Itraconazole for the treatment of pulmonary aspergillosis in heart transplant recipients.

The objective of this study was to evaluate the effects of itraconazole as a first choice drug in the treatment of pulmonary aspergillosis in heart transplant recipients. Heart transplant recipients suffering from invasive pulmonary aspergillosis were included in this study. Group 1 included 4 patients treated with i.v. itraconazole (Janssen Pharmaceutica) 400 mg daily, as a first choice drug for 28 d. Itraconazole was discontinued and amphotericin-B was started before the 28th day if clinical or radiographic worsening was observed. Group 2 included 3 patients treated with amphotericin-B as a first choice drug. Itraconazole was discontinued in all patients of Group 1 after 12-26 d of treatment because of radiographic worsening (n = 3) or combined clinical and radiographic worsening (n = 1). Subsequent treatment with amphotericin-B resulted in improvement of all patients. On a 5-yr follow-up period no relapse of aspergillosis was observed in 3 of them. The fourth patient expired from cerebral hemorrhage. The 3 patients of Group 2 treated with amphotericin-B showed a gradual improvement, and all were doing well on a 2-yr follow-up. In conclusion, in our study population consisted of heart transplant recipients amphotericin-B was superior to itraconazole in the treatment of invasive pulmonary aspergillosis.

Effect of acute ventricular pressure changes on QRS duration.

The effect of acute changes in ventricular pressure is examined on the QRS duration to clarify the mechanism of ventricular pressure-related arrhythmogenesis. Ventricular pressure was changed acutely by arterial transfusion-bleeding into an open-air ventricular pressure reservoir that was either off or on a metaraminol intravenous drip. While maintaining ventricular pressure at several levels, the QRS duration was measured at 200 mm/s paper speed. The QRS duration correlated significantly with the left ventricular pressure in all 14 dogs examined. An average change in ventricular by 100 mmHg was associated with a change of about 18% in the QRS duration. An acute ventricular pressure elevation impairs the ventricular conduction, which may contribute to ventricular pressure-related arrhythmogenicity.

Induced electrophysiological isolation of the myocardium prevents ventricular fibrillation.

STUDY OBJECTIVE: to investigate whether an encircling procedure without ventriculotomy, not involving the endocardium, may have a protective effect against ventricular fibrillation (VF), by achieving a physiological rather than anatomic entrenchment. DESIGN: the occurrence of VF was tested by DC application within an area entrenched by a circular "dotted" line formed by LASER (Nd-Yag) point by point applications. The result was compared with that from similar DC applications before the successful LASER entrenchment or beyond the restricted area. SUBJECTS: 16 anaesthetized mongrel dogs, weights 14-20 kg were used. MEASUREMENTS AND RESULTS: VF occurred 13/118 times by applying DC within the entrenched area and 86/114 times by applying the current outside this area or before the intervention (P less than 0.0005). The pacing threshold was significantly (P less than 0.001) increased within the circumscribed area (4.625 +/- 5.335 vs 0.859 +/- 0.947 mA). The maximal rate at which the ventricles could be driven by pacing at double threshold intensity was not significantly altered by the encircling procedure. Histological examination showed crater-like epicardial destruction with necrosis, loss of myocardial striation, haemorrhage, and polymorphonuclear infiltration, extending about 0.5 cm from the necrotic tissue. The subendocardial area was spared showing only hyperaemia, while the endocardium was intact. CONCLUSIONS: Encircling a small area by LASER point by point applications prevents the occurrence of VF when DC is applied within the restricted area, while permitting the conduction of paced beats. The size of the encircled area necessary to this effect is of importance, possibly reflecting the critical mass needed for the occurrence and maintenance of VF.

Effect of adrenergic blockade on pressure-related ventricular arrhythmias.

This paper examines whether adrenergic blockade (B1) may prevent the arrhythmogenic effect of acute arterial pressure (AP) elevation. In 7 anesthetized dogs iv propranolol (0.2 mg/kg) was given and in another 2 dogs stellate ganglion excision was performed. Before and after these B1 manoeuvres the AP was repeatedly increased by either elevating an open-air arterial pressure reservoir or administering iv metaraminol and decreased by abating the pressure reservoir. In a continuous recording of AP and ECG the systolic (S) AP and the presence (or absence) of ventricular arrhythmia (A) was noted. Before B1 A was noted in 652/1715 (38.0%) 5-sec periods at a SAP of 160.3 +/- 69.9 mm Hg which was significantly higher than in the 1063 5-sec periods without A (104.2 +/- 54.3) in all experiments. Following B1 it was impossible to cause A in 3 experiments. In the remaining experiments the A incidence was reduced (significantly in 5/9 experiments) to a total of 253/983 (25.7%) periods (P less than 0.001). In the 5/9 experiments with post-B1 A, the mean SAP was higher with (185.0 +/- 97.9 mm Hg) than without A (113.7 +/- 59.9 mm Hg) (significantly in 2/9 experiments). Following fitting of the SAP distributions before and after B1 to their common distribution (i.e. the same AP), the incidence of A was higher before than after B1 in all experiments (significantly in 7/9). It is concluded that B1 has an antiarrhythmic action on AP-related A. This antiarrhythmic effect seems to be due partly to an antihypertensive effect of B1 and partly to an antiarrhythmic effect of B1 for a given AP.

