Myocardial energetics in patients with dilated cardiomyopathy. Influence of nitroprusside and enoximone.

Hasenfuß, Gerd; Holubarsch, C; Heiß, H. W.; Meinertz, Thomas; Bonzel, T.; Wais, U; Lehmann, M.; Just, Hanjörg

doi:10.1161/01.cir.80.1.51

Cited by 76 publications

(24 citation statements)

References 54 publications

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“…19,20 Baseline dP/dt max values in the present study group were remarkably low despite the absence of bradycardia or systolic hypotension. Many previous studies of DCM in which patients with conduction delay were not targeted 8,[21][22][23] have reported consistent values for dP/dt max of Ϸ900 mm/s, 30% higher than in the present study but similar to values during pacing. Yet, the functional status, ejection fraction, etc, of the present patient group was indistinguishable from those in these previous studies.…”

Section: Discussionsupporting

confidence: 86%

Predictors of Systolic Augmentation From Left Ventricular Preexcitation in Patients With Dilated Cardiomyopathy and Intraventricular Conduction Delay

et al. 2000

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Background-VDD pacing can enhance systolic function in patients with dilated cardiomyopathy and discoordinate contraction; however, identification of patients likely to benefit is unclear. We tested predictors of systolic responsiveness on the basis of global parameters as well as directly assessed mechanical dyssynchrony. Methods and Results-Twenty-two DCM patients with conduction delay were studied by cardiac catheterization with a dual-sensor micromanometer to measure LV and aortic pressures during sinus rhythm and LV free-wall pacing. Pacing enhanced isovolumetric (dP/dt max ) and ejection-phase (pulse pressure, PP) systolic function by 35Ϯ21% and 16.4Ϯ11%, respectively, and these changes correlated directly (rϭ0.7, Pϭ0.001). %⌬dP/dt max was weakly predicted by baseline QRS (rϭ0.6, PϽ0.02), more strongly by baseline dP/dt max (rϭ0.7, Pϭ0.001), and best by bidiscriminate analysis combining baseline dP/dt max Յ700 mm Hg/s and QRS Ն155 ms to predict %⌬dP/dt max Ն25% and %⌬PP Ն10% (PϽ0.0005, 2 ), with no false-positives. Benefit could not be predicted by %⌬QRS. To test whether basal mechanical dyssynchrony predicted responsiveness to LV pacing, circumferential strains were determined at Ϸ80 sites throughout the LV by tagged MRI in 8 DCM patients and 7 additional control subjects. Strain variance at time of maximal shortening indexed dyssynchrony, averaging 28.0Ϯ7.1% in normal subjects versus 201.4Ϯ84.3% in DCM patients (Pϭ0.001). Mechanical dyssynchrony also correlated directly with %⌬dP/dt max (rϭ0.85, Pϭ0.008). Conclusions-These results show that although mechanical dyssynchrony is a key predictor for pacing efficacy in DCM patients with conduction delay, combining information about QRS and basal dP/dt max provides an excellent tool to identify maximal responders.

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Section: Discussionsupporting

confidence: 86%

Predictors of Systolic Augmentation From Left Ventricular Preexcitation in Patients With Dilated Cardiomyopathy and Intraventricular Conduction Delay

et al. 2000

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“…A positive effect of stretch on oxygen consumption was demonstrated in intact quiescent rat hearts exposed to increased ventricular preload (15) and also in humans: a good direct linear correlation was found in normal volunteers and in patients (with chronic pressure overload, chronic volume overload, or CAD) between end-diastolic and peak systolic stress, on the one hand, and LV oxygen consumption, on the other (72,153). Increased energetic demand caused by wall stress could explain experimental (46, 63) and clinical findings of surprisingly high oxygen consumption and, consequently, impaired mechanical efficiency in dysfunctional regions in patients with CAD (70).…”

Section: Myocardial Wall Stressmentioning

confidence: 89%

Mechanisms leading to reversible mechanical dysfunction in severe CAD: alternatives to myocardial stunning

