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Eugene Patterson

Publications and source records attributed to Eugene Patterson.

At least 19 recordsLinked to original sources
PubMed2006

Interactive atrial neural network: Determining the connections between ganglionated plexi.

BACKGROUND: The electrophysiologic functions of the intrinsic cardiac autonomic nervous system (ANS) are not well understood. OBJECTIVES: The purpose of this study was to investigate the functional interactions between ganglionated plexi within the intrinsic cardiac ANS. METHODS: The hearts of 21 dogs were exposed via right and/or left thoracotomy to expose the (1) anterior right ganglionated plexi near the caudal end of the sinoatrial node, (2) inferior right ganglionated plexi at the junction of inferior vena cava and atria, and (3) superior left ganglionated plexi near the junction of left superior pulmonary vein and left pulmonary artery. Ganglionated plexi were stimulated at 0.6 to 8.0 V (square waves, 20 Hz, 0.1-ms duration). Sinus rate, AH interval during atrial pacing, and ventricular rate during atrial fibrillation were compared before and after ganglionated plexi stimulation and after their ablation. RESULTS: Anterior right ganglionated plexi stimulation induced significant AH prolongation and slowing of ventricular rate and sinus rate. When inferior right ganglionated plexi was ablated, slowing of sinus rate by anterior right ganglionated plexi stimulation was unaltered, but inhibition of AV conduction was eliminated. Superior left ganglionated plexi stimulation induced similar effects on sinus and AV nodal function, and sinus rate slowing was markedly attenuated by anterior right ganglionated plexi ablation. Ablation of both anterior right ganglionated plexi and inferior right ganglionated plexi eliminated AV conduction inhibition but not sinus rate slowing by superior left ganglionated plexi stimulation. CONCLUSION: This study provides functional evidence for the interconnections between ganglionated plexi to modulate sinus and AV nodal function, supporting clinical evidence that interconnections within the intrinsic cardiac ANS are critical elements in identifying the targets for atrial fibrillation ablation.

Animals↗
PubMed2006

The neural basis of atrial fibrillation.

This review addresses recent basic and clinical studies which suggest that targeting autonomic nerves and ganglia on the heart can result in suppression of atrial fibrillation (AF) with less damage to myocardium than the presently employed procedure which involves extensive pulmonary vein (PV) isolation from the rest of the left atrium. CLINICAL STUDIES: Clinical electrophysiologists in 1998 discovered that the majority of patients with paroxysmal form of AF, resistant to drugs and cardioversion, had focal, ectopic firing arising from the myocardial sleeves covering the PVs. They developed a strategy which called for inducing radiofrequency lesions which would supposedly isolate the PVs from the atria thereby curing this form of AF. To date this strategy has had limited success (70-85%). A new approach relies on targeting the ganglionated plexi (GP) at the entrances of the PVs. Several clinical reports provide evidence that this new approach can increase the success rate for radiofrequency ablation of paroxysmal AF (91-99%). BASIC STUDIES: Experimental investigations in animal studies, both in vivo and in vitro, have accumulated evidence for a mechanistic basis for the ablation of GP to terminate paroxysmal AF. Specifically, release of the neurotransmitter, acetylcholine, from these GP causes shortening of atrial and PV sleeve refractoriness. In addition, the concomitant release of adrenergic neurotransmitters mobilizes excess calcium intracellularly leading to early afterdepolarizations and triggered firing particularly in PV cells. We conclude that hyperactivity of these local cardiac GP play a critical role in initiating the paroxysmal form of AF resistant to drugs and cardioversion. Targeting the GP for ablation can substantially increase the success rate for terminating AF in these patients.

Action Potentials↗
PubMed2006

Sodium-calcium exchange initiated by the Ca2+ transient: an arrhythmia trigger within pulmonary veins.

