Pacing In Dogs Research Articles

Effect of body position on transesophageal atrial pacing in dogs

ObjectiveTo evaluate the effect of body position on transesophageal atrial pacing (TEAP) in dogs. Study designProspective, experimental trial. AnimalsA total of eight mixed-breed dogs, median body mass 25 kg (range 11–31 kg). MethodsTEAP was performed using a 6 Fr (2 mm) pacing catheter introduced transorally and positioned in the lower esophagus in left lateral recumbency. The catheter was withdrawn in 5 mm increments until successful TEAP. The minimum pacing threshold (MPT) was determined at each 5 mm increment until atrial capture could not be achieved at a maximal pulse amplitude of 40 mA. The zone of capture (ZOC) was the total distance over which TEAP was achieved. The same process was repeated in right lateral, ventral and dorsal recumbency. A linear mixed model was used to assess the impact of body position on TEAP and ZOC. ResultsTEAP was achieved in all body positions. There was significant random effect of individual dogs on ZOC (p = 0.048) but not on MPT (p = 0.109). MPT was 11.56 ± 8.65 mA (mean ± SD), 8.43 ± 2.29 mA, 10.63 ± 6.91 mA and 10 ± 7.44 mA for dorsal, left and right lateral, and ventral recumbency, respectively. ZOC was 5.12 ± 2.08 cm, 6.35 ± 2.41 cm, 5.94 ± 3.23 cm and 5.31 ± 2.2 cm for dorsal, left lateral and right lateral, and ventral recumbency, respectively. Neither ZOC (p = 0.363) nor MPT (p = 0.716) varied significantly between body positions. Conclusions and clinical relevanceTEAP can be performed successfully in all body positions in dogs. Body position did not significantly influence MPT or ZOC values for TEAP. Further studies are needed to compare the efficacy of TEAP with the efficacy of standard pharmacological therapy for management of bradycardia during general anesthesia in dogs.

Optimizing single-chamber pacing in dogs Part 1: Rate determinations, rate interventions and hysteresis

Determining ideal pacing rates to meet physiological needs and optimizing programming to prevent unnecessary right ventricular pacing in dogs requires an understanding of heart rate profiles and applicable pacing technology. The heart rate and rhythm of the dog is complex necessitating investigation of rate requirements of activity and circadian influences. Overlaying this information are a multiplicity of other factors such as age, breed, temperament, cardiovascular disease and underlining rhythm disorders that contribute to the difficulty in making general conclusions. However, all such information permits better implementation of programming options with the goal of better outcomes. In this review (Part 1 of a two-part review) instantaneous heart rate, rolling average heart rate, simple average heart rate, heart rate tachograms, RR interval tachograms (2D, 3D and dynamic), and Poincaré plots (2D, 3D and dynamic) are discussed as they apply to decisions in the determination and examination of pacing rates for dogs programmed in the VVI pacing mode (Ventricular paced, Ventricular sensed, Inhibited pacing). The applicable pacing operations available for three pacemaker companies are reviewed (Abbott, Biotronik/Dextronix, and Medtronic). The programmable options considered include: slowest pacing rate without additional features to extend the pacing interval, sleep/rest rate preferences, hysteresis to lengthen pacing interval following intrinsic beats, and intermittent increases in pacing following abrupt loss of intrinsic rhythm. Recommendations are suggested for follow-up of individual dogs with examination of pacing statistics and Holter monitoring.

Toward Biological Pacing by Cellular Delivery of Hcn2/SkM1.