Response of tertiary centres to pressure changes. Is there a mechano-electrical association?

STUDY OBJECTIVE: To investigate the mechanism of pressure related ventricular arrhythmias by examining them during atrioventricular (AV) block. DESIGN: Complete AV block, where all ventricular beats are ectopic, was induced by AV node ablation and/or by toxic digitalisation, and rhythm changes were studied while arterial blood pressure was repeatedly raised and lowered. SUBJECTS: 15 anaesthetised mongrel dogs, weight 15-28 kg, were used. AV block was induced in eight by chemical or mechanical ablation of the AV node. In five of these and in seven other dogs, 5.0-7.5 mg digoxin was also given. MEASUREMENTS AND RESULTS: Following AV block due to ablation, a heart rate increase (or no change) was found in 87.5% of 56 arterial pressure increases produced by elevation of an open arterial blood reservoir or by metaraminol infusion, but in only 21.8% of 55 pressure decreases caused by arterial bleeding (p much less than 0.001). Following AV block due to digitalisation, the equivalent figures were 96% of 50 pressure increases and 27.3% of 55 pressure decreases (p much less than 0.001). While arterial pressure was increased there was moderate acceleration of the escape rhythm, then appearance of premature ventricular beats, then non-sustained and finally sustained ventricular tachycardia. The reverse occurred, with some hysteresis, on decreasing the arterial pressure. In five of the digitalised animals, arterial pressure reduction to nearly zero caused reproducible sudden arrest, with resumption of the ordinary escape rhythm on increasing the pressure again. CONCLUSIONS: The findings suggest the possibility of two kinds of ectopic rhythm in AV block: the "normal" escape rhythm which is only moderately affected by arterial pressure changes; and an "abnormal" faster pressure dependent rhythm which is generated by high arterial pressure and abolished by pressure near zero, as if there were a mechano-electrical association. This abnormal rhythm may prevail completely in digitalis toxicity so that if cardiac arrest occurs, no automaticity can be expected to appear unless arterial pressure is raised.

Arrhythmogenic effect of high blood pressure: some observations on its mechanism.

An increase in aortic pressure is a reproducible way of causing ventricular ectopic rhythms. This study sought to determine whether it is the aortic pressure per se or the concommitant increase in afterload or preload that has a direct arrhythmogenic effect. Experiments were carried out in 17 anaesthetised dogs. For each 10 s period the pressure and the presence of a ventricular arrhythmia (at least one ectopic beat) were noted. In nine animals an aortic valve gradient was created (and released). The results were compared to those obtained by impeding the aortic flow at the ascending aorta. The mean systolic left ventricular pressure was significantly higher in the arrhythmia associated periods in 8/9 experiments when there was an aortic valve gradient and in 5/9 experiments when there was not. In 4/9 experiments the mean aortic pressure associated with arrhythmia was significantly lower with an aortic valve gradient than when there was no gradient and no arrhythmia. In 7/9 of these experiments, coronary sinus flow was measured volumetrically during the manoeuvres applied. The coronary flow was significantly lower when there was neither arrhythmia nor aortic valve gradient than when there was an arrhythmia (with or without an aortic valve gradient). In another eight experiments a pressure reservoir in the aorta was either raised or lowered while another pressure reservoir in the left atrium was moved in the opposite direction. Thus the mean aortic pressure could be increased while the left atrial pressure was decreased and vice versa. If the left atrial pressure was taken into account, the mean difference of the aortic pressure from its expected value, derived from the aortic v left atrial pressure regression equation, was significantly higher when there was an arrhythmia than it was when there was no arrhythmia in all eight experiments. On the other hand, the mean difference in the left atrial pressure from its expected value was significantly higher when there was an arrhythmia in 1/8, lower in 2/8 and not significantly different in 5/8 experiments. It is concluded that when the blood pressure is raised, it is the increase in afterload rather than an increase in aortic pressure itself or in the preload that has an arrhythmogenic effect on the ventricles.