Plasma ATP during exercise: possible role in regulation of coronary blood flow

2005 ◽  
Vol 288 (4) ◽  
pp. H1586-H1590 ◽  
Author(s):  
Martin Farias ◽  
Mark W. Gorman ◽  
Margaret V. Savage ◽  
Eric O. Feigl
Keyword(s):  
Blood Flow ◽  
Coronary Blood Flow ◽  
Oxygen Tension ◽  
Luciferase Assay ◽  
Concentration Difference ◽  
Flow Transducer ◽  
Atp Concentration ◽  
Arterial Plasma ◽  
Myocardial Oxygen Extraction ◽  
Venous Plasma

It was previously shown that red blood cells release ATP when blood oxygen tension decreases. ATP acts on microvascular endothelial cells to produce a retrograde conducted vasodilation (presumably via gap junctions) to the upstream arteriole. These observations form the basis for an ATP hypothesis of local metabolic control of coronary blood flow due to vasodilation in microvascular units where myocardial oxygen extraction is high. Dogs ( n = 10) were instrumented with catheters in the aorta and coronary sinus, and a flow transducer was placed around the circumflex coronary artery. Arterial and coronary venous plasma ATP concentrations were measured at rest and during three levels of treadmill exercise by using a luciferin-luciferase assay. During exercise, myocardial oxygen consumption increased ∼3.2-fold, coronary blood flow increased ∼2.7-fold, and coronary venous oxygen tension decreased from 19 to 12.9 mmHg. Coronary venous plasma ATP concentration increased significantly from 31.1 to 51.2 nM ( P < 0.01) during exercise. Coronary blood flow increased linearly with coronary venous ATP concentration ( P < 0.01). Coronary venous-arterial plasma ATP concentration difference increased significantly during exercise ( P < 0.05). The data support the hypothesis that ATP is one of the factors controlling coronary blood flow during exercise.

The Release of Renin into the Renal Circulation of the Anaesthetized Dog

1970 ◽  
Vol 38 (2) ◽  
pp. 157-174 ◽  
Author(s):  
K. F. Hosie ◽  
J. J. Brown ◽  
A. M. Harper ◽  
A. F. Lever ◽  
R. F. MacAdam ◽  
...  
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Plasma Renin ◽  
Renin Release ◽  
Concentration Difference ◽  
Plasma Renin Concentration ◽  
Renal Lymph ◽  
Arterial Blood ◽  
Arterial Plasma ◽  
Venous Plasma

1. In anaesthetized dogs the rate at which renin was released into the circulation of the right and left kidneys was estimated from renal blood flow, haematocrit, and the V-A renin concentration difference across the kidney. Renin was also measured in samples of renal lymph collected at the same time. 2. The effect on renin release of reducing blood flow in one kidney was studied. For all observations (control and experimental), renal venous plasma renin concentration (RVR) was directly related to arterial plasma renin concentration and to renin release; RVR was inversely related to renal plasma flow. 3. The concentration of renin in renal lymph was considerably higher than that in renal venous plasma taken at the same time. Arterial plasma renin concentration was directly related to the sum of the rates at which renin was released from the two kidneys. 4. Clamping the renal artery of one kidney for 1 hr led to a marked reduction of renal blood flow, to a marked increase in RVR and to a variable change in renin release. Removal of the clamp was followed by increased renin release and by reversal of a previously positive V-A renin difference in the control kidney. 5. On several other occasions negative V-A renin differences were observed. That is, more renin appeared to enter the kidney in arterial blood than left in the renal vein.

Is Calcium a Coronary Vasoconstrictor In Vivo? 

1998 ◽  
Vol 88 (3) ◽  
pp. 735-743 ◽  
Author(s):  
George J. Crystal ◽  
Xiping Zhou ◽  
Ramez M. Salem
Keyword(s):  
Blood Flow ◽  
Oxygen Consumption ◽  
Coronary Blood Flow ◽  
Myocardial Oxygen Consumption ◽  
Extraction Ratio ◽  
Oxygen Extraction ◽  
Oxygen Extraction Ratio ◽  
Myocardial Oxygen Extraction ◽  
Dose Dependent