OBJECTIVES: The hypothesis that an increased or prolonged Ca2+ transient during an abbreviated action potential can give rise to early afterdepolarizations (EADs) and triggered arrhythmia by enhanced forward sodium-calcium (Na-Ca) exchange was examined. BACKGROUND: Because pulmonary veins have the shortest action potential of any cardiac tissue, we examined this hypothesis in canine pulmonary vein sleeves during interventions further shortening the action potential and increasing the calcium transient. METHODS: Extracellular bipolar electrode, intracellular microelectrode, and isometric force (a surrogate marker for the Ca2+ transient) recordings were obtained from superfused canine pulmonary veins. RESULTS: An elevation and prolongation of the terminal phase of repolarization (EADs) were observed during interventions increasing contractile force; isoproterenol or norepinephrine (3.2 x 10(-11) to 3.2 x 10(-7)M), hypothermia, and pacing (post-extrasystolic potentiation, post-pacing pause). The EAD formation was prevented by ryanodine (10 microM) or reversed by transiently increasing [Ca2+](o) from 1.35 to 5 mM (inhibition of forward Na-Ca exchange). Pacing-induced EADs were enhanced by re-introduction of normal Tyrode solution (Na+ = 130 mM) after substitution of 30 mM NaCl with 30 mM LiCl (stimulation of forward Na-Ca exchange). With norepinephrine or isoproterenol (3.2 x 10(-8)M) + acetylcholine (10(-7)M) (to enhance the Ca2+ transient and further shorten the abbreviated action potential, respectively), tachycardia-pause initiated arrhythmia (1,132 +/- 153 beats/min) lasting >1 s was observed. Rapid firing was prevented by either suppression of the Ca2+ transient (ryanodine) or transiently increasing [Ca2+](o). CONCLUSIONS: The data show EAD formation in superfused canine pulmonary veins, enhanced by an increased Ca2+ transient and increased Na-Ca exchange current. With subsequent shortening of the action potential with acetylcholine, tachycardia-pause triggers rapid firing within the PV sleeve.

Action Potentials↗
PubMed2006

Suppression of autonomic-mediated triggered firing in pulmonary vein preparations, 24 hours postcoronary artery ligation in dogs.

INTRODUCTION: Rapid arrhythmia originating within pulmonary veins (PVs) precipitates atrial fibrillation (AF) in man. To determine a possible basis for an increased incidence of AF observed peri-myocardial infarction in man, we compared AF induction in vivo and triggered arrhythmia formation within isolated PVs in vitro in normal dogs and dogs studied 24 hours postcoronary artery ligation. METHODS AND RESULTS: The incidence of AF initiated by atrial premature stimuli was increased in dogs postcoronary artery ligation (6/9) versus normal (2/12) (P = 0.03). In isolated PVs from normal hearts, pause-dependent early afterdepolarizations (EADs) were enhanced by catecholamines. Rapid arrhythmia (1,182 +/- 213 beats/min) was triggered during isoproterenol/norepinephrine (32 nM) + acetylcholine (100 nM) (N = 16/23) using the same pacing pauses eliciting EADs. Rapid arrhythmia (802 +/- 161 beats/min) was also triggered by local autonomic nerve stimulation (ANS; N = 18/23). Despite equivalent pause-dependent afterdepolarization formation in PVs from infarcted hearts, a rightward 45-fold and 28-fold shift in the dose-response curve for afterdepolarization enhancement was observed for isoproterenol and norepinephrine, respectively (P < 0.02). ANS (N = 1/19) and isoproterenol/norepinephrine (32 nM) + acetylcholine (100 nM) (N = 0/9 and 0/12, respectively) (P = 0.0001) failed to elicit arrhythmia formation. Beta-adrenergic receptor desensitization was associated with a 2.5-fold increase in PV beta-adrenergic receptor kinase (ARK). CONCLUSION: The data demonstrate decreased susceptibility of isolated canine PVs for arrhythmia triggered by local ANS, or pacing pauses in the presence of a catecholamine + acetylcholine, postmyocardial infarction, despite a greater susceptibility of the intact heart to AF. The decreased arrhythmia susceptibility was observed coincident with an increase in beta-ARK and a decreased responsiveness to beta-adrenergic receptor agonists.

Animals↗
PubMed2005

Proteasome degradation of GRK2 during ischemia and ventricular tachyarrhythmias in a canine model of myocardial infarction.

