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.

Myocardial temperatures during in vivo endocardial Nd:YAG laser irradiation.

To determine safety and efficacy of neodymium:YAG laser irradiation of the endocardium, temperatures at both the epicardium and the endocardium were recorded for thermal damage evaluation. A total of 48 coagulation lesions were created at power settings of 20 and 30 W in 20 open chest dogs by transcatheter endocardial laser irradiation. Tissue temperatures were monitored by epicardial thermography (Tepi), and by endocardial thermocouples at the catheter tip (Tprox) and 4 mm below the endocardial surface (Tdist). In group I the optical fiber extended 1 mm from the catheter and irradiation times ranged from 3 to 60 sec. Tepi reached > or = 57 degrees after a weighted average of 5 sec of laser irradiation (n = 44). In group II the fiber was retracted 1 mm from the catheter tip, and irradiation times were 100 to 150 sec. Tepi reached > or = 57 degrees C after a weighted average of 30 sec (n = 4). Blood vessels were recognized as heat sinks until coagulation occurred. Lesion volume showed a proportional increase with total delivered energy. From the observed timeframes in epicardial temperature rise it is suggested that total direct light absorption at the epicardium was the main contribution to Tepi, and the Nd:YAG laser can efficiently create transmural lesions. The epicardial temperatures remained below 80 degrees C in combination with the constant movement of the epicardial wall suggested safety from thermal damage to the ambient organs.

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.

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.

Ultrasonic characterization of myocardial photocoagulation lesion size in vivo during Nd:YAG laser irradiation.

Endocardial coagulation lesions were created using transcatheter continuous-wave Nd:YAG laser irradiation. Ultrasound monitoring of thermal lesion dimensions was performed using 7.5-MHz and 10-MHz transducers directly from the epicardial surface in short-axis configuration (group A) or through the chest wall (group B). A total of 33 lesions were created in 10 dogs at energy levels ranging from 300 J to 1000 J. Mean histological lesion width (HW) compared with ultrasonically determined mean width (UW) showed that the differences (mean +/- standard deviation) in group A (UW - HW) was = 1.14 +/- 0.8 mm, which was not statistically significantly different from zero. In group B, (UW - HW) = 2.04 mm +/- 0.7 mm (p < .05), which was statistically significantly different from zero. Mean histological depth (HD) differentially related to ultrasound mean depth (UD) for group A and B combined showed (UD - HD) = -0.19 mm +/- 0.46 mm, not statistically significantly different from zero. The frequency distribution for width in group A showed magnitude of UW-HW > 3 mm in 32% of cases. In group B magnitude of UW-HW > 3 mm in 15%, whereas ultrasound width was larger than histology in 75% of the cases. For depth, magnitude of UD-HD > 3 mm in 15% of cases. With further refinement of the technique, ultrasonic tissue characterization may become a useful adjunct to monitoring lesion dimensions during transcatheter laser photocoagulation.

Catheterization technique for laser photoablation of atrioventricular conduction from the aortic root in dogs.

A simple catheterization technique for producing suppression or block of atrioventricular (AV) conduction in dogs by neodymium:YAG (Nd:YAG) laser photocoagulation from the aortic root is described. In 14 canines, electrode catheters were percutaneously advanced to the high right atrium, to the His bundle area at the tricuspid valve (right His [RH]), and the noncoronary cusp of the aortic valve (left His [LH]). A 400 microns optical fiber was fed into the lumen of the LH catheter. Continuous wave Nd:YAG lasing at lambda = 1,064 nm at 15-20 watts was performed at the site of the largest recorded LH deflection, opposite to the RH catheter, until complete AV block (CAVB, group I, eight dogs) or persistent A-H prolongation (AHPr, group II, four dogs) occurred; in two animals, laser photoablation was unsuccessful. CAVB and AHPr were achieved in < 140 seconds of lasing. Mean lasing time was 51 +/- 41 seconds, total energy delivered, 776 +/- 601 J. There were no complications. Dogs were followed for up to 120 days. In group I, 6/6 dogs followed for at least 1 week continued to have CAVB (three AV nodal, five infra-His). In group II, 1/4 dog progressed to infra-His CAVB; 3/4 had depressed AV nodal function. AV block was not reversed by isoproterenol. Aortic root angiograms revealed intact valve function in all. Histology showed various degrees of damage and repair of AV junctional tissue. There were no valvular perforations. Transcatheter Nd:YAG laser photocoagulation of the AV junction from the aortic root is a fast, simple, and safe method for creating AV conduction block in dogs.

