Asynchronous development of electrical remodeling and cardiac hypertrophy in the complete AV block dog

Schoenmakers, Marieke; Ramakers, Christian; Opstal, Jurren M. van; Leunissen, Jet D.M.; Londoño, Camila; Vos, Marc A.

doi:10.1016/s0008-6363(03)00430-9

Cited by 53 publications

(53 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cardiac cycle alterations in hibernators bear many similarities to human disease states. Low heart rates and cardiac output generally lead to chamber dilation due to volume overload (Verduyn et al, 2001;Schoenmakers et al, 2003). These conditions in hibernators may have led to a noted variety of cardiac adaptations (Folk et al, 1970;Caprette and Senturia, 1984;Milsom et al, 1993;Milsom et al, 1999;Burlington and Darvish, 1998;Brauch et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…During bouts of torpor over a 6 month hibernation, these animals may be completely inactive for 2 weeks at a time at near-freezing temperatures, while arousals may last 24 h. Cardiovascular adaptations must occur for the myocardium to remain healthy and efficient during a period of extremely low temperatures, and low heart rate and cardiac output (Folk et al, 1970;Caprette and Senturia, 1984;Milsom et al, 1993;Milsom et al, 1999;Burlington and Darvish, 1998;Brauch et al, 2005). Non-hibernators that suffer from low heart rate conditions alone will develop cardiac chamber remodeling and congestive heart failure over time (Kertesz et al, 1997;Verduyn et al, 2001;Schoenmakers et al, 2003). The mechanisms that circumvent cardiac dysfunction during hibernation are not well understood, but they may partly involve alterations in sarcomeric proteins (Nelson et al, 2008;Barrows et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Increase in cardiac myosin heavy-chain (MyHC) alpha protein isoform in hibernating ground squirrels, with echocardiographic visualization of ventricular wall hypertrophy and prolonged contraction.

Nelson

Rourke

2013

Journal of Experimental Biology

View full text Add to dashboard Cite

SUMMARYDeep hibernators such as golden-mantled ground squirrels (Callospermophilus lateralis) have multiple challenges to cardiac function during low temperature torpor and subsequent arousals. As heart rates fall from over 300 beats min -1 to less than 10, chamber dilation and reduced cardiac output could lead to congestive myopathy. We performed echocardiography on a cohort of individuals prior to and after several months of hibernation. The left ventricular chamber exhibited eccentric and concentric hypertrophy during hibernation and thus calculated ventricular mass was ~30% greater. Ventricular ejection fraction was mildly reduced during hibernation but stroke volumes were greater due to the eccentric hypertrophy and dramatically increased diastolic filling volumes. Globally, the systolic phase in hibernation was ~9.5 times longer, and the diastolic phase was 28× longer. Left atrial ejection generally was not observed during hibernation. Atrial ejection returned weakly during early arousal. Strain echocardiography assessed the velocity and total movement distance of contraction and relaxation for regional ventricular segments in active and early arousal states. Myocardial systolic strain during early arousal was significantly greater than the active state, indicating greater total contractile movement. This mirrored the increased ventricular ejection fraction noted with early arousal. However, strain rates were slower during early arousal than during the active period, particularly systolic strain, which was 33% of active, compared with the rate of diastolic strain, which was 67% of active. As heart rate rose during the arousal period, myocardial velocities and strain rates also increased; this was matched closely by cardiac output. Curiously, though heart rates were only 26% of active heart rates during early arousal, the cardiac output was nearly 40% of the active state, suggesting an efficient pumping system. We further analyzed proportions of cardiac myosin heavy-chain (MyHC) isoforms in a separate cohort of squirrels over 5 months, including time points before hibernation, during hibernation and just prior to emergence. Hibernating individuals were maintained in both a 4°C cold room and a 20°C warm room. Measured by SDS-PAGE, relative percentages of cardiac MyHC alpha were increased during hibernation, at both hibernacula temperatures. A potential increase in contractile speed, and power, from more abundant MyHC alpha may aid force generation at low temperature and at low heart rates. Unlike many models of cardiomyopathies where the alpha isoform is replaced by the beta isoform in order to reduce oxygen consumption, ground squirrels demonstrate a potential cardioprotective mechanism to maintain cardiac output during torpor. Received 25 March 2013; Accepted 4 September 2013Key words: hibernation, MyHC, echocardiogram, atrial contraction, cardiac function. Echocardiogram and myosin of hibernatorsThe myosin heavy-chain isoforms (MyHC) are crucial determinants of contractile performance in cardiac muscle t...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Increase in cardiac myosin heavy-chain (MyHC) alpha protein isoform in hibernating ground squirrels, with echocardiographic visualization of ventricular wall hypertrophy and prolonged contraction.

