Distribution of cardiac output during diurnal changes of activity in rats

Delp, Michael D.; Manning, R. O.; Bruckner, James V.; Armstrong, R. B.

doi:10.1152/ajpheart.1991.261.5.h1487

Cited by 72 publications

(70 citation statements)

References 16 publications

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“…The plasma volume, 2.97% of body weight (Delp et al, 1991;Davies and Morris, 1993), is 3.3 times the volume of the stomach lumen, 0.91% of body weight (Roth et al, 1993). Therefore, an amount of nitrite taken up from the stomach increases the plasma concentration only 0.3 times as much as it decreases the stomach lumen concentration.…”

Section: Figmentioning

confidence: 99%

Pharmacokinetics of Sodium Nitrite-Induced Methemoglobinemia in the Rat

Kohn

Melnick²,

Ye³

et al. 2002

Drug Metab Dispos

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ABSTRACT:A biologically based mathematical model was created to characterize time and dose-dependent relationships between exposure to nitrite and induction of methemoglobinemia. The model includes mass action equations for processes known to occur: oral absorption of nitrite, elimination from the plasma, partitioning between plasma and erythrocytes, binding of nitrite to hemoglobin and methemoglobin, and the free radical chain reaction for hemoglobin oxidation. The model also includes Michaelis-Menten kinetics for methemoglobin reductase-catalyzed regeneration of hemoglobin. Body weight-scaled rate constants for absorption (k a ) and elimination (k e ), the effective erythrocyte/plasma partition coefficient (P), and the apparent K m for methemoglobin reductase were the only parameters estimated by formal optimization to reproduce the observed time course data. Time courses of plasma nitrite concentrations and blood levels of hemoglobin and methemoglobin in male and female rats that had received single intravenous or oral doses of sodium nitrite were measured. Peak plasma levels of nitrite were achieved in both sexes approximately 30 min after oral exposure, and peak methemoglobin levels were achieved after 100 min. The model predicts that 10% of the hemoglobin is oxidized to the ferric form after oral doses of 15.9 mg/kg in male rats and 11.0 mg/kg in female rats and after intravenous doses of 8.9 and 7.1 mg/kg in male and female rats, respectively. The t 1/2 for recovery from methemoglobinemia was 60 to 120 min depending on dose and route of administration. A sensitivity analysis of the model was performed to identify to which parameters the predictions of the model were most sensitive and guide attempts to simplify the model. Replacement of the V max of methemoglobin reductase with a value representative of humans predicted a 10% methemoglobinemia following an intravenous dose of 5.8 mg/kg, in close agreement with an observed value of 5.7 mg/kg for humans.

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Section: Figmentioning

confidence: 99%

Pharmacokinetics of Sodium Nitrite-Induced Methemoglobinemia in the Rat

Kohn

Melnick²,

Ye³

et al. 2002

Drug Metab Dispos

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“…This is in agreement with previous in vivo studies that have shown that cardiac output is greater in the dark phase for rats. 8 However, such studies did not investigate the intrinsic properties of the heart alone, where contractile performance in vivo was undoubtedly affected by external factors, such as sympathetic tone, in addition to the intrinsic sensitivity of the heart to its environment.…”

Section: Diurnal Variation In Cardiac Performance and Metabolismmentioning

confidence: 99%

Intrinsic Diurnal Variations in Cardiac Metabolism and Contractile Function

Young

Razeghi

Cedars

et al. 2001

Circulation Research

185

162

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Abstract-Diurnal variation of cardiac function in vivo has been attributed primarily to changes in factors such as sympathetic activity. No study has investigated previously the intrinsic properties of the heart throughout the day. We therefore investigated diurnal variations in metabolic flux and contractile function of the isolated working rat heart and how this related to circadian expression of metabolic genes. Contractile performance, carbohydrate oxidation, and oxygen consumption were greatest in the middle of the night, with little variation in fatty acid oxidation. The expression of all metabolic genes investigated (including regulators of carbohydrate utilization, fatty acid oxidation, and mitochondrial function) showed diurnal variation, with a general peak in the night. In contrast, pressure overloadinduced cardiac hypertrophy completely abolished this diurnal variation of metabolic gene expression. Thus, over the course of the day, the normal heart anticipates, responds, and adapts to physiological alterations within its environment, a trait that is lost by the hypertrophied heart. We speculate that loss of plasticity of the hypertrophied heart may play a role in the subsequent development of contractile dysfunction. Key Words: function Ⅲ gene expression Ⅲ metabolism Ⅲ perfusions Ⅲ rat C ells are able to anticipate, respond, and adapt to fluctuations in their environment. Anticipation is achieved through self-sustained intracellular clocks, providing advantageous priming of the cell in preparation to a given stimulus. 1 The response of any cell is dictated by the level of the stimulus, as well as the sensitivity to that stimulus. The latter is affected by both intracellular (genotype, circadian clocks) and extracellular (eg, neuronal and humoral factors) influences. The resultant adaptation can be either immediate (alterations in preexisting proteins) or prolonged (changes in gene and protein expression) depending on the length of exposure to the stimulus.The heart, not unlike other organs, possesses both internal clocks and the ability to respond to external stimuli, both of which could potentially influence gene expression, metabolism, and function. [2][3][4] It is well known that the onset of heart failure, myocardial infarction, and sudden death is greatest in the early hours of the morning. 5-7 For this reason, several studies have investigated diurnal variation in cardiac function in vivo, in both rodents and humans, and have correlated findings with fluctuations in neurohumoral influences. 5,8 -11 However, to date, no study has either postulated or investigated whether the intrinsic properties of the heart fluctuate during the day, or whether loss of synchronization between the presence of a stimulus (eg, sympathetic activity) and responsiveness of the heart plays a role in the development of contractile dysfunction.We set out to characterize the diurnal variation in contractile function and metabolic flux of the heart in the absence of confounding extracardiac influences by using the isolat...