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.

Neodymium:YAG contact laser photocoagulation of the in vivo canine epicardium: dosimetry, effects of various lasing modes, and histology.

UNLABELLED: Neodymium:YAG laser photocoagulation (LPC) is an investigational technique for the treatment of drug-resistant postinfarction ventricular tachycardia that requires cardiopulmonary bypass and open heart surgery. The purpose of this experimental study was to evaluate the feasibility of contact epicardial LPC to reach subepicardial, deep myocardial, and subendocardial regions without ventriculotomy and to analyze the dose-response relationships of this new technology. In 24 open-chest, closed heart dogs, a total of 219 epicardial laser lesions were generated under sterile conditions. Laser source was a continuous wave 1064 nm Nd:YAG; the delivery system consisted of a 400 mu bare quartz fiber fed into an 8F electrode catheter in direct contact with the epicardial surface. Laser variables were power at 10-15-20 W; lasing time, 6-12-18-24 s; lasing mode, continuous and pulse-pause; fiber mode, optical fiber tip inside and extending out from the electrode catheter. Hearts were harvested at 1 week. Histologic measurements included lesion surface diameter, internal diameter, and depth. RESULTS: Significant linear correlation was found between the total delivered energy and all measured lesion parameters. Transmural lesions were found at energy levels of 270-480 J. Maximum depth measured up to 1.68 cm; at high energies, it was limited by myocardial thickness only. At constant energy levels, power and lasing time did not independently affect lesion dimensions; lasing mode and fiber mode had statistically significant but minor effects. Laser lesions were homogeneous and sharply demarcated without epicardial crater or endocardial thrombus formation. Endocardial surface cooling by circulating blood and the presence of epicardial vessels resulted in modifications in lesion morphology. In 29 out of 74 grossly transmural lesions, there was a 0.082 +/- 0.127 cm thin surviving subendocardium. Forty-five coagulation lesions were truly transmural with no surviving myocardial strands. In conclusion, contact epicardial LPC can result in deep, transmural myocardial coagulation lesions. Lesion dimensions can be adequately controlled by total delivered energy. Closed heart epicardial Nd:YAG laser photocoagulation could become a new, less invasive surgical technique for the treatment of drug-resistant ventricular tachycardia.

Thermal laser arterial injury and prostacyclin administration in dogs: thrombotic and hyperplastic consequences.

Angioplasty is considered as an alternative to surgical reconstruction of arteriosclerotic vessels especially since lasers and atherectomy devices have become clinically available. However, the resulting arterial injury may lead to acute thrombotic occlusion and chronic restenosis because of hyperplastic vascular repair. The purpose of this experimental study was to evaluate the consequences of thermal laser arterial injury on platelet deposition and myointimal hyperplasia in dog femoral arteries. An intraarterial, short-term prostacyclin (PGI2) infusion was given to evaluate the antithrombotic and antiproliferative effects of this drug. Severe arterial necrosis, partly carbonized and vacuolized, extending to the adventitia was induced by a transluminal heated laser probe motion. The platelet deposition after one hour was 33.62 +/- 6.56 (x 10(6)/cm2.) (mean +/- SEM) without prostacyclin, after 40 ng/kg/min prostacyclin (PGI2) 24.70 +/- 5.45 and after 400 ng/kg/min 9.3 +/- 2.26 (p less than 0.005 no PGI2 vs 400 ng/kg/min PGI2). Myointimal hyperplasia was present eight weeks after thermal laser vascular injury independent of the initially administered prostacyclin. In conclusion, acutely thrombotic and chronically hyperplastic femoral arteries were found following transluminal thermal arterial injury in dogs. Prostacyclin administration could be clinically beneficial in reducing acute vascular thrombosis following thermal angioplasty. Short-term use of this substance, however, may not prevent a hyperplastic response to angioplasty.

Effects of vascular runoff on myointimal hyperplasia after mechanical balloon or thermal laser arterial injury in dogs.

