Abnormal coronary vascular response to exercise in dogs with severe right ventricular hypertrophy.

Murray, Paul A.; Vatner, Stephen F.

doi:10.1172/jci110160

Cited by 39 publications

(8 citation statements)

References 26 publications

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“…A direct relationship was found between the impaired septal perfusion reserve and exercise capacity (septal MBFR 1.915+0.016 percentage of predicted workload, r=0.312, p=0.023). This is consistent with the findings in dogs with experimentally induced RVH 24. Contrary to the present study and the aforementioned positron emission tomography perfusion study, a single-photon emission CT study has found a surprising discrepancy between perfusion defects and exercise tolerance 33.…”

Section: Discussionsupporting

confidence: 91%

“…In dogs with RVH due to pressure overload, the microvascular density and its cross-sectional area are decreased 24. At the capillary level, this may result in an increase in the diffusion distance for oxygen to the mitochondria 25.…”

Section: Discussionmentioning

confidence: 99%

“…At the capillary level, this may result in an increase in the diffusion distance for oxygen to the mitochondria 25. Consequently, the resistance vessels are predilated at rest, which leads to a reduced dilatation capacity 24. In rats with congenital pulmonary stenosis, microcirculatory density was adequate in contrast to rats with adult onset of pulmonary stenosis, thus highlighting the relevance of the onset of hypertrophy with regard to the microcirculatory sequelae 26.…”

Section: Discussionmentioning

confidence: 99%

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Right ventricular absolute myocardial blood flow in complex congenital heart disease

Rutz

Marchi²,

Schwerzmann³

et al. 2010

Heart

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Right ventricular absolute myocardial blood flow in complex congenital heart disease

Rutz

Marchi²,

Schwerzmann³

et al. 2010

Heart

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“…It is also unlikely that the CCRA-induced decrease in right coronary blood flow was the result of an increase in systolic extravascular compressive forces (Sabiston and Gregg, 1957). Unlike the left coronary circulation, significant perfusion of the normal right coronary artery occurs during both diastole and systole (Lowensohn et al, 1976;Murray and Vatner, 1981a), indicating that the effects of systolic extravascular compression are less prominent in the right coronary circulation. Moreover, the degree of systolic extravascular compression is largely dependent on levels of heart rate, ventricular inotropy, and afterload.…”

Section: Discussionmentioning

confidence: 99%

Alpha-adrenergic-mediated reduction in coronary blood flow secondary to carotid chemoreceptor reflex activation in conscious dogs.

Murray

Lavallée

Vatner

1984

Circulation Research

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SUMMARY. We examined the late coronary vascular response to carotid chemoreceptor reflex activation in normal, conscious dogs instrumented for the measurement of right main and left circumflex coronary artery blood flows, arterial and right ventricular pressures, and arterial and coronary sinus blood gases and O 2 contents. With heart rate held constant by electrical stimulation, and with respiration controlled or allowed to vary spontaneously, carotid chemoreceptor reflex activation (induced by intracarotid nicotine) elicited a striking biphasic coronary vascular response characterized by an early dilation (previously described) and a late constriction. For example, with respiration controlled and with the autonomic nervous system intact, carotid chemoreceptor reflex activation resulted in a late increase in arterial pressure (19 ± 4%; P < 0.002), absolute reductions in right main (24 ± 4%; P < 0.002), and left circumflex (12 ± 2%; P < 0.004) coronary blood flows, and increases in right (62 ± 13%; P < 0.002) and left (26 ± 3%; P < 0.0001) coronary resistances. This carotid chemoreceptor reflex activation-induced late coronary constriction was also associated with a concomitant increase in myocardial oxygen extraction, i.e., arterial oxygen content remained constant, while coronary sinus oxygen content decreased (19 ± 6%; P < 0.04). Neither propranolol nor atropine had any significant effect on the magnitude of the right coronary constriction. However, both the absolute reduction in right coronary blood flow and increase in right coronary resistance were abolished by phentolamine. Furthermore, either total cardiac denervation or adrenalectomy significantly attenuated (P < 0.01) carotid chemoreceptor reflex activation-induced reductions in right coronary blood flow and increase in right coronary resistance. We conclude that, with autonomic nervous system activity intact, carotid chemoreceptor reflex activation can elicit an absolute reflexly mediated reduction in coronary blood flow in the normal, conscious dog, despite an increase in arterial pressure. The mechanism of this vasoconstriction involves a-adrenergic receptor stimulation mediated by both cardiac sympathetic nerves and circulating catecholamines. {Circ Res 54: 96-106, 1984) THERE NOW exists a relatively large body of experimental evidence which supports the concept that sympathetic activation can result in a-adrenergic coronary vasoconstriction. This concept is based primarily on experiments in which sympathetic activation has resulted in increases in arterial pressure which have been greater than concomitant increases in coronary blood flow, with a consequent increase in coronary resistance. It is somewhat surprising that despite recent interest in the role of coronary vasoconstriction in the pathogenesis of coronary artery vasospasm (Hillis and Braunwald, 1978;Maseri et al., 1978), there is little compelling evidence that aadrenergic vasoconstriction can mediate an absolute reduction in coronary blood flow in the presence of an intact autonomic n...