Electronic pacemakers still face major shortcomings that are largely intrinsic to their hardware-based design. Radical improvements can potentially be generated by gene or cell therapy-based biological pacemakers. Our previous work identified adenoviral gene transfer of Hcn2 and SkM1, encoding a “funny current” and skeletal fast sodium current, respectively, as a potent combination to induce short-term biological pacing in dogs with atrioventricular block. To achieve long-term biological pacemaker activity, alternative delivery platforms need to be explored and optimized. The aim of the present study was therefore to investigate the functional delivery of Hcn2/SkM1 via human cardiomyocyte progenitor cells (CPCs). Nucleofection of Hcn2 and SkM1 in CPCs was optimized and gene transfer was determined for Hcn2 and SkM1 in vitro. The modified CPCs were analyzed using patch-clamp for validation and characterization of functional transgene expression. In addition, biophysical properties of Hcn2 and SkM1 were further investigated in lentivirally transduced CPCs by patch-clamp analysis. To compare both modification methods in vivo, CPCs were nucleofected or lentivirally transduced with GFP and injected in the left ventricle of male NOD-SCID mice. After 1 week, hearts were collected and analyzed for GFP expression and cell engraftment. Subsequent functional studies were carried out by computational modeling. Both nucleofection and lentiviral transduction of CPCs resulted in functional gene transfer of Hcn2 and SkM1 channels. However, lentiviral transduction was more efficient than nucleofection-mediated gene transfer and the virally transduced cells survived better in vivo. These data support future use of lentiviral transduction over nucleofection, concerning CPC-based cardiac gene delivery. Detailed patch-clamp studies revealed Hcn2 and Skm1 current kinetics within the range of previously reported values of other cell systems. Finally, computational modeling indicated that CPC-mediated delivery of Hcn2/SkM1 can generate stable pacemaker function in human ventricular myocytes. These modeling studies further illustrated that SkM1 plays an essential role in the final stage of diastolic depolarization, thereby enhancing biological pacemaker functioning delivered by Hcn2. Altogether these studies support further development of CPC-mediated delivery of Hcn2/SkM1 and functional testing in bradycardia models.

Reversible third-degree atrioventricular block in a Poodle-Toy with degenerative mitral valve disease and pyometra

Third degree atrioventricular block is a severe arrhythmia, being the most common indication for artificial cardiac pacing in dogs. Spontaneous reversion to normal sinus rhythm is very rare or exceptional. A 12-year-old Poodle-Toy was referred because of history of abdominal enlargement, anorexia, vomiting and weakness. Abdominal ultrasonography revealed large pyometra. Then, a six-lead electrocardiogram presented third-degree atrioventricular block, while transthoracic Doppler echocardiography showed myxomatous mitral valve disease, presence of mitral, tricuspid and aortic regurgitation, accompanied by mitral and tricuspid diastolic insufficiency. Two days after the ovariohysterectomy, a new electrocardiogram revealed spontaneous reversal to the sinus rhythm, while the diastolic reflux of mitral and tricuspid valves disappeared. The patient showed rapid clinical amelioration and eight months after surgery was still alive, on treatment for heart failure. As far as we know, this is the first canine case of third-degree heart block, secondary to endocardiosis and pyometra, which was spontaneously reverted to sinus rhythm after surgery.

English

Little is currently known about the pacing gait in dogs and it has been speculated that pacing may be utilized by dogs with musculoskeletal pathology. The goals of the present study were to determine if pacing in dogs is associated with musculoskeletal disease and to establish if controlled speed impacts pacing. Dogs underwent orthopedic and lameness assessments. Musculoskeletal pathology, when identified, was further defined with radiography of the affected area. Dogs were considered musculoskeletally normal (MSN) if no pathology was detected and they had no history of musculoskeletal disease. All others were considered musculoskeletally abnormal (MSA). Animals were then evaluated for pacing using digital-video-imaging under three conditions: Off-lead, lead-controlled, and on a treadmill. Thirty-nine dogs were enrolled (MSN: n = 20; MSA: n = 19). Overall, pacing was observed more frequently in dogs under lead-controlled than off-lead conditions (P < 0.001). Lead-controlled MSN dogs were observed to pace significantly more frequently (n = 17/20) than lead-controlled MSA dogs (n = 10/19; P = 0.029). There was no significant difference within each group for the frequency of pacing under treadmill or off-lead conditions. Pacing always occurred at speeds between a walk and a trot, speeds ranged from 0.98 to 2.84 m/s, (mean 1.8 m/s). Pacing was demonstrated in MSN and MSA dogs under all study conditions. Pacing should be considered a gait variation that can be observed in clinically normal dogs. Relative speed and leash walking was determined to be a factor in the use of the pacing gait. Key words: Pacing, gait analysis, lameness, canine locomotion, symmetrical gait, lateral gait, amble.

