Diastolic Dysfunction and Collagen Structure in Canine Pacing-Induced Heart Failure

Neumann, Till; Vollmer, Alan; Schaffner, Th.; Hess, Otto M.; Heusch, Gerd

doi:10.1006/jmcc.1998.0853

Cited by 26 publications

(26 citation statements)

References 2 publications

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“…The elevated collagenbased muscle stiffness is consistent with the reported Ͼ5-fold increase in the steepness of the LV end-diastolic pressurestrain relation in canine pacing-induced heart failure, 17 although possible differences in the diastolic SL range and changes in the geometry of the chamber during heart failure preclude a direct comparison between muscle stiffness and chamber stiffness. It seems unlikely that the large increase in collagen-based stiffness that we found results solely from increased collagen content, because this is only Ϸ50% increased after 5 to 6 weeks of pacing 29 and is virtually unchanged after 3 weeks of rapid pacing.…”

Section: Collagensupporting

confidence: 81%

“…On the day after surgery, the pacing rate was set at 235 bpm and maintained at that level for 4 weeks. Numerous studies have documented that 4 weeks of pacing is sufficient to consistently cause myocardial failure with chamber dilatation, reduced ejection fraction, reduced ventricular chamber compliance, and increased muscle stiffness (see, for example, Solomon et al 16 and Neumann et al 17 and references therein). Accordingly, we did not measure hemodynamics or left ventricular (LV) function at the end of this study to avoid stressing and possibly losing animals at the end of the pacing period.…”

Section: Tachycardia-induced Cardiac Failurementioning

confidence: 99%

“…It seems unlikely that the large increase in collagen-based stiffness that we found results solely from increased collagen content, because this is only Ϸ50% increased after 5 to 6 weeks of pacing 29 and is virtually unchanged after 3 weeks of rapid pacing. 17,30 Thus, other changes in collagen that increase stiffness may take place during pacing, such as increased cross-linking 31 and changes in the type. The extracellular matrix contains both type I and III collagens.…”

Section: Collagenmentioning

confidence: 99%

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Changes in Titin Isoform Expression in Pacing-Induced Cardiac Failure Give Rise to Increased Passive Muscle Stiffness

et al. 2002

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Background-Titin contains a molecular spring segment that underlies passive myocardial stiffness. Myocardium coexpresses titin isoforms with molecular spring length variants and, consequently, distinct stiffness characteristics: the stiff N2B isoform (short spring) and more compliant N2BA isoform (long spring). We tested whether changes in titin isoform expression occur in the diastolic dysfunction that accompanies heart failure. Methods and Results-We used the tachycardia-induced dilated cardiomyopathy canine model (4-week pacing) and found that control myocardium coexpresses the N2B and N2BA isoforms at similar levels, whereas in dilated cardiomyopathy the expression ratio had shifted, without affecting the amount of total titin, toward more prominent N2B expression. This shift was accompanied by elevated titin-based passive muscle stiffness. Pacing also resulted in significant upregulation of obscurin, an Ϸ800-kDa elastic protein with several signaling domains. Conclusions-Coexpression of titin isoforms with distinct mechanical properties allows modulation of passive stiffness via adjustment of the isoform expression ratio. The canine pacing-induced heart failure model uses this mechanism to increase myocardial stiffness. Thus, changes in titin isoform expression may play a role in diastolic dysfunction in heart failure.

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Section: Collagensupporting

confidence: 81%

Section: Tachycardia-induced Cardiac Failurementioning

confidence: 99%

Section: Collagenmentioning

confidence: 99%

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Changes in Titin Isoform Expression in Pacing-Induced Cardiac Failure Give Rise to Increased Passive Muscle Stiffness

et al. 2002

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“…All affect LV relaxation (55). Previous studies have shown that reduction in the lusitropic performance is mainly related to changes in calcium homeostasis and that reduced diastolic compliance is frequently observed in pacing-induced HF and has been attributed to, among other things, an increase in interstitial collagen formation and/or its nonuniform orientation (28,54).…”

Section: Discussionmentioning

confidence: 99%

Heart failure attenuates muscle metaboreflex control of ventricular contractility during dynamic exercise