Arrhythmia-prone subepicardial border zone (EBZ) tissue demonstrates decreased G protein receptor kinase 2 (GRK2) activity and increased sensitivity to isoproterenol 6-24 h after coronary artery ligation (CAL) in the dog. With the use of a semiquantitative immunofluorescence technique, the relative fluorescence intensity (RF) of GRK2 in EBZ decreased to 24% of that in a remote site (RS) (P < 0.01, n = 30 cells from 3 dogs), whereas GRK5 RF did not change. Confocal studies of cardiac tissue from transgenic mice overexpressing GRK2 validated the use of a semilogarithmic relationship between RF and GRK2 activity. As shown with the use of quantitative real-time RT-PCR, both GRK2 and GRK5 mRNA were not decreased at 24 h in EBZ (n = 6 dogs) relative to RS control, indicating that the decrease of GRK2 in the EBZ is likely due to posttranscriptional degradation following CAL. Pretreatment of six dogs with the selective proteasome inhibitor bortezomib provided 100% (EBZ) and 50% (infarct) protection against loss of GRK2 at 24 h. There was an absence of rapid (>300 beats/min) and very rapid (>360 beats/min) ventricular triplets that are highly predictive of sudden cardiac death during ECG monitoring in the bortezomib-pretreated animals in contrast to nonpretreated infarcted animals. We have demonstrated that the dramatic decrease in GRK2 in cardiac ischemic tissue can be largely blocked by prior proteasome blockade and that this is associated with significant cardioprotection against malignant ventricular tachyarrhythmias.

Animals↗
PubMed2005

Rapid and stable re-entry within the pulmonary vein as a mechanism initiating paroxysmal atrial fibrillation.

OBJECTIVES: We investigated the hypothesis that re-entrant pulmonary vein (PV) tachycardias may serve as a mechanism for initiating and sustaining paroxysmal atrial fibrillation (PAF). BACKGROUND: The mechanisms of rapid repetitive discharges from the PV initiating PAF remain incompletely understood. Pulmonary vein myocardial sleeves appear to provide a favorable substrate for re-entry formation. METHODS: The electrophysiologic properties of canine PV sleeves were investigated using a combination of high-resolution optical mapping (n = 5) and extracellular bipolar and intracellular microelectrode recordings (n = 56) in a superfused PV preparation. RESULTS: From the left atrium to distal PV, there was progressive shortening of the action potential (AP) duration, reduction in AP and bipolar electrogram amplitude, and depolarization of resting membrane potentials. Sustained PV tachycardias were induced exclusively in the presence of acetylcholine (10(-7) to 10(-6) mol/l, n = 12). Sustained PV tachycardias were rapid (mean cycle length = 93 +/- 15 ms), regular, and capable of induction, termination, and resetting by single extrastimuli. Re-entry as the mechanism underlying PV tachycardias was confirmed by optical mapping (n = 5). Acetylcholine also reduced the slope of the AP restitution curve and suppressed AP alternans (n = 6). Importantly, PV tachycardias exhibited 1:1 conduction into the atrium at short cycle lengths (<100 ms), emphasizing the potential role of re-entrant PV tachycardia in atrial fibrillation. CONCLUSIONS: Pulmonary veins provide a favorable substrate for re-entry formation. Heterogeneity of the electrophysiologic properties and marked abbreviation of action potential duration and refractoriness by acetylcholine combine to produce rapid and stable re-entrant PV tachycardias. Elevated parasympathetic tone and re-entrant PV tachycardia may serve as a mechanism underlying the perpetuation of PAF.

Acetylcholine↗
PubMed2005

Delineation of AV conduction pathways by selective surgical transection: effects on antegrade and retrograde transmission.

INTRODUCTION: The role for transitional cells as determinants of AH and HA conduction was examined in the superfused rabbit AV junction. METHODS: Bipolar electrodes and microelectrodes were used to record antegrade A-H and retrograde H-A activation, before and after transection of the transitional cell input to the compact AV node. RESULTS: During pacing from the high right atrium, inferior to the coronary sinus os, beneath the fossa ovalis, or on the anterior limbus, AV Wenckebach block (WB) was mediated by identical transitional cells grouped in close apposition to the compact AV node. Paced WB cycle lengths were shorter from the high right atrium (196+/-12 msec) and inferior to the coronary sinus os (195+/-8 msec) versus the fossa ovalis (217+/-9 msec) or anterior limbus (206+/-11 msec). With His bundle pacing, retrograde HA WB (211+/-17 msec) was observed within the N cell region within the compact AV node. After transection of posterior and superior transitional cell input to the compact AV node, the antegrade AH WB cycle length was prolonged (245+/-18 msec), with an increased WB incidence within the NH region (compact AV node)(5% to 41%; p=0.014). The incidence of retrograde HA WB determined within the NH region was increased (30% to 88%), with a decrease in the stimulus-fast pathway conduction time (98+/-7 to 49+/-6 msec; p<0.01). CONCLUSIONS: The data demonstrate (1) a common transitional cell population determining AH WB, independent of atrial stimulation site, and (2) a plasticity of transitional cell-compact AV node connections, with rapid AH and HA conduction favored by removal of posterior/superior AV nodal input.