Effect of pulse width on transesophageal atrial pacing in dogs

ObjectiveTo determine the impact of stimulus pulse width (PW) on pacing threshold (PT), zone of capture (ZOC) and extraneous muscular stimulation (EMS). Study designExperimental trial in client-owned dogs. AnimalsSeventeen dogs, median weight 16.1 kg (interquartile range: 11.4–21.5). MethodsTransesophageal atrial pacing (TAP) involved a 6 Fr pacing catheter inserted trans-orally into the esophagus to a position aboral to the heart in anesthetized dogs. The catheter was slowly withdrawn until atrial pacing was noted on an electrocardiogram. The catheter was withdrawn in 1 cm increments until TAP could not be achieved. PTs were recorded at each pacing site using PWs of 10.0, 5.0, 2.0 and 1.8 ms, always in that order. ResultsThe overall lowest mean PTs for all dogs were 6 ± 3 mA, 9 ± 4 mA, 11 ± 5 mA and 13 ± 5 mA at PWs of 10.0, 5.0, 2.0 and 1.8 ms, respectively. A significant decrease in overall minimum PT was noted using a PW of 10.0 ms compared with either 2.0 or 1.8 ms (p = 0.043 and p = 0.001, respectively) and pacing using 5.0 ms compared with 1.8 ms (p = 0.028). A significant increase in ZOC was noted using a PW of 10.0 ms compared with PWs of 5.0, 2.0 and 1.8 ms (p = 0.0047, p = 0.0006 and p = 0.0003, respectively), using a PW of 5.0 ms compared with PWs of 2.0 and 1.8 ms (p = 0.0011 and p = 0.0003, respectively) and using a PW of 2.0 compared with one of 1.8 ms (p = 0.0084). Conclusions and clinical relevanceUse of 10.0 or 5.0 ms PW to perform TAP minimized the power required to pace the atria, while a PW of 10.0 ms maximized the size of the ZOC.

Relevance of HCN2-expressing human mesenchymal stem cells for the generation of biological pacemakers.

BackgroundThe transfection of human mesenchymal stem cells (hMSCs) with the hyperpolarization-activated cyclic nucleotide-gated ion channel 2 (HCN2) gene has been demonstrated to provide biological pacing in dogs with complete heart block. The mechanism appears to be the generation of the ion current (If) by the HCN2-expressing hMSCs. However, it is not clear how the transfection process and/or the HCN2 gene affect the growth functions of the hMSCs. Therefore, we investigated survival, proliferation, cell cycle, and growth on a Kapton® scaffold of HCN2-expressing hMSCs.MethodshMSCs were isolated from the bone marrow of healthy volunteers applying a selective cell adhesion procedure and were identified by their expression of specific surface markers. Cells from passages 2–3 were transfected by electroporation using commercial transfection kits and a pIRES2-EGFP vector carrying the pacemaker gene, mouse HCN2 (mHCN2). Transfection efficiency was confirmed by enhanced green fluorescent protein (EGFP) fluorescence, quantitative real-time polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). After hMSCs were transfected, their viability, proliferation, If generation, apoptosis, cell cycle, and expression of transcription factors were measured and compared with non-transfected cells and cells transfected with pIRES2-EGFP vector alone.ResultsIntracellular mHCN2 expression after transfection increased from 22.14 to 62.66 ng/mg protein (p < 0.05). Transfection efficiency was 45 ± 5 %. The viability of mHCN2-transfected cells was 82 ± 5 %; they grew stably for more than 3 weeks and induced If current. mHCN2-transfected cells had low mitotic activity (10.4 ± 1.24 % in G2/M and 83.6 ± 2.5 % in G1 phases) as compared with non-transfected cells (52–53 % in G2/M and 31–35 % in G1 phases). Transfected cells showed increased activation of nine cell cycle-regulating transcription factors: the most prominent upregulation was of AMP-dependent transcription factor ATF3 (7.11-fold, p = 0.00056) which regulates the G1 phase. mHCN2-expressing hMSCs were attached and made anchorage-dependent connection with other cells without transmigration through a 12.7-μm thick Kapton® HN film with micromachined 1–3 μm diameter pores.ConclusionsmHCN2-expressing hMSCs preserved the major cell functions required for the generation of biological pacemakers: high viability, functional activity, but low proliferation rate through the arrest of cell cycle in the G1 phase. mHCN2-expressing hMSCs attached and grew on a Kapton® scaffold without transmigration, confirming the relevance of these cells for the generation of biological pacemakers.

