Ventricular activation process in minipigs

doi:10.1016/S0022-0736(75)80018-5

Journal of Electrocardiology

Volume 8, Issue 2, 1975, Pages 113-116

https://doi.org/10.1016/S0022-0736(75)80018-5 Get rights and content

Summary

Because the form of QRS from the body surface of pigs is different from that of carnivores or ungulates, and because that form is dependent upon pathways of ventricular activation, this study was designed to study pathways of ventricular activation in pigs. Twelve pigs were anesthetized and right or left hemithoracotomies were performed to expose the heart. Contiguous bipolar electrograms were recorded from button electrodes on the epicardium and from both faces of the interventricular septum, and from multipolar plunge electrodes introduced into the intramural regions of both ventricles. Electrograms were recorded simultaneous with the Z-axis ECG at 625 mm/sec paper speed on a photographic oscillograph. Times of arrival of waves of activation at numerous points in the ventricle were referenced to the peak of the R-wave in the Z-axis ECG.

During the initial 10 msec of QRS, the apical-third of the interventricular septum is activated from left to right. During the next 40 msec of QRS, waves of activation originating at the cranial portion of the right ventricle and the caudal portion of the left ventricle engulf the epicardium toward the interventricular septum and slightly in an apico-basilar direction. Activity begins slightly earlier at the caudal aspect of the left ventricular free-wall and terminates on the pulmonary conus region. During the terminal 30 msec of QRS, the basilar third of the interventricular septum is activated in a general apico-basilar direction. Through no regions of either right or left ventricular free-walls was a general endocardial to epicardial activation observed. These pathways of ventricular activation may be explained by the rather complete penetration of Purkinje fibers through both ventricular free-walls in a manner similar to that of ungulates but different from carnivores and primates.