Analysis of Variance↗
PubMed2005

Electrical stimulation to identify neural elements on the heart: their role in atrial fibrillation.

EXPERIMENTAL STUDIES: Anesthetized dogs were subjected to a right then left thoracotomy. Two modes of electrical stimulation were used to activate ganglionated plexi (GP) on the epicardium of the atria: (1) Near the base of each pulmonary vein (PV), trains of high frequency stimuli (HFS) were coupled to each atrial paced beat so as to fall within the refractory period to achieve nerve stimulation without atrial excitation; and (2) Continuous HFS was applied via plaque electrodes sutured to epicardial fat pads (containing a GP) near the right superior (RS) and left superior (LS) PVs. The chest was then closed. An ablation catheter, inserted percutaneously, was positioned fluoroscopically in the right atrium across from the epicardial plaque electrode near the RSPV. Transeptal puncture was used to place an ablation catheter at the LSPV-left atrial junction. HFS applied to each of the epicardial fat pads induced atrial fibrillation (AF) and also caused high grade AV block due to a strong parasympathetic effect on the AV node. Radiofrequency ablation from the right and left atrial endocardium abolished the vagal response to HFS delivered to the plaque electrodes on the fat pads close to the RSPV and LSPV, respectively. CLINICAL STUDIES: Sixty (60) patients with paroxysmal or persistent AF underwent PV antrum isolation (27 patients) or PV antrum isolation plus left atrial GP ablation (33 patients). Endocardial HFS at the border of the PV antra near the 4 GPs produced AF and high grade AV block (vagal response) during AF. RFA at these sites abolished the vagal response. Testing in a small number of patients with very short follow-up suggests that adding GP ablation to PV antrum isolation may increase ablation success (absence of AF recurrence) from 70% to 91%. CONCLUSIONS: These basic and clinical studies suggest that localized cardiac autonomic ganglia (GPs) may play a critical role in the initiation and maintenance of AF.

Animals↗
PubMed2005

Triggered firing in pulmonary veins initiated by in vitro autonomic nerve stimulation.

BACKGROUND: Rapid firing within pulmonary vein sleeves frequently initiates atrial fibrillation. The role of the autonomic nervous system in facilitating spontaneous firing is unknown. OBJECTIVES: The purpose of this study was to determine if autonomic nerve stimulation within canine atrium and pulmonary vein sleeves initiates arrhythmia formation. METHODS: Extracellular bipolar and intracellular microelectrode recordings were obtained from isolated superfused canine pulmonary veins (N = 28) and right atrium (N = 5) during local autonomic nerve stimulation. RESULTS: Autonomic nerve stimulation decreased pulmonary vein sleeve action potential duration (APD90 = 160 +/- 17 to 92 +/- 24 ms; P < .01) and initiated rapid (782 +/- 158 bpm) firing from early afterdepolarizations in 22 of 28 pulmonary vein preparations. The initial spontaneous beat had a coupling interval of 97 +/- 26 ms. Failure to induce arrhythmia was associated with a failure to shorten APD90 (151 +/- 18 to 142 +/- 8 ms; P = .39). Muscarinic receptor blockade (atropine: 3.2 x 10(-8) M) prevented APD90 shortening in 8 of 8 preparations and suppressed firing in 6 of 8 preparations, whereas beta1-adrenergic receptor blockade (atenolol: 3.2 x 10(-8) M) suppressed firing in 8 of 8 preparations. Suppression of the Ca transient with ryanodine (10(-5) M) completely suppressed firing in 6 of 6 preparations. Inhibition of forward Na/Ca exchange by a transient increase in [Ca+2]o completely suppressed firing in 4 of 6 preparations. The same stimulus trains produce atropine-suppressed APD90 shortening in superfused right atrial free wall but fail to produce triggered arrhythmia. CONCLUSIONS: The data demonstrate triggered firing within canine pulmonary veins with combined parasympathetic and sympathetic nerve stimulation. Both an enhanced Ca transient and increased Na/Ca exchange may be required for arrhythmia formation.

