scholarly journals Coupling of Coronary Blood Flow to Cardiac Metabolism: Role of TRPV1 Channels and Local Changes in pH

2011 ◽  
Vol 25 (S1) ◽  
Author(s):  
Giacinta Guarini ◽  
Vahagn A. Ohanyan ◽  
Phani K. Talasila ◽  
Ian N. Bratz
Keyword(s):  
Blood Flow ◽  
Coronary Blood Flow ◽  
Cardiac Metabolism ◽  
Trpv1 Channels

Disruption of TRPV1-mediated coupling of coronary blood flow to cardiac metabolism in diabetic mice: role of nitric oxide and BK channels

2012 ◽  
Vol 303 (2) ◽  
pp. H216-H223 ◽  
Author(s):  
Giacinta Guarini ◽  
Vahagn A. Ohanyan ◽  
John G. Kmetz ◽  
Daniel J. DelloStritto ◽  
Roslin J. Thoppil ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Coronary Blood Flow ◽  
Cardiac Metabolism ◽  
Bk Channels ◽  
Bk Channel ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Channels ◽  
Channel Dependent

We have previously shown transient receptor potential vanilloid subtype 1 (TRPV1) channel-dependent coronary function is compromised in pigs with metabolic syndrome (MetS). However, the mechanisms through which TRPV1 channels couple coronary blood flow to metabolism are not fully understood. We employed mice lacking TRPV1 [TRPV1(−/−)], db/db diabetic, and control C57BKS/J mice to determine the extent to which TRPV1 channels modulate coronary function and contribute to vascular dysfunction in diabetic cardiomyopathy. Animals were subjected to in vivo infusion of the TRPV1 agonist capsaicin to examine the hemodynamic actions of TRPV1 activation. Capsaicin (1–100 μg·kg−1·min−1) dose dependently increased coronary blood flow in control mice, which was inhibited by the TRPV1 antagonist capsazepine or the nitric oxide synthase (NOS) inhibitor N-nitro-l-arginine methyl ester (l-NAME). In addition, the capsaicin-mediated increase in blood flow was attenuated in db/db mice. TRPV1(−/−) mice exhibited no changes in coronary blood flow in response to capsaicin. Vasoreactivity studies in isolated pressurized mouse coronary microvessels revealed a capsaicin-dependent relaxation that was inhibited by the TRPV1 inhibitor SB366791 l-NAME and to the large conductance calcium-sensitive potassium channel (BK) inhibitors iberiotoxin and Penetrim A. Similar to in vivo responses, capsaicin-mediated relaxation was impaired in db/db mice compared with controls. Changes in pH (pH 7.4–6.0) relaxed coronary vessels contracted to the thromboxane mimetic U46619 in all three groups of mice; however, pH-mediated relaxation was blunted in vessels obtained from TRPV1(−/−) and db/db mice compared with controls. Western blot analysis revealed decreased myocardial TRPV1 protein expression in db/db mice compared with controls. Our data reveal TRPV1 channels mediate coupling of myocardial blood flow to cardiac metabolism via a nitric oxide-dependent, BK channel-dependent pathway that is corrupted in diabetes.

scholarly journals Computational Analysis of Coronary Blood Flow: The Role of Asynchronous Pacing and Arrhythmias

Mathematics ◽  
2020 ◽  
Vol 8 (8) ◽  
pp. 1205
Author(s):  
Timur Gamilov ◽  
Philipp Kopylov ◽  
Maria Serova ◽  
Roman Syunyaev ◽  
Andrey Pikunov ◽  
...  
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Coronary Blood Flow ◽  
Long Qt Syndrome ◽  
Premature Ventricular Contraction ◽  
Cardiac Pacing ◽  
Long Qt ◽  
Computational Evaluation ◽  
Qt Syndrome

In this work we present a one-dimensional (1D) mathematical model of the coronary circulation and use it to study the effects of arrhythmias on coronary blood flow (CBF). Hydrodynamical models are rarely used to study arrhythmias’ effects on CBF. Our model accounts for action potential duration, which updates the length of systole depending on the heart rate. It also includes dependency of stroke volume on heart rate, which is based on clinical data. We apply the new methodology to the computational evaluation of CBF during interventricular asynchrony due to cardiac pacing and some types of arrhythmias including tachycardia, bradycardia, long QT syndrome and premature ventricular contraction (bigeminy, trigeminy, quadrigeminy). We find that CBF can be significantly affected by arrhythmias. CBF at rest (60 bpm) is 26% lower in LCA and 22% lower in RCA for long QT syndrome. During bigeminy, trigeminy and quadrigeminy, respectively, CBF decreases by 28%, 19% and 14% with respect to a healthy case.

