Oxygen cost of stress development in hypertrophied and failing hearts from the spontaneously hypertensive rat.

Brooks, Wesley W.; Healey, Nancy A.; Sen, Subha; Conrad, Chester H.; Bing, O.

doi:10.1161/01.hyp.21.1.56

Cited by 25 publications

(19 citation statements)

References 33 publications

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“…Myocardial oxygen consumption was calculated as the product of arteriovenous oxygen difference and coronary flow and expressed as micromoles per minute per gram of left ventricle. 34 Each sample was assayed twice.…”

Section: Oxygen Consumptionmentioning

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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Section: Oxygen Consumptionmentioning

confidence: 99%

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

et al. 2005

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“…Each LV parameter of interest was subsequently normalized to Vol/Vol max to achieve comparable loading conditions in hearts of different sizes. Wall thickness, relative wall thickness, and peak systolic, peak diastolic, and developed circumferential wall stresses were derived from LV pressure measurements, balloon volume, and weight of the left ventricle, as previously described by Brooks et al 21 The digital LV pressure tracing was analyzed to obtain LV peak systolic pressure, time to peak systolic pressure, peak positive and peak negative dP/dt, end-diastolic pressure, developed pressure, developed wall stress, and time from peak systolic pressure to 90% of relaxation. After the baseline assessment, 15 minutes of zero-flow ischemia was induced by turning off the perfusion pump and simultaneously clamping the perfusion line.…”

Section: Isolated Isovolumic Buffer-perfused Mouse Preparationmentioning

confidence: 99%

Cardiovascular Abnormalities in Transgenic Mice With Reduced Brown Fat

et al. 1999

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Background-A new model of murine obesity has recently been developed through transgenic ablation of brown adipose tissue that manifests typical metabolic complications of obesity, including insulin resistance and non-insulin-dependent diabetes mellitus. The cardiovascular phenotype has not been defined. Methods and Results-Transthoracic echocardiography, aortic catheterization, isolated whole-heart studies, and morphometric histology defined cardiac structure and function in 30 transgenic mice with reduced brown fat and 30 matched wild-type controls. Obesity was indicated by a 77% increase in body weight and was accompanied by elevated systemic pressures (mean aortic blood pressure 85Ϯ1 versus 66Ϯ2 mm Hg; PϽ0.01), left ventricular dilation and hypertrophy (mass/body weight 4.0Ϯ0.2 versus 2.7Ϯ0.3 mg/g; PϽ0.01), and high cardiac output (cardiac index 3.2Ϯ0.4 versus 2.4Ϯ0.1 mL ⅐ kg Ϫ1 ⅐ min

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“…15 Briefly, at the time of study the rats were decapitated. Their hearts were quickly removed and placed in oxygenated bicarbonate-buffered physiological salt solution containing heparin at 23° to 25°C.…”

Section: Preparation Of Isolated Perfused Heartmentioning

confidence: 99%

Effects of treppe and calcium on intracellular calcium and function in the failing heart from the spontaneously hypertensive rat.

Brooks¹,

Bing²,

Litwin³

et al. 1994

Hypertension

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We studied functional and intracellular calcium responses to treppe and extracellular calcium in spontaneously hypertensive rat (SHR) hearts during the transition from compensated pressure overload to failure. Intracellular calcium was measured using aequorin, a bioluminescent Ca 2+ indicator. Experiments were performed with intact, isovolumically contracting, buffer-perfused hearts from three rat groups: (1) aging SHR with evidence of heart failure (SHR-F), (2) age-matched SHR with no evidence of heart failure (SHR-NF), and (3) age-matched normotensive Wistar-Kyoto (WKY) rats. In each experiment, left ventricular pressure and intracellular calcium transients were simultaneously recorded. Hearts were studied at 30°C and paced at a rate of 1.6 Hz while being perfused with oxygenated Krebs-Henseleit solution (95% O 2 /5% CO 2 ) at 100 mm Hg. At the baseline state, peak systolic pressure was greatest in the SHR-NF group and lowest in the SHR-F group. Peak and resting [Ca 2+ ]i were not significantly different among groups; however, the calcium transient was prolonged in the SHR-NF and SHR-F groups. With increasing perfusate [Ca 2+ ] o from 0.5 to 3.0 mmol/L, the relative increases in peak [Ca 2+ ]| and peak systolic pressure were similar among groups. When stimulation rate was increased from 1.6 to 2.0, 2.4, 2.8, and 3.2 Hz, peak [Ca 2+ ]i, peak R elatively few models of cardiac pressure overload have stable hypertrophy persisting over most of the animal's life followed by a state in which chamber and muscle function are impaired. The spontaneously hypertensive rat (SHR) is a model that in many respects parallels the course of human hypertensive heart disease. Studies of both failing human 13 ], and pressure decrease in parallel in the SHR-F heart with increasing stimulation rate, suggesting that impaired calcium cycling may contribute to compromised pump function in the SHR-F heart. (Hypertension. 1994^4J47-356.) Keywords • calcium • heart hypertrophy muscle, cardiac heart failure, congestive in the force-frequency response between failing and nonfailing human myocardia and a reduced ability of the failing heart to increase force at increasing stimulation rates.6 Studies of isolated ventricular strips from failing human ventricles demonstrate that increased stimulation rates enhance disturbances in calcium handling 1 ' 2 and force development.6 It is well recognized that treppe and increasing [Ca 2+ ] o lead to an increase in [Ca 2+ ], and the number of occupied crossbridges per unit time, which in turn results in an increase in myocardial energy demands. In addition, both of these interventions lead to increases in [Ca 2+ ], and a greater load on intracellular calcium control systems. However, one problem with isolated muscle studies is the uncertainty regarding diffusion, inherent in isolated muscle studies, and the applicability to in vivo physiology. To bridge the gap between isolated muscle studies and in vivo physiology, we have carried out studies in the isolated perfused heart prepa...

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Oxygen cost of stress development in hypertrophied and failing hearts from the spontaneously hypertensive rat.

Cited by 25 publications

References 33 publications

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

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

Cardiovascular Abnormalities in Transgenic Mice With Reduced Brown Fat

Effects of treppe and calcium on intracellular calcium and function in the failing heart from the spontaneously hypertensive rat.

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