New-onset angina preceding acute myocardial infarction is associated with improved contractile recovery after thrombolysis.

BACKGROUND: Ischaemic preconditioning reduces myocardial infarct size in animal models. Clinical data suggest that episodes of angina immediately before acute myocardial infarction may be associated with smaller infarct size in man. However, it is unclear whether ischaemic episodes preceding acute myocardial infarction also affect contractile recovery in patients. OBJECTIVE: In this study we investigated the recovery of regional myocardial function after thrombolysis in two groups of patients at their first Q-wave acute myocardial infarction; in one group (n = 42) myocardial infarction occurred unheralded, whereas patients of the second group (n = 48) had experienced new-onset angina in the 48 h that preceded infarction. Echocardiographic analysis of myocardial regional function in the infarct area was done at 2, 24 and 72 h after thrombolysis, and at 1 week, and 1 and 3 months follow-up. RESULTS: Peak level of MB-creatine kinase was significantly lower in patients with new-onset angina (96 +/- 47 as compared with 221 +/- 108 IU.l-1, P < 0.01), as was the area under the MB-creatine kinase curve (1321 +/- 876 as compared to 3879 +/- 1555 U.l-1/36 h, P < 0.01). Hypokinetic segments were fewer in patients with pre-infarction angina. Similarly, wall motion score improved significantly earlier in patients who had new-onset angina before acute myocardial infarction. Thus, contractile recovery was more rapid in patients with previous angina than in those in whom infarction occurred unheralded. Complications during the in-hospital outcome and other variables considered during the 4-week follow-up were similar between groups. CONCLUSIONS: Patients who experienced new-onset angina before acute myocardial infarction showed better recovery of regional function after thrombolysis. Our study supports the hypothesis that brief periods of ischaemia immediately before myocardial infarction may precondition the human heart, thus improving contractile recovery.

Propafenone in the conversion of atrial fibrillation in patients suffering from chronic renal failure.

Propafenone is a class Ic agent for the treatment of atrial arrhythmias with a main hepatic metabolism. This approach might play an important role in the management of atrial arrhythmias in patients with chronic renal failure. The goal of this study was to investigate the effects of propafenone in patients with atrial fibrillation and chronic renal failure. We studied 24 patients with atrial fibrillation that was associated with chronic renal failure. The conversion time was 8.4 +/- 3.2 minutes (range, 5-19 minutes) with intravenous propafenone at 1 mg/kg bolus over 5 minutes. In 21 patients (87%) sinus rhythm was restored and no serious adverse and proarrhythmic effects were noted. Corrected QT interval was not prolonged after conversion (from 0.33+/-0.06 mm to 0.32+/-0.04 mm, p = not significant). Two and 6 months later the cardioversion left atrial size significantly decreased in 19 patients who had been converted to sinus rhythm. The parameters of renal function were unchanged after propafenone therapy. We concluded that: 1) propafenone is active and acts significantly faster in converting atrial fibrillation in patients with chronic renal insufficiency; 2) propafenone administration appears to be safe in patients with chronic renal failure; and 3) left atrial size decreases upon conversion to sinus rhythm as seen at 6-month follow-up.

Relations between vasoactive hormones and diastolic function in hypertensive uraemic patients.

BACKGROUND: Arterial hypertension is a significant risk factor for the high rate of cardiovascular disease in chronic uraemic (CU) patients. Any role that hypertension may play in CU patient outcomes assumes added significance. The elevation of some hormonal factors in early clinical stage could represent a valuable marker of cardiac disease in CU. AIM: This study first investigated the role of several hormones on cardiac diastolic properties in CU patients. Moreover, the study investigated the association of hypertension with both diastolic function and release of vasoactive hormones in CU patients. RESULTS: We have reported that the early impairment of diastolic function is correlated with the elevation of both circulating plasma atrial natriuretic factor and endothelin-1 (ET-1) in hypertensive CU patients. Since the effect of ET-1 on diastolic function is still poorly understood, we have investigated also this issue. In eight additional patients with reduced E/A ratio, but without uraemia, hypertension or chronic heart failure, we have showed a high inverse correlation between the values of E/A ratio and ET-1 plasma concentrations. CONCLUSIONS: These results strongly suggest that the elevation in ET-1 levels was correlated with diastolic dysfunction in man. This phenomenon may have important pathophysiological implications suggesting the possibility of an early therapeutic approach in these patients.