Effects of catheter shape, interelectrode spacing, and electrode size on transesophageal atrial pacing in dogs

To determine effects of catheter shape, interelectrode spacing (IS), and electrode size (ES) on pacing threshold (PT), extraneous muscular stimulation (EMS), and zone of capture (ZOC) for dogs undergoing transesophageal atrial pacing (TAP). 10 purpose-bred dogs without cardiac conduction disturbances. 7 configurations for TAP catheters were tested in each dog to evaluate effects of catheter shape (curved or straight), IS (5, 15, and 25 mm), and ES (2, 4, and 6 mm). Each catheter was passed into the esophagus to a location aboral to the heart and slowly withdrawn until atrial pacing was achieved. Then, catheters were withdrawn in 5-mm increments until pacing could not be achieved. Outcomes measured at each pacing site included PT, degree of EMS, and ZOC. There was a significantly lower PT, wider ZOC, and less EMS for the curved catheter than for the straight catheter. An ES of 6 mm induced significantly more EMS than was induced by an ES of 2 or 4 mm. An IS of 5 mm induced significantly less EMS and a significantly narrower ZOC but required a significantly higher PT, compared with results for an ES of 15 or 25 mm. Additionally, there was a significant direct correlation between IS and ZOC. Results indicated that a curved catheter with multiple 4-mm electrodes that provides for variable IS would be ideal for TAP in dogs. TAP catheters currently used in human medicine are straight. The PT in humans may potentially be reduced with curved catheters.

Response to exercise and mechanical efficiency in non-ischaemic stunning, induced by short-term rapid pacing in dogs: a role for calcium?

Rapid pacing (RP) is a regularly used model to induce heart failure in dogs. The aim of the study was to evaluate Ca2+ handling, left ventricular (LV) contractile response during Ca2+ administration compared to exercise, as well as oxygen consumption and mechanical efficiency after 48h of RP. Fifty-three mongrel dogs were instrumented to measure LV pressure, LV fractional shortening, regional wall thickening and coronary blood flow. Contractile reserve was measured with isoproterenol and intravenous (IV) Ca2+ administration. To assess the function of the sarcoplasmic reticulum (SR), post-extrasystolic potentiation (PESP) and SR Ca2+ uptake were measured. A graded treadmill test was performed in baseline and after RP (n=14). In a separate group of animals (n=5), myocardial performance and oxygen consumption were measured using a wide range of loading conditions. Left ventricular contractility was significantly decreased upon cessation of pacing. The contractile response to isoproterenol was blunted compared to a preserved response to IV Ca2+ . Post-extrasystolic potentiation was slightly increased after RP. Maximal velocity (Vmax ) of SR Ca2+ uptake was unchanged. Contractile response during exercise is attenuated after RP. External work is reduced, whereas oxygen consumption is preserved, provoking a reduced mechanical efficiency. Forty-eight-hours RP provokes a reversible LV dysfunction, while the SR function and response to exogenous Ca2+ are preserved. This is compatible with an intracellular functional remodelling to counteract Ca2+ overload provoked by RP. Left ventricular dysfunction is accompanied by a reduced contractile reserve, but an unchanged oxygen consumption, illustrating an alteration in oxygen utilization.