Animals↗
PubMed2005

Tumor necrosis factor alpha, rapid ventricular tachyarrhythmias, and infarct size in canine models of myocardial infarction.

Etanercept (2 mg/kg), a TNFalpha sequestrant, was administered 24 hours and 1 hour before LAD coronary artery ligation to examine the role of TNFalpha on lethal ventricular tachyarrhythmias and myocardial necrosis. Dogs treated with etanercept had decreased very rapid (>360 bpm) ventricular triplets (6 +/- 1/h, n = 8) 2 to 24 hours following coronary artery ligation compared with saline (21 +/- 6/h, n = 10, P < 0.05). This was concordant with 8-fold salvage of beta-adrenergic receptor kinase 1 (betaARK) activity compared with control (33.8 +/- 7.2% versus 4.3 +/- 2.2% of unoperated control tissue, P < 0.01, n = 5). Salvage of betaARK occurred without change in the thickness of the epicardial tissue overlying the infarct. In dogs pretreated with etanercept before a 2-hour occlusion/4-hour reperfusion of the LAD coronary artery, infarct mass decreased by 61% (% area at risk) and 55% (% left ventricular mass) in the etanercept group (n = 8) compared with saline (n = 9, P < 0.05). This was concordant with an etanercept-mediated six-fold decrease in leukocyte accumulation within ischemically injured myocardium. TNFalpha antagonism decreases malignant ventricular tachyarrhythmias and may relate to partial protection of normal betaARK-mediated desensitization of beta-adrenergic receptors. TNFalpha sequestration also decreases infarct size in an occlusion/reperfusion model of myocardial ischemia.

Adrenergic beta-Agonists↗
PubMed2004

Variability of AV nodal potentials recorded, in vivo: direct demonstration of dual AV nodal physiology.

OBJECTIVES OF STUDY: We developed a method to record extracellular A-V nodal potentials in the beating dog heart, in vivo. METHODS: In eleven Na-pentobarbital anesthetized, open-chest dogs, an octapolar electrode catheter (2 mm rings, 2 mm spacing) was inserted through a purse-string suture in the coronary sinus (CS) distal to the ostium and positioned electrographically so that the tip electrode recorded a His bundle (Hb) potential. RESULTS: Stable recordings of A-V nodal potentials (amplitude, 178 +/- 94 microV; duration 78 +/- 26 msec) were consistently made during sinus rhythm from the second and/or third bipolar pairs of electrodes. Programmed atrial stimulation and vagal stimulation resulted in loss of amplitude and increased duration of the A-V nodal potentials associated with A-H prolongation. In another series of experiments, crushing the sinus node in 6 dogs resulted in AV nodal rhythms with AV nodal potentials of varying amplitudes (132 to 840 microV) and durations (range 25 to 71 msec) as the earliest activation which preceded the Hb, atrial and ventricular deflections. One dog, showing dual AV nodal physiology as documented from the AV nodal function curve, had two distinctly different AV nodal potentials. The low-level, longer duration potentials were associated with longer (slow pathway) A-H intervals; whereas the shorter higher amplitude potentials (fast pathway) showed shorter A-H intervals, each occurring at a critical paced cycle length. CONCLUSION: We conclude that consistent extracellular AV nodal electrograms can be recorded in vivo although the configuration of these potentials varies depending on heart rate, autonomic stimulation and different arrhythmic conditions such as AV nodal escape rhythms and dual AV nodal physiology.

Action Potentials↗
PubMed2004

Fast pathway-His bundle connections in the rabbit heart.

OBJECTIVES: The incidence and the physiologic roles for direct fast pathway-His bundle connections were examined in 102 rabbit hearts. METHODS: Extracellular bipolar and intracellular microelectrode recordings were made from the superfused rabbit AV junction. RESULTS: In 13 of 27 preparations demonstrating anterior extensions of the fast pathway, the retrograde HA ERP and 2:1 block cycle length were shortened (128 +/- 12 and 145 +/- 5 msec, respectively) versus the remaining 89 preparations (178 +/- 15 and 185 +/- 10 msec, respectively, p < 0.01). The former values were similar to the ERP and 2:1 block cycle length of fast pathway transitional cells (128 +/- 23 and 141 +/- 4 msec, respectively), suggestive of a direct fast pathway-His bundle connection. A deflection recorded between the A and H potentials of the His bundle electrogram could be dissociated from both atrial and His bundle activation. Intracellular microelectrode recordings and light microscopy confirmed the deflection to be an accessory pathway consisting of an anterior extension of fast pathway transitional cells connecting the atrium and His bundle. Transection along the AV groove anterior to the compact AV node ( N = 5) increased the retrograde ERP and Wenckebach block cycle length by severing the AH connection, or transection of the penetrating bundle ( N = 4) produced antegrade AH block without altering rapid retrograde conduction. CONCLUSIONS: Fast pathway-His bundle connections were present in 13 of 102 rabbit hearts, providing an anatomic and physiologic basis for rapid retrograde VA conduction and a possible retrograde pathway for sustained AV nodal reentrant tachycardia.

