ANTI-THROMBOTIC EFFECT IN CANINE CORONARY ARTERIES OF A COMBINED TXA2 synthetase/TXA2-prostaglandin ENDOPEROXIDE RECEPTOR INHIBITOR (R 68070)

1987 ◽  
Author(s):  
A Van de Water ◽  
R Xhonneux ◽  
F De Clerck
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Electrical Stimulation ◽  
Coronary Artery ◽  
Coronary Blood Flow ◽  
Coronary Arteries ◽  
Endothelial Injury ◽  
Receptor Blockade ◽  
Steel Electrode ◽  
Prostaglandin Endoperoxide

The effects of R 68070 an oxime-alkane carboxylic acid derivative combining specific thromboxane A2 (TXA2) synthetase inhibition with TXA2/prostaglandin endoperoxide receptor blockade in one molecule, on thrombus formation in a coronary artery following electrically-induced endothelial injury and on its myocardial repercussions were examined in dogs. In an open-chest model in anaesthetized dogs, a stainless steel electrode was inserted into the left anterior descending coronary artery (LAD) distally (+ 1 cm) from an electromagnetic flow probe. ECG and heart rate were derived from limb leads. Serum TXB2 levels were measured by RIA on venous spontaneously coagulated blood (1 h, 37°C). Endothelial cell injury in the LAD coronary artery was induced by the application of an anodal current of 300 μA during 30 min; after an additional 60 min observation period, the thrombus wet weight was determined.In comparison with solvent treatment (n = 8), R 68070 (1.25 mg/kg I.V. 10 min before electrical stimulation, n = 7), significantly reduced the thrombus mass (solvent : 43 mg; R 68070 : 18 mg median value, p < 0.05), the incidence of ECG changes indicative for myocardial ischemia (fibrillation : solvent 1/8; R 68070 0/7; arