K+ATP channels and adenosine are not necessary for coronary autoregulation

1997 ◽  
Vol 273 (3) ◽  
pp. H1299-H1308 ◽  
Author(s):  
D. W. Stepp ◽  
K. Kroll ◽  
E. O. Feigl
Keyword(s):  
Carbon Dioxide ◽  
Blood Flow ◽  
Coronary Blood Flow ◽  
Left Main Coronary Artery ◽  
Perfusion Pressure ◽  
Carbon Dioxide Tension ◽  
Coronary Pressure ◽  
Adenosine Concentration ◽  
The Face

Autoregulation is defined as the intrinsic ability of an organ to maintain constant flow in the face of changing perfusion pressure. The present study evaluated the role of several potential mediators of coronary autoregulation: interstitial adenosine, ATP-sensitive K+ (K+ATP) channels, and myocardial oxygen and carbon dioxide tensions as reflected by coronary venous oxygen and carbon dioxide tensions. The left main coronary artery was cannulated, and blood was perfused at controlled pressures in closed-chest dogs. Interstitial adenosine concentration was estimated from arterial and venous adenosine concentrations with a previously described mathematical model. Autoregulation of coronary blood flow was observed between 100 and 60 mmHg. Glibenclamide, an inhibitor of K+ATP channels, reduced coronary blood flow by 19% at each perfusion pressure, but autoregulation was preserved. After stepwise reductions in coronary pressure to values > or = 70 mmHg, adenosine concentrations did not increase above basal levels. Adenosine concentration was elevated at 60 mmHg, suggesting a role for adenosine at the limit of coronary autoregulation. Adenosine is not required because glibenclamide, an inhibitor of adenosine-mediated vasodilation, did not reduce autoregulation or increase adenosine concentration. Coronary venous oxygen and carbon dioxide tensions were little changed during autoregulation before the inhibition of K+ATP channels and adenosine vasodilation with glibenclamide. However, coronary venous carbon dioxide tension rose progressively with decreasing coronary pressure after glibenclamide. The increase in carbon dioxide indirectly suggests that carbon dioxide-mediated vasodilation compensated for the loss of K+ATP-channel function. In summary, neither K+ATP channels nor adenosine is necessary to maintain coronary flow in the autoregulatory range of coronary arterial pressure from 100 to 60 mmHg.

Role of myocardial oxygen and carbon dioxide in coronary autoregulation

1992 ◽  
Vol 262 (4) ◽  
pp. H1231-H1237 ◽  
Author(s):  
T. P. Broten ◽  
E. O. Feigl
Keyword(s):  
Carbon Dioxide ◽  
Left Main Coronary Artery ◽  
Perfusion Pressure ◽  
Coronary Perfusion Pressure ◽  
Coronary Perfusion ◽  
Vascular Conductance ◽  
Anesthetized Dogs ◽  
Coronary Conductance ◽  
A Prospective Study

Myocardial oxygen (PO2) and carbon dioxide tensions (PCO2) are likely mediators of the local control of coronary blood flow. A previous study demonstrated that myocardial PO2 and PCO2, estimated by coronary venous values, interact synergistically to determine coronary flow. This synergistic relation was used in a prospective study to test the hypothesis that myocardial PO2 and PCO2 mediate changes in coronary vascular conductance during autoregulation. The left main coronary artery was pump perfused at controlled pressures in closed-chest anesthetized dogs. Autoregulation curves were obtained by increasing coronary perfusion pressure from 80 to 160 mmHg in 20-mm increments. Steady-state measurements of coronary venous PO2 and PCO2 and coronary conductance were obtained at each perfusion pressure. The coronary venous PO2 and PCO2 were used in the previously determined synergistic relation to predict the coronary vascular conductance during autoregulation. The predicted changes in coronary vascular conductance were compared with the actual changes in coronary vascular conductance for the pressure range of 80-160 mmHg. The data indicate that the synergistic interaction of oxygen and carbon dioxide accounts for approximately 23% of the change in coronary vascular conductance during autoregulation. These results suggest that other factors are also involved in autoregulation.