Afferent Pathways↗
PubMed2004

Encapsulation of a plasminogen activator speeds reperfusion, lessens infarct and reduces blood loss in a canine model of coronary artery thrombosis.

In the present study, a polymer-encapsulated plasminogen activator was investigated as an alternative to restore blood flow more effectively than free plasminogen activator. While current fibrinolytic agents have limited efficacy, attributable to delayed onset of sustained reperfusion and bleeding complications, encapsulated plasminogen activators have shown promise in addressing these shortcomings. A polymer-encapsulated plasminogen activator could offer an effective formulation with a prolonged shelf-life. In this study, coronary artery thrombosis was produced in the anesthetized dog by the injection of thrombin + whole blood, and then one of five randomly selected formulations was administered intravenously: saline, blank microcapsules, free streptokinase (FREE SK), streptokinase and blank microcapsules (FREE SK + BLANK), or streptokinase entrapped in polymer microcapsules (MESK). MESK significantly accelerated the time to reperfusion compared to FREE SK or FREE SK + BLANK. Additionally, substantial reductions were observed in residual clot mass, infarct mass, reocclusion episodes, fibrinogen depletion and blood loss with MESK compared to FREE SK. The results of this study demonstrate that MESK accelerates thrombolysis and the restoration of blood flow compared to identical dosages of FREE SK while also reducing systemic fibrinogenolysis and blood loss. Microencapsulation may produce an improved dosage form for restoring arterial blood flow and reducing bleeding complications with thrombolytic therapy.

Animals↗
PubMed2004

Improving thrombolysis with encapsulated plasminogen activators and clinical relevance to myocardial infarction and stroke.

Our efforts have focused on investigating the potential benefit of encapsulated thrombolytic agents for treatment of clot-based crises. Liposome encapsulated plasminogen activators (LEPAs) have demonstrated improved thrombolysis in vivo in multiple laboratories. Compared to free agents, LEPAs demonstrate faster reperfusion times, reduced residual clot masses, and more rapid and complete restoration of blood flow. We have encapsulated streptokinase in both liposomes (LESK) and polymer microcapsules (MESK). Both formulations demonstrated reductions in reperfusion times, residual clot mass, and improved return of flow compared to identical dosages of free streptokinase in a thrombosed rabbit carotid, with MESK resulting in comparable or even greater improvements. In addition, marked reductions in bleeding complications and ventricular infarct size have been observed in a canine model of acute myocardial infarction. The mechanism for MESK has recently been explored in our laboratory using multiple microscopic techniques. MESK appears to resist adsorption to the leading edge of the thrombus, a common limitation for the permeation of free plasminogen activators. By avoiding adsorption and penetrating the thrombus, greater spatial distribution of the agent within the clot can be achieved. This data suggests that encapsulation of streptokinase could provide a therapeutic option for treatment of thrombosed arteries.

Animals↗
PubMed2003

Slow:fast and slow:slow AV nodal reentry in the rabbit resulting from longitudinal dissociation within the posterior AV nodal input.

