Effects of tilt and exercise on signal-averaged electrocardiogram after acute myocardial infarction.

To determine whether enhanced sympathetic activity could alter a non-invasive index of cardiac instability, we analysed the effects of 90 degrees head-up tilt and submaximal exercise stress test on high amplification signal-averaged electrocardiogram in 64 patients after acute myocardial infarction. At rest, ventricular late potentials were detected in 25% of patients, characterized by a significant prolongation of filtered QRS complex (137 +/- 3 vs 115 +/- 2 ms) and of its components smaller than 40 microV (38 +/- 2 vs 16 +/- 1 ms), as well as by a reduced root mean square voltage calculated for the terminal 40 ms of QRS complex (RMS40 voltage) (19 +/- 1 vs 75 +/- 9 microV) in comparison to patients without micropotentials. Sympathetic activation induced by tilt caused a significant increase in heart rate (from 67 +/- 3 to 79 +/- 3 beats min-1) but did not modify either the incidence of ventricular late potentials or the values of any of the signal-averaged electrocardiogram parameters considered. In 19 patients, recordings were also obtained during a submaximal bicycle exercise stress test at a heart rate of 114 +/- 4 beats min-1 and with systolic arterial blood pressure at 153 +/- 6 mmHg. No effect on signal-averaged electrocardiogram parameters was detectable during this experimental intervention. These data indicate that after myocardial infarction, sympathetic activation does not seem to modify signal-averaged electrocardiogram parameters.

Heart rate variability as an index of sympathovagal interaction after acute myocardial infarction.

By analysis of spectral components of heart rate variability, sympathovagal interaction was assessed in patients after acute myocardial infarction (AMI). At 2 weeks after AMI (n = 70), the low-frequency component was significantly greater (69 +/- 2 vs 53 +/- 3 normalized units [NU], p less than 0.05) and the high-frequency component was significantly smaller (17 +/- 1 vs 35 +/- 3 NU) than in 26 age-matched control subjects. This difference was likely to reflect an alteration of sympathovagal regulatory outflows with a predominance of sympathetic activity. At 6 (n = 33) and 12 (n = 29) months after AMI, a progressive decrease in the low- (62 +/- 2 and 54 +/- 3 NU) and an increase in the high-frequency (23 +/- 2 and 30 +/- 2 NU) spectral components was observed, which suggested a normalization of sympathovagal interaction. An increase in sympathetic efferent activity induced by tilt did not further modify the low-frequency spectral component (78 +/- 3 vs 74 +/- 3 NU) in a subgroup of 24 patients at 2 weeks after AMI. Instead, 1 year after AMI, this maneuver was accompanied by an increase in the low-frequency component (77 +/- 3 vs 53 +/- 3 NU, p less than 0.05) of a magnitude similar to the one observed in control subjects (78 +/- 3 vs 53 +/- 3 NU). These data indicate that the sympathetic predominance that is detectable 2 weeks after AMI is followed by recovery of vagal tone and a normalization of sympathovagal interaction, not only during resting conditions, but also in response to a sympathetic stimulus.

Effects of sympathetic activation on ventricular ectopic beats in subjects with and without evidence of organic heart disease.

In a selected group of 10 apparently healthy subjects and 22 patients with organic heart disease, all with frequent ventricular ectopic beats on Holter monitoring, we assessed the influence of sympathetic activation by comparing the arrhythmogenic effects of a symptom-limited bicycle exercise stress test and 90 degree head up tilt. Tilting reduced ventricular arrhythmias in the normal subjects (-48 +/- 18% from 9 +/- 2 beats min-1, P less than 0.05). Exercise stress testing caused small and insignificant changes in arrhythmias during the early (50-75 W) phases and an almost complete suppression of ventricular ectopic beats in the final stages (-99 +/- 1%, P less than 0.01). In six of the 10 subjects, ventricular arrhythmias reappeared in the early recovery phase. In the 22 patients with organic heart disease, tilting increased ventricular ectopic beats (43 +/- 17% from 9 +/- 3 beats min-1, P less than 0.05); augmented repetitive forms in 12 patients (179 +/- 88% from 1.4 +/- 0.6 per 3 min) and produced repetitive forms in six of the 10 remaining patients who did not show repetitive forms during control conditions. Exercise stress testing caused a marked increase in ectopic activity in the early phase (84 +/- 35%) while the response during the maximal phase of exercise as well as during recovery was related to the effort capabilities. Arrhythmias were increased in 12 patients with limited exercise duration and were reduced in 10 patients with good exercise tolerance. These data indicate that sympathetic activation has different effects on ventricular arrhythmias depending on the clinical setting and that tilting is a useful maneuver to evaluate the arrhythmogenic effects of increased sympathetic activity.

[Propafenone in ventricular hyperkinetic arrhythmias. Dynamic ECG evaluation of the acute oral test and short-term treatment]. / II propafenone nelle aritmie ipercinetiche ventricolari. Valutazione mediante ECG dinamico del test orale acuto e della terapia a breve termine.

The antiarrhythmic efficacy of Propafenone (PF) was evaluated in 24 patients with ventricular hyperkinetic arrhythmias by means of 24-hour Holter monitoring. The drug was administered as an acute bolus (450 mg) and, subsequently, in continuous therapy for 7 days at an average dose of 600 mg/day followed by a 5 days wash-out. The results of our study can be summarized as follows: High antiarrhythmic efficacy of the drug and good tolerability: 19 out of 24 patients showed, in continuous therapy, suppression of ventricular tachycardias (VT), reduction greater than or equal to 90% of couples, reduction greater than or equal to 70% of ventricular premature beats (VPBs). High predictivity value of the oral acute test with PF, (91.6%). Occurrence of first degree atrioventricular block in 4 patients (16.5%) and left bundle branch block in 3 patients (12.5%) with chronic treatment.