Role of adenosine in norepinephrine-induced coronary vasodilation

1997 ◽  
Vol 273 (2) ◽  
pp. H557-H565 ◽  
Author(s):  
R. Van Bibber ◽  
D. W. Stepp ◽  
K. Kroll ◽  
E. O. Feigl
Keyword(s):  
Blood Flow ◽  
Oxygen Consumption ◽  
Coronary Blood Flow ◽  
Adenosine Receptor ◽  
Myocardial Oxygen Consumption ◽  
Temporal Correlation ◽  
Distributed Model ◽  
Receptor Blockade ◽  
Adenosine Concentration

Adenosine has been postulated to be the physiological transmitter coupling increases in coronary blood flow to increases in myocardial metabolism. The purpose of this experiment was to evaluate the role of adenosine in the coronary hyperemia due to norepinephrine. In 11 anesthetized, closed-chest canine preparations, the left main coronary artery was cannulated and perfused with blood at 100 mmHg. Coronary blood flow and myocardial oxygen consumption were measured, and interstitial adenosine concentration was estimated from arterial and coronary venous measurements using a distributed model. Adenosine receptor blockade with 8-phenyltheophylline (8-PT) was used to shift the adenosine dose-response curve 12-fold. During intracoronary norepinephrine infusion, coronary blood flow and myocardial oxygen consumption increased similarly before and after 8-PT, demonstrating a lack of an effect from the adenosine receptor blockade. Before 8-PT, estimated interstitial adenosine increased to a vasoactive concentration (220 nM); however, the temporal correlation with coronary blood flow was poor. After 8-PT, a similar increase in estimated interstitial adenosine was found, demonstrating that there was no augmentation in adenosine concentration to overcome the adenosine receptor blockade. Thus adenosine could not be responsible for the increase in coronary blood flow after adenosine receptor blockade and therefore is not required for norepinephrine-induced hyperemia.

Independent role of arterial O2 tension in local control of coronary blood flow

1990 ◽  
Vol 258 (5) ◽  
pp. H1388-H1394 ◽  
Author(s):  
J. F. Baron ◽  
E. Vicaut ◽  
X. Hou ◽  
M. Duvelleroy
Keyword(s):  
Blood Flow ◽  
Coronary Blood Flow ◽  
Perfusion Pressure ◽  
Rabbit Heart ◽  
Coronary Resistance ◽  
Heart Preparation ◽  
Myocardial O2 Consumption ◽  
O2 Delivery ◽  
Arterial Po2

The aim of this study of a blood-perfused isolated rabbit heart preparation was to differentiate the effects on coronary resistance of large changes in arterial O2 tension (arterial PO2 = 45-400 Torr) from the effects of variations in arterial O2 content or myocardial O2 delivery. Standard stored human blood was resuspended in Krebs-Henseleit buffer and was oxygenated to obtain normal PO2, high PO2, and low PO2. Hemoglobin concentrations were adjusted to obtain the same arterial O2 content (CaO2) for the three PO2s. In a first set of experiments, in which coronary blood flow (CBF) was free and adapted to a constant perfusion pressure, switching from control [138 +/- 17 (SE) Torr] to high PO2 blood (380 +/- 27 Torr) induced a significant decrease in CBF and myocardial O2 consumption (MVO2). Switching from control (125 +/- 3 Torr) to low PO2 blood (49 +/- 5 Torr) induced a significant increase in CBF and MVO2. In a second set of experiments, the switch from control (159 +/- 5 Torr) to high PO2 (389 +/- 32 Torr) was performed in a preparation in which CBF and consequently O2 delivery were constant. Under these conditions, the increase in perfusion pressure demonstrated that PO2 affected coronary resistance, even though the O2 delivery was constant. No significant change in myocardial performance was observed in any of these experimental procedures. These results show that arterial PO2 may affect coronary blood flow regulation independently of any mediation by the autonomic nervous system and of any associated changes in O2 content or O2 delivery.

Role of adenosine in local metabolic coronary vasodilation

1999 ◽  
Vol 276 (5) ◽  
pp. H1425-H1433 ◽  
Author(s):  
Toyotaka Yada ◽  
Keith Neu Richmond ◽  
Richard van Bibber ◽  
Keith Kroll ◽  
Eric O. Feigl
Keyword(s):  
Blood Flow ◽  
Oxygen Consumption ◽  
Coronary Blood Flow ◽  
Adenosine Receptor ◽  
Myocardial Oxygen Consumption ◽  
Receptor Blockade ◽  
Coronary Vasodilation ◽  
Paired Pulse ◽  
Adenosine Concentration

Adenosine has been postulated to mediate the increase in coronary blood flow when myocardial oxygen consumption is increased. The aim of this study was to evaluate the role of adenosine when myocardial oxygen consumption was augmented by cardiac paired-pulse stimulation without the use of catecholamines. In 10 anesthetized closed-chest dogs, coronary blood flow was measured in the left circumflex coronary artery, and myocardial oxygen consumption was calculated using the arteriovenous oxygen difference. Cardiac interstitial adenosine concentration was estimated from coronary venous and arterial plasma adenosine measurements using a previously described multicompartmental, axially distributed mathematical model. Paired stimulation increased heart rate from 55 to 120 beats/min, increased myocardial oxygen consumption 104%, and increased coronary blood flow 92%, but the estimated interstitial adenosine concentration remained below the threshold for coronary vasodilation. After adenosine-receptor blockade with 8-phenyltheophylline (8-PT), coronary blood flow and myocardial oxygen consumption were not significantly different from control values. Paired-pulse pacing during adenosine-receptor blockade resulted in increases in myocardial oxygen consumption and coronary blood flow similar to the response before 8-PT. Coronary venous and estimated interstitial adenosine concentration did not increase to overcome the adenosine blockade by 8-PT. These results demonstrate that adenosine is not required for the local metabolic control of coronary blood flow during pacing-induced increases in myocardial oxygen consumption.