Background Calcium produces constriction in isolated coronary vessels and in the coronary circulation of isolated hearts, but the importance of this mechanism in vivo remains controversial. Methods The left anterior descending coronary arteries of 20 anesthetized dogs whose chests had been opened were perfused at 80 mmHg. Myocardial segmental shortening was measured with ultrasonic crystals and coronary blood flow with a Doppler flow transducer. The coronary arteriovenous oxygen difference was determined and used to calculate myocardial oxygen consumption and the myocardial oxygen extraction ratio. The myocardial oxygen extraction ratio served as an index of effectiveness of metabolic vasodilation. Data were obtained during intracoronary infusions of CaCl2 (5, 10, and 15 mg/min) and compared with those during intracoronary infusions of dobutamine (2.5, 5.0, and 10.0 microg/min). Results CaCl2 caused dose-dependent increases in segmental shortening, accompanied by proportional increases in myocardial oxygen consumption. Although CaCl2 also increased coronary blood flow, these increases were less than proportional to those in myocardial oxygen consumption, and therefore the myocardial oxygen extraction ratio increased. Dobutamine caused dose-dependent increases in segmental shortening and myocardial oxygen consumption that were similar in magnitude to those caused by CaCl2. In contrast to CaCl2, however, the accompanying increases in coronary blood flow were proportional to the increases in myocardial oxygen consumption, with the result that the myocardial oxygen extraction ratio remained constant. Conclusions Calcium has a coronary vasoconstricting effect and a positive inotropic effect in vivo. This vasoconstricting effect impairs coupling of coronary blood flow to the augmented myocardial oxygen demand by metabolic vascular control mechanisms. Dobutamine is an inotropic agent with no apparent direct action on coronary resistance vessels in vivo.

Coronary physiology

1983 ◽  
Vol 63 (1) ◽  
pp. 1-205 ◽  
Author(s):  
E. O. Feigl
Keyword(s):  
Blood Flow ◽  
Metabolic Control ◽  
Coronary Blood Flow ◽  
Oxygen Tension ◽  
Nerve Stimulation ◽  
Left Ventricular ◽  
Strenuous Exercise ◽  
Unexpected Finding ◽  
Coronary Vasoconstriction ◽  
Coronary Physiology

The major areas of normal coronary physiological research since Berne's 1964 review have been the measurement of ventricular transmural blood flow distribution with microspheres, the adenosine hypothesis of local metabolic control of coronary blood flow, and the autonomic control of coronary blood flow. There is an improved understanding of intramyocardial tissue pressure and extravascular compressive forces on coronary vessels. However, the unexpected finding of zero flow during a prolonged diastole with a coronary artery pressure of 40 mmHg (PZF) is a reminder that the physical forces, including vascular smooth muscle contraction, that determine coronary vascular resistance are incompletely understood. During normal circumstances, the left ventricular subendocardium probably receives more blood flow than the subepicardium does, but the difference is small. When the coronary circulation is compromised by stenosis or aortic valve lesions, the subendocardium is much more vulnerable to underperfusion than is the subepicardium. The coronary vasodilating effect of arterial hypoxia has been confirmed in many studies, but the role of tissue oxygen tension in local metabolic control of coronary blood flow during normoxia is unknown. The coronary vasodilating action of carbon dioxide has received renewed attention, but its role in local control is also unknown. The adenosine hypothesis has passed several critical tests, but despite much research the importance of adenosine in normal coronary regulation is not established. Local metabolic control of coronary blood flow probably involves more than just one factor, but a unified hypothesis has not been put forward. Sympathetic alpha-receptor-mediated coronary vasoconstriction has been demonstrated by nerve stimulation and during a carotid sinus baroreceptor reflex. Sympathetic coronary vasoconstriction is capable of competing with local metabolic control to lower coronary venous oxygen tension under experimental circumstances, but its importance during normal resting conditions is not established. Parasympathetic muscarinic coronary vasodilation has been shown by vagal nerve stimulation, but a role for it during normal blood flow regulation has yet to be demonstrated. There have been elegant descriptive studies of the coronary blood flow response during excitement and exercise, where coronary blood flow increases pari passu with myocardial metabolism; however, there are also data that indicate a concomitant sympathetic vasoconstrictor effect during strenuous exercise. Overall there has been encouraging progress in coronary physiology. Inevitably new knowledge has focused old questions and presented new ones.

