Mechanical alternans and restitution  in failing SHHF rat left ventricles

Dumitrescu, Cristian; Narayan, Prakash; Efimov, Igor R.; Cheng, Yuanna; Radin, M. Judith; McCune, Sylvia A.; Altschuld, Ruth A.

doi:10.1152/ajpheart.00466.2001

Cited by 29 publications

(29 citation statements)

References 29 publications

(30 reference statements)

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“…condition can be provoked in normal isolated rat hearts by pacing with at least twice the normal heart rate, and it usually occurs after an abrupt jump in pacing rate [30]. The present pacing experiments do by far not reach this level.…”

Section: Heterometric Autoregulative Component (Frank-starling)contrasting

confidence: 64%

“…The present pacing experiments do by far not reach this level. Alternating pulse is characterised by a substantial difference ∆P max LV changing its sign from beat to beat, and is related to insufficient recovery time for sarcoplasmatic Ca 2+ reuptake [30]. This seems to discriminate alternans from duorhythm.…”

Section: Heterometric Autoregulative Component (Frank-starling)mentioning

confidence: 99%

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Autocorrelation Patterns in the Left-Ventricular Pressure Course of Isolated Working Hearts at Sinus Rhythm

Langer¹

2016

ICFJ

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<pre class="western">Background Observations of short term uniformity or microrhythmical undulation in ventricular pressure courses at sinus rhythm are lacking but necessary to describe cardiac status. The present investigation aims for (a) detecting repetitive similarity patterns in ventricular pressure at isolated sinus rhythm, (b) tagging hemodynamic parameters which contribute most to dissimilarity, and (c) for a stochastical characterisation of the random component in mutual similarity. Methods Left-ventricular pressure curves from isolated working small animal hearts, at sinus rhythm and electrical stimulation, are analysed by autocorrelation. Results Ventricular pressure courses consistently reach their peak coefficient of autocorrelation either at one-beat lag (monorhythm) or at two-beat lag (duorhythm). Replacing sinus rhythm with strictly even electrical right-atrial stimulation provokes more duorhythms to occur (Langer paradox). Duorhythms become scarcer at hypothermia and high cardiac output. Repetition of very similarly shaped beats accords with an exponential law. Variability of twelve hemodynamic parameters, regarding microrhythm, is given as a Table. Conclusions (a) Incidence of alternating patterns (duorhythms) suggests the presence of effective heterometric autoregulation (Frank-Starling law). Consequently, a pacing test may assess contractile reserve in certain conditions. Higher multi-beat patterns occur by chance at isolated sinus rhythm. (b) Interbeat variability of relevant hemodynamic parameters complies with the initial conclusion. Statistical pooling of data from consecutive beats seems permissible; pooling alterant beats separately will do better. (c) Random fluctuation is a constituent part of medium-term ventricular pressure course. Mutually very similar beats occur stochastically by a Poisson process with fade-out. Deviations accord with the presence of mono- or duorhythms.</pre>

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Section: Heterometric Autoregulative Component (Frank-starling)contrasting

confidence: 64%

Section: Heterometric Autoregulative Component (Frank-starling)mentioning

confidence: 99%

Autocorrelation Patterns in the Left-Ventricular Pressure Course of Isolated Working Hearts at Sinus Rhythm

Langer¹

2016

ICFJ

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“…SHHF rats of either sex were studied at 2 and 8 mo of age and after the development of overt heart failure. As previously described, heart failure was identified between 16 and 22 mo of age and was defined as a left ventricular ejection fraction Ͻ40% by echocardiography, with signs of labored breathing, cyanosis, subcutaneous edema, piloerection, cold extremities (tails), and orthopnea (8,26). Age-matched Wistar-Furth or Wistar rats (Harlan, Indianapolis, IN) of either sex were used as controls (8,31).…”

Section: Methodsmentioning

confidence: 99%

Abnormal diastolic currents in ventricular myocytes from spontaneous hypertensive heart failure rats