Randomized placebo controlled blinded study to assess valsartan efficacy in preventing left ventricle remodeling in patients with dual chamber pacemaker — Rationale and design of the trial

BackgroundDual chamber pacing is known to have detrimental effect on cardiac performance and heart failure occurring eventually is associated with increased mortality. Experimental studies of pacing in dogs have shown contractile dyssynchrony leading to diffuse alterations in extracellular matrix. In parallel, studies on experimental ischemia/reperfusion injury have shown efficacy of valsartan to inhibit activity of matrix metalloproteinase-9, to increase the activity of tissue inhibitor of matrix metalloproteinase-3 and preserve global contractility and left ventricle ejection fraction. PurposeTo present rationale and design of randomized blinded trial aimed to assess whether 12month long administration of valsartan will prevent left ventricle remodeling in patients with preserved left ventricle ejection fraction (LVEF≥40%) and first implantation of dual chamber pacemaker. MethodsA total of 100 eligible patients will be randomized into three parallel arms: placebo, valsartan 80mg/daily and valsartan 160mg/daily added to previously used drugs. The primary endpoint will be assessment of valsartan efficacy to prevent left ventricle remodeling during 12month follow-up. We assess patients' functional capacity, blood plasma activity of matrix metalloproteinases and their tissue inhibitors, NT-proBNP, tumor necrosis factor alpha, and Troponin T. Left ventricle function and remodeling is assessed echocardiographically: M-mode, B-mode, tissue Doppler imaging. ConclusionIf valsartan proves effective, it will be an attractive measure to improve long term prognosis in aging population and increasing number of pacemaker recipients. ClinicalTrials.org (NCT01805804).

Long-term outcome of physiologic VDD pacing versus non-physiologic VVI pacing in dogs with high-grade atrioventricular block

ObjectiveTo compare the long-term outcome associated with physiologic VDD and non-physiologic VVI or VVIR pacing in dogs with high-grade atrioventricular block. AnimalsForty-nine paced dogs with high-grade atrioventricular block were included. MethodsRetrospective review of medical records, thoracic radiographs and echocardiograms for all dogs. Patient owners and referring veterinarians were contacted for survival times and a satisfaction questionnaire was submitted to the owners. Survival times, complication rates, resolution of clinical signs, and owner satisfaction were compared between the pacing modalities. ResultsA single lead VDD pacemaker was implanted in 19 dogs (39%) whereas 30 dogs (61%) were treated with VVI pacing. The median survival time for all dogs post-pacemaker implantation was 24.5 months. Survival time was significantly decreased in dogs that were older at the time of presentation or that presented with ventricular tachycardia or reduced left ventricular fractional shortening. Median survival times after implantation were not significantly different between pacing modalities (P = 0.29). Major complication rates were 11% within the VDD group and 20% within the VVI group and were not significantly different (P = 0.46). Minor complications were significantly higher within the VDD group than within the VVI group (47% versus 7% respectively; P < 0.01) due to a higher number of dogs in the VDD group experiencing transient ventricular premature contractions in the immediate post-implantation time period. Resolution of clinical signs, owner satisfaction, and quality of life perception were considered excellent in both groups. ConclusionsNo long-term clinical benefit of VDD over VVI pacing could be identified in the present study.

Acute electrical and hemodynamic effects of multisite left ventricular pacing for cardiac resynchronization therapy in the dyssynchronous canine heart

