Effects of Isoflurane on Regional Coronary Blood Flow and Myocardial Tissue Pressure in Chronically Instrumented Dogs

We investigated the effect of muscle metaboreflex activation on left circumflex coronary blood flow (CBF) and vascular conductance (CVC) in conscious, chronically instrumented dogs during treadmill exercise ranging from mild to severe workloads. Metaboreflex responses were also observed during mild exercise with constant heart rate (HR) of 225 beats/min and β1-adrenergic receptor blockade to attenuate the substantial reflex increases in cardiac work. The muscle metaboreflex was activated via graded partial occlusion of hindlimb blood flow. During mild exercise, with muscle metaboreflex activation, hindlimb ischemia elicited significant reflex increases in mean arterial pressure (MAP), HR, and cardiac output (CO) (+39.0 ± 5.2 mmHg, +29.9 ± 7.7 beats/min, and +2.0 ± 0.4 l/min, respectively; all changes, P < 0.05). CBF increased from 51.9 ± 4.3 to 88.5 ± 6.6 ml/min, ( P < 0.05), whereas no significant change in CVC occurred (0.56 ± 0.06 vs. 0.59 ± 0.05 ml · min−1 · mmHg−1; P > 0.05). Similar responses were observed during moderate exercise. In contrast, with metaboreflex activation during severe exercise, no further increases in CO or HR occurred, the increases in MAP and CBF were attenuated, and a significant reduction in CVC was observed (1.00 ± 0.12 vs. 0.90 ± 0.13 ml · min−1 · mmHg−1; P < 0.05). Similarly, when the metaboreflex was activated during mild exercise with the rise in cardiac work lessened (via constant HR and β1-blockade), no increase in CO occurred, the MAP and CBF responses were attenuated (+15.6 ± 4.5 mmHg, +8.3 ± 2 ml/min), and CVC significantly decreased from 0.63 ± 0.11 to 0.53 ± 0.10 ml · min−1 · mmHg−1. We conclude that the muscle metaboreflex induced increases in sympathetic nerve activity to the heart functionally vasoconstricts the coronary vasculature.

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Adenosine and coronary blood flow in conscious dogs during normal physiological stimuli

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1982.243.4.h628 ◽

1982 ◽

Vol 243 (4) ◽

pp. H628-H633 ◽

Cited By ~ 8

Author(s):

A. N. Bacchus ◽

S. W. Ely ◽

R. M. Knabb ◽

R. Rubio ◽

R. M. Berne

Keyword(s):

Blood Flow ◽

Oxygen Consumption ◽

Coronary Blood Flow ◽

Myocardial Oxygen Consumption ◽

Oxygen Supply ◽

Physiological Mechanism ◽

Oxygen Demand ◽

The Relationship ◽

Chronically Instrumented Dogs

The role of adenosine in matching myocardial oxygen supply to demand by regulating coronary blood flow has been the subject of intensive study. The present experiments were designed to determine the relationship among myocardial oxygen consumption, coronary blood flow, and adenosine production as estimated by pericardial adenosine accumulation under several physiological conditions in the same animal. Conscious chronically instrumented dogs were used to measure changes in coronary blood flow, myocardial oxygen consumption, and pericardial adenosine accumulation during two levels of treadmill exercise, excitement caused by loud noises, and feeding (the presentation and consumption of a meal). The results show significant increases in the adenosine production with all experimental procedures and significant linear correlations between myocardial oxygen consumption and coronary blood flow (r = 0.78), myocardial oxygen consumption and adenosine production (r = 0.73), and adenosine production and coronary blood flow (r = 0.88). These data show that increases in adenosine production by the normally oxygenated myocardium can be the physiological mechanism for matching oxygen supply to increased oxygen demand in the conscious dog.

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COMPARISON OF CORONARY BLOOD FLOW DURING HALOTHANE AND ISOFLURANE ANESTHESIA (WITH AND WITHOUT N2O) IN CHRONICALLY INSTRUMENTED DOGS

Anesthesiology ◽

10.1097/00000542-199109001-00502 ◽

1991 ◽

Vol 75 (3) ◽

pp. A503-A503

Author(s):

AIH Khalil ◽

R M Jones ◽

P. Foex

Keyword(s):

Blood Flow ◽

Coronary Blood Flow ◽

Isoflurane Anesthesia ◽

Chronically Instrumented Dogs

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Disentangling the Gordian knot of local metabolic control of coronary blood flow

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00325.2019 ◽

2020 ◽

Vol 318 (1) ◽

pp. H11-H24

Author(s):

Johnathan D. Tune ◽

Adam G. Goodwill ◽

Alexander M. Kiel ◽

Hana E. Baker ◽

Shawn B. Bender ◽

...

