scholarly journals Obesity decreases the contribution of Kv channels to hypoxic coronary vasodilation

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Hannah E. Clark ◽  
Hana E. Baker ◽  
Adam G. Goodwill ◽  
Bianca S. Blaettner ◽  
Michael C. Kozlowski ◽  
...  
Keyword(s):  
Blood Flow ◽  
Coronary Blood Flow ◽  
Coronary Flow ◽  
Functional Expression ◽  
K Channel ◽  
Coronary Vasodilation ◽  
Kv Channels ◽  
Arterial Blood ◽  
Before And After ◽  
Arterial Po2

Background and Hypothesis: Our group previously demonstrated that reductions in the functional expression of voltage-dependent K+ (Kv) channels contribute to impaired metabolic control of coronary blood flow in the setting of obesity. This study tested the hypothesis that obesity diminishes the contribution of Kv channels to coronary vasodilation in response to hypoxemia. Experimental Design or Project Methods: Control lean (n = 7) and obese (n = 5) swine were anesthetized and the heart exposed via left lateral thoracotomy. Coronary blood flow was measured in response to hypoxemia, before and after inhibition of Kv channels by 4-aminopyridine (4-AP; 0.3 mg/kg, iv), by a flow probe placed about the left anterior descending coronary artery. Hypoxemia was induced by progressive increases in the amount of nitrogen introduced into the ventilator. Arterial blood samples were obtained at each reduction in arterial oxygenation via a catheter placed in the femoral artery. Results: Blood pressure decreased from ~88 ± 5 mmHg to ~68 ± 6 mmHg (P = 0.01) as arterial PO2 was reduced below 50 mmHg in both lean and obese swine (P = 0.51). In lean swine, coronary flow progressively increased from ~0.6 to >3.0 ml/min/g as arterial PO2 was reduced. This response was decreased by ~40% in obese swine and by ~30% in lean swine treated with 4-AP. Administration of 4AP had no effect on coronary flow in obese swine. Conclusion and Potential Impact: These data support that Kv channels contribute to increases in coronary flow in response to hypoxemia in lean swine and that reductions in Kv channel function contribute to impaired hypoxic coronary vasodilation in obese swine. We propose that therapeutic targeting of obesity associated pathways (angiotensin-aldosterone system) known to influence K+ channel expression could improve coronary microvascular function and cardiovascular outcomes in subjects with obesity. Supported by R01 HL136386; T35 HL 110854.

Preliminary observations on blood flow in the coronary arteries of two school sharks (Galeorhinus australis)

1993 ◽  
Vol 71 (6) ◽  
pp. 1238-1241 ◽  
Author(s):  
Peter S. Davie ◽  
Craig E. Franklin
Keyword(s):  
Blood Flow ◽  
Arterial Pressure ◽  
Coronary Blood Flow ◽  
Coronary Flow ◽  
Cardiac Cycle ◽  
Arterial Blood Flow ◽  
Ventricular Systole ◽  
Arterial Blood ◽  
Ventricular Mass ◽  
Aortic Blood Velocity

Coronary arterial blood flow and pressure, intraventricular blood pressure, and ventral aortic blood velocity were measured in two anaesthetized school sharks (Galeorhinus australis) in order to examine the phasic relationships between these flows and pressures. Maximum instantaneous flow recorded in the ventral coronary artery was 0.37 mL∙min−1∙kg−1 body mass (estimated 0.63 mL∙min−1∙g−1 ventricular mass). The average mean coronary blood flow was estimated as 0.28 mL∙min−1∙g−1 ventricular mass during periods of high coronary blood flow. On average, 86% of coronary flow occurred during diastole. Coronary arterial flow began during the last quarter of ventricular systole. Coronary blood flow peaked when intraventricular pressure fell to just below zero immediately after ventricular systole. Coronary blood flow fell slightly as diastole continued and reflected the small fall in coronary arterial pressure. Coronary flow reversed briefly during isovolumic ventricular contraction. Increases in the proportion of the cardiac cycle occupied by ventricular diastole, which occur during hypoxic bradycardia, have the potential to more than double coronary blood flow provided coronary arterial pressure is maintained.