OBJECTIVE: The anatomic and electrophysiologic bases for multiple forms of sustained AV nodal tachycardia were determined in the rabbit. METHODS: Intracellular microelectrode recordings were used to identify antegrade and retrograde conduction limbs of sustained tachycardias observed in 23 of 152 superfused rabbit AV junctions. RESULTS: Slow:slow tachycardias (196 +/- 12 msec cycle length) with nearly equal AH and HA intervals (99 +/- 12; 97 +/- 11 msec, respectively) and early atrial activation near the coronary sinus os were observed in 14 preparations and slow:fast tachycardias (189 +/- 11 msec cycle length) with an AH > HA interval (141 +/- 12; 48 +/- 10 msec, respectively) and early atrial activation along the anterior limbus of the fossa ovalis were observed in 11 preparations. Both tachycardias were associated with longitudinal dissociation and localized reentry within the triangle of Koch. Slow:fast and slow:slow tachycardias exhibited counterclockwise and clockwise reentry circuits, respectively. Both circuits were present in two preparations. Slow:fast AV nodal reentrant tachycardias could be reset with stimuli introduced near the coronary sinus os and the anterior AV nodal input. Slow:slow tachycardias could be reset only by stimuli introduced near the coronary sinus os. The fraction of the tachycardia cycle length contained within the compact AV node was greater for slow:fast (0.35 +/- 0.07) than slow:slow reentry (0.15 +/- 0.05, p = 0.026), suggesting a longer lower common pathway for slow:fast tachycardia. CONCLUSIONS: Longitudinal dissociation within the posterior AV nodal input incorporating the AV node can provide the reentrant substrate for two different clinical forms of sustained AV nodal tachycardias.

Animals↗
PubMed2003

Accelerated thrombolysis in a rabbit model of carotid artery thrombosis with liposome-encapsulated and microencapsulated streptokinase.

The present study compares the efficacy of two formulations of encapsulated streptokinase to streptokinase in a rabbit model of carotid artery thrombosis. Arterial thrombosis followed the injection of thrombin mixed with autologous whole blood into a carotid artery of New Zealand white rabbits. Thirty minutes after the confirmation of an occlusive thrombus, one of four streptokinase formulations was infused at a dosage of 6000 IU/kg into the jugular vein. Free streptokinase (FREE SK) was compared to identical dosages of streptokinase encapsulated in a liposome (LESK), streptokinase entrapped in a water-soluble polymer (MESK), and free streptokinase admixed with blank microparticles (FREE SK + BLANK). Carotid arterial blood flow was determined by pulsed Doppler flowmetry to confirm clot formation and reperfusion. Two hours after drug infusion, the rabbits were killed and the residual thrombus mass was determined. Compared to FREE SK (74.5 +/- 16.9 min; mean +/- SEM), LESK demonstrated significantly reduced reperfusion times (19.3 +/- 4.6 min) while MESK exhibited even greater improvement (7.3 +/- 1.6 min). FREE SK + BLANK showed no statistical improvement versus FREE SK. LESK and MESK also resulted in reduced residual clot mass and greater return of arterial blood flow. These studies suggest that encapsulation of streptokinase offers a potential method of improved fibrinolytic treatment for patients with clot-based disorders. MESK performed slightly better than LESK with improved production and storage characteristics.

Animals↗
PubMed2002

The elusive extracellular AV nodal potential: studies from the canine heart, ex vivo.

Various forms of extracellular recordings from the AV node (AVN) have been reported. However, lack of consistent validation have precluded the use of such recordings in experimental and clinical studies. In 14 Langendorff perfused dog hearts, the triangle of Koch (TOK) was exposed and an octapolar electrode catheter (2 mm rings, 2 mm spacing) was inserted under the endocardium so that the bipolar pairs recorded electrograms from the apex to the base of the TOK. All recording were filtered between 0.05 and 250 Hz, except for a His bundle (Hb) recording (30-250 Hz) made from another bipolar electrode catheter placed in the aortic root. Transmembrane action potentials (AP) were recorded close to the sites of extracellular electrograms. Pin electrodes at the periphery of the bath were arranged to register two ECG leads from the volume conductor. During recovery of electrical activity 11 of 14 preparations developed a junctional rhythm that initially manifested only an AV nodal extracellular and corresponding intracellular AV nodal potentials followed gradually by conduction to the Hb and ventricles but no retrograde atrial activation; 3 preparations initially produced Hb rhythms based on extracellular and transmembrane AP recordings from the AVN and Hb. The amplitude and duration of the AVN extracellular potentials (average: 97 +/- 26 microV and 92 +/- 25 msec, respectively) during AVN rhythms, significantly differed from those during atrial pacing (262 +/- 185 microV and 78 +/- 26 msec, p < 0.05). Histologic sections of the sites underlying the electrodes recording AVN potentials showed AVN tissue throughout. We conclude that extracellular AV nodal potentials are independent waveforms with specific qualitative and quantitative characteristics that distinguish them from adjacent atrial, transitional, Hb or ventricular potentials.

Action Potentials↗