Jan R. Tuntelder

MODIFICATION OF ATRIOVENTRICULAR NODE TRANSMISSION PROPERTIES BY INTRAOPERATIVE NEODYMIUM-YAG LASER PHOTOCOAGULATION IN DOGS

The purpose of this study was to test the feasibility of neodymium-yttrium-aluminum-garnet (Nd-YAG) laser photocoagulation of the atrioventricular (AV) node to control the ventricular rate during rapid atrial rhythms without creating AV block. In 12 dogs on normothermic cardiopulmonary bypass, short laser pulses were delivered to an area between the coronary sinus orifice and the site of the most proximally recorded His deflection until second degree AV block occurred at a paced atrial rate of 200 beats/min. Long-term effects on AV node function were followed up for 3 months. Three animals developed chronic high grade AV block. In nine animals with preserved 1:1 conduction, the mean (+/- SEM) critical atrial cycle length resulting in AV node Wenckebach periodicity increased from 183 +/- 6 to 261 +/- 24 ms (+43%), the mean RR interval during induced atrial fibrillation increased from 248 +/- 14 to 330 +/- 27 ms (+32%) and the shortest RR interval during atrial fibrillation increased from 215 +/- 11 to 275 +/- 20 ms (+28%). Laser effects were not reversed by isoproterenol infusion. Histologic examination of the irradiated area showed fibrotic changes in the AV node and fatty metamorphosis. This study suggests that 1) graded Nd-YAG laser photocoagulation of the AV node region in dogs results in long-term modification of anterograde AV node transmission properties; 2) 1:1 conduction during sinus rhythm usually remains preserved, but ventricular rate during rapid atrial rhythms is chronically reduced; and 3) progression to high grade AV block occurs in a minority of animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminophylline fails to improve the outcome of cardiopulmonary resuscitation from prolonged ventricular fibrillation : a placebo-controlled, randomized, blinded experimental study

OBJECTIVES The purpose of this study was to evaluate systematically the effects of the adenosine antagonist aminophylline on resuscitation outcome in a canine model of postcardioversion nonperfusing rhythm. BACKGROUND Theoretic considerations and experimental studies indicate that myocardial adenosine accumulation during prolonged ventricular fibrillation might play a significant role in postcardioversion asystole and electromechanical dissociation. A recent uncontrolled clinical trial has suggested that the adenosine antagonist aminophylline might improve the outcome of cardiopulmonary resuscitation from refractory bradyasystolic cardiac arrest. METHODS Two placebo-controlled, randomized, blinded experimental studies were performed. In protocol 1 (20 dogs), ventricular fibrillation was induced and maintained for 7.5 min. Sixty seconds before cardioversion, dogs received 1 mg of epinephrine followed by 250 mg of aminophylline or placebo. In protocol 2 (20 dogs), dogs were cardioverted to electromechanical dissociation after 5 min of unsupported ventricular fibrillation. Sixty seconds later, all dogs received 1 mg of epinephrine followed by 250 mg of aminophylline or placebo. In both experiments, resuscitation efforts were continued until return of spontaneous circulation, or up to 30 min. The primary end point was survival to 1 h. RESULTS In protocol 1, 4 of 10 dogs survived in the aminophylline group, whereas 7 of 10 dogs survived in the placebo group, a nonsignificant trend toward unfavorable outcome from aminophylline. Pretreatment with aminophylline increased the number of cardioversion applications required to terminate ventricular fibrillation. In protocol 2, 5 of 10 and 6 of 10 dogs survived in the aminophylline and placebo groups, respectively. CONCLUSIONS The results of this study suggest that aminophylline fails to improve the outcome of resuscitation from prolonged ventricular fibrillation. It does not reverse established electromechanical dissociation and may in fact increase the number of cardioversion applications required to terminate ventricular fibrillation. The rationale for conducting clinical trials with aminophylline during cardiopulmonary resuscitation is questionable.

Selective coagulation necrosis of canine adventitia and media induces extracellular matrix accumulation without neointima formation

Endothelial cell injury, the disruption of the internal elastic membrane and medial damage represent important stimuli for the development of a neointima. It is unclear whether selective adventitial and medial injury also induce neointima formation. Incremental argon laser energies (11.4-180 J/cm2) were applied to the external surface of dog femoral arteries to evaluate the vascular repair of acute adventitial or medial necrosis without injury of the intima. The animals were sacrificed either one hour after the initial procedure or after an 8 week follow up period for histologic examination. Acute, and mild to moderate necrosis of the arterial wall was found above 50 J/cm2. Ablation of the internal elastic membrane or mural thrombi was not detected. Eight weeks after photocoagulation with laser energies above 50 J/cm2, a significant increase in mean wall thickness of the media was observed. The medial thickening was characterised by an accumulation of extracellular matrix and a loss of smooth muscle cells. Necrosis of adventitia and media resulted in arterial wall thickening without neointima formation. It is concluded that, in dogs, an acute, selective injury of adventitia and media stimulates the production of extracellular matrix and not the proliferation of cells. Smooth muscle cell migration and subsequently neointima formation are induced by viable smooth muscle cells when blood-borne stimuli are available.