Role of K ATP + channels and adenosine in regulation of coronary blood flow in the hypertrophied left ventricle

1999 ◽  
Vol 277 (2) ◽  
pp. H617-H625 ◽  
Author(s):  
Peter J. Melchert ◽  
Dirk J. Duncker ◽  
Jay H. Traverse ◽  
Robert J. Bache
Keyword(s):  
Blood Flow ◽  
Left Ventricle ◽  
Coronary Blood Flow ◽  
Coronary Flow ◽  
Rate Pressure Product ◽  
Receptor Blockade ◽  
Channel Activity ◽  
Channel Blockade ◽  
Coronary Vasodilation ◽  
Exercise Induced

In the hypertrophied heart, increased extravascular forces acting to compress the intramural coronary vessels might require augmentation of metabolic vasodilator mechanisms to maintain adequate coronary blood flow. Vascular smooth muscle ATP-sensitive potassium ([Formula: see text]) channel activity is important in metabolic coronary vasodilation, and adenosine contributes to resistance vessel dilation in the hypoperfused heart. Consequently, this study was performed to determine whether[Formula: see text] channels and adenosine have increased importance in exercise-induced coronary vasodilation in the hypertrophied left ventricle. Studies were performed in dogs in which banding of the ascending aorta had resulted in a 66% increase in left ventricular mass in comparison with historic normal animals. Treadmill exercise resulted in increases of coronary blood flow that were linearly related to the increase of heart rate or rate-pressure product. During resting conditions, [Formula: see text]channel blockade with glibenclamide caused a 17 ± 5% decrease in coronary blood flow, similar to that previously observed in normal hearts. Unlike normal hearts, however, glibenclamide blunted the increase in coronary flow that occurred during exercise, causing a significant decrease in the slope of the relationship between coronary flow and the rate-pressure product. Adenosine receptor blockade with 8-phenyltheophylline did not alter coronary blood flow at rest or during exercise. Furthermore, even after[Formula: see text] channel blockade with glibenclamide, the addition of 8-phenyltheophylline had no effect on coronary blood flow. This finding was different from normal hearts, in which the addition of adenosine receptor blockade after glibenclamide impaired exercise-induced coronary vasodilation. The data suggest that, in comparison with normal hearts, hypertrophied hearts have increased reliance on opening of [Formula: see text] channels to augment coronary flow during exercise. Contrary to the initial hypothesis, however, adenosine was not mandatory for exercise-induced coronary vasodilation in the hypertrophied hearts either during control conditions or when [Formula: see text] channel activity was blocked with glibenclamide.

Regulation of coronary flow

2021 ◽  
pp. 11-13
Author(s):  
Nico Bruining ◽  
Eric Boersma ◽  
Dirk J. Duncker
Keyword(s):  
Blood Flow ◽  
Coronary Blood Flow ◽  
Coronary Flow ◽  
Left Ventricular ◽  
Left Ventricular Wall ◽  
Ventricular Wall ◽  
Arterial Blood ◽  
Arterial Inflow ◽  
Systolic Phase ◽  
Vascular Beds

This chapter describes the regulation of coronary blood flow. The left ventricle generates the systemic arterial blood pressure that is required to maintain coronary blood flow. The coronary circulation is unique among regional vascular beds in that its perfusion is impeded during the systolic phase of the cardiac cycle by the surrounding contracting cardiac muscle. Systolic contraction increases left ventricular wall tension and compresses the intramyocardial microvessels, thereby impeding coronary arterial inflow. This compression is not uniformly distributed across the left ventricular wall, resulting in a redistribution of blood flow from the subendocardium to subepicardium.

scholarly journals Overview of mathematical modeling of myocardial blood flow regulation

2020 ◽  
Vol 318 (4) ◽  
pp. H966-H975
Author(s):  
Ravi Namani ◽  
Yoram Lanir ◽  
Lik Chuan Lee ◽  
Ghassan S. Kassab
Keyword(s):  
Blood Flow ◽  
Coronary Blood Flow ◽  
Coronary Flow ◽  
Oxygen Demand ◽  
Flow Regulation ◽  
Flow Reserve ◽  
Arterial Blood ◽  
Blood Flow Regulation ◽  
Highly Nonlinear ◽  
Coronary Flow Regulation