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“…Oscillations in cardiovascular functions are firmly established, including time-of-day-dependent fluctuations in blood pressure, heart rate, and cardiac output (9,10,31). Night shift work and frequent time zone changes result in a dissociation between this intrinsic timekeeping mechanism and the environment, which is associated with increased risk of adverse cardiovascular effects (such as myocardial infarction and sudden cardiac death) (5,15,33).…”

mentioning

confidence: 99%

Cardiomyocyte-specific Bmal1 deletion in mice triggers diastolic dysfunction, extracellular matrix response, and impaired resolution of inflammation

Ingle

Kain

Goel

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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Ingle KA, Kain V, Goel M, Prabhu SD, Young ME, Halade GV. Cardiomyocyte-specific Bmal1 deletion in mice triggers diastolic dysfunction, extracellular matrix response, and impaired resolution of inflammation. Am J Physiol Heart Circ Physiol 309: H1827-H1836, 2015. First published October 2, 2015; doi:10.1152/ajpheart.00608.2015.-The mammalian circadian clock consists of multiple transcriptional regulators that coordinate biological processes in a time-of-day-dependent manner. Cardiomyocyte-specific deletion of the circadian clock component, Bmal1 (aryl hydrocarbon receptor nuclear translocator-like protein 1), leads to age-dependent dilated cardiomyopathy and decreased lifespan in mice. We investigated whether cardiomyocytespecific Bmal1 knockout (CBK) mice display early alterations in cardiac diastolic function, extracellular matrix (ECM) remodeling, and inflammation modulators by investigating CBK mice and littermate controls at 8 and 28 wk of age (i.e., prior to overt systolic dysfunction). Left ventricles of CBK mice exhibited (P Ͻ 0.05): 1) progressive abnormal diastolic septal annular wall motion and reduced pulmonary venous flow only at 28 wk of age; 2) progressive worsening of fibrosis in the interstitial and endocardial regions from 8 to 28 wk of age; 3) increased (Ͼ1.5 fold) expression of collagen I and III, as well as the matrix metalloproteinases MMP-9, MMP-13, and MMP-14 at 28 wk of age; 4) increased transcript levels of neutrophil chemotaxis and leukocyte migration genes (Ccl2, Ccl8, Cxcl2, Cxcl1, Cxcr2, Il1␤) with no change in Il-10 and Il-13 genes expression; and 5) decreased levels of 5-LOX, HO-1 and COX-2, enzymes indicating impaired resolution of inflammation. In conclusion, genetic disruption of the cardiomyocyte circadian clock results in diastolic dysfunction, adverse ECM remodeling, and proinflammatory gene expression profiles in the mouse heart, indicating signs of early cardiac aging in CBK mice.aging; Bmal1; circadian clock; extracellular matrix; inflammation; diastolic dysfunction NEW & NOTEWORTHYCardiomyocyte-specific Bmal1 gene deletion in heart progresses to 1) diastolic dysfunction with significant age-dependent hypertrophy; 2) dilative hypertrophy marked with endocardial fibrosis and interstitial fibrosis in an age-dependent manner; and 3) age-dependent ventricular fibrosis displaying aggravated extracellular matrix deposition and defective resolution of the inflammation response.THE CIRCADIAN CLOCK is a timekeeping system that regulates physiological performance and behavior relative to day-night cycles. Oscillations in cardiovascular functions are firmly established, including time-of-day-dependent fluctuations in blood pressure, heart rate, and cardiac output (9, 10, 31). Night shift work and frequent time zone changes result in a dissociation between this intrinsic timekeeping mechanism and the environment, which is associated with increased risk of adverse cardiovascular effects (such as myocardial infarction and sudden cardiac death) (5, 15, 33). In mammals, the timekeeping ...

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Distribution of cardiac output during diurnal changes of activity in rats

Cited by 72 publications

References 16 publications

Pharmacokinetics of Sodium Nitrite-Induced Methemoglobinemia in the Rat

Pharmacokinetics of Sodium Nitrite-Induced Methemoglobinemia in the Rat

Intrinsic Diurnal Variations in Cardiac Metabolism and Contractile Function

Cardiomyocyte-specific Bmal1 deletion in mice triggers diastolic dysfunction, extracellular matrix response, and impaired resolution of inflammation

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