Atrial natriuretic factor and sympathetic activation in human heart failure.

The neurohormonal changes occur early, have important prognostic value, and may play a role in the evolution and progression of heart failure in man. Atrial natriuretic factor (ANF) is a natriuretic and vasorelaxant peptide. Previous studies indicated that plasma ANF provides prognostic information and, ANF levels closely related to both severity of disease and catecholamine levels but, it is still unclear if high circulating levels of ANF, which are present in heart failure constantly, may be to correlate with sympathetic nervous activity in man. Thus, the aim of the present study was to investigate the relations between the release of ANF and the sympathetic system in human heart failure. We studied 18 patients with heart failure (CHF) and a control Group (n = 14) of healthy subjects. To induce adrenergic activation in physiologic way patients were underwent to a low-exercise by cycle-ergometer in supine position. Blood was collected at rest, and immediately after exercise for determination of plasma levels of ANF, norepinephrine and epinephrine levels. ANF values at rest were 35.9 +/- 19.2 pg/ml in controls and 190.7 +/- 34.2 pg/ml (p < 0.001 vs controls) in CHF patients. As well norepinephrine levels showed higher values in patients (295.7 +/- 47.8 pg/ml), than in normal subjects (143.5 +/- 33.3 pg/ml; p < 0.01). In CHF patients epinephrine levels were 100.1 +/- 21.2 pg/ml (p < 0.01 vs controls). ANF levels were in normal subjects 87.9 +/- 19.2 pg/ml (p < 0.01 vs rest) after exercise. In CHF patients ANF values were 275.3 +/- 59.8 pg/ml; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

[The relations between atrial natriuretic factor release and adrenergic activation in hypertrophic cardiomyopathy]. / Relazioni tra rilascio di fattore natriuretico atriale ed attivazione adrenergica nella cardiomiopatia ipertrofica.

Atrial natriuretic factor (ANF) is a potent natriuretic and vasoactive (vasorelaxant) peptide localized in the secretory-like atrial specific granules. The main peptide in this storage granules is the 126 amino acid proatrial natriuretic peptide, but the principal circulating form in human plasma is the 28 amino acid, alpha-human natriuretic peptide. Animal and in vitro studies have suggested that ANF modulates autonomic circulatory control, probably with a dose-dependent mechanism. Moreover, recent human studies have resulted contradictory. In particular, it is still unclear if high circulating levels of ANF, which are present in congestive heart diseases constantly, may be correlated with sympathetic nervous system activity in man. Previously we have shown that in congestive diseases there is a relation between ANF and catecholamine secretion. From these basis, the aim of this study was to investigate on the pathophysiological relations between atrial natriuretic factor (ANF) release and adrenergic activation in patients with obstructive hypertrophic cardiomyopathy (n = 6) and non obstructive hypertrophic cardiomyopathy (n = 4). Sympathetic activation in physiologic way was induced by cycloergometer sub-maximal exercise. Then specimens of venous blood were achieved for plasma determination of ANF and catecholamines pre- and post-exercise. Results have shown that in obstructive hypertrophic cardiomyopathy patients basal levels of ANF and catecholamines were higher than levels of these parameters in non obstructive hypertrophic cardiomyopathy patients.(ABSTRACT TRUNCATED AT 250 WORDS)

[Angiotensin II stimulates endothelin-1 release from human endothelial cells]. / L'angiotensina II stimola il rilascio di endotelina-1 da cellule endoteliali umane.