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Preclinical QT safety assessment: Cross-species comparisons and human translation from an industry consortium
2014, Journal of Pharmacological and Toxicological Methods
Citation Excerpt :
Like all quadrupeds, the position and orientation of the heart is different than in the human, requiring adjustments to standard lead conventions when using surface electrodes (Nahas, Baneux, & Detweiler, 2002). As with other preclinical species, adequate representation of the ECG is less of an issue when employing epicardial leads (Cavero, 2010; Hamlin et al., 1975; Henriques et al., 2010; Holzgrefe, Cavero, Buchanan, et al., 2007; Holzgrefe, Cavero, Gleason, et al., 2007). Anatomical differences also exist in the conduction system of the porcine heart, which has augmented neuromyogenic components, including adrenergic and cholinergic nerve fibers in the AV node and bundle branches, larger and more differentiated Purkinje fibers and endocardial–epicardial Purkinje fiber distribution (Hamlin, 2005; Swindle, 2007).
In vivo models have been required to demonstrate relative cardiac safety, but model sensitivity has not been systematically investigated. Cross-species and human translation of repolarization delay, assessed as QT/QTc prolongation, has not been compared employing common methodologies across multiple species and sites. Therefore, the accurate translation of repolarization results within and between preclinical species, and to man, remains problematic.
Six pharmaceutical companies entered into an informal consortium designed to collect high-resolution telemetered data in multiple species (dog; n = 34, cynomolgus; n = 37, minipig; n = 12, marmoset; n = 14, guinea pig; n = 5, and man; n = 57). All animals received vehicle and varying doses of moxifloxacin (3–100 mg/kg, p.o.) with telemetered ECGs (≥ 500 Hz) obtained for 20–24 h post-dose. Individual probabilistic QT–RR relationships were derived for each subject. The rate-correction efficacies of the individual (QTca) and generic correction formulae (Bazett, Fridericia, and Van de Water) were objectively assessed as the mean squared slopes of the QTc–RR relationships. Normalized moxifloxacin QTca responses (Veh Δ%/μM) were derived for 1 h centered on the moxifloxacin Tmax.
All QT–RR ranges demonstrated probabilistic uncertainty; slopes varied distinctly by species where dog and human exhibited the lowest QT rate-dependence, which was much steeper in the cynomolgus and guinea pig. Incorporating probabilistic uncertainty, the normalized QTca-moxifloxacin responses were similarly conserved across all species, including man.
The current results provide the first unambiguous evidence that all preclinical in vivo repolarization assays, when accurately modeled and evaluated, yield results that are consistent with the conservation of moxifloxacin-induced QT prolongation across all common preclinical species. Furthermore, these outcomes are directly transferable across all species including man. The consortium results indicate that the implementation of standardized QTc data presentation, QTc reference cycle lengths, and rate-correction coefficients can markedly improve the concordance of preclinical and clinical outcomes in most preclinical species.
Cardiac safety of conducted electrical devices in pigs and their effect on pacemaker function
2011, American Journal of Emergency Medicine
Citation Excerpt :
For us, it was easier to mimic the weight of human adults by using pigs for these experiments. Interestingly, pigs are sensitive to VF because of their long QT intervals and a short repolarization reserve in addition to the intramural Purkinje fibers [17–19]. In spite of the well-recognized susceptibility of swine to VF, we were never able to induce VF with the Stinger S-200 in the dart orientations we tested.
The aims of this study are to evaluate the cardiac safety of the Stinger S-200 Conducted Energy Weapon Device (CED) (Stinger Systems, Tampa, Fla) on a human-sized pig model and to test the effect of various commercially available CEDs, specifically the Stinger S-200, TASER M26 (Taser International, Scottsdale, Ariz), and TASER X26 on pacemaker function.
Two groups of pigs, divided based on weight as group 1 (n = 3, 67.3 ± 4.7 kg) and group 2 (n = 3, 89.3 ± 1.2 kg), were used. In protocol 1, the Stinger S-200 was applied in multiple different orientations to simulate possible field scenarios across the heart. In protocol 2, a single-chamber bipolar lead connected to a pacemaker was placed in the right ventricle of the pig, and different CEDs were applied to test the pacemaker function during CED application.
In protocol 1, the S-200 was applied a total of 216 times in the 6 pigs, and neither episodes of ventricular fibrillation nor episodes of sustained ventricular tachycardia were noted. In protocol 2, the CED discharges (1) were recognized by the pulse generator and sensed as either high-rate atrial or ventricular activity, (2) did not affect the native rhythm, (3) did not conduct down the lead systems to cause any extra systoles, and (4) had no effect on paced rhythm.
In this model, the application of the S-200 in various orientations across the heart did not result in any sustained abnormal cardiac rhythms. None of the tested CEDs adversely affected the functioning of the tested pacemaker. Stinger Systems has now replaced the S-200 with the S-200T with a different output.
Distorted T-vector loop and increased heart rate are associated with ventricular fibrillation in a porcine ischemia-reperfusion model
2009, Journal of Electrocardiology
Citation Excerpt :
The completely opposite response patterns in humans and pigs were probably due to a species-specific difference. In pigs, the Purkinje fibers penetrate through both ventricular free walls as opposed to in humans, where the Purkinje system spreads subendocardially, resulting in different ventricular activation.16,17 Furthermore, the pig's heart is oriented with the apex near the anterior thoracic wall close to the xiphoid process, resulting in different activations of the QRS vector in pigs and humans.