Myocardial temperature distribution under cw Nd:YAG laser irradiation in in vitro and in vivo situations: theory and experiment

Tissue samples ranging from 2 to 16 mm in thickness were irradiated at 1064 nm with energies ranging from 40 to 2400 J. Coagulation lesions of in vitro and in vivo experiments were subjected to temperature profiling and submitted for histology. Irreversible damage was calculated with the damage integral formalism, following the bioheat equation solved with Monte Carlo computer light-distribution simulations. Numerical temperature rise and coagulation depth compared well with the in vitro results. The in vivo data required a change in the optical properties based on integrating sphere measurements for high irradiance to make the experimental and numerical data converge. The computer model has successfully solved several light-tissue interaction situations in which scattering dominates over absorption.

Computer simulated light distributions in myocardial tissues at the Nd-YAG wavelength of 1064 nm

Continuous wave Nd-YAG myocardial laser photocoagulation of ventricular tachycardia at the 1064 nm wavelength is a new investigational procedure in the treatment of arrhythmias. Computer simulated light diffusion patterns, generated by the Monte Carlo technique, are used to illustrate the calculated light distribution in myocardial tissues such as normal, and photocoagulated (canine) myocardium, epicardial fat on myocardium, and aneurysm for the optical properties at the Neodymium-YAG wavelength of 1064 nm.Calculated total reflection from myocardial tissue increased from 16% to 28% as a result of photocoagulation in the Monte Carlo light distribution simulations. The calculated total transmission dropped from 0.8% to 0.1% as a result of coagulation. Transmission reduced from 5% to 0.8% due to an increase in absorption from 0.04 mm−1 to 0.1 mm−1, based on capillary blood absorption. Adding an epicardial fat layer to normal myocardium total reflection and backscatter increased from 16% to 44%.Computer simulations for normal and pathological myocardium showed a wide diversity in light propagation characteristics, indicating the importance of including all myocardial tissues in light dosimetry analyses.

Computerized three-dimensional activation mapping study of spontaneous ventricular arrhythmias during acute myocardial ischemia in dogs: evidence against macroreentrant mechanism

This study was undertaken to investigate the activation patterns of spontaneous ventricular arrhythmias during acute myocardial ischemia in dogs. In 14 open-chest dogs, the left anterior descending coronary artery was occluded for 2 hours. Three-dimensional activation maps were derived from 240 bipolar sites by insertion of 60 plunge needle electrodes into both ventricles and the septum. Global ventricular activation sequences were displayed in five planes in 10 dogs, whereas the high density regional activation maps of the anterior wall were displayed in four layers in 4 dogs. Three-dimensional activation maps of 95 sinus beats, 82 premature ventricular complexes (PVCs), and 210 beats of ventricular tachycardia (VT) were analyzed. Sinus beats had a uniform activation pattern with total ventricular activation times measuring 42 +/- 4 ms and 67 +/- 8 ms during baseline and ischemia, respectively (P < .05). The PVCs and VTs originated from the subendocardial and intramural layers, and activation patterns invariably suggested focal excitation. Macroeentry was not operative because (1) the breakthrough sites were always remote from the latest activation areas; (2) there was no electrical activity bridging the gap between the termination of a beat and initiation of the subsequent beat; and (3) impulse conduction was not sufficiently delayed to reexcite the area of impulse origin even though functional conduction block was frequently present. In high-density regional activation maps, fragmented activity spanning the diastolic interval was never found. In conclusion, spontaneously occurring PVCs and VTs during acute myocardial ischemia in dogs display focal excitation with no evidence of macroreentry.

Selective elimination of retrograde conduction by intraoperative neodymium: YAG laser photocoagulation in dogs

