicerina sopprime le aritmie indotte da slorzo in pazienti con cardiopatia ischemica: indicazioni per il trattamento cronico.

In patients with ischemic heart disease and arrhythmias, selection of antiarrhythmic treatment is often difficult as it is hard to separate "primary" from ischemic arrhythmias. We studied 20 patients with ischemic heart disease, who developed ventricular arrhythmias consistently during exercise test. Exercise test was performed twice during infusion of placebo and then during intravenous administration of nitroglycerin, titrated to reduce systolic blood pressure by 10 mmHg. Exercise duration was 7.8 +/- 1.7 and 7.9 +/- 1.5 min, in the 2 placebo tests (NS). Angina developed in 5 patients and ischemic ST changes in 10. With nitroglycerin exercise duration increased to 8.4 +/- 20 min (p less than 0.05), diagnostic ST segment depression was observed in 2 patients and only 1 had angina. In all 20 patients, ventricular arrhythmias were consistently present during both tests on placebo, that were markedly reduced by nitroglycerin. In fact, ventricular ectopic beats were 455 (mean 35.8 +/- 16.8) and 418 (mean 34.4 +/- 11.1) in the 2 exercise tests with placebo, and 11 during nitroglycerin infusion (mean 0.6 +/- 0.1; p less than 0.001). Couplets were 28 and 29 during placebo (NS) and 0 during nitroglycerin (p less than 0.001). Ventricular tachycardia was present in 6 and 8 patients during placebo but in none during nitroglycerin (p less than 0.001). Reduction of exercise-induced arrhythmias was maintained during chronic treatment with oral vasodilators. Prevention of exercise-related arrhythmias by nitroglycerin infusion appears a good indicator of their ischemic origin and may provide valuable information for long-term profilaxis with oral vasodilators, then avoiding the use of antiarrhythmic agents and their potential side effects.

Effects of acute smoking on the hemostatic system in humans.

Habitual smoking is one of the best established risk factors for cardiovascular disease. The pathogenesis of smoke-induced damage is not so well clarified, but it probably includes--among some other aspects--an activation of the hemostatic system. Recently it has been shown that smoking a single cigarette can significantly decrease the coronary blood flow in coronary patients as well as in normal subjects. We tested the hypothesis that the acute effects of smoke are mediated by the hemostatic system. Seven healthy male volunteers, aged 20-40 years (mean 32 +/- 6 years), entered the study. All were habitual smokers, but had abstained from smoking in the 12 hours preceding the test. After lying in absolute rest for about 30 minutes, each subject smoked a cigarette containing 1.2 mg of nicotine. Immediately before and after smoking, blood was drawn by clear venipuncture for the evaluation of the following hemostatic variables: collagen-induced platelet aggregation by the method of Born; thromboxane B2 (TxB2) production by platelets stimulated with collagen, radioimmunoassay (RIA); plasma beta thromboglobulin (TG) (RIA); plasma fibrinopeptide A (FPA) (RIA); plasma fibrinolytic activity in the euglobulin fraction (NEF) (fibrin plate method). The following results, respectively before and after smoking, were observed: collagen-induced platelet aggregation 55 +/- 3 vs. 57 +/- 6%; TxB2 100.5 +/- 5.9 vs. 90.3 +/- 9.0 ng/10(8) platelets; plasma beta-TG 20.8 +/- 2.2 vs. 19.2 +/- 2.3 ng/ml; plasma FPA 2.3 +/- 0.3 vs. 2.2 +/- 0.1 ng/ml; NEF, lysis diameter 16.8 +/- 1.6 vs. 16.7 +/- 1.7 mm; NEF + C1 inhibitor lysis diameter 8.8 +/- 0.7 vs. 9.1 +/- 0.7 mm.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormal cardiovascular response to exercise in young asymptomatic diabetic patients with retinopathy.