Effect of D-glucitol-hexanicotinate on platelet aggregability in patients with coronary heart disease.

D-glucitol-hexanicotinate (sorbinicate) was administered at a daily dose of 1.6 mg to 16 male patients who had survived myocardial infarction. Platelet aggregation induced by collagen (5 micrograms/ml), by ADP (2, 1.2, 0.8, and 0.4 X 10(-6)M), and by epinephrine (1 and 0.5 X 10(-6)M) was significantly decreased after 3 months of therapy. In a group of 13 comparable patients, who did not receive sorbinicate, platelet aggregation induced by ADP (1.2, 0.8, and 0.4 X 10(-6)M) and by epinephrine (1 X 10(-5)M and 1 X 10(-6)M) was significantly increased 3 months after entry into the study. Sorbinicate has effective lipid-lowering activity; the combination of hypolipidemic and anti-aggregating properties may prove important in primary and secondary prevention of atherosclerotic disease.

[Echocardiographic study of left ventricular performance during sitting bicycle exercise (author's transl)]. / L'ecocardiografia da sforzo nello studio computerizzato della funzione ventricolare sinistra.

Twelve healthy volunteers, mean age 25.4 +/- 4.18 years, performed sitting bicycle ergometer graded exercise to exhaustion. Recordings of left ventricular echocardiographic dimension, heart rate, arterial blood pressure, were obtained at rest and at two minutes intervals during exercise and recovery. Echocardiographic tracings were digitized and the values of three complexes were combined and means determined for the overall analysis. Heart rate increased from 76.92 +/- 15.09 to 154.91 +/- 12.13 (p less than 0.001) at peak exercise and decreased to 98.50 +/- 11.60 (P less than 0.001) at six minutes recovery. Similarly behaved blood pressure. End diastolic Echo dimension varied significantly from 46.50 +/- 4.66 mm to 51.44 +/- 5.38 mm (P less than 0.005) at peak exercise and to 45.91 +/- 4.52 mm (P less than 0.005) at six minutes recovery, but resulted unchanged at lower levels of exercise. It started to return towards resting values, from two to four minutes of recovery. End systolic dimension did not change significantly at any heart rate. Shortening fraction increased progressively and significantly at every step of exercise, decreasing in the same way during recovery: rest 38.42 +/- 3.62%; peak exercise 44.28 +/- 5.32% (P less than 0.005); end recovery 39.28 +/- 5.89% (P less than 0.001). So did respectively: Stroke volume (Teichholtz) 69.50 +/- 12.16 cc; 84.92 +/- 24.14 cc (P less than 0.005); 67.64 +/- 16.48 cc (P less than 0.005). Cardiac output 5.27 +/- 1.18 lt/min; 12.46 +/- 3.83 (P less than 0.001); 6.25 +/- 1.00 (P less than 0.005). Ejection fraction 68.33 +/- 4.68%, 78.58 +/- 8.80 (P less than 0.001); 68.82 +/- 8.16 (P less than 0.005). Mean normalized velocity of circumferential fibre shortening 1.33 +/- 0.25 circ/sec; 2.37 +/- 0.33 (P less than 0.001); 1.55 +/- 0.031 (P less than 0.001). These results indicate that in untrained healthy subjects, variations of cardiac output during exercise and recovery depend mainly on heart rate and left ventricular fibre shortening rate. Severe exertion produces an increase of left ventricular dimension due to a Frank-Starling effect. Sitting bicycle exercise Echocardiography appears to be a suitable method to assess Left ventricular performance with a chest position relevant to normal human conditions.

[The lipoproteic state in patients with coronary heart disease (author's transl)]. / Variazioni del quadro lipoproteico in pazienti affetti da cardiopatia coronarica.

The lipoproteic state of 28 patients with coronary heart disease (CDH) and 44 normal subjects (total N. 72) has been analyzed. In normal subjects the results showed an increase of triglyceride (TG), VLDL with age. For subjects between 20 and 40 years of age, higher values of HDL and lower RF were observed in women than in men. In CHD patients, between 40 and 60 years, higher values of total cholesterol (TC) were observed in women than in men (p less than 0,05). The comparison between male CHD patients and normal male subjects indicated a reduction of HDL and an increase of the risk factor (RF) (p less than 0,05) in coronary patients. However, the female patients showed lower levels of HDL in combination with higher values of TC, LDL, RF, and TG when compared with the control group.

Kinetics of rifampicin and isoniazid administered alone and in combination to normal subjects and patients with liver disease.

The possible existence of kinetic interactions between rifampicin and isoniazid and the effect of the concomitant presence of an impaired liver function were investigated in man. In a first study normal healthy subjects and patients with chronic liver disease received, on three different occasions, a single dose of 600 mg rifampicin or isoniazid and of rifampicin and isoniazid associated in randomized sequences. The results have shown that in both groups the serum levels, half-life values, and urinary excretion of each drug given alone are not significantly different from those observed when the other drug is associated. Serum levels and half-life of rifampicin and isoniazid were significantly higher in patients with chronically impaired liver. In a second study, rifampicin and isoniazid were given in combination at the same doses as in the first study over a period of one week. The results have shown a trend to decrease in the serum levels of rifampicin of the healthy subjects and a trend to increase in the patients with chronic liver disease on day 7 of treatment. In both groups a reduction in the half-life of rifampicin was also observed. No changes in serum isoniazid concentrations were observed between day 1 and day 7 in the healthy subjects, whereas a significant increase was observed in the patients. No significant changes in the half-life of isoniazid were observed.