Takashi Nitta

Profound systemic hypothermia inhibits the release of neurotransmitter amino acids in spinal cord ischemia

Profound hypothermia induced with cardiopulmonary bypass has a protective effect on spinal cord function during operations on the thoracoabdominal aorta. The mechanism of this protection remains unknown. It has been proposed that the release of excitatory amino acids in the extracellular space plays a causal role in irreversible neuronal damage. We investigated the changes in extracellular neurotransmitter amino acid concentrations with the use of in vivo microdialysis in a swine model of spinal cord ischemia. All animals underwent left thoracotomy and right atrium-femoral artery cardiopulmonary bypass with additional aortic arch perfusion. Lumbar laminectomies were then done and microdialysis probes were inserted stereotactically in the anterior horn of the second and fourth segments of the lumbar spinal cord. The probes were perfused with artificial cerebrospinal fluid at a rate of 2 microliters/min and 15-minute samples were assayed by high-performance liquid chromatography. Group 1 animals (n = 6) underwent aortic clamping distal to the left subclavian artery and proximal to the renal arteries for 60 minutes at normothermia (37 degrees C) and group 2 animals (n = 5) were cooled to a rectal temperature of 20 degrees C before application of aortic clamps, maintained at this level during cardiopulmonary bypass until the aorta was unclamped, and then slowly rewarmed to 37 degrees C. Seven amino acids were studied, including two excitatory neurotransmitters (glutamate and aspartate) and five putative inhibitory neurotransmitters (glycine, gamma-aminobutyric acid, serine, adenosine, and taurine). Glutamate exhibited a threefold increase in extracellular concentration during normothermic ischemia compared with baseline values and remained elevated until 60 minutes after reperfusion. The increase in aspartate concentration was not significant. The extracellular concentrations of glycine and gamma-aminobutyric acid also increased significantly during ischemia and reperfusion. Hypothermia uniformly prevented the release of amino acids in the extracellular space. Glutamate levels remained significantly decreased even after rewarming to normothermia whereas glycine levels returned to baseline values. These results are consistent with a role for excitatory amino acids in the production of ischemic spinal cord injury and suggest that the mechanism of hypothermic protection may be related to decreased release of these amino acids in the ischemic spinal cord.

Radial Approach: A New Concept in Surgical Treatment for Atrial Fibrillation I. Concept, Anatomic and Physiologic Bases and Development of a Procedure

BACKGROUND The maze procedure cures atrial fibrillation; however, it isolates the pulmonary vein area and results in discordant activation in certain adjacent left atrial segments, which affects left atrial function. To preserve a more physiologic atrial transport function, we developed a new concept of surgical treatment for atrial fibrillation-the radial approach. The atrial incisions radiate from the sinus node toward the atrioventricular annular margins to allow a more physiologic atrial activation sequence and parallel the atrial coronary arteries to preserve blood supply to most atrial segments. METHODS We examined the atrial coronary arteries and the activation sequence during sinus rhythm in normal canine hearts to design the atrial incisions according to the concept of a radial approach. RESULTS The pattern of coronary artery distribution was centripetal, branching from the right coronary or left circumflex coronary artery at the right or left atrioventricular groove and spreading toward the sinus node. The endocardial mapping of the atria disclosed some important findings in designing the atrial incisions of the radial approach: the activation sequence at the left atrial septum and at the posterior left atrium between the pulmonary vein orifices. The atrial incisions were designed according to these findings. CONCLUSIONS The radial approach may represent a more physiologic atrial transport function.

Radial approach: a new concept in surgical treatment for atrial fibrillation. II. Electrophysiologic effects and atrial contribution to ventricular filling.

BACKGROUND In a previous study the atrial incisions that follow the concept of the radial approach were designed according to the activation sequence during sinus rhythm and the atrial coronary artery anatomy in normal dogs. The purpose of the present study was to determine whether the radial approach provides a more physiologic activation sequence and atrial transport function than the maze procedure. METHODS Ten dogs that had undergone the radial approach (n = 5) or the maze procedure (n = 5) were studied 6 weeks postoperatively. Sinus node function and inducibility of atrial fibrillation were examined before and after operation. The atria were mapped endocardially with 212 electrodes, and atrial activation sequences during sinus rhythm and right atrial pacing were examined. Atrial transport function was assessed by transepicardial Doppler echocardiography. RESULTS No dogs developed sinus node dysfunction postoperatively. Both the radial approach and the maze procedure equally prevented sustained atrial fibrillation. The atrial activation sequence was more synchronous after the radial approach than after the maze procedure. There was no electrically isolated region after the radial approach. The total activation time of the left atrium was significantly shorter after the radial approach than after the maze procedure (53.6+/-9.8 versus 70.5+/-9.6 ms, p<0.05). The ratio of peak flow velocity of the E wave to the A wave (peak E/A) of the transmitral Doppler flow was significantly smaller after the radial approach than after the maze procedure (1.7+/-0.4 versus 3.5+/-1.7, p<0.05). The atrial filling fraction of the transmitral Doppler flow was significantly larger after the radial approach than after the maze procedure (29.9%+/-7.3% versus 14.8%+/-5.0%, p<0.01). There was no significant difference in peak E/A and atrial filling fraction of the transtricuspid Doppler flow between the two procedures. CONCLUSIONS The radial approach provides a more synchronous activation sequence and atrial transport function, and thus may represent a more physiologic alternative to the maze procedure as a surgical treatment for atrial fibrillation.