Coronary vascular sympathetic beta-receptor innervation

1976 ◽  
Vol 230 (6) ◽  
pp. 1569-1576 ◽  
Author(s):  
FN Hamilton ◽  
EO Feigl
Keyword(s):  
Blood Flow ◽  
Coronary Blood Flow ◽  
Oxygen Tension ◽  
Coronary Sinus ◽  
Stellate Ganglion ◽  
Coronary Vessels ◽  
Coronary Perfusion ◽  
Receptor Blockade ◽  
Langendorff Preparation ◽  
Beta 2

Recent studies indicate that coronary vessels have alpha- and beta-2-adrenergic receptors and that the alpha receptors are functionally innervated. We studied whether the beta-2-vasodilator receptors are functionally innervated, using a dog in situ modified Langendorff preparation with constant coronary perfusion pressure. The beating, nonworking heart and systemic circulation were supported with a pump oxygenator. Stimulation of the left stellate ganglion increased coronary blood flow and decreased coronary sinus oxygen tension from prestimulation control values. After beta-1-receptor blockade (practolol, 10 mg/kg), stellate stimulation decreased coronary blood flow and decreased coronary sinus oxygen tension from prestimulation control values, revealing alpha-receptor vasoconstriction. After the addition of alpha-receptor blockade (Dibozane, 5 mg/kg), stellate stimulation increased coronary blood flow and coronary sinus oxygen tension a small amount from prestimulation values. Finally, after the addition of beta-2-receptor blockade (propranolol, 2 mg/kg), stellate stimulation increased flow and coronary sinus oxygen tension slightly from prestimulation control values. Direct intracoronary injections of isoproterenol, norepinephrine, and epinephrine gave results consistent with the presence of beta-1 myocardial receptors and alpha and beta-2 coronary receptors. We conclude that there is little functional innervation of coronary vascular beta-2 receptors. Intracoronary injections of isoproterenol and epinephrine activated beta-2-receptor coronary vasodilation after beta-1-receptor blockade, but norepinephrine did not.

scholarly journals 995-20 Effect of Hypoxia on Coronary Blood Flow and Myocardial Oxygen Extraction in Patients with Coronary Artery Disease

1995 ◽  
Vol 25 (2) ◽  
pp. 322A
Author(s):  
Achille Gaspardone ◽  
Patrizio Polisca ◽  
Filippo Crea ◽  
Fabrizio Tomai ◽  
Francesco Versaci ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Blood Flow ◽  
Coronary Artery ◽  
Coronary Blood Flow ◽  
Oxygen Extraction ◽  
Artery Disease ◽  
Myocardial Oxygen Extraction

Cannula-tip coronary blood flow transducer for use in closed-chest animals.

1974 ◽  
Vol 37 (4) ◽  
pp. 592-595 ◽  
Author(s):  
F D Smith ◽  
L G D'Alecy ◽  
E O Feigl
Keyword(s):  
Blood Flow ◽  
Coronary Blood Flow ◽  
Flow Transducer ◽  
Closed Chest

Role of mitochondrial oxidative phosphorylation in regulation of coronary blood flow

1982 ◽  
Vol 243 (2) ◽  
pp. H159-H169 ◽  
Author(s):  
E. M. Nuutinen ◽  
K. Nishiki ◽  
M. Erecinska ◽  
D. F. Wilson
Keyword(s):  
Blood Flow ◽  
Oxidative Phosphorylation ◽  
Coronary Blood Flow ◽  
Oxygen Tension ◽  
Coronary Flow ◽  
Perfusion Pressure ◽  
Energy State ◽  
Work Load ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Tissue Oxygen

Regulation of coronary blood flow was studied in isolated rat hearts perfused under various metabolic conditions. Alterations in coronary flow were induced by hypoxia, amobarbital (Amytal) infusion, increase in work load of the heart, and adenosine infusion. Hypoxia induced, on the average, a 92.5% rise in coronary flow; 0.88 mM Amytal, a 85.7% increase; 12 microM adenosine, a 49.5% rise; and increased work load (elevation of the perfusion pressure from 6.9 kPa to 12.8 kPa), a 53.4% increase. In normoxia, adenosine, inosine, and hypoxanthine were present in the effluent in very low concentrations, and these greatly increased in response to hypoxia. In contrast, increased coronary flow caused by Amytal infusion or by elevated perfusion pressure was not accompanied by elevation in the effluent concentration of adenosine and its catabolites. Infusion of Amytal was followed by decrease in oxygen consumption of the heart and increase in oxygen tension in the effluent. This indicates that tissue oxygen tension per se can not be responsible for the regulation of coronary blood flow. Analysis of the data showed that under conditions in which there was a decrease in the tissue [ATP]free/[ADP]free[Pi] an increase in coronary flow was observed irrespective of the nature of the vasodilatory stimulus. It is concluded that mitochondrial oxidative phosphorylation provides a link between tissue oxygen metabolism and coronary blood flow. Mechanisms are discussed whereby changes in the cellular energy state ([ATP]free/[ADP]free[Pi]) are coupled to vasodilation, including possible direct effects on the vascular smooth muscle and/or generation of "second messengers."