scholarly journals Role of adenosine in coronary blood flow regulation after reductions in perfusion pressure.

1985 ◽  
Vol 56 (4) ◽  
pp. 517-524 ◽  
Author(s):  
W P Dole ◽  
N Yamada ◽  
V S Bishop ◽  
R A Olsson
Keyword(s):  
Blood Flow ◽  
Coronary Blood Flow ◽  
Perfusion Pressure ◽  
Flow Regulation ◽  
Blood Flow Regulation

Role of KATP + channels and adenosine in the control of coronary blood flow during exercise

2000 ◽  
Vol 89 (2) ◽  
pp. 529-536 ◽  
Author(s):  
Keith Neu Richmond ◽  
Johnathan D. Tune ◽  
Mark W. Gorman ◽  
Eric O. Feigl
Keyword(s):  
Blood Flow ◽  
Coronary Blood Flow ◽  
Treadmill Exercise ◽  
Katp Channels ◽  
Channel Blockade ◽  
Channel Function ◽  
Physiol Heart Circ ◽  
Adenosine Concentration ◽  
Control Exercise

The present study was designed to examine the role of ATP-sensitive potassium (KATP +) channels during exercise and to test the hypothesis that adenosine increases to compensate for the loss of KATP + channel function and adenosine inhibition produced by glibenclamide. Graded treadmill exercise was used to increase myocardial O2 consumption in dogs before and during KATP + channel blockade with glibenclamide (1 mg/kg iv), which also blocks adenosine mediated coronary vasodilation. Cardiac interstitial adenosine concentration was estimated from arterial and coronary venous values by using a previously tested mathematical model (Kroll K and Stepp DW. Am J Physiol Heart Circ Physiol 270: H1469–H1483, 1996). Coronary venous O2 tension was used as an index of the balance between O2 delivery and myocardial O2consumption. During control exercise, myocardial O2consumption increased ∼4-fold, and coronary venous O2tension fell from 19 to 14 Torr. After KATP +channel blockade, coronary venous O2 tension was decreased below control vehicle values at rest and during exercise. However, during exercise with glibenclamide, the slope of the line of coronary venous O2 tension vs. myocardial O2 consumption was the same as during control exercise. Estimated interstitial adenosine concentration with glibenclamide was not different from control vehicle and was well below the level necessary to overcome the 10-fold shift in the adenosine dose-response curve due to glibenclamide. In conclusion, KATP + channel blockade decreases the balance between resting coronary O2 delivery and myocardial O2 consumption, but KATP +channels are not required for the increase in coronary blood flow during exercise. Furthermore, interstitial adenosine concentration does not increase to compensate for the loss of KATP +channel function.

Role of K ATP + channels in local metabolic coronary vasodilation

1999 ◽  
Vol 277 (6) ◽  
pp. H2115-H2123 ◽  
Author(s):  
Keith Neu Richmond ◽  
Johnathan D. Tune ◽  
Mark W. Gorman ◽  
Eric O. Feigl
Keyword(s):  
Blood Flow ◽  
Coronary Blood Flow ◽  
Coronary Vasodilator ◽  
Paired Stimulation ◽  
Adenosine Concentration ◽  
Coronary Vascular Tone ◽  
Arterial Plasma ◽  
Plasma Adenosine

ATP-sensitive potassium ([Formula: see text]) channels have been shown to play a role in the maintenance of basal coronary vascular tone in vivo. [Formula: see text] channels are also involved in the coronary vasodilator response to adenosine. The aim of this study was to determine the role of[Formula: see text] channels in local metabolically mediated increases in coronary blood flow during cardiac electrical paired pacing without catecholamine effects. In 10 anesthetized closed-chest dogs, coronary blood flow was measured in the left circumflex coronary artery, and myocardial O2 consumption was calculated using the arteriovenous O2difference. Cardiac interstitial adenosine concentration was estimated from coronary venous and arterial plasma adenosine measurements using a previously described, multicompartmental, axially distributed, mathematical model. Paired stimulation increased heart rate from 57 to 120 beats/min, myocardial O2consumption 88%, and coronary blood flow 76%. During[Formula: see text] channel blockade with glibenclamide, baseline coronary blood flow decreased in relation to myocardial O2 consumption and thus coronary sinus O2 tension fell. Paired-pulse pacing with glibenclamide resulted in increases in myocardial O2 consumption and coronary blood flow similar to those during control pacing. Coronary venous and estimated interstitial adenosine concentration did not increase sufficiently to overcome the glibenclamide blockade. In conclusion, [Formula: see text] channels are not required for locally mediated metabolic increases in coronary blood flow that accompany myocardial O2consumption during pacing tachycardia without catecholamines, and adenosine levels do not increase sufficiently to overcome the glibenclamide blockade.