Mazzadi

André‐Fouët²,

Costes³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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Croisille, Didier Revel, and Marc F. Janier. Mechanisms leading to reversible mechanical dysfunction in severe CAD: alternatives to myocardial stunning. Am J Physiol Heart Circ Physiol 291: H2570 -H2582, 2006. First published July 21, 2006 doi:10.1152/ajpheart.01249.2005.-Patients with severe chronic coronary artery disease (CAD) exhibit a highly altered myocardial pattern of perfusion, metabolism, and mechanical performance. In this context, the diagnosis of stunning remains elusive not only because of methodological and logistic considerations, but also because of the pathophysiological characteristics of the myocardium of these patients. In addition, a number of alternative pathophysiological mechanisms may act by mimicking the functional manifestations usually attributed to stunning. The present review describes three mechanisms that could theoretically lead to reversible mechanical dysfunction in these patients: myocardial wall stress, the tethering effect, and myocardial expression and release of auto-and paracrine agents. Attention is focused on the role of these mechanisms in scintigraphically "normal" regions (i.e., regions usually showing normal perfusion, glucose metabolism, and cellular integrity as assessed by nuclear imaging techniques), in which stunning is usually considered, but these mechanisms could also operate throughout the viable myocardium. We hypothesize that reversion of these three mechanisms could partially explain the unexpected functional benefit after reperfusion recently highlighted by high-spatial-resolution imaging techniques. stunned myocardium; hibernating myocardium; inotropic reserve; cardiac imaging; myocardial wall stress; ventricular remodeling SUMMARY OF CLINICAL PROBLEMIN RECENT YEARS, WIDESPREAD utilization of noninvasive cardiac imaging methods has greatly improved the synergy between clinical and basic investigation of cardiac ischemic pathophysiology. Thus imaging methods have shown that the reversible left ventricular (LV) dysfunction arising from brief coronary occlusion and reflow (myocardial stunning), first described in animal models (80), occurs in humans. Two major hypotheses explain this phenomenon: 1) the oxyradical hypothesis, which proposes that oxidant stress impairs LV function (18), and 2) the calcium hypothesis, which postulates that stunning results from disturbed myocyte calcium homeostasis (98). On the other hand, the hibernating myocardium (136, 137) was first discovered by imaging methods in humans, and it was originally defined as "resting LV dysfunction due to reduced coronary blood flow that can be partially or completely reversed by myocardial revascularization and/or by reducing myocardial oxygen demand" (136). The concept was refined when ultrastructural investigations showed a distinctive morphology for hibernating myocardium, generally without necrosis, but with loss of sarcomeres and myofibrils (suggesting a "dedifferentiation" process toward an embryonic phenotype), with loss of mitochondria and increased glycogen storage (9,19,27,162)...

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“…20 On the other hand, the decline of MVO 2 upon administration of vasodilators such as nitroprusside or inhibitors of phosphodiesterase III that elevate cAMP and combine vasodilating and inotropic effects is not due to direct myocardial effect but is rather secondary to the vasodilation. 21 …”

Section: Discussionmentioning

confidence: 99%

Adenoviral gene transfer of Akt enhances myocardial contractility and intracellular calcium handling

et al. 2005

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The serine-threonine kinase Akt/PKB mediates stimuli from different classes of cardiomyocyte receptors, including the growth hormone/insulin like growth factor and the b-adrenergic receptors. Whereas the growth-promoting and antiapoptotic properties of Akt activation are well established, little is known about the effects of Akt on myocardial contractility, intracellular calcium (Ca 2+ ) handling, oxygen consumption, and b-adrenergic pathway. To this aim, Sprague-Dawley rats were subjected to a wild-type Akt in vivo adenoviral gene transfer using a catheter-based technique combined with aortopulmonary crossclamping. Left ventricular (LV) contractility and intracellular Ca 2+ handling were evaluated in an isolated isovolumic bufferperfused, aequorin-loaded whole heart preparations 10 days after the surgery. The Ca 2+ -force relationship was obtained under steady-state conditions in tetanized muscles. No significant hypertrophy was detected in adenovirus with wild-type Akt (Ad.Akt) versus controls rats (LV-to-body weight ratio 2.670.2 versus 2.770.1 mg/g, controls versus Ad.Akt, P, NS). LV contractility, measured as developed pressure, increased by 41% in Ad.Akt. This was accounted for by both more systolic Ca 2+ available to the contractile machinery (+19% versus controls) and by enhanced myofilament Ca 2+ responsiveness, documented by an increased maximal Ca 2+ -activated pressure (+19% versus controls) and a shift to the left of the Ca 2+ -force relationship. Such increased contractility was paralleled by a slight increase of myocardial oxygen consumption (14%), while titrated dose of dobutamine providing similar inotropic effect augmented oxygen consumption by 39% (Po0.01). Phospholamban, calsequestrin, and ryanodine receptor LV mRNA and protein content were not different among the study groups, while sarcoplasmic reticulum Ca 2+ ATPase protein levels were significantly increased in Ad.Akt rats. b-Adrenergic receptor density, affinity, kinase-1 levels, and adenylyl cyclase activity were similar in the three animal groups. In conclusion, our results support an important role for Akt/PKB in the regulation of myocardial contractility and mechanoenergetics.

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Myocardial energetics in patients with dilated cardiomyopathy. Influence of nitroprusside and enoximone.

Cited by 76 publications

References 54 publications

Predictors of Systolic Augmentation From Left Ventricular Preexcitation in Patients With Dilated Cardiomyopathy and Intraventricular Conduction Delay

Predictors of Systolic Augmentation From Left Ventricular Preexcitation in Patients With Dilated Cardiomyopathy and Intraventricular Conduction Delay

Mechanisms leading to reversible mechanical dysfunction in severe CAD: alternatives to myocardial stunning

Adenoviral gene transfer of Akt enhances myocardial contractility and intracellular calcium handling

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