The oxygen consumption by the heart and its extraction from the coronary arterial blood are the highest among all organs. Any increase in oxygen demand due to a change in heart metabolic activity requires an increase in coronary blood flow. This functional requirement of adjustment of coronary blood flow is mediated by coronary flow regulation to meet the oxygen demand without any discomfort, even under strenuous exercise conditions. The goal of this article is to provide an overview of the theoretical and computational models of coronary flow regulation and to reveal insights into the functioning of a complex physiological system that affects the perfusion requirements of the myocardium. Models for three major control mechanisms of myogenic, flow, and metabolic control are presented. These explain how the flow regulation mechanisms operating over multiple spatial scales from the precapillaries to the large coronary arteries yield the myocardial perfusion characteristics of flow reserve, autoregulation, flow dispersion, and self-similarity. The review not only introduces concepts of coronary blood flow regulation but also presents state-of-the-art advances and their potential to impact the assessment of coronary microvascular dysfunction (CMD), cardiac-coronary coupling in metabolic diseases, and therapies for angina and heart failure. Experimentalists and modelers not trained in these models will have exposure through this review such that the nonintuitive and highly nonlinear behavior of coronary physiology can be understood from a different perspective. This survey highlights knowledge gaps, key challenges, future research directions, and novel paradigms in the modeling of coronary flow regulation.

Coronary blood flow reserve during +Gz stress and treadmill exercise in miniature swine

1988 ◽  
Vol 64 (6) ◽  
pp. 2589-2596 ◽  
Author(s):  
M. H. Laughlin ◽  
J. W. Burns ◽  
J. Fanton ◽  
J. Ripperger ◽  
D. F. Peterson
Keyword(s):  
Blood Flow ◽  
Steady State ◽  
Coronary Blood Flow ◽  
Maximal Exercise ◽  
Exercise Stress ◽  
Coronary Vasodilation ◽  
Miniature Swine ◽  
Flow Reserve ◽  
Before And After ◽  
Coronary Blood Flow Reserve

The purpose of this study was to compare the coronary blood flow reserve (CBFR) that exists during maximal +Gz stress to the CBFR during maximal exercise stress. Maximal exercise stress was defined as an exercise intensity greater than or equal to that necessary to produce maximal levels of O2 consumption (VO2max). Coronary blood flows (CBF) were determined with the use of the microsphere technique in chronically instrumented conscious miniature swine during +Gz stress and exercise stress at 70 and 100% of maximal tolerance (for each stress) before and after maximal coronary vasodilation with 1–2 mg/kg dipyridamole. CBFR was measured as the amount of blood flow increase produced by maximal coronary vasodilation. During exercise at VO2max, dipyridamole produced 20–30% increases in CBF, whereas it induced no coronary vasodilation or changes in CBF during +Gz stress. Dipyridamole also produced decreases in the animals' tolerance to +Gz in that all five animals could maintain a steady state for 60 s at 7 +Gz before dipyridamole, whereas only two of these animals could maintain a steady state for 60 s at 7 +Gz after dipyridamole. These results confirm that CBFR exists during maximal exercise in normal mammals. However, this dose of dipyridamole produced no coronary vasodilation during either level of +Gz stress.

Role of adenosine in regulation of coronary flow in dogs with inhibited synthesis of endothelium-derived nitric oxide

1996 ◽  
Vol 270 (2) ◽  
pp. H427-H434 ◽  
Author(s):  
T. Matsunaga ◽  
K. Okumura ◽  
R. Tsunoda ◽  
S. Tayama ◽  
T. Tabuchi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Coronary Blood Flow ◽  
Coronary Flow ◽  
Oxygen Metabolism ◽  
Myocardial Oxygen Demand ◽  
Wall Thickening ◽  
Atrial Pacing ◽  
Adenosine Release ◽  
Before And After

Endothelium-derived nitric oxide (NO) regulates coronary blood flow, but it is unclear how NO synthesis inhibition affects myocardial metabolism. In pentobarbital sodium-anesthetized dogs, myocardial oxygen metabolism, adenosine release, lactate extraction rate (LER), and systolic ventricular wall thickening (SWT) at baseline and during atrial pacing were estimated before and after intracoronary NG-nitro-L-arginine methyl ester (L-NAME) infusion. Coronary blood flow and PO2 in the anterior interventricular vein at baseline were both significantly decreased by L-NAME (3 x 10(-4) M in the coronary blood). Coronary flow was increased during pacing, which was not affected by L-NAME. Myocardial adenosine release remained unchanged during pacing before L-NAME, but it was significantly increased after L-NAME infusion. Neither LER nor SWT changed during pacing performed before and after L-NAME. The experiment was also performed in dogs pretreated with 8-phenyltheophyl-line. After L-NAME, pacing-induced increase in coronary flow was suppressed, and both LER and SWT were significantly decreased during pacing. In conclusion, when NO synthesis is inhibited, adenosine release is increased in response to the increase in myocardial oxygen demand. With this compensatory adenosine release, coronary flow is increased and ventricular function is unaffected.

