Tolerance of the hypertrophic heart to ischemia. Studies in compensated and failing dog hearts with pressure overload hypertrophy.

Gaasch, William H.; Zile, Michael R.; Hoshino, P K; Weinberg, Ellen O.; Rhodes, Daniel R.; Apstein, Carl S.

doi:10.1161/01.cir.81.5.1644

Cited by 96 publications

(39 citation statements)

References 58 publications

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“…Although the mechanisms responsible for the greater impairment of postischemic mechanical function in hypertrophied hearts remain unclear, we speculate that regulation of glucose transport plays an important role. The slower glucose uptake rate demonstrated in hypertrophied myocardium may in part explain the accelerated loss of high-energy phosphates during ischemia and worse recovery of contractile function during reperfusion [6,24]. As suggested by several investigators, rapid recovery of aerobic glycolysis is crucial during early reperfusion for recovery of contractile function after ischemia [25,26].…”

Section: Commentmentioning

confidence: 99%

Inhibition of Glycogen Synthase Kinase-3β Improves Tolerance to Ischemia in Hypertrophied Hearts

Barillas

Friehs

Cao-Danh

et al. 2007

The Annals of Thoracic Surgery

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Background-Hypertrophied myocardium is more susceptible to ischemia/reperfusion injury, in part owing to impaired insulin-mediated glucose uptake. Glycogen synthase kinase-3β (GSK-3β) is a key regulatory enzyme in glucose metabolism that, when activated, phosphorylates/inactivates target enzymes of the insulin signaling pathway. Glycogen synthase kinase-3β is regulated upstream by Akt-1. We sought to determine whether GSK-3β is activated in ischemic hypertrophied myocardium owing to impaired Akt-1 function, and whether inhibition with lithium (Li) or indirubin-3′-monoxime,5-iodo-(IMI), a specific inhibitor, improves post-ischemic myocardial recovery by improving glucose metabolism.

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Section: Commentmentioning

confidence: 99%

Inhibition of Glycogen Synthase Kinase-3β Improves Tolerance to Ischemia in Hypertrophied Hearts

Barillas

Friehs

Cao-Danh

et al. 2007

The Annals of Thoracic Surgery

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“…Concentric left ventricular (LV) hypertrophy (LVH), which occurs to compensate for increased wall stress, is a compensatory mechanism which may have detrimental effects, including increased sensitivity to ischemia with consequent systolic or diastolic dysfunction. 13 Earlier AV replacement (AVR) may be considered in asymptomatic AS before severe LVH or dysfunction develops.…”

Section: Clinical Perspective On P 725mentioning

confidence: 99%

Association of Myocardial Deformation With Outcome in Asymptomatic Aortic Stenosis With Normal Ejection Fraction

Yingchoncharoen

Gibby

Rodriguez

et al. 2012

Circ: Cardiovascular Imaging

161

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Background-Current guidelines recommend intervention for symptomatic aortic stenosis, but the management of asymptomatic aortic stenosis remains controversial. As left ventricular global longitudinal strain (GLS) has been shown to predict cardiovascular outcome, we sought to find whether its use could guide the assessment of risk in these patients. Methods and Results-We prospectively followed 79 patients with severe asymptomatic aortic stenosis (39 men; mean age, 77 ± 12 years; aortic valve [AV] area index, 0.36 cm 2 /m 2 ). In addition to standard echocardiography, speckle strain was measured to assess GLS. Patients were followed for cardiac death and AV replacement driven by symptom development. A multivariable Cox regression was performed to identify associations with events. During 23 ± 20 months, 3 patients had cardiac death and 49 underwent AV replacement. Event-free survival was 72 ± 5% at 1 year, 50 ± 5% at 2 years, and 24 ± 5% at 4 years. Death and AV replacement were predicted by GLS (hazard ratio [HR] Methods Patient SelectionThe study population included patients with severe AS who were studied in our echocardiography laboratory from March 2004 to August 2010. Severe AS was defined as AV area <1 cm 2 or transaortic jet velocity >4 m/s. Patients were excluded if they had any additional hemodynamically significant valvular lesions, presented with symptoms (angina, dyspnea, or syncope) or LV ejection fraction (LVEF)<50%. After these exclusions, we enrolled 79 patients (39 men; 77 ± 12 years; AV area index, 0.36 cm 2 ). The protocol was approved by the institutional review board of the Cleveland Clinic. Clinical CharacteristicsClinical data were entered prospectively into an electronic health record, including age, sex, height, weight, history of coronary artery disease (previous positive coronary angiogram or stress test), history of diabetes mellitus (fasting blood glucose >126 mg/dL on 2 occasions or patients currently receiving treatment for diabetes mellitus), history of hypercholesterolemia (total cholesterol >190 mg/dL or patients receiving lipid lowering agents), history of hypertension (blood pressure ≥140/90 mm Hg or patients receiving antihypertensive drugs) were collected at baseline. The Society of Thoracic Surgeons (STS) Predicted Risk of Morbidity or Mortality (STS-PRMM) for AV procedures was calculated by entering patient data into an online STS risk calculator (http://riskcalc.sts.org/ STSWebRiskCalc273/). The STS-PRMM uses 24 variables of >50 total risk factors collected by algorithm to predict mortality for valve procedures. 17 EchocardiographyPatients underwent a standard echocardiogram performed by experienced echocardiographers, using commercially available ultrasound systems. The LV dimensions, wall thickness, and outflow tract diameter were measured according to the recommendations of the American Society of Echocardiography. 18 The degree of calcification of the AV was scored as: (1) no calcification; (2) mildly calcified (small isolated foci); (3) moderately calcified (multipl...