Multisite left ventricular (multi-LV) epicardial pacing has been proposed as an alternative to conventional single-site LV (single-LV) pacing to increase the efficacy of cardiac resynchronization therapy. To compare the effects of multi-LV versus single-LV pacing in dogs with left bundle branch block (LBBB). Studies were performed in 9 anaesthetized dogs with chronic LBBB using 7 LV epicardial electrodes. Each electrode was tested alone and in combination with 1, 2, 3, and 6 other electrodes, the sequence of which was chosen on the basis of practical real-time electrical mapping to determine the site of the latest activation. LV total activation time (LVTAT) and dispersion of repolarization (DRep) were measured by using approximately 100 electrodes around the ventricles. LV contractility was assessed as the maximum derivative of left ventricular pressure (LVdP/dtmax ). Single-LV pacing provided, on average, a -4.0% ± 9.3% change in LVTAT and 0.2% ± 13.7% change in DRep. Multi-LV pacing markedly decreased both LVTAT and DRep in a stepwise fashion to reach -41.3% ± 5% (P < .001 for overall comparison) and -14.2% ± 19.5% (P < .02 for overall comparison) in the septuple-LV pacing configuration, respectively. Single-LV pacing provided a mean increase of 10.7% ± 7.7% in LVdP/dtmax. LVdP/dtmax incrementally increased by the addition of pacing electrodes to 16.4% ± 8.7% (P < .001 for overall comparison). High response to single-LV pacing could not be improved further during multi-LV pacing. Compared with single-LV pacing, multi-LV pacing can considerably reduce both LVTAT and DRep in dogs with LBBB, but the improvement in contractility is limited to conditions where single-LV pacing provides suboptimal improvement. Further studies are warranted to determine whether these acute effects translate in antiarrhythmic properties and better long-term outcomes.

Early Detection of Cardiac Injuries Related to Transcutaneous Pacing in Dogs Using Cardiac Biomarker Assay

Early Detection of Cardiac Injuries Related to Transcutaneous Pacing in Dogs Using Cardiac Biomarker Assay

Efficacy of two commercially available cardiac pacing catheters for transesophageal atrial pacing in dogs

ObjectiveCompare the efficacy of two cardiac pacing catheters for transesophageal atrial pacing (TAP). AnimalsTen healthy dogs. MethodsTransesophageal atrial pacing was attempted in left lateral recumbency under general anesthesia. In series, a curved electrophysiologic (EP) catheter and a straight transesophageal pacing (TP) catheter were passed transorally into the distal esophagus, caudal to the heart. Each catheter was slowly withdrawn until pacing was initiated. The catheter continued to be withdrawn in 5 mm increments until capture was no longer achieved at maximal pacing setting creating a total zone of capture (tZOC). Minimum pacing threshold (Thmin) and degree of extraneous muscle stimulation (EMS) were determined at each site. ResultsThe EP catheter achieved TAP in 10/10 dogs with a Thmin of 8.8 ± 4.8 mA and tZOC of 4.0 ± 1.7 cm. The TP catheter achieved TAP in 7/10 dogs with a Thmin of 22.5 ± 5.6 mA and tZOC of 1.2 ± 1.6 cm. No EMS was noted during TAP at Thmin using the EP catheter. Of the 7 dogs in which TAP was successful, 3/7 experienced considerable EMS at Thmin. There was no significant relationship between patient body weight and Thmin with either catheter (EP catheter P = 0.09; TP catheter P = 0.81). ConclusionsThe electrophysiology catheter captured the atria of more dogs over a larger area without EMS as compared to the TP catheter. The electrophysiology catheter is recommended for transesophageal atrial pacing in dogs.

The involvement of gap junctions in the delayed phase of the protection induced by cardiac pacing in dogs