α-Adrenoceptor-mediated coronary vasoconstriction is augmented during exercise in experimental diabetes mellitus

2004 ◽  
Vol 97 (1) ◽  
pp. 431-438 ◽  
Author(s):  
Srinath Setty ◽  
Wei Sun ◽  
Rodolfo Martinez ◽  
H. Fred Downey ◽  
Johnathan D. Tune
Keyword(s):  
Diabetes Mellitus ◽  
Heart Rate ◽  
Blood Flow ◽  
Coronary Blood Flow ◽  
Aortic Pressure ◽  
Flow Transducer ◽  
Coronary Vasoconstriction ◽  
Before And After ◽  
The Difference ◽  
Diabetic Dogs

This study tested whether α-adrenoceptor-mediated coronary vasoconstriction is augmented during exercise in diabetes mellitus. Experiments were conducted in dogs instrumented with catheters in the aorta and coronary sinus and with a flow transducer around the circumflex coronary artery. Diabetes was induced with alloxan monohydrate ( n = 8, 40 mg/kg iv). Arterial plasma glucose concentration increased from 4.7 ± 0.2 mM in nondiabetic, control dogs ( n = 8) to 21.4 ± 1.9 mM 1 wk after alloxan injection. Coronary blood flow, myocardial oxygen consumption (MV̇o2), aortic pressure, and heart rate were measured at rest and during graded treadmill exercise before and after infusion of the α-adrenoceptor antagonist phentolamine (1 mg/kg iv). In untreated diabetic dogs, exercise increased MV̇o2 2.7-fold, coronary blood flow 2.2-fold, and heart rate 2.3-fold. Coronary venous Po2 fell as MV̇o2 increased during exercise. After α-adrenoceptor blockade, exercise increased MV̇o2 3.1-fold, coronary blood flow 2.7-fold, and heart rate 2.1-fold. Relative to untreated diabetic dogs, α-adrenoceptor blockade significantly decreased the slope of the relationship between coronary venous Po2 and MV̇o2. The difference between the untreated and phentolamine-treated slopes was greater in the diabetic dogs than in the nondiabetic dogs. In addition, the decrease in coronary blood flow to intracoronary norepinephrine infusion was significantly augmented in anesthetized, open-chest, β-adrenoceptor-blocked diabetic dogs compared with the nondiabetic dogs. These findings demonstrate that α-adrenoceptor-mediated coronary vasoconstriction is augmented in alloxan-induced diabetic dogs during physiological increases in MV̇o2.

scholarly journals Open-loop (feed-forward) and feedback control of coronary blood flow during exercise, cardiac pacing, and pressure changes

2016 ◽  
Vol 310 (11) ◽  
pp. H1683-H1694 ◽  
Author(s):  
Ranjan K. Pradhan ◽  
Eric O. Feigl ◽  
Mark W. Gorman ◽  
George L. Brengelmann ◽  
Daniel A. Beard
Keyword(s):  
Blood Flow ◽  
Feedback Control ◽  
Coronary Blood Flow ◽  
Coronary Flow ◽  
Adenine Nucleotide ◽  
Purinergic Receptor ◽  
Cardiac Pacing ◽  
Open Loop ◽  
Feed Forward ◽  
Venous Plasma

A control system model was developed to analyze data on in vivo coronary blood flow regulation and to probe how different mechanisms work together to control coronary flow from rest to exercise, and under a variety of experimental conditions, including cardiac pacing and with changes in coronary arterial pressure (autoregulation). In the model coronary flow is determined by the combined action of a feedback pathway signal that is determined by the level of plasma ATP in coronary venous blood, an adrenergic open-loop (feed-forward) signal that increases with exercise, and a contribution of pressure-mediated myogenic control. The model was identified based on data from exercise experiments where myocardial oxygen extraction, coronary flow, cardiac interstitial norepinephrine concentration, and arterial and coronary venous plasma ATP concentrations were measured during control and during adrenergic and purinergic receptor blockade conditions. The identified model was used to quantify the relative contributions of open-loop and feedback pathways and to illustrate the degree of redundancy in the control of coronary flow. The results indicate that the adrenergic open-loop control component is responsible for most of the increase in coronary blood flow that occurs during high levels of exercise. However, the adenine nucleotide-mediated metabolic feedback control component is essential. The model was evaluated by predicting coronary flow in cardiac pacing and autoregulation experiments with reasonable fits to the data. The analysis shows that a model in which coronary venous plasma adenine nucleotides are a signal in local metabolic feedback control of coronary flow is consistent with the available data.

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