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“…21,22 With elevated plasma norepinephrine for 28 days, resting systolic and diastolic cardiac functions are preserved, and there are no signs of heart failure. 8,9 Whether the hypertrophied myocardium in this setting is able to respond to additional functional loads has not been examined.…”

mentioning

confidence: 99%

Altered function and structure of the heart in dogs with chronic elevation in plasma norepinephrine.

et al. 1991

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BACKGROUND We have previously shown that chronic elevation of plasma norepinephrine leads to a functional independent increase in left ventricular weight. The goals of the present study were to determine quantitatively the component of the myocardium that accounted for the observed structural changes and to determine the function of the hypertrophied myocardium. METHODS AND RESULTS Mongrel dogs were chronically instrumented for measurement of arterial and left ventricular pressures, left ventricular internal diameter, and left ventricular wall thickness. Subcutaneous osmotic pumps were implanted to release norepinephrine continuously for 28 days. Hemodynamics were measured with dogs in the quietly resting state and during infusions of isoproterenol at 0.1 and 0.5 micrograms/kg/min before and on days 14 and 28 during the infusion of norepinephrine. The hemodynamic response to 10 micrograms/kg phenylephrine, given as a bolus, was also assessed before norepinephrine and 28 days during the infusion of norepinephrine, and the end-systolic pressure-diameter or wall-stress-diameter relations were calculated. On day 28, hearts were arrested in diastole and perfusion fixed in situ. Tissue samples were prepared for electron microscopy and morphometry. Hemodynamic studies showed that isoproterenol (0.5 micrograms/kg/min) reduced mean arterial pressure (MAP) to the same point on each experimental day, and the increases in indexes of contractility were reduced during norepinephrine infusion. Left ventricular dP/dtmax increased 131 +/- 24% on control day, only 67 +/- 20% on day 14, and 55 +/- 18% on day 28. Similar changes were observed in dP/dt/DP40 and dP/dt/end-diastolic circumference. However, Emax, the slope of the end-systolic pressure-diameter or wall stress diameter relations, was unchanged, suggesting that inotropic state was not altered. Morphometric studies showed that the cross-sectional area of myocytes increased by 55%, but myocyte and capillary densities decreased by 34% and 29%, respectively (p less than 0.05) in dogs with high norepinephrine levels. There were no differences in volume fractions of myocytes, capillary lumen, or interstitium or capillary-to-myocyte ratio. CONCLUSIONS The myocardium of dogs with high norepinephrine levels shows reduced inotropic response to beta-adrenergic stimulation despite the increases in left ventricular mass and left ventricular wall thickness, which are a result of growth of the cardiac myocytes and characteristic of concentric hypertrophy. These data suggest that chronic adrenergic stimulation of the heart reduces the beta-receptor coupling to the contractile response without importantly compromising left ventricular function.

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Abnormal coronary vascular response to exercise in dogs with severe right ventricular hypertrophy.

Cited by 39 publications

References 26 publications

Right ventricular absolute myocardial blood flow in complex congenital heart disease

Right ventricular absolute myocardial blood flow in complex congenital heart disease

Alpha-adrenergic-mediated reduction in coronary blood flow secondary to carotid chemoreceptor reflex activation in conscious dogs.

Altered function and structure of the heart in dogs with chronic elevation in plasma norepinephrine.

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