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“…5 These pathological changes slow myocardial relaxation, which in turn diminishes normal ventricular filling and reduces coronary blood flow. 6,7 This is compounded by the increase in work and myocardial mass, which results in elevated myocardial oxygen demand and a decrease in microvascular density, 8 leading to reduced coronary vascular reserve. 9 As the severity of the aortic stenosis increases, this process is exacerbated by ever-increasing afterload and decreasing coronary perfusion pressures, leading to the development of ischemia, which has been reported with the use of several different techniques.…”

Section: Clinical Perspective On Pmentioning

confidence: 99%

“…[13][14][15][16][17] Our group has demonstrated similar findings in humans using wave intensity analysis. 7,18 Specifically, during systole, when the LV is contracting, coronary flow is limited by compression of the coronary microcirculation by the contracting myocardium. It is not until LV relaxation occurs that compression of the microcirculation is relieved and coronary blood flow increases.…”

mentioning

confidence: 99%

Arterial Pulse Wave Dynamics After Percutaneous Aortic Valve Replacement

et al. 2011

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Background-Aortic stenosis causes angina despite unobstructed arteries. Measurement of conventional coronary hemodynamic parameters in patients undergoing valvular surgery has failed to explain these symptoms. With the advent of percutaneous aortic valve replacement (PAVR) and developments in coronary pulse wave analysis, it is now possible to instantaneously abolish the valvular stenosis and to measure the resulting changes in waves that direct coronary flow. Methods and Results-Intracoronary pressure and flow velocity were measured immediately before and after PAVR in 11 patients with unobstructed coronary arteries. Using coronary pulse wave analysis, we calculated the intracoronary diastolic suction wave (the principal accelerator of coronary blood flow). To test physiological reserve to increased myocardial demand, we measured at resting heart rate and during pacing at 90 and 120 bpm. Before PAVR, the basal myocardial suction wave intensity was 1.9Ϯ0.3ϫ10 Ϫ5 W ⅐ m Ϫ2 ⅐ s Ϫ2 , and this increased in magnitude with increasing severity of aortic stenosis (rϭ0. 59, Pϭ0.05). This wave decreased markedly with increasing heart rate (␤ coefficientϭϪ0. ; Pϭ0.014). Conclusions-In aortic stenosis, the coronary physiological reserve is impaired. Instead of increasing when heart rate rises, the coronary diastolic suction wave decreases. Immediately after PAVR, physiological reserve returns to a normal positive pattern. This may explain how aortic stenosis can induce anginal symptoms and their prompt relief after PAVR. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01118442. Key Words: aortic stenosis Ⅲ aortic valve Ⅲ coronary arteries Ⅲ coronary flow Ⅲ heart valve prosthesis implantation Ⅲ microvessels Ⅲ wavelet analysis U ncorrected severe aortic stenosis has an extremely poor prognosis, carrying a 3-year mortality of Ͼ50%, 1 which rises to Ͼ80% in subjects with significant cardiac comorbidity. 2 As the severity of aortic stenosis increases, physiological and pathological adaptations occur in the left ventricle (LV). 3 These include increases in the inotropic state and the development of LV hypertrophy. 4 Editorial see p 1505 Clinical Perspective on p 1572Although LV hypertrophy can be viewed as a physiological adaptation to the increase in afterload, it encompasses a pathological hypertrophic response with increased extracellular matrix deposition and perivascular fibrosis. 5 These pathological changes slow myocardial relaxation, which in turn diminishes normal ventricular filling and reduces coronary blood flow. 6,7 This is compounded by the increase in work and myocardial mass, which results in elevated myocardial oxygen demand and a decrease in microvascular density, 8 leading to reduced coronary vascular reserve. 9 As the severity of the aortic stenosis increases, this process is exacerbated by ever-increasing afterload and decreasing coronary perfusion pressures, leading to the development of ischemia, which has been reported with the use of several different techniques. 10...

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Tolerance of the hypertrophic heart to ischemia. Studies in compensated and failing dog hearts with pressure overload hypertrophy.

Abstract: Tolerance of the canine heart to prolonged ischemic arrest was studied in 10 hearts from normal control dogs and 15 hearts from dogs with left ventricular hypertrophy (LVH); experiments were performed 1 year after banding the aorta in 8-week-old puppies. At

Cited by 96 publications

References 58 publications

Inhibition of Glycogen Synthase Kinase-3β Improves Tolerance to Ischemia in Hypertrophied Hearts

Inhibition of Glycogen Synthase Kinase-3β Improves Tolerance to Ischemia in Hypertrophied Hearts

Association of Myocardial Deformation With Outcome in Asymptomatic Aortic Stenosis With Normal Ejection Fraction

Arterial Pulse Wave Dynamics After Percutaneous Aortic Valve Replacement

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