Keyword(s):

Blood Flow ◽

Metabolic Control ◽

Coronary Blood Flow ◽

Tissue Oxygenation ◽

Coronary Circulation ◽

Myocardial Metabolism ◽

Data Interpretation ◽

Myocardial Tissue ◽

Tightly Coupled ◽

Microvascular Resistance

Recognition that coronary blood flow is tightly coupled with myocardial metabolism has been appreciated for well over half a century. However, exactly how coronary microvascular resistance is tightly coupled with myocardial oxygen consumption (MV̇o2) remains one of the most highly contested mysteries of the coronary circulation to this day. Understanding the mechanisms responsible for local metabolic control of coronary blood flow has been confounded by continued debate regarding both anticipated experimental outcomes and data interpretation. For a number of years, coronary venous Po2 has been generally accepted as a measure of myocardial tissue oxygenation and thus the classically proposed error signal for the generation of vasodilator metabolites in the heart. However, interpretation of changes in coronary venous Po2 relative to MV̇o2 are quite nuanced, inherently circular in nature, and subject to confounding influences that remain largely unaccounted for. The purpose of this review is to highlight difficulties in interpreting the complex interrelationship between key coronary outcome variables and the arguments that emerge from prior studies performed during exercise, hemodilution, hypoxemia, and alterations in perfusion pressure. Furthermore, potential paths forward are proposed to help to facilitate further dialogue and study to ultimately unravel what has become the Gordian knot of the coronary circulation.

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Coronary flow during exercise after selective alpha 1- and alpha 2-adrenergic blockade

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1989.256.4.h1148 ◽

1989 ◽

Vol 256 (4) ◽

pp. H1148-H1155 ◽

Cited By ~ 10

Author(s):

X. Z. Dai ◽

E. Sublett ◽

P. Lindstrom ◽

J. S. Schwartz ◽

D. C. Homans ◽

...

Keyword(s):

Blood Flow ◽

Coronary Blood Flow ◽

Vascular Resistance ◽

Treadmill Exercise ◽

Adrenergic Blockade ◽

Relative Importance ◽

Coronary Vascular Resistance ◽

Circumflex Coronary Artery ◽

Coronary Vasoconstriction ◽

Chronically Instrumented Dogs

This study was carried out to determine the relative importance of alpha 1- and alpha 2-adrenergic vasoconstriction in opposing the increase in coronary blood flow, which occurs during exercise. The response of left circumflex coronary artery blood flow was examined during treadmill exercise in 16 chronically instrumented dogs during control conditions, after selective alpha 1-adrenergic blockade with intracoronary prazosin, and after alpha 2-blockade with intracoronary idazoxan. During control conditions, graded treadmill exercise resulted in progressive increases of coronary blood flow and decreases of coronary vascular resistance. Prazosin produced highly selective alpha 1-adrenergic blockade; coronary blood flow was significantly higher and coronary vascular resistance significantly lower during all but the heaviest exercise stage after prazosin. Idazoxan produced highly effective, but only moderately selective, alpha 2-adrenergic blockade. However, after idazoxan, coronary blood flow and coronary vascular resistance during exercise were not significantly different from control. Combined alpha 1- and alpha 2-adrenergic blockade was not more effective in increasing coronary blood flow during exercise than was alpha 1-adrenergic blockade alone. These data support a role for alpha 1-adrenergic coronary vasoconstriction in limiting the increase in coronary blood flow, which occurs during exercise, but do not support a role for alpha 2-mediated coronary vasoconstriction during exercise.

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Nonuniform distribution of blood flow and gradients of oxygen tension within the heart

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1964.207.3.661 ◽

1964 ◽

Vol 207 (3) ◽

pp. 661-668 ◽

Cited By ~ 186

Author(s):

Edward S. Kirk ◽

Carl R. Honig

Keyword(s):

Blood Flow ◽

Pressure Gradient ◽

Oxygen Tension ◽

Cardiac Cycle ◽

Myocardial Tissue ◽

Local Blood Flow ◽

Tissue Pressure ◽

Oxygen Tensions ◽

Sufficient Magnitude ◽

Transmural Gradient

Myocardial tissue pressure increases from epicardium to endocardium, and in the deeper layers exceeds ventricular blood pressure during one-third of the cardiac cycle (21). The effect of this tissue pressure gradient on local blood flow was studied using the depot clearance technique. Blood flow was found to be at least 25% lower in the deep regions as compared with superficial ones. With total coronary inflow held constant, vagal arrest of the heart removed the tissue pressure gradient, and simultaneously redistributed flow from superficial to deeper layers. We conclude that the gradient in tissue pressure, and hence in the extravascular component of coronary resistance, is at least in part, the cause of the nonhomogeneous blood flow across the wall. By use of the oxygen cathode, a gradient of oxygen tensions was observed which paralleled the blood flow gradient; mean oxygen tension in the subepicardium averaged twice that in the subendocardium. The gradient in oxygen tension appears to be of sufficient magnitude to determine a transmural gradient in aerobic metabolism.

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