Transcatheter endomyocardial laser revascularization: a feasibility test.

By means of a special catheter system, a total of 76 endomyocardial laser channels were percutaneously produced in a controllable manner at selected sites in 6 beating canine hearts. Acute patency of channels (length = 4-11 mm, diameter = 0.5-1.2 mm) was documented angioscopically and histologically. This minimally invasive method might be useful for revascularising certain patients with ischemic heart disease without resorting to open-chest surgery.

Laser catheter coagulation of normal and scarred ventricular myocardium in dogs.

BACKGROUND AND OBJECTIVE: Larger lesions would increase success rates of catheter ablation of ventricular arrhythmias. Therefore, improved radio frequency current application techniques, but also alternative energy sources, are being investigated. The purpose of this study was to determine morphology and dimensions of ventricular lesions induced by transcatheter application of laser energy. MATERIAL AND METHODS: A total of 244 lesions were produced by Nd:YAG laser pulses, 1,064 nm, 10-30 W, 15-60 s, percutaneously (endocardial approach, n = 124) and under visual control (epicardial approach, n = 120) in the left ventricular walls of 24 anesthetized dogs. RESULTS: Dimensions of lesions increased with the amount of energy applied. Maximal values were obtained at 20 W, 60 s: depth = 12.6 +/- 1.1 mm (transmural); width = 15.0 +/- 2.8 mm; volume = 1,582 +/- 777 mm3. Volumes of lesions did not change significantly when induced through previously scarred myocardium. Histologically, lesions were clear-cut, without crater or thrombus formation. Procedures and follow-up periods of up to 22 months were without complications. CONCLUSION: Nd:YAG laser pulses at 10-20 W and 15-60 s produce homogeneous myocardial lesions of coagulation necrosis of reproducible sizes, in a controllable manner, without unwanted effects on the ventricular walls, in normal and through scarred myocardium of dogs. The laser method is a promising alternative for ablation of ventricular arrhythmias including candidates with ischemic heart disease.

2-Nitrosoimino-3,6-dihydro-2H-1,3,4-thiadiazines with antiplatelet and antithrombotic properties.

The successful synthesis of 17 nitrosimines of 2 H-1,3,4-thiadiazines is reported. They are best characterized by their electronic spectra (lambda max = 504-522 nm). Some of the compounds were able to inhibit the aggregation of blood platelets in the Born-test (inducer collagen). The most active compound was the 3-nonyl-5-phenyl-derivative 10c which showed an IC50 = 6.5 mumol.l-1. In mesenteric arterioles of rats after p.o. administration (60 mg/kg) a 13% inhibition of thrombus formation is observed. The reason for the rather small effects is the high chemical stability of the title compounds and the fact that decomposition occurs mainly by the evolution of molecular nitrogen. Only small yields of NO are formed.

Spectral variations of laser-induced tissue emission during in vivo detection of malignancies in the female genital tract.

A laser-based fluorescence-guided biopsy system has been developed for the screening and early detection of malignancies in the female inner/outer genital tract. Fluorescence spectra were recorded during in vivo exposure of normal and malignant tissue to He-Cd laser (442 nm) radiation. Spectral distribution of tissue natural fluorescence allowed for the development of simple algorithms, based on spectral intensity variations. A subsequent index of discrimination between normal and various malignant tissues has been calculated. This study focuses on the variability of the experimental data and the possible sources of spectral variations. These results suggest that monitoring of this index during colposcopy could enhance selective detection of the malignant tissue, reducing the risk of leaving pathologic tissue untreated during standard exploratory surgical procedures.

Laser versus radiofrequency catheter ablation of ventricular myocardium in dogs: a comparative test.

To compare the effects of laser light with those of radiofrequency (RF) current on ventricular myocardium, a total of 36 lesions (endocardial approach n = 10 each and epicardial approach n = 8 each) were produced by either transcatheter laser (Nd:YAG, 1,064 nm, 30 W, 30 s) or RF (70 degrees C, 30 s) catheter applications in the beating hearts of 4 dogs. Volumes of coagulated myocardium in endo-/epicardial approaches were 996 +/- 73/1,075 +/- 82 (laser) and 111 +/- 38/44 +/- 5 mm3 (RF). RF lesions showed intramural bleeding, rupture and dissociation of myocardial fibers, tissue vaporization with crater and thrombus formation. Transcatheter application of laser light produced significantly larger and better reproducible lesions than RF current, without undesirable effects on the ventricular walls.

Laser-induced fluorescence detection of malignancies in the female genital tract via their natural emission and hypocrellin (HA) probing.