The present study has examined the role of GJ (gap junctions) in the delayed anti-arrhythmic effect of cardiac pacing, with particular reference to the time-course changes in Cx43 (connexin43) expression both after pacing (4×5min, at a rate of 240 beats/min) and 24h later, when the dogs were subjected to a 25min occlusion and reperfusion of the LAD (left anterior descending coronary artery). Compared with the SP (sham-paced) controls (n=20), in dogs paced 24h previously (n=16) there were reductions in arrhythmia severity [e.g. number of VPB (ventricular premature beats) during occlusion 294±78 compared with 63±25; survival from the combined ischaemia/reperfusion insult 20% compared with 78%], and in other ischaemic changes [epicardial ST-segment, TAT (total activation time) and tissue impedance]. Pacing also prevented the ischaemia-induced structural impairment of the intercalated discs, and preserved GJ permeability and Cx43 phosphorylation, without modifying Cx43 protein content. Following cardiac pacing the membrane and total Cx43 protein contents were unchanged up to 6h, but were significantly reduced 12h later (preceded by a down-regulation of Cx43 mRNA at 6h), and returned to normal by 24h. Interestingly, dogs that were subjected to ischaemia 12h after cardiac pacing showed increased arrhythmia generation. We conclude that cardiac pacing results in time-dependent changes in Cx43 expression, which may alter GJ function and influence arrhythmia generation during a subsequent ischaemia/reperfusion insult. This effect is manifested in protection 24h after pacing, but of potential clinical interest is the finding that there is a time interval after pacing during which an ischaemic event may generate severe ventricular arrhythmias.

Use of transesophageal atrial pacing to provide temporary chronotropic support in a dog undergoing permanent pacemaker implantation

A 14.5-kg, 13-year-old female spayed Cocker spaniel was evaluated because of episodic hind limb weakness. Results of examination were consistent with sick sinus syndrome with intermittent second-degree atrioventricular block. Transesophageal atrial pacing was successful in providing chronotropic support during permanent pacemaker implantation. Transesophageal atrial pacing appears to be a viable option for temporary atrial pacing in dogs with hemodynamically marked bradycardia without significant atrioventricular blockade.

Vagal Stimulation Promotes Atrial Electrical Remodeling Induced by Rapid Atrial Pacing in Dogs: Evidence of a Noncholinergic Effect

Atrial electrical remodeling (AER) is one of the mechanisms by which atrial fibrillation (AF) begets AF. It is known that vagal activity increases the propensity for AF. However, vagal effects on AER have not been fully investigated. Adult mongrel dogs were divided in four groups: group I, rapid atria pacing (RAP); group II, RAP plus vagal nerve stimulation (VNS); group III, RAP and VNS with atropine (0.2 mg/kg/h, intravenous), and group IV, group III plus vasoactive intestinal polypeptide (VIP) antagonist ([D-p-Cl-Phe(6), Leu(17)]-VIP, 0.125 μg/kg/h). VNS was performed bilaterally through vagosympathetic trunks to achieve second-degree AV block or sinus rate slowing of >30 beats per minute. Atrial effective refractory periods (AERPs) were determined in the coronary sinus and right atrial appendage every hour at drive cycle lengths (DCLs) 350 ms, 300 ms, and 250 ms. During 5 hours RAP with or without VNS, AERP shortened progressively from baseline at both pacing sites and at all DCLs (P < 0.01). Furthermore, RAP-induced AERP shortening was more pronounced with VNS (P < 0.01). With atropine, the AERP shortening during VNS was blunted (P < 0.01), but was still significantly more pronounced than that in group I (P < 0.05). However, VNS effect on AERP shortening was eliminated completely with the combination of atropine and VIP antagonist (P = 0.15 vs group I). Increased vagal activity promotes RAP-induced AER, which could not be totally accounted for by cholinergic effect but could be blocked by the combination of atropine and VIP antagonist. Vagally released VIP may have important role in the vagal promotion of AER.

Cardiac troponin-I concentrations in dogs with bradyarrhythmias before and after artificial pacing