Retrograde Infusion of Lidocaine or l-Arginine Before Reperfusion Reduces Myocardial Infarct Size

BACKGROUND Retrograde perfusion preserves ischemic myocardium when initiated shortly after coronary artery occlusion. However, benefits diminish as the delay increases. In this study, we used this technique to deliver agents known to reduce the injury associated with the reperfusion of ischemic myocardium. We proposed that the local delivery of lidocaine or L-arginine before reperfusion would reduce the damage caused during reperfusion, even after a delay between onset of ischemia and intervention designed to approximate clinical reality. METHODS In a porcine model of myocardial ischemia, the left anterior descending coronary artery was snared immediately distal to its second diagonal branch. After 1 hour of occlusion, 34 animals were randomized into six groups: no intervention (control) (n = 6); administration of normal saline solution into the great cardiac vein (Retro-NS) (n = 6); administration of lidocaine either intravenously (i.v.-LID) (n = 6) or retrograde (Retro-LID) (n = 6); and administration of L-arginine either intravenously (i.v.-L-ARG) (n = 5) or retrograde (Retro-L-ARG) (n = 5). After 90 minutes of ischemia, the snare was released, and the myocardium was reperfused for 3 hours. Two-dimensional echocardiograms were made prior to occlusion and 60, 150, 210, and 270 minutes after occlusion. The infarct size and the area at risk were determined by lissamine green and triphenyltetrazolium chloride staining with computer planimetric quantification. Regional wall motion was assessed by a wall motion score: normal = 1; mild hypokinesia = 2.0; severe hypokinesia = 2.5; and akinesia = 3. RESULTS The area of the left ventricle at risk for infarction was similar in all groups and represented 25.4% (5.2% [standard deviation]) of the left ventricular mass (p = 0.63). The percent area of infarction in the area at risk after 3 hours of reperfusion was 76.7% (7.1% for the control group, 73.9% (5.7%) for the Retro-NS group, 72.1% (8.7%) for the i.v.-LID group, 54.5% (10.2%) for the Retro-LID group, 58.8% (4.0%) for the i.v.-L-ARG group, and 54.3% (4.0%) for the Retro-L-ARG group p < 0.005, Retro-LID and Retro-L-ARG versus Control, Retro-NS, and i.v.-LID; p < 0.03, i.v.-L-ARG versus control and Retro-NS). No significant difference in wall motion scores between groups was detected by echocardiography (p = 0.578). CONCLUSIONS Retrograde delivery of lidocaine or L-arginine before reperfusion reduces infarct size without acutely affecting wall motion after 90 minutes of ischemia and 3 hours of reperfusion. Lidocaine must be present before reperfusion to have an effect, whereas L-arginine is beneficial if it is delivered at the time of reperfusion.

Human ventricular tachycardia: Precise intraoperative localization with potential distribution mapping

Electrophysiologically guided operations for ventricular tachycardia (VT) have been directed exclusively by activation time maps. Even with computer-assisted mapping, extensive editing is required, which prolongs the duration of the operation and which may introduce significant error. In contrast, potential distribution maps can be constructed in less than 3 minutes and can be viewed as a movie of developing and receding potentials. In 4 patients undergoing operation for VT, endocardial mapping was performed using form-fitting electrodes containing 160 points. A computerized mapping system, capable of simultaneously recording 256 channels of data, was used to analyze data and to display potential distribution maps sequentially at 1-millisecond intervals as a color movie. A total of eight morphologies of sustained VT were mapped. The mean VT cycle length was 340 +/- 40 milliseconds (range, 274 to 394 milliseconds). In 3 patients with ischemic heart disease, four VT morphologies originated from the subendocardium. All were successfully ablated with cryoablation alone or in conjunction with aneurysmectomy and endocardial resection. A fourth patient with VT secondary to cardiomyopathy had multiple morphologies and received an implantable cardioverter defibrillator. Potential distribution maps correlated well with the concomitant activation time maps. Thus, potential distribution mapping provides a rapid and accurate means of identifying the site of origin of VT facilitating intraoperative mapping in patients undergoing surgical ablation.

Return Cycle Mapping After Entrainment of Ventricular Tachycardia

BACKGROUND The central common pathway, which is the target for ablation in reentrant ventricular tachycardia, can be localized by entrainment mapping techniques. However, localization of the pathway is not always possible because of the elevated pacing threshold and the low voltage and fractionated potentials at the pathway. We examined whether return cycle mapping after entrainment localizes the pathway without pacing at the pathway or recording the potentials from the pathway and determined the required electrode resolution to localize the pathway. METHODS AND RESULTS Epicardial mapping was performed with 253 unipolar electrodes during and after entrainment of 13 morphologies of ventricular tachycardia that were induced in dogs 4 days after infarction. The return cycle was calculated by subtracting the first activation time from the second activation time after the last stimulus and the return cycle distribution map was constructed for each stimulation site. The return cycle isochrones equal to the ventricular tachycardia cycle length converged on the lines of conduction block irrespective of the stimulation site, and the central common pathway was localized at the region between the intersections of the return cycle isochrones after entrainment from different stimulation sites. The potentials from the central common pathway were not required to localize the pathway, and the mapping accuracy did not change with or without analysis of the potentials from the pathway. According to the correlation between the electrode resolution and the mapping accuracy, an interelectrode distance of 8.5 mm was estimated as sufficient resolution for successful tachycardia termination during radiofrequency ablation guided by return cycle mapping. CONCLUSIONS Return cycle mapping after entrainment localizes the central common pathway without pacing at the pathway or recording the potentials from the pathway. This new mapping technique could improve the success rate of the ablative procedures.