Heart rate, blood pressure, and left ventricular ejection fraction (LVEF) were measured by means of Au 195 m first-pass angiocardiography, during maximal supine bicycle exercise in 20 young asymptomatic patients with insulin-dependent diabetes (IDD) (10 retinopathic and 10 uncomplicated) and in 10 control subjects. Five patients with retinopathic IDD also had mild subclinical autonomic neuropathy. Exercise capacity was diminished, although not significantly, in patients with retinopathic IDD. Heart rate and LVEF were similar in all groups at rest and at submaximal exercise. At peak exercise patients with retinopathic IDD had significantly lower heart rate (134 +/- 4 bpm) and LVEF (62.9 +/- 3.7%) than those with umcomplicated IDD (158 +/- 8 bpm and 76.6 +/- 2.4%, respectively) and control subjects (152 +/- 6 bpm and 73.5 +/- 1.9%, respectively). LVEF increased vs baseline in all control subjects and patients with uncomplicated IDD, but in only three with retinopathic IDD. Leg muscle blood flow (MBF) was also evaluated at rest and during exercise by 133Xe washout. Exercise MBF was significantly lower in patients with retinopathic IDD (40.5 +/- 2.23 ml X min-1 X 100 gm-1) than in control subjects (49.9 +/- 1.87 ml X min-1 X 100 gm-1) and in those with uncomplicated IDD (49.0 +/- 1.87 ml X min-1 X 100 gm-1). Diffuse microangiopathy, alone or in combination with neuropathy, might be responsible for the impairment of cardiovascular function in diabetes.

Evaluation in dogs and humans of three potential technetium-99m myocardial perfusion agents.

The biodistribution of the three cationic 99mTc complexes [99mTc(TMP)6]+, [99mTc(POM-POM)3]+, and [99mTc(TBIN)6]+--where TMP represents trimethylphosphite, POM-POM represents 1,2-bis(dimethyoxyphosphino)ethane, and TBIN represents t-butylisonitrile--have been evaluated in humans and dogs. Each agent was studied in three normal volunteers at rest, while [99mTc(POM-POM)3]+ and [99mTc(TBIN)6]+ were each studied in one normal volunteer at exercise. Even though all three agents yield good myocardial images in dogs, none appear suitable for clinical use as myocardial perfusion imaging radiopharmaceuticals. In humans, [99mTc(TMP)6]+ and [99mTc(POM-POM)3]+ clear very slowly from the blood and provide myocardial images only several hours after injection. [99mTc(TBIN)6]+ clears rapidly from the blood, but accumulation in the lung obscures the myocardial image for the first hour after injection; at later times, activity in the liver and spleen masks the apical wall. These results correlate with the blood-binding properties of the three complexes. [99mTc(TMP)6]+ and [99mTc(POM-POM)3]+ bind tightly to the plasma of human blood, but not to the plasma of dog blood; [99mTc(TBIN)6]+ does not bind tightly to the plasma of either dog or human blood. Among the Tc(I) complexes studied to date in humans, [99mTc(TBIN)6]+ appears to be unique in biodistribution pattern, blood-binding properties, and the fact that exercise improves the ultimate myocardial image. All the Tc(I) complexes appear to undergo myocardial accumulation by a mechanism different from that utilized by Tc(III) complexes. Animal studies alone are not adequate to evaluate the potential utility of 99mTc cationic complexes for myocardial perfusion studies.

Early improvement of left ventricular function during caloric restriction in obesity.

Left ventricular function (LVF) was studied in 25 obese patients (four males and 21 females) by serial poligraphic measurements, namely systolic time intervals (STI), during a short period of dieting (2721 kJ/day (650 kcal/day) as single daily meal regimen). In the same period, all the patients underwent also three standardized exercise tests at the cycloergometer. At the end of the study (20th day), statistically significant differences were obtained in weight loss (P less than 0.001); two main parameters of STI, namely pre-ejection period index (PEPI) and PEP/LVET ratio were lowered (P less than 0.001): furthermore, peak and recovery systolic blood pressure (SBP) and heart rate (HR) during exercising, were also significantly reduced. These data suggest that an improvement of LVF and cardiac performance are present since the early phases of caloric restriction in obesity.

[Changes in hemorheological parameters during physical exertion in coronary disease patients]. / Alterazione di parametri emoreologici durante sforzo fisico in pazienti coronaropatici.

Blood viscosity and filtrability have been studied in 7 patients with ischemic heart disease and in 9 control subjects before and after maximal stress test on cycloergometer. The diagnosis of ischemic heart disease has been previously established on the basis of the clinical history, abnormal stress test or coronary arteriography. No significant differences were observed, at rest, in the two groups. On the contrary, after stress test blood filtrability resulted significantly reduced in ischemic patients when compared to controls. Blood viscosity resulted substantially unchanged in both groups. Our data may suggest the existence of an alteration in blood filtrability during stress test with a possible pathogenetic role.