A laser-induced fluorescence-guided biopsy system has been developed for the screening and early detection of malignancies in the female inner/outer genital tract. Fluorescence spectra were recorded during exposure of normal and malignant tissue to He-Cd laser (442 nm) radiation. A characteristic increase in the fluorescence signal at 600 nm for malignant tissue was observed after treatment of the samples with hypocrellin (HA). This, combined with the spectral distribution of tissue natural fluorescence, allowed for the development of simple algorithms, based on the intensity difference. A subsequent index of discrimination between normal and various malignant tissues has been calculated. These results suggest that monitoring of this index during colposcopy could enhance selective detection of the malignant tissue, reducing the risk of leaving pathologic tissue untreated during standard exploratory surgical procedures.

In vivo temperature measurement during transcatheter endomyocardial Nd-YAG laser irradiation in dogs.

Intramural temperatures were monitored during catheter-directed endomyocardial non-contact laser irradiation by means of an array of thermocouples inserted epicardially. Via a novel electrode-laser catheter, a total of 30 Nd-YAG laser pulses, 1064 nm, 25 W/15 s, 20 W/30 s, 15 W/45 s,n = 10 each, were aimed at various endocardial sites in the ventricles of four dogs. Temperatures increased gradually after the onset of the laser pulses. Maximum values were measured in the central area of the irradiated spots: 100 +/- 15 double daggerC at 25 W, 78+/- 23 double daggerC at 20 W and 80 +/- 13 double daggerC at 15 W. Application of 300 J of laser energy induced significantly higher temperatures at 25 W (p< 0.02) than at 20 or 15 W (20vs 15 W: p> 0.05). Initial temperature rise and lesion formation was accompanied by dwindling of local electrical potentials. There was no crater formation. Transcatheter non-contact Nd-YAG laser coagulation of healthy ventricular myocardium can be performed in a safe and controllable manner at power settings up to 20 W and laser energies up to 675 J.

New NO-donors with antithrombotic and vasodilating activities, Part 14. 1,3,4-Triazol-1-oles.

Five 1,3,4-triazol-1-oles (5a-f) with different alkyl, aryl, and arylalkyl substituents in 2,5-position were synthesized and tested for their antithrombotic properties. The 2,5-dimethyl derivative 5a was most active. 2 h after administration of 60 mg/kg to rats thrombus formation by a laser beam was inhibited by 42% in arterioles and by 33% in venules. At the same dose the blood pressure of SHR rats was slightly (5%) but significantly decreased even 4 h after application of 5a. This pattern of activities suggests a nitric oxide mediated mechanism of action. 1,1'-Azo-bis-ethanone oxime(7)-the synthetic precursor of 5a-inhibited the aggregation of blood platelet (Born test) with an IC50 = 15 mumol/L.

Mapping guided laser catheter ablation of the atrioventricular conduction in dogs.

Safety and efficacy of mapping guided laser catheter ablation of the AV junction was tested in a canine model. A total of 43 laser pulses (continuous wave, Nd:YAG, 1,064 nm, 30 W, irradiated spot diameter 2.0-2.5 mm) were delivered in 15 dogs (2-5 per dog) via a novel laser catheter system. Pulses were selectively aimed at: (1) the AV node; (2) the His bundle; and (3) the bundle branches. Laser pulses of 9.7 +/- 1.1 seconds (n = 31) produced reversible conduction disturbances in the targeted segment of the AV conduction system, while pulses of 28.6 +/- 7.9 seconds (n = 9) resulted in chronic block. The dogs survived the procedure without complications. Follow-up was 6.5-10.5 months. Histopathologically, lesions showed clear-cut oval-shaped areas of fibrosis of 0.5-18.0 mm in diameter and 0.5-3.5 mm (transmural) in depth, depending on the irradiation time. Pervenous mapping guided laser catheter irradiation of the AV junction can produce AV block consistently and selectively in the targeted segment of the right ventricular conduction system in dogs. The method is safe and can be performed in a controllable manner by using the catheter system presented.

[Computer-controlled laser irradiation unit for studies of light-induced processes in cell cultures]. / Computergesteuerte Laserbestrahlungseinheit für Untersuchungen lichtinduzierter Prozesse an Zellkulturen.

For the photodynamic treatment of tumours, synergistic effects of photosensitizing substances and light (today usually laser light) are used. With the aim of optimizing photosensitizing drugs and therapy, the effects of light and drug dose were studied in cell experiments. To automate and standardize such in vitro experiments, a laser irradiation chamber was developed. Cells cultured from tumour cell lines are placed on micro-titre plates or in petri dishes, together with the photosensitizer, and subsequently irradiated in the irradiation chamber with a well-defined dose of laser light of a wavelength corresponding to the absorbance of the photosensitizing agent. The plates or dishes are irradiated from below. In this way, light dose errors due to refraction from the meniscus of the cell suspension as occurs with irradiation from above, are avoided. During irradiation, speckle effects on the underside of the plates or petri dishes lead to variation in irradiation. A vibrator keeps the light transmission fibre and thus speckle pattern in motion, guaranteeing a homogeneous irradiation of the cells.

Tracheoesophageal anastomosis, continent gastrostomy and oesophagostomy--a new experimental model in minipiglets.

Tracheoesophageal fistulae endanger newborn children by aspiration pneumonia. An animal model of this dangerous malformation was thought to be impossible until now. By tracheoesophageal anastomosis, occlusion of the oesophagogastral junction, proximal cervical oesophagostomy and continent gastrostomy in 25 minipiglets a reliable model of tracheoesophageal fistula has been developed. After establishing the model in a pilot study the mortality following the establishment of this procedure was 5.6% and the minipiglets survived in excellent condition for 2-10 week periods under complete alimentary restriction and gastrostomy feeding. Therefore the method seems to be suitable for long-term investigations on major oesophagotracheal surgery.

The interaction of laser energy with ureter tissues in a long-term investigation.

This study investigates tissue responses after laser irradiation of the rabbit ureter, which serves as an experimental model for rectourogenital fistulae of children. Twenty-five rabbit ureters were irradiated intraluminally by a Nd:YAG laser 1320 nm (2 Watt, 20 seconds and 3 Watt, 8 seconds) via an applicator with radialsymmetrical light distribution. Immediately, 2 weeks, 4 weeks, 8 weeks, and 16 weeks after irradiation, the ureters were X-rayed with contrast solution and prepared for light and transmission electron microscopy. For the parameters employed, no apparent morphological differences could be observed. Immediately, the central laser zone showed a transmural thermonecrosis prevailed by cellular destruction, condensed ground substance and occlusion of most vascular lumina. Peripheral laser zones displayed urothelial vacuolations. Between 2 and 16 weeks, urothelial regeneration and ingrowth of granulation tissue caused a luminal stenosis or occlusion followed by transformation into scar tissue. In some peripheral laser zones, a hydroureter with marked luminal dilatation developed. We conclude that the ureter is occluded if the expanding force of the growing scar tissue exceeds the hydrostatic pressure of the obstructed urine. A laser occlusion of rectourogenital fistulae will be easier to achieve since fistula occlusion does not entail an obstruction of the urine flow.

Catheter-directed laser coagulation of atrial myocardium in dogs.

The feasibility of transcatheter laser coagulation of atrial myocardium was tested in a canine model by using a combined electrode-laser catheter. In 17 anaesthetized beagles a total of 264 lesions, 12-19 per dog, and 3-5 in each area were produced in: (1) the lateral walls, (2) the posterior right atrial walls, (3) the inter-atrial septum, and (4) the atrial appendage. The power source was a continuous wave Nd:YAG laser. Irradiance was 1 kW.cm-2, at a wave length of 1064 nm, the irradiated spot diameter was 2.0-2.5 mm, and the pulse duration 5-60 s. Local intra-cardiac atrial potentials recorded from the targeted areas during laser irradiation dwindled after onset of the laser pulse, and their amplitude was reduced persistently by pulses of 15 s or longer. Histopathologically, the acute lesions showed intramural haemorrhage and coagulation necrosis, but there was no tissue vaporization or crater formation. Chronic lesions showed clear-cut oval-shaped areas of transmural fibrosis. Diameters of lesions, dependent on the amount of laser energy applied, measured from 4.6 +/- 0.5 mm (450 J) to 7.8 +/- 1.4 mm (1800 J). Follow-up lasted 6-25 months (average 10.5). All the animals survived the procedure without complications. Transcatheter laser coagulation of atrial myocardium is safe and can be performed in a controllable manner by using the catheter system presented.

The rat esophagus: ultrastructure and radiological aspects of tissue response after 1320 nm Nd:YAG laser irradiation.

Morphological tissue response towards laser treatment was investigated in the esophagi of adult Wistar rats by light- and transmission electron microscopy. The specimens were fixed by perfusion immediately, 2 days and 14 days after laser treatment in order to assess different stages of the healing process. The epithelium of the lasercentre was completely destroyed in the immediate group. The connective tissue showed damaged cells, fused collagenous fibres and occluded blood vessels. Smooth muscle cells presented a vacuolated sarcoplasm and pycnotic nuclei. The cross striation of skeletal muscle cells had disappeared and their nuclei were karyolytic. In a distance of 4 mm from the lasercentre all wall tissues had an almost normal appearance. After 2 days the morphological feature of the lasercentre was the same as in the immediate group. In a distance of 2 mm some layers of flat and intact epithelial cells were observed below the necrotic epithelium. The adjacent connective tissue was infiltrated by inflammatory cells. After 14 days the formation of granulation tissue had caused an occlusion of the lumen in the lasercentre. In a distance of 2 mm the lumen was patent and the wall tissues had been partly restored. As the rat esophagus serves as a model for esophagotracheal fistulae in newborn children we assume the 1320 nm Nd:YAG laser to be a possible application in occlusion of these fistulae.