Sala‐Mercado¹,

Hammond²,

Kim³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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DS. Heart failure attenuates muscle metaboreflex control of ventricular contractility during dynamic exercise. Am J Physiol Heart Circ Physiol 292: H2159 -H2166, 2007. First published December 22, 2006; doi:10.1152/ajpheart.01240.2006.-Underperfusion of active skeletal muscle elicits a reflex pressor response termed the muscle metaboreflex (MMR). In normal dogs during mild exercise, MMR activation causes large increases in cardiac output (CO) and mean arterial pressure (MAP); however, in heart failure (HF) although MAP increases, the rise in CO is virtually abolished, which may be due to an impaired ability to increase left ventricular contractility (LVC). The objective of the present study was to determine whether the increases in LVC seen with MMR activation during dynamic exercise in normal animals are abolished in HF. Conscious dogs were chronically instrumented to measure CO, MAP, and left ventricular (LV) pressure and volume. LVC was calculated from pressure-volume loop analysis [LV maximal elastance (E max) and preload-recruitable stroke work (PRSW)] at rest and during mild and moderate exercise under free-flow conditions and with MMR activation (via partial occlusion of hindlimb blood flow) before and after rapid ventricular pacing-induced HF. In control experiments, MMR activation at both workloads [mild exercise (3.2 km/h) and moderate exercise (6.4 km/h at 10% grade)] significantly increased CO, E max, and PRSW. In contrast, after HF was induced, CO, Emax, and PRSW were significantly lower at rest. Although CO increased significantly from rest to exercise, E max and PRSW did not change. In addition, MMR activation caused no significant change in CO, E max, or PRSW at either workload. We conclude that MMR causes large increases in LVC in normal animals but that this ability is abolished in HF. pressor response; elastance; preload recruitable stroke work WHEN EXERCISING SKELETAL MUSCLE does not receive sufficient blood flow to meet the ongoing metabolic demands, by-products of metabolism such as lactic acid, H ϩ , adenosine, potassium, diprotonated phosphate, and arachidonic acid products, among others, accumulate within the muscle and stimulate group III and IV afferent neurons, which evokes a reflex response known as the muscle metaboreflex (MMR). This reflex response consists of increases in efferent sympathetic nerve activity (SNA) and mean arterial pressure (MAP) (1, 3, 11, 17, 18, 24, 31-35, 39, 40, 43, 46, 47, 52, 53). In addition, MMR activation causes increases in cardiac output (CO), heart rate (HR), and plasma levels of vasoactive hormones and produces vasoconstriction in the renal and the nonischemic active skeletal muscle vasculature to partially restore arterial O 2 delivery and blood flow to the hypoperfused muscles (25,33,36). The rise in CO likely results from increases in ventricular performance, HR, and central blood volume mobilization (32,42,43). By this means the MMR-induced increases in ventricular performance act to slightly increase or sustain stroke volume (SV) despite decreas...

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“…Progressive hyperplasia/hypertrophy of smooth and cardiac muscle and excessive collagen deposition are directly involved in a self-perpetuated vicious cycle of high-stiffness-associated cardiovascular dysfunction (for example, hypertension and cardiac diastolic dysfunction). 4 Large arteries with preserved elastic properties are able to stretch during systole, thus retaining some of the blood volume to be returned to the circulation during diastole. This reduces cardiac cycle-dependent fluctuations in blood pressure (BP), reduces cardiac afterload and improves coronary perfusion pressure during diastole.…”

Section: Introductionmentioning

confidence: 99%

Vascular ventricular coupling in patients with malignant phase hypertension: the West Birmingham malignant hypertension project

et al. 2012

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Patients with malignant hypertension (MHT) have persistent vascular dysfunction and a much worse clinical prognosis than non-MHT hypertensive patients, despite good long-term blood pressure (BP) control. We hypothesized that abnormal arterial (arterial elastance (Ea); arterial elastance index (EaI)) and ventricular (End-systolic elastance (Ees) and End-diastolic elastance (Eed)) elastances are present in treated MHT patients, compared with non-MHT hypertensive controls. Echocardiographic parameters of cardiac and vascular stiffness (EaI, Ees and Eed) were quantified in patients with stable MHT and treated 'high-risk' hypertension patients (HHT, but non-MHT). All patients had well-controlled BP, with a median follow-up time for MHT of 144 months. Ea was calculated from stroke volume and systolic BP and adjusted by body area (EaI). Ees was calculated using systolic and diastolic BP, stroke volume, ejection fraction, time intervals and estimated normalized ventricular elastance at arterial end diastole. Eed was calculated from Doppler parameters and the diastolic filling volume. Both study groups had preserved left ventricular contractility, with no significant differences on 3D-echocardiography (P ¼ 0.10) There were no significant differences in EaI (P ¼ 0.83), Ees (P ¼ 0.32), Eed (P ¼ 0.23) and arterial-ventricular interaction (Ees/Ea, P ¼ 0.69). In the MHT group, Eed positively correlated with age (r ¼ 0.56, P ¼ 0.38) and systolic BP (r ¼ 0.68, P ¼ 0.008). On multivariable regression analysis, MHT status was not predictive of the ventricular and Ea. Despite documented vascular dysfunction in patients with previously diagnosed stable MHT, the arterial and systolic elastances were similar to HHT patients, suggesting that adequate BP control in MHT patients allows preservation or restoration of normal arterial-ventricular coupling.

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Diastolic Dysfunction and Collagen Structure in Canine Pacing-Induced Heart Failure

Cited by 26 publications

References 2 publications

Changes in Titin Isoform Expression in Pacing-Induced Cardiac Failure Give Rise to Increased Passive Muscle Stiffness

Changes in Titin Isoform Expression in Pacing-Induced Cardiac Failure Give Rise to Increased Passive Muscle Stiffness

Heart failure attenuates muscle metaboreflex control of ventricular contractility during dynamic exercise

Vascular ventricular coupling in patients with malignant phase hypertension: the West Birmingham malignant hypertension project

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