Sridhar¹,

Dech²,

Lacombe³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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Abnormal diastolic currents in ventricular myocytes from spontaneous hypertensive heart failure rats. Am J Physiol Heart Circ Physiol 291: H2192-H2198, 2006. First published June 9, 2006 doi:10.1152/ajpheart.01146.2005.-Hypertension is a common cause of heart failure, and ventricular arrhythmias are a major cause of death in heart failure. The spontaneous hypertension heart failure (SHHF) rat model was used to study altered ventricular electrophysiology in hypertension and heart failure. We hypothesized that a reduction in the inward rectifier K ϩ current (IK1) and expression of pacemaker current (If) would favor abnormal automaticity in the SHHF ventricle. SHHF ventricular myocytes were isolated at 2 and 8 mo of age and during end-stage heart failure (Ն17 mo); myocytes from age-matched rats served as controls. Inward IK1 was significantly reduced at both 8 and Ն17 mo in SHHF rats compared with controls. There was a reduction in inward IK1 due to aging in the controls only at Ն17 mo. We found a significant increase in If at all ages in the SHHF rats, compared with young controls. In controls, there was an age-dependent increase in If. Action potential recordings in the SHHF rats demonstrated abnormal automaticity, which was abolished by the addition of an If blocker (10 M zatebradine). Increased If during hypertension alone or combined increases in If with reduced IK1 during the progression to hypertensive heart failure contribute to a substrate for arrhythmogenesis. aging; pacemaker current; inward rectifier potassium current; abnormal automaticity HYPERTENSION CAN LEAD TO COMPENSATORY hypertrophy in cardiac muscle. Chronically, these compensatory mechanisms can become maladaptive, and cardiomyopathy and heart failure can result (22). Experimental animal studies in hypertrophy and heart failure have shown abnormalities in ion channel function, altered expression and function of proteins involved in excitation-contraction coupling, and an increased propensity for cardiac arrhythmias (16,30,32). Clinically, ventricular arrhythmias occur in 80% of heart failure patients (11). However, the mechanisms of arrhythmogenic electrophysiological remodeling during hypertension and hypertensive heart failure are not fully elucidated.Spontaneous hypertensive heart failure (SHHF) rats develop hypertension at an early age. In contrast to spontaneously hypertensive rats (SHRs), the SHHF rats consistently develop reproducible, hypertensive heart failure in an age-dependent manner (26). Echocardiographic studies in the SHHF rat demonstrate left ventricular dysfunction (left ventricular ejection fraction Ͻ40%) at 17-18 mo of age (31). There is also evidence of progressive cardiac hypertrophy in the SHHF rats, evidenced as an increase in heart weights (36).Hypertension and heart failure can increase the pacemaker current (I f ) in the ventricular myocardium (4 -7). This can pathologically alter the diastolic phase of the action potential and enhance abnormal automaticity. In addition, aging has been shown to increase I f density i...

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“…Picht et al (2006) used direct measurements of intra-SR free calcium to show that pacing induced calcium alternans does not require SR calcium content alternans but, rather, may depend more on RyR recovery. (Dumitrescu et al, 2002) In addition to artificial means of depressing SR calcium release, ischemia (Kurz et al, 1993;Mohabir et al, 1991;Wilson et al, 2006) and metabolic inhibition (Hüser et al, 2000;Kockskamper et al, 2002) have been associated with calcium transient alternans as well. In a series of studies, Qian et al (2003) have shown the development of significant alternans during the acute phases of ischemia.…”

Section: Mechanisms Of Calcium Transient Alternans: Sr Calcium Releasementioning

confidence: 99%

Cellular mechanisms of arrhythmogenic cardiac alternans

Laurita

Rosenbaum

2008

Progress in Biophysics and Molecular Biology

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Mechanical dysfunction remains as one of the best predictors of sudden cardiac death (SCD), but despite this close association the causal relationships between electrical instability and mechanical dysfunction are not fully understood. (Bigger et al., 1984;Buxton et al., 1984) Even though the effects of electrical instability on mechanical dysfunction of the heart is well appreciated and relatively clear, the reverse effects that mechanical dysfunction have electrical instability, or mechano-electrical feedback (MEF), are not. (Kohl et al., 2006;Lab, 1996) Stretch activated channels, for example, are one way mechanical activity can directly influence electrical activity at the cellular level under physiologic and pathophysiological conditions. (Hu et al., 1997) Alternatively, intracellular calcium, which regulates mechanical contraction, can significantly influence electrical function of the heart as well. The mechanisms by which intracellular calcium governs electrical instability of the heart is the main focus of this manuscript. Traditionally, calcium mediated arrhythmogenesis is associated with delayed after depolarizations and abnormal impulse formation. (Katra et al., 2007;Liu et al., 2006;Rosen, 1985;Ter Keurs et al., 2006;Wehrens et al., 2003) However, in this manuscript we focus on how cardiac alternans, a mechanisms of reentrant excitation, is another significant way mechanical dysfunction and arrhythmogenesis are causally related.Cardiac alternans can refer to either mechanical (contractile) or electrical (repolarization) oscillations that occur on an every other beat basis. Cardiac alternans has been recognized for more than 100 years. Shown in Figure 1 (Panel A) is a very early record of arterial pressure measured during a steady state heart rate, where pulse magnitude alternates on every other beat (arrows). (Traube, 1872) At this time, the ECG had not been invented; however, soon after its introduction electrical alternans was reported as well. Shown in Panel B (Figure 1) is an early example of electrical alternans as evidenced by oscillations of the ECG T-wave (arrows) and QRS. (Lewis, 1910) Soon after cardiac alternans was first reported, it was associated with a poor prognosis. (Windle, 1913) Surprisingly, at this same time several important characteristics of cardiac alternans were observed, such as alternans occurring in a structurally normal heart and appearing at faster heart rates. Subsequently, Twave alternans was more directly related to coronary artery occlusion and shown to be highly reproducible. (Hellerstein et al., 1950)

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Mechanical alternans and restitution in failing SHHF rat left ventricles

Cited by 29 publications

References 29 publications

Autocorrelation Patterns in the Left-Ventricular Pressure Course of Isolated Working Hearts at Sinus Rhythm

Autocorrelation Patterns in the Left-Ventricular Pressure Course of Isolated Working Hearts at Sinus Rhythm

Abnormal diastolic currents in ventricular myocytes from spontaneous hypertensive heart failure rats

Cellular mechanisms of arrhythmogenic cardiac alternans

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