Effects of O2, CO2, and drugs on estimating coronary blood flow from Rb86 clearance

1965 ◽  
Vol 208 (6) ◽  
pp. 1206-1210 ◽  
Author(s):  
William D. Love ◽  
Myra D. Tyler ◽  
Ralph E. Abraham ◽  
Robert S. Munford
Keyword(s):  
Blood Flow ◽  
Coronary Blood Flow ◽  
Coronary Flow ◽  
Arterial Oxygen Saturation ◽  
Drug Effects ◽  
Carbon Dioxide Tension ◽  
Arterial Oxygen ◽  
Vasoactive Drugs ◽  
Arterial Blood ◽  
Valid Index

The accuracy of predictions of myocardial blood flow based on Rb86 clearance rates was determined in dogs receiving vasoactive drugs or subjected to hypoxemia or hypercapnia. In controls, the highest rate of coronary blood flow was 16.5 ml/g myocardium per 10 min. Flow could be predicted from clearance (tissue Rb86 uptake/arterial blood Rb86 concentration) with a mean error of 7.8% in this group. With hypoxemia estimates of flow averaged 13.8% too low when arterial blood was from 50 to 75% saturated with oxygen, and were more unreliable at lower values. Carbon dioxide tension had no effect in the range from 20 to 60 mm Hg, but at higher levels estimates of flow were frequently much too low. Reserpine slowed the pulse and resulted in predicted rates of flow which averaged 13.7% below actual rates. Angiotensin, l-norepinephrine, dipyridamole, and digitoxin had no significant effect on the prediction of flow from clearance in the range of flow observed in controls. Thus Rb86 clearance is a valid index of coronary flow in the range of CO2 tension, arterial oxygen saturation, and drug effects commonly observed.

Adenosine regulates coronary blood flow during increased work and decreased supply

1993 ◽  
Vol 264 (5) ◽  
pp. H1438-H1446 ◽  
Author(s):  
S. E. Martin ◽  
S. D. Lenhard ◽  
L. S. Schmarkey ◽  
S. Offenbacher ◽  
B. M. Odle
Keyword(s):  
Blood Flow ◽  
Oxygen Consumption ◽  
Coronary Blood Flow ◽  
Coronary Flow ◽  
Coronary Resistance ◽  
Coronary Vasodilation ◽  
Work Related

Adenosine may mediate coronary vasodilation during work-related hyperemia and during ischemia. We tested whether adenosine blockade with 8-p-sulfophenyltheophylline (PSPT) prevented dobutamine-induced hyperemia or magnified the reductions in flow due to vasopressin. Control (n = 8) and test (n = 7) dogs received paired infusions of dobutamine (70 micrograms/min iv for 5 min). Test dogs received PSPT (10 mg/kg iv) between doses. In both groups, paired infusions elicited comparable increases in oxygen consumption. However, in test dogs, the hyperemia was reduced significantly. Thus adenosine mediates the hyperemia of dobutamine. Separately, control dogs (n = 9) received vasopressin (0.6 microgram ic over 5 min); test dogs (n = 7) received PSPT before vasopressin. Vasopressin maximally increased coronary resistance by 3 min; effects were gone by 10 min. With PSPT, coronary resistance was increased further and remained high beyond 10 min. Thus adenosine-mediated vasodilation moderates the severity and duration of ischemia. These results indicate the importance of adenosine in mediating coronary flow during increased demand and reduced supply.

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.

Coronary vasodilation mediated by T cells expressing choline acetyltransferase

2021 ◽  
Vol 321 (5) ◽  
pp. H933-H939
Author(s):  
Adrian H. Chester ◽  
Ann McCormack ◽  
Edmund J. Miller ◽  
Mohamed N. Ahmed ◽  
Magdi H. Yacoub
Keyword(s):  
T Cells ◽  
Blood Flow ◽  
Blood Vessel ◽  
Coronary Blood Flow ◽  
Choline Acetyltransferase ◽  
Vascular Endothelium ◽  
Coronary Circulation ◽  
Direct Interaction ◽  
Coronary Vasodilation ◽  
Ischemic Events

This study shows ChAT-expressing T cells can induce vasodilation of the blood vessel in the coronary circulation and that this effect relies on a direct interaction between T cells and the coronary vascular endothelium. The study establishes a potential immunomodulatory role for T cells in the coronary circulation. The present findings offer an additional possibility that a deficiency of ChAT-expressing T cells could contribute to reduced coronary blood flow and ischemic events in the myocardium.

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