Nelson

Rourke

2013

Journal of Experimental Biology

View full text Add to dashboard Cite

show abstract

“…Spatial dispersion between the two ventricles reflects heterogeneity of pathological changes in an affected heart leading to appearance of malignant arrhythmias [1] . Dispersion of repolarization reveals a status of non-homogeneity in the heart, where two sorts of dispersion can be found: special difference in repolarization in the regions either among LV, S, and RV, or between the two chambers [1,27] , or from the apex to the base, and transmural dispersion among the three layers of the LV free wall [28] . Given the dispersed QTc, what happens to the entity of arrhythmogenetic substrate has not yet been clarified.…”

Section: Discussionmentioning

confidence: 99%

Isoproterenol disperses distribution of NADPH oxidase, MMP-9, and pPKCε in the heart, which are mitigated by endothelin receptor antagonist CPU0213

2009

View full text Add to dashboard Cite

Aim: Spatial dispersion of bioactive substances in the myocardium could serve as pathological basis for arrhythmogenesis and cardiac impairment by β-adrenoceptor stimulation. We hypothesized that dispersed NADPH oxidase, protein kinase Cε (PKCε), early response gene (ERG), and matrix metalloproteinase 9(MMP-9) across the heart by isoproterenol (ISO) medication might be mediated by the endothelin (ET) -ROS pathway. We aimed to verify if ISO induced spatially heterogeneous distribution of pPKCε, NAPDH oxidase, MMP-9 and ERG could be mitigated by either an ET receptor antagonist CPU0213 or iNOS inhibitor aminoguanidine. Methods: Rats were treated with ISO (1 mg/kg sc) for 10 days, and drug interventions (mg/kg) either CPU0213 (30 sc) or aminoguanidine (100 ip) were administered on days 8−10. Expression of NADPH oxidase, MMP-9, ERG, and PKCε in the left and right ventricle (LV, RV) and septum (S) were measured separately. Results: Ventricular hypertrophy was found in the LV, S, and RV, in association with dispersed QTc and oxidative stress in ISO-treated rats. mRNA and protein expression of MMP-9, PKCε, NADPH oxidase and ERG in the LV, S, and RV were obviously dispersed, with augmented expression mainly in the LV and S. Dispersed parameters were re-harmonized by either CPU0213, or aminoguanidine. Conclusion: We found at the first time that ISO-induced dispersed distribution of pPKCε, NADPH oxidase, MMP-9, and ERG in the LV, S, and RV of the heart, which were suppressed by either CPU0213 or aminoguanidine. It indicates that the ET-ROS pathway plays a role in the dispersed distribution of bioactive substances following sustained β-receptor stimulation.

show abstract

“…Cardiovascular adaptations must occur for the myocardium to remain healthy and efficient during a period of extremely low heart rates and cardiac output (6,7,8,12,26). Nonhibernators that suffer from bradycardic conditions will develop cardiac chamber dilation due to volume overload during the excessively long diastolic pauses (23,35,42). Over time, chamber dilation and elevated end-diastolic pressures lead to congestive heart failure if no intervention is sought (23, 35).…”

mentioning

confidence: 99%

Titin isoform switching is a major cardiac adaptive response in hibernating grizzly bears