Coronary transport reserve in normal dogs

1984 ◽  
Vol 57 (2) ◽  
pp. 551-561 ◽  
Author(s):  
M. H. Laughlin
Keyword(s):  
Blood Flow ◽  
Coronary Blood Flow ◽  
Perfusion Pressure ◽  
Ethylenediaminetetraacetic Acid ◽  
Blood Gases ◽  
Diffusion Method ◽  
Coronary Perfusion ◽  
Base Line ◽  
Coronary Pressure ◽  
Flow Reserve

This study was designed to determine an acceptable method for producing maximal coronary vasodilation for quantifying coronary blood flow reserve and coronary capillary transport reserve. The anterior descending branch of the left coronary artery was cannulated and pump-perfused while aortic, central venous, and coronary perfusion pressures, heart rate, electrocardiogram, blood gases, and coronary blood flow (CBF) were continuously monitored. All parameters were measured at four to six points along the coronary pressure-flow autoregulation curve. Myocardial extraction and permeability-surface area products (PS) of 51Cr-ethylenediaminetetraacetic acid were determined with the single-injection indicator-diffusion method in intact working hearts of anesthetized dogs. Maximal vasodilations were produced with 2-min coronary occlusions and with intracoronary infusions of adenosine (ADO), dipyridamole, ADO + dipyridamole, papaverine, and ADO + alpha 1-receptor blockade. ADO was chosen to quantify coronary transport reserve because it produced maximal CBF's and PS's that were reproducible within and among animals and produced minimal effects on the cardiovascular system. Under base-line conditions, there was no relationship between PS and perfusion pressure. Base-line PS averaged 20 +/- 2 ml X min-1 X 100 g-1. Maximal vasodilation with constant CBF had no significant effect on PS. During maximal vasodilation, CBF and PS increased linearly with increasing perfusion pressure, and PS increased linearly with increasing plasma flow. Constant pressure maximal vasodilation with ADO caused PS to increase to 36 +/- 4 ml X min-1 X 100 g-1, and CBF was increased 380%.

Contribution of extravascular compression to reduction of maximal coronary blood flow

1992 ◽  
Vol 262 (1) ◽  
pp. H68-H77
Author(s):  
F. L. Abel ◽  
R. R. Zhao ◽  
R. F. Bond
Keyword(s):  
Blood Flow ◽  
Coronary Blood Flow ◽  
Coronary Flow ◽  
Perfusion Pressure ◽  
Left Ventricular Pressure ◽  
Coronary Perfusion Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Coronary Perfusion ◽  
Storage Site

Effects of ventricular compression on maximally dilated left circumflex coronary blood flow were investigated in seven mongrel dogs under pentobarbital anesthesia. The left circumflex artery was perfused with the animals' own blood at a constant pressure (63 mmHg) while left ventricular pressure was experimentally altered. Adenosine was infused to produce maximal vasodilation, verified by the hyperemic response to coronary occlusion. Alterations of peak left ventricular pressure from 50 to 250 mmHg resulted in a linear decrease in total circumflex flow of 1.10 ml.min-1 x 100 g heart wt-1 for each 10 mmHg of peak ventricular to coronary perfusion pressure gradient; a 2.6% decrease from control levels. Similar slopes were obtained for systolic and diastolic flows as for total mean flow, implying equal compressive forces in systole as in diastole. Increases in left ventricular end-diastolic pressure accounted for 29% of the flow changes associated with an increase in peak ventricular pressure. Doubling circumferential wall tension had a minimal effect on total circumflex flow. When the slopes were extrapolated to zero, assuming linearity, a peak left ventricular pressure of 385 mmHg greater than coronary perfusion pressure would be required to reduce coronary flow to zero. The experiments were repeated in five additional animals but at different perfusion pressures from 40 to 160 mmHg. Higher perfusion pressures gave similar results but with even less effect of ventricular pressure on coronary flow or coronary conductance. These results argue for an active storage site for systolic arterial flow in the dilated coronary system.

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