Complete AV-block secondary to lithium-clozapine therapy and relapsing multiple sclerosis in a bipolar patient.

A complete atrioventricular block (CAVB) can be a lethal complication when it is not treated directly with isoprenaline and pacemaker therapy. The overall incidence of CAVB varies between 4 to 8 per cent with a mortality OR of 3.2 within 30 days if untreated. Main causes of CAVB are inferior myocardial infarction, congenital AV node malformation, mitral valve insufficiency and valve surgery, metabolic disorders and intoxications. The authors describe a case with a CAVB due to lithium-clozapine therapy and relapsing multiple sclerosis.

Aminolaevulinic acid-induced protoporphyrin IX pharmacokinetics in central and peripheral arteries of the rat.

Photodynamic therapy (PDT) based on the photosensitive protoporphyrin IX (PpIX) may prevent restenosis after transluminal angioplasty. PpIX is synthesized in mitochondria, which differ in number and activity among various tissues. Therefore, we questioned whether the course of PpIX concentration after systemic aminolaevulinic acid (ALA) administration differed among various arteries. ALA was administered intravenously (200 mg/kg) to male Wistar rats (n = 21). At varying time intervals (0, 1, 2, 3, 6, 12 and 24 h) both central and peripheral arteries were isolated and homogenized, and the concentration of the various heme intermediates was determined by a fluorometric extraction method. The maximal PpIX concentration was more than two-fold higher in peripheral arteries (20.49 +/- 3.0 to 24.0 +/- 7.5 pmol/mg protein) than in central arteries (0-9.46 +/- 0.01 pmol/mg protein) (P < 0.004). However, the amount of citrate synthase, reflecting the mitochondrial mass, was lower (0.14-0.61 and 1.87-2.32 U/mg protein, respectively). Apparently, the level of PpIX cannot simply be explained by the mitochondrial content of the arteries. The time interval of maximal PpIX accumulation was similar in peripheral and central arteries (2 h and 27 min vs. 2 h and 8 min) (P = 0.13). Thus, if the efficacy of PDT in vivo is directly related to the tissue concentration of PpIX, more effect can be expected in peripheral arteries than in central arteries.

Arterial wall strength after endovascular photodynamic therapy.

BACKGROUND AND OBJECTIVES: Vascular photodynamic therapy (PDT) inhibits intimal hyperplasia (IH) induced by angioplasty in rat iliac arteries by eradicating the proliferating smooth muscle cells. This process may jeopardise the structure and strength of the arterial wall, reflected by a decreased bursting pressure. STUDY DESIGN/MATERIALS AND METHODS: Thirty male Wistar rats of 250-300 g were subdivided into 3 groups (n = 10). In all groups, IH was induced by balloon injury (BI). One experimental group received PDT at 50 J/cm diffuser length, the other group at 100 J/cm diffuser length. The third group served as control group and received no PDT. In half of each group the bursting pressure was analyzed after 2 hours (n = 5), in the other half after 1 year. RESULTS: Two hours after the procedure the bursting pressure was 3.37 +/- 0.58 (+/-SEM) bar in the BI + PDT 50 and 3.96 +/- 0.43 bar in the BI + PDT 100 group, compared to 2.20 +/- 0.27 bar in the BI group (P < 0.05). After 1 year these values were 3.18 +/- 0.87 bar in the BI + PDT 50 (P < 0.05) and 2.02 +/- 0.31 bar in the BI + PDT 100 group, compared to 2.10 +/- 0.30 bar in the BI group (NS). In the BI + PDT 100 group, 3 out of 5 rats appeared to have aneurysmal dilatation after 1 year. CONCLUSIONS: Endovascular PDT increases the arterial wall strength as measured by the bursting pressure at short-term. After 1 year, wall strength is not diminished as measured by bursting pressure, but aneurysmal dilatation nevertheless developed with 100 J/cm. dl. This may limit the use of high energy PDT.

In situ light dosimetry during photodynamic therapy of Barrett's esophagus with 5-aminolevulinic acid.

BACKGROUND AND OBJECTIVES: Previous studies with PhotoDynamic Therapy (PDT) in bladder and bronchi have shown that due to scattering and reflection, the actually delivered fluence rate on the surface in a hollow organ can be significantly higher than expected. In this pilot study, we investigated the differences between the primary calculated and the actual measured fluence rate during PDT of Barrett's Esophagus (BE) using 23 independent clinical measurements in 15 patients. STUDY DESIGN/MATERIALS AND METHODS: A KTP-dye module laser at 630 nm was used as light source. Light delivery was performed using a cylindrical light diffuser inserted in the center of an inflatable transparent balloon with a length corresponding to the length of the Barrett's epithelium. The total light output power of the cylindrical diffuser was calibrated using an integrating sphere to deliver a primary fluence rate of 100 mW cm(-2). Two fiber-optic pseudo sphere isotropic detectors were placed on the balloon and were used to measure fluence rate at the surface of the esophageal wall during PDT. RESULTS AND CONCLUSIONS: The actual fluence rate measured was 1.5-3.9 times higher than the primary fluence rate for 630 nm. In general, the fluence rate amplification factor decreased with increasing redness of the tissue and was less for shorter diffusers. Fluence rate variations in time were observed which coincided with patients coughing, movement, and esophageal spasms. These factors combined with inter patient variability of the fluence rate measured appears to justify the routine application of this technique in PDT of BE.

A comparison of balloon injury models of endovascular lesions in rat arteries.

BACKGROUND: Balloon injury (BI) of the rat carotid artery (CCA) is widely used to study intimal hyperplasia (IH) and decrease in lumen diameter (LD), but CCA's small diameter impedes the evaluation of endovascular therapies. Therefore, we validated BI in the aorta (AA) and iliac artery (CIA) to compare it with CCA. METHODS: Rats underwent BI or a sham procedure (control). Light microscopic evaluation was performed either directly or at 1, 2, 3, 4 and 16 weeks follow-up. The area of IH and the change in LD (LD at 16 weeks minus LD post BI) were compared. RESULTS: In the BI-groups the area of IH increased to 0.14 +/- 0.08 mm2 (CCA), 0.14 +/- 0.03 mm2 (CIA) and 0.12 +/- 0.04 mm2 (AA) at 16 weeks (NS). The LD decreased with 0.49 +/- 0.07 mm (CCA), compared to 0.22 +/- 0.07 mm (CIA) and 0.07 +/- 0.10 mm (AA) at 16 weeks (p < 0.05). The constrictive vascular remodelling (CVR = wall circumference loss combined with a decrease in LD) was -0.17 +/- 0.05 mm in CIA but absent in CCA and AA. No IH, no decrease in LD and no CVR was seen in the control groups. CONCLUSIONS: BI resulted in: (1.) a decrease in LD in CCA due to IH, (2.) a decrease in LD in CIA due to IH and CVR, (3.) no change in LD in AA, (4.) Comparable IH development in all arteries, (5.) CCA has no vasa vasorum compared to CIA and AA, (6.) The CIA model combines good access for 2 F endovascular catheters with a decrease in LD due to IH and CVR after BI.