The ventricular repolarization (VR) response to short-lasting coronary occlusion has been characterized by 3-dimensional vectorcardiography during angioplasty in humans; the T-vector loop becomes distorted (increased T_avplan) and more circular (decreased T_eigenvalue), but these changes have not been related to ventricular arrhythmias.
The VR response was therefore explored in a porcine ischemia-reperfusion model and compared in pigs with (n = 16) vs without (n = 17) ventricular fibrillation (VF).
Different aspects of VR were evaluated at baseline, at maximum ischemia, before reperfusion and at the subsequent ST maximum, after 1 hour of reperfusion, and before VF. Three aspects of the VR response were assessed: the ST-segment, the T-vector angles, and the T-vector loop morphology.
All parameters changed significantly from baseline during ischemia and/or reperfusion. The early changes were similar to those previously observed in humans during angioplasty. The VF episodes were preceded by a significantly exaggerated T-loop distortion (increased T_avplan) and increased heart rate.
Aggravated T-loop distortion might, in this porcine ischemia-reperfusion model, reflect aspects of VR relevant to arrhythmogenesis.
Transmural and endocardial Purkinje activation in pigs before local myocardial activation after defibrillation shocks
2007, Heart Rhythm
Citation Excerpt :
Thus, shocks near the DFT in strength may create secondary sources large enough to defibrillate the working myocardium but not create secondary sources large enough to defibrillate the Purkinje fibers so that activation appears there first after the shock. While the Purkinje fibers in pigs traverse the ventricular wall and extend nearly to the epicardial surface,17–19,29 in humans the Purkinje fiber system is limited primarily to the endocardial surface.41,42 Therefore, transmural Purkinje activation would not be expected in humans.
Earliest recorded postshock myocardial activations in pigs originate in the subepicardium of the apex and lateral free wall of the left ventricle (LV) 30–90 ms after the shock.
The purpose of this study was to determine whether the Purkinje system is a candidate for the source of postshock activations by performing endocardial and transmural postshock activation mapping.
In five pigs, 32 plunge needles with 12 electrodes (1-mm spacing) were inserted into the LV apex and lateral free wall. Up to 70 plunge needles with six electrodes (2-mm spacing) were spread throughout the remainder of the LV, while 9–12 plunge needles with four electrodes (2-mm spacing) were inserted into the right ventricle. A basket catheter with 32 bipolar recording sites was inserted into the LV. Defibrillation-threshold (DFT)-level shocks were delivered during 10 episodes of electrically induced ventricular fibrillation. Electrograms of postshock activation cycles were analyzed for Purkinje and myocardial activations.
Purkinje activations were recorded before local myocardial activation in 9% of basket electrograms and in 15% of plunge needles during the first postshock activation cycle. Purkinje activations were identified during the first and subsequent several postshock activation cycles in at least one basket and one needle electrogram in 96% and 98% of defibrillation episodes, respectively.
The Purkinje system is active during the early postshock activation cycles after DFT-level shocks. Further studies are required to determine whether activation initiates in the Purkinje system or whether it is activated by the myocardium or by Purkinje-myocardial junctional cells.
Activation and repolarization patterns in the ventricular epicardium under sinus rhythm in frog and rabbit hearts
2007, Comparative Biochemistry and Physiology - A Molecular and Integrative Physiology
Our study compared the contributions of activation sequence and local repolarization durations distribution in the organization of epicardial repolarization in animals with fast (rabbit) and slow (frog) myocardial activation under sinus rhythm. Activation times, repolarization times and activation–recovery intervals (ARI) were obtained from ventricular epicardial unipolar electrograms recorded in 13 Chinchilla rabbits (Oryctolagus cuniculus) and 10 frogs (Rana temporaria). In frogs, depolarization travels from the atrioventricular ring radially. ARIs increased progressively from the apex to the middle portion and finally to the base (502 ± 75, 557 ± 73, 606 ± 79 ms, respectively; P < 0.01). In rabbits, depolarization spread from two epicardial breakthroughs with the duration of epicardial activation being lower than that in frogs (17 ± 3 vs. 44 ± 18 ms; P < 0.001). ARI durations were 120 ± 37, 143 ± 45, and 163 ± 40 ms in the left ventricular apex, left, and right ventricular bases, respectively (P < 0.05). In both species, repolarization sequence was directed from apex to base according to the ARI distribution with dispersion of repolarization being higher than that of activation (P < 0.001). Thus, excitation spread sequence and velocity per se do not play a crucial role in the formation of ventricular epicardial repolarization pattern, but the chief factor governing repolarization sequences is the distribution of local repolarization durations.
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^†

The research reported in this paper was conducted by personnel of the Environmental Sciences Division, USAF School of Aerospace Medicine, AFSC, United States Air Force, Brooks AFB, Texas. Further reproduction is authorized to satisfy the needs of the U.S. Government.

The animals involved in this study were maintained and used in accordance with the Animal Welfare Act of 1970 and the “Guide for the Care and Use of Laboratory Animals” prepared by the National Academy of Sciences—National Research Council.

^*: From the Department of Veterinary Physiology and Pharmacology, The Ohio State University, Columbus, Ohio 43210.

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Ventricular activation process in minipigs†

Summary

J Electrocardiol

The ventricular activation process in cattle

Ann NY Acad Sci

Excitation of the left ventricular wall of the dog and goat

Ann NY Acad Sci

Electrocardiogram of the bottle-nosed dolphin (tursiops truncatus)

Am J Vet Res

Electrocardiogram of pinnipeds

Am J Vet Res

Electrocardiogram and vectorcardiogram of Macaca mulatta in various postures

Am J Physiol