Adenosine potentiates insulin-stimulated myocardial glucose uptake in vivo

1988 ◽  
Vol 254 (5) ◽  
pp. H970-H975 ◽  
Author(s):  
W. R. Law ◽  
R. M. Raymond
Keyword(s):  
Blood Flow ◽  
Glucose Uptake ◽  
Coronary Blood Flow ◽  
Metabolic Regulation ◽  
Metabolic Response ◽  
Dose Response Relationship ◽  
Circumflex Artery ◽  
Myocardial Glucose Uptake

Myocardial adenosine (ADO) has long been regarded as a regulator of coronary blood flow. In other tissues, such as adipose and skeletal muscle, much attention has focused on the role of ADO as a metabolic regulator of the actions of insulin. In the present study, we determined the effect of ADO infusion on insulin-stimulated myocardial glucose uptake (MGU). Mongrel dogs of either sex were instrumented to obtain arterial-coronary sinus differences for glucose, lactate, and oxygen. These were multiplied by circumflex artery blood flow (Q) to obtain uptake values. Measurements were made before and during hyperinsulinemic (4 U/min)-euglycemic clamp (clamp) with intracoronary infusions of saline, ADO, adenosine deaminase (ADA), or nitroprusside (NP). During clamp, MGU increased from a basal value of 3.0 +/- 0.8 mg/min (mean +/- SE) to 5.53 +/- 0.8 mg/min. Adenosine infusion potentiated this response, raising MGU further to 9.02 +/- 1.1 mg/min while not significantly affecting lactate or oxygen uptakes. Infusion of ADA confirmed the specificity of the response by blocking the metabolic effect of exogenously infused ADO. When NP was infused, Q increased significantly without altering MGU, indicating that the metabolic response to ADO was independent of the changes it caused in Q. A dose-response relationship existed between ADO and insulin-stimulated MGU. The metabolic response to ADO was more sensitive than the vasodilator response. It is concluded that ADO acts as a regulator of insulin in heart. This metabolic regulation occurs independent of changes in coronary blood flow.

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.

scholarly journals Role of nitric oxide in regulation of coronary blood flow during myocardial ischemia in dogs

1996 ◽  
Vol 27 (7) ◽  
pp. 1804-1812 ◽  
Author(s):  
Masafumi Kitakaze ◽  
Koichi Node ◽  
Tetsuo Minamino ◽  
Hiroaki Kosaka ◽  
Yoshiro Shinozaki ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Myocardial Ischemia ◽  
Coronary Blood Flow

scholarly journals 106 Role of neuronal vs endothelial nitric oxide synthase in the coronary blood flow response to pacing

Heart ◽  
2012 ◽  
Vol 98 (Suppl 1) ◽  
pp. A60.2-A61
Author(s):  
H Shabeeh ◽  
N Melikian ◽  
R Dworakowski ◽  
B Casadei ◽  
P Chowienczyk ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Nitric Oxide Synthase ◽  
Coronary Blood Flow ◽  
Endothelial Nitric Oxide Synthase ◽  
Blood Flow Response ◽  
Flow Response ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Augmentation of Coronary Blood Flow by Ace Inhibition: Role of Angiotensin and Bradykinin

1995 ◽  
Vol 17 (7) ◽  
pp. 1059-1072 ◽  
Author(s):  
Nicholas A. Ruocco ◽  
Bruce A. Bergelson ◽  
Tse-Kuan Yu ◽  
Irene Gavras ◽  
Haralambos Gavras
Keyword(s):  
Blood Flow ◽  
Coronary Blood Flow ◽  
Ace Inhibition

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.

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