Nelson

Robbins

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

The hibernation phenomenon captures biological as well as clinical interests to understand how organs adapt. Here we studied how hibernating grizzly bears (Ursus arctos horribilis) tolerate extremely low heart rates without developing cardiac chamber dilation. We evaluated cardiac filling function in unanesthetized grizzly bears by echocardiography during the active and hibernating period. Because both collagen and titin are involved in altering diastolic function, we investigated both in the myocardium of active and hibernating grizzly bears. Heart rates were reduced from 84 beats/min in active bears to 19 beats/min in hibernating bears. Diastolic volume, stroke volume, and left ventricular ejection fraction were not different. However, left ventricular muscle mass was significantly lower (300 Ϯ 12 compared with 402 Ϯ 14 g; P ϭ 0.003) in the hibernating bears, and as a result the diastolic volume-to-left ventricular muscle mass ratio was significantly greater. Early ventricular filling deceleration times (106.4 Ϯ 14 compared with 143.2 Ϯ 20 ms; P ϭ 0.002) were shorter during hibernation, suggesting increased ventricular stiffness. Restrictive pulmonary venous flow patterns supported this conclusion. Collagen type I and III comparisons did not reveal differences between the two groups of bears. In contrast, the expression of titin was altered by a significant upregulation of the stiffer N2B isoform at the expense of the more compliant N2BA isoform. The mean ratio of N2BA to N2B titin was 0.73 Ϯ 0.07 in the active bears and decreased to 0.42 Ϯ 0.03 (P ϭ 0.006) in the hibernating bears. The upregulation of stiff N2B cardiac titin is a likely explanation for the increased ventricular stiffness that was revealed by echocardiography, and we propose that it plays a role in preventing chamber dilation in hibernating grizzly bears. Thus our work identified changes in the alternative splicing of cardiac titin as a major adaptive response in hibernating grizzly bears.collagen; bradycardia; diastolic function; echocardiography MANY MAMMALS UNDERGO A UNIQUE state of energy conservation in response to harsh climatic conditions. Grizzly bears (Ursus arctos horribilis) do not eat, drink, or urinate and demonstrate minimal activity during their annual 4 -6 mo hibernation period. Cardiovascular adaptations must occur for the myocardium to remain healthy and efficient during a period of extremely low heart rates and cardiac output (6,7,8,12,26). Nonhibernators that suffer from bradycardic conditions will develop cardiac chamber dilation due to volume overload during the excessively long diastolic pauses (23,35,42). Over time, chamber dilation and elevated end-diastolic pressures lead to congestive heart failure if no intervention is sought (23, 35). However, hibernating grizzly bears tolerate extremely low heart rates without ventricular chamber dilation (30). The mechanisms that circumvent chamber dilation are not well understood, but they might involve increased ventricular stiffness (30).Molecular changes in sarcomeric and ext...

show abstract

Asynchronous development of electrical remodeling and cardiac hypertrophy in the complete AV block dog

Abstract: In the CAVB dog ventricular hypertrophy is not a prerequisite for electrical remodeling or drug-induced torsade de pointes, and the AT1-receptor has no dominant role in the completion of these remodeling processes.

Cited by 53 publications

References 30 publications

Increase in cardiac myosin heavy-chain (MyHC) alpha protein isoform in hibernating ground squirrels, with echocardiographic visualization of ventricular wall hypertrophy and prolonged contraction.

Increase in cardiac myosin heavy-chain (MyHC) alpha protein isoform in hibernating ground squirrels, with echocardiographic visualization of ventricular wall hypertrophy and prolonged contraction.

Isoproterenol disperses distribution of NADPH oxidase, MMP-9, and pPKCε in the heart, which are mitigated by endothelin receptor antagonist CPU0213

Titin isoform switching is a major cardiac adaptive response in hibernating grizzly bears

Contact Info

Product

Resources

About