Objectives To quantify cardiac troponin-I (cTnI) concentration in dogs with symptomatic bradyarrhythmias before and after artificial pacing and to correlate cTnI concentration with diagnosis, echocardiographic parameters, serology, and outcome. Animals, materials and methods Medical records from the University of Pennsylvania from 2006 to 2009 were reviewed, and 14 dogs with cTnI assay results before and after pacemaker were identified. The ECG diagnosis included complete atrioventricular block (AVB), sick sinus syndrome, 2nd degree AVB, and atrial standstill. Serology, presence of premature beats, echocardiographic measurements, and pacing modality were recorded. Results Mean cTnI concentration was elevated both pre- and post-pacing, and was significantly higher pre-pacing vs. post-pacing. Post-pacing cTnI concentration in 9 of 14 dogs (64%) remained above the reference range. Four dogs yielded high serum titers for Bartonella spp. Four dogs with markedly increased cTnI concentration had progressive left ventricular enlargement and myocardial failure as compared to pre-pacing examination. Conclusions Elevated cTnI concentration suggests that cardiac injury persists after artificial pacing in dogs with bradyarrhythmias. Myocarditis secondary to Bartonella spp. or other causes may be an important cause of AVB in dogs. Prospective studies investigating the correlation of cTnI to potential etiology and development of post-pacing LV dysfunction and outcome are needed.

The Prototype Serotonin 5-HT1B/1D Agonist Sumatriptan Increases the Severity of Myocardial Ischemia During Atrial Pacing in Dogs With Coronary Artery Stenosis

The triptans, serotonin 5-HT 1B/1D agonists exemplified by sumatriptan, are an effective class of migraine therapy but have class labeling contraindicating their use in patients with coronary artery disease. Triptans have been shown to constrict human coronary artery in vitro, and there have been case reports of myocardial infarction in patients using sumatriptan. However, preclinical in vivo studies with sumatriptan in normal dogs have failed to demonstrate an effect on coronary flow. The present studies were conducted in a canine model in which regional myocardial ischemia was evoked by atrial pacing in the presence of a 40% stenosis of the left anterior descending coronary artery. Ischemic severity was quantified by changes in local epicardial electrograms (EGs) recorded in the ischemic zone. The intra-atrial administration of 10 microg x kg x min sumatriptan variably but not significantly increased the severity of regional ischemia (pre- vs. posttreatment: Delta EG: 2.00 +/- 0.17 vs. 3.05 +/- 1.15 mV). Sumatriptan at 30 microg x kg x min significantly increased ischemic severity (Delta EG: 1.88 +/- 0.19 vs. 3.32 +/- 0.58 mV, P < 0.05) concomitant with a significant reduction in coronary blood flow (8.9 +/- 0.5 vs. 7.2 +/- 0.8 mL/min, P < 0.05). These results demonstrate that a reduction in coronary flow with proischemic consequence can be modeled preclinically with sumatriptan in a canine model of cardiac stress.

Evaluation of changes in cardiac biomarker concentrations and enzyme activities in serum after short- and long-duration transcutaneous cardiac pacing in dogs

To evaluate serum cardiac biomarker concentrations and selected enzyme activities in dogs with experimentally induced bradyarrhythmias after short- (1-hour) and long- (3-hour) duration transcutaneous cardiac pacing (TCP). 10 healthy Beagles. In each dog, anesthesia was induced with propofol (5 mg/kg, IV) and maintained via inhalation of isoflurane in oxygen. To induce bradyarrhythmia, diltiazem was administered IV (20 to 50 mg/dog). Transcutaneous cardiac pacing was performed for 1 hour (5 dogs) or 3 hours (5 dogs) by use of an automated external cardiac pulse generator and a transdermal electrode. Serum concentrations of creatine kinase-MB fraction and cardiac troponin I and activities of aspartate transaminase, creatine kinase, and lactate dehydrogenase were evaluated the day before (baseline) and at intervals until 7 days after TCP. Increases (from baseline) in serum cardiac biomarker concentrations and enzyme activities were detected in the long-duration TCP group; changes in the short-duration TCP group were more minor and largely not significant. Although severity of myocardial and skeletal muscular injuries was apparently greater with greater duration of TCP, the injuries were not persistent; most variables were within reference range within 3 days after TCP. Results indicated that application of TCP for > 1 hour in dogs may cause myocardial and skeletal muscular injuries. Serum concentrations of creatine kinase-MB fraction and cardiac troponin I and activities of aspartate transaminase, creatine kinase, and lactate dehydrogenase should be more carefully monitored after TCP of > 1 hour's duration to evaluate potential myocardial damages.