BACKGROUND: Clinical evidence suggests that poor vascular runoff reduces the long-term success rate of femoral angioplasty procedures. The purpose of this experimental study was to examine myointimal hyperplasia of dog femoral arteries after balloon denudation, thermal laser arterial injury, or sham operation in normal and reduced vascular runoff conditions. METHODS AND RESULTS: Before mechanical balloon injury or transluminal heated laser probe motion, the peripheral vascular runoff of dogs was reduced by ligating the femoral artery below its three distal side branches, decreasing the femoral flow rate from 114 +/- 9 to 52 +/- 5 ml/min (mean +/- SEM). Endothelial denudation with a predominantly intact elastic internal membrane and circumferential structural changes in the media were noted by light microscopy 1 hour after balloon injury. Focal completely necrotic lesions of intima and media were found 1 hour after thermal laser arterial injury. After 8 weeks, the maximal thickness of neointima plus media of the site of previous intervention was greater after balloon injury (0.45 +/- 0.03 mm) and thermal laser injury (0.54 +/- 0.03 mm) than after sham operation (0.40 +/- 0.01 mm; p less than 0.001) in normal runoff dogs. Reduced vascular runoff augmented myointimal hyperplasia both in the balloon-injured and thermally damaged arteries; the wall thickness increased from 0.45 +/- 0.03 to 0.93 +/- 0.10 mm and from 0.54 +/- 0.03 to 0.65 +/- 0.05 mm, respectively (p less than 0.001). The neointimal and medial wall area of the balloon-injured arteries contributed 48% to the area encompassed by the external elastic membrane compared with an 81% portion when vascular runoff was reduced (p less than 0.01). A 47% neointimal and medial wall area was found in thermally injured arteries with normal runoff compared with 63% after runoff reduction (p less than 0.05). CONCLUSION: This study suggests that hemodynamic factors associated with poor vascular runoff play an important role in extending myointimal hyperplasia independent of method and severity of the arterial injury during angioplasty.

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)

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)

Influence of probe motion on laser probe temperature in circulating blood.

The purpose of this study was to evaluate the effect of probe motion on laser probe temperature in various blood flow conditions. Laser probe temperatures were measured in an in vitro blood circulation model consisting of 3.2 nm-diameter plastic tubes. A 2.0 mm-diameter metal probe attached to a 300 microns optical quartz fiber was coupled to an argon laser. Continuous wave 4 watts and 8 watts of laser power were delivered to the fiber tip corresponding to a 6.7 +/- 0.5 and 13.2 +/- 0.7 watts power setting at the laser generator. The laser probe was either moved with constant velocity or kept stationary. A thermocouple inserted in the lateral portion of the probe was used to record probe temperatures. Probe temperature changes were found with the variation of laser power, probe velocity, blood flow, and duration of laser exposure. Probe motion significantly reduced probe temperatures. After 10 seconds of 4 watts laser power the probe temperature in stagnant blood decreased from 303 +/- 18 degrees C to 113 +/- 17 degrees C (63%) by moving the probe with a velocity of 5 cm/sec. Blood flow rates of 170 ml/min further decreased the probe temperature from 113 +/- 17 degrees C to 50 +/- 8 degrees C (56%). At 8 watts of laser power a probe temperature reduction from 591 +/- 25 degrees C to 534 +/- 36 degrees C (10%) due to 5 cm/sec probe velocity was noted. Probe temperatures were reduced to 130 +/- 30 degrees C (78%) under the combined influence of 5 cm/sec probe velocity and 170 ml/min blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Optical properties of normal, diseased, and laser photocoagulated myocardium at the Nd: YAG wavelength.

Laser photocoagulation of the myocardium effectively destroys arrhythmogenic foci. The purpose of this study was 1) to compare the optical properties of canine myocardium before and after photocoagulation, 2) to compare the canine model with clinical cases by measuring the optical properties of human myocardium, and 3) to assess the optical properties of human myocardial scar and epicardial fat tissue. Measured optical properties were the absorption coefficient, mu a; scattering coefficient, mu s; and scattering anisotropy factor, g. Optical measurements were performed at 1064 nm wavelength on thin plane parallel tissue slices using the integrating sphere method with glass hemispheres on either side of the sample. The study showed 1) an increase of the scattering coefficient by 40% and a two- to threefold increase in reduced scattering coefficient as a result of photocoagulation; 2) that the mu a (0.035 +/- 0.024 mm-1) and mu s (17.9 +/- 3.8 mm-1) of human myocardium were not significantly different from mu a (0.043 +/- 0.021 mm-1) and mu s (17.3 +/- 2.2 mm-1) of canine myocardium, whereas the human g (0.964 +/- 0.005) was slightly different from the canine g (0.974 +/- 0.008); and 3) that the mu a (0.021 +/- 0.016 mm-1) of epicardial fat and mu s (13.8 +/- 1.1 mm-1) of myocardial scar were significantly lower than those of normal myocardium. A dynamic model of laser-tissue interaction incorporating these changes and inhomogeneities is necessary to better describe light distribution during laser photocoagulation.