Endothelin-1 (ET-1) is an endothelium-derived vasoconstrictor peptide isolated from the culture supernatant of porcine aortic endothelial cells. This 21 amino-acid residue peptide has potent vasoconstrictive properties in vitro and in vivo. ET-1 action involves phosphatidylinositol turnover, calcium mobilization and protein kinase C activation. Endothelial cells have distinct receptors for different operating through hydrosoluble hormones. The aim of this study was to investigate on a possible role of angiotensin II (ANG II) to modulate the release ET-1 from human endothelial cells in vitro. These data revealed a time- and a dose-dependent increase of ET-1 production in response to ANG II. This mechanism may have important pathophysiological implications in vivo. In fact, a double-mechanism of secretion of ET-1 from endothelial cells could exist: one active in a physiological condition and an other in response to a vasoconstrictor stimuli (as well as ANG II). Furthermore, these results may suggest an additional favourable effect of ACE-inhibition in human hypertension therapy.

Role of arterial hypertension in plasma secretion of prostacyclin during renal failure in man.

Cardiac function and morphology in chronic hemodialyzed patients are modified in consequence of both vascular and neurohormonal factors. In the present study we investigate on the role of prostacyclin (PGI2) vasodilator agent, during hemodialytic (HD) treatment. Twenty-four patients (13 males and 11 females; 9 hypertensive and 15 normotensive) aged 58.5 +/- 14.4 years were studied; 2.5 ml of venous blood were collected before (time 0) and 15', 120', and 240' of dialytic session. The PGI2 levels were measured in plasma, after extraction in ethyl acetate by RIA method, as levels of 6-Keto-PGF1 alpha, a stable metabolite. The results have shown as increase of PGI2 levels at 15' in hypertensive HD patients (HHD) from the begin of dialysis that increased until 240'. This phenomenon was more significant in hypertensive than in normotensive group (NHD) (p < 0.05 vs NHD). These preliminary data suggest that in HHD patients the role of PGI2 is more important than in NHD patients as regards the effects on regulation of circulatory tone. The increment of PGI2 levels could be in relation with the sympathetic activation occurred during hemodialytic treatment.

Intravenous propafenone for suppression of symptomatic atrial fibrillation and atrial flutter in a first aid hospital.

The efficacy and safety of propafenone (PPF) were prospectively evaluated in 20 patients (13 men and 7 women, age 39 +/- 14 years) with atrial arrhythmias (AA) (atrial fibrillation: n = 13; atrial flutter: n = 7). All patients had arrhythmias from 109 +/- 63 minutes, (iT) without clinical evidence of heart failure. Intravenous PPF was given as a 1 mg/kg bolus over 5 minutes, with a therapeutical possibility of a second bolus (1 mg/kg) after 10 minutes if sinus rhythm was not restored. The conversion time (cT) was 6.4 +/- 2.2 minutes (range 3 to 18 minutes). In 19 patients (95%) sinus rhythm was restored and no serious adverse and proarrhythmic effects were noted in each patient. We conclude that 1) PPF is effective and acted significantly faster in controlling AA; 2) PPF appears to be well tolerated and relative safe with a low incidence of adverse and proarrhythmic effects in patients in a first aid station.

[Use of propafenone in emergency therapy]. / Impiego del propafenone nella terapia d'urgenza.

15 patients (10 M, 5 F; age 24-55) with paroxysmal supraventricular tachyarrhythmias (onset: 0.5-4 hours; 8 atrial tachycardias, 5 atrial fibrillation, 2 atrial flutter) were treated with 1 mg/kg i.v. propafenone. Propafenone terminated tachyarrhythmias in all patients during or within a few minutes after stopping infusion (mean conversion time: 6.4 min.). No significant changes in the main electrocardiographic parameters (QRS from 67 +/- to 80 +/- 21 msec., n.s.; QTc from 330 +/- 60 to 320 +/- 40 msec, n.s.), nor in blood pressure (from 128/82 +/- 21/10 to 135/83 +/- 11/8 mmHg, n.s.) were observed. No side effects appeared. In conclusion, propafenone proved to be effective and well tolerated in the acute treatment of supraventricular tachyarrhythmias.