OBJECTIVES The purpose of this study was to test the feasibility of selective elimination of ventriculoatrial (VA) conduction by limited laser photocoagulation of the atrioventricular (AV) node, and to analyze the histologic substrate of unidirectional retrograde block. BACKGROUND Atrioventricular node reentry requires intact retrograde conduction. METHODS Neodymium:yttrium-aluminum-garnet laser photocoagulation was performed during cardiopulmonary bypass through a right atriotomy in 15 dogs that had intact retrograde conduction before operation. Short laser pulses were delivered to an area between the coronary sinus orifice and the proximal His bundle. The end point of lasing was second-degree AV node block at a paced atrial cycle length of 250 ms. RESULTS Complete retrograde block developed immediately in 11 of the 15 dogs (group I), while AV conduction persisted in all 11. In 4 of the 15 dogs (group II), both AV and VA conduction remained intact. During a 3-month follow-up period, retrograde conduction remained absent in all group I dogs. Retrograde block was not reversed by isoproterenol. Anterograde AV node characteristics (Wenckebach cycle length, functional refractory period, ventricular rate during atrial fibrillation) were unchanged in five dogs and modified in six. Complete AV block did not develop. In four control dogs (group III, sham operation), anterograde and retrograde AV node characteristics were unchanged. The anterograde Wenckebach cycle lengths in groups I, II and III at 3 months measured 192 +/- 15 ms, 195 +/- 6 ms and 170 +/- 22 ms, respectively, whereas the retrograde Wenckebach cycle lengths in groups II and III measured 345 +/- 62 ms and 278 +/- 25 ms, respectively. Histologic study at 3 months in cases with unidirectional VA block showed the compact part of the AV node intact with destruction of the atrial approaches and the superficial layers of the proximal end of the node on the right side. CONCLUSIONS 1) With limited laser photocoagulation of the proximal AV node area, VA conduction can be eliminated and anterograde AV node transmission maintained. 2) Destruction of the atrial approaches on the right side with preservation of the compact part of the AV node may result in unidirectional retrograde block.

Determination of optical properties in situ from radial backscattering profile using a CCD camera

Local tissue optical parameters are of principal importance in determining the ideal dosage of laser energy and choosing the most suitable therapeutic wavelength for a specific organ. We have developed a non-invasive method for the determination of optical parameters of whole tissue in-situ. Backscattered laser light from a pencil beam incident on the tissue surface was measured using a CCD camera interfaced with a personal computer. Backscatter measurements were performed on in-vitro canine myocardium and on phantoms, with optical properties predetermined by the integrating sphere method. Backscattering radiance proved to be a function of the distance to the incident beam. Regression analysis of the backscatter showed that the backscatter can be expressed as an exponential function of the distance to the beam with a regression coefficient ((mu) r) resembling the tissue diffusion coefficient ((mu) eff), for tissue thickness much greater than optical free path. The CCD derived backscatter radiance exponent showed excellent agreement with the diffusion coefficient, with a correlation coefficient of 0.91. The backscattering technique might prove to be a simple, non-invasive, accurate new technique in the determination of in-vivo optical properties.

Electrophysiologic characteristics of manifest and latent retrograde conduction in dogs

Atrioventricular (AV) nodal reentry requires intact retrograde ventriculoatrial (VA) conduction. The purpose of this study was to assess the contribution of various pacing and pharmacologic techniques to uncover VA conduction during apparent unidirectional VA block, and to evaluate the role of several biologic and electrophysiologic factors in concealment of retrograde conduction. Forty healthy dogs underwent catheter-electrophysiologic studies of AV and VA conduction. Group I (20 animals) had intact VA conduction. Group II (six animals) had VA dissociation with ventricular pacing initiated during sinus rhythm, but the presence of VA conduction was confirmed by isoproterenol infusion or by premature ventricular stimulation. In group III (14 animals), the above techniques failed to uncover VA conduction. Eight of 14 group III animals underwent thoracotomy and crushing or freezing of the sinoatrial (SA) node. Ventricular pacing initiated during sinus standstill was associated with 1:1 VA conduction in each experiment. VA conduction time and retrograde Wenckebach cycle length, both in the baseline state and during isoproterenol infusion, were significantly longer in the eight animals in group III than in those in group I. Age, gender, weight, breed, sinus cycle length, and anterograde AV conduction properties were not significantly different between groups I, II, and III. The data suggest that (1) in normal dogs, complete unidirectional VA block probably does not exist; (2) in the presence of anterograde input to the AV node, even sophisticated pacing and pharmacologic maneuvers may fail to uncover the presence of VA conduction; (3) although anterograde input is essential for concealment of VA conduction, the phenomenon is more closely associated with depressed retrograde than with anterograde AV nodal characteristics.(ABSTRACT TRUNCATED AT 250 WORDS)

Non-linear optical phenomena in contact fiber laser-photocoagulation of myocardium

The rise time of epicardial temperatures on the left ventricular free wall during endocardial transcatbeter delivery of Nd:YAG laser energy, recorded by thermography has sparked interest in anomalous optical phenomena. Transmission measurements on whole blocks of myocardium showed a decrease in the attenuation coefficient at high power densities. The definition of the attenuation coefficient is the natural log of the ratio of the incident and the transmitted beams, divided by the physical thickness of the sample. When Nd:YAG laser light at the 1064 um wavelength irradiated fresh myocardial tissue from the free left ventricular wall, the incident power density increased from 0.0026 W/mm2 to approximately 200 W/mm2, the attenuation coefficient dropped from 0.97 ± 0.11 mm−1 to 0.77 ± 0.07 mm−1. This would indicate a non-linearity in the optical properties of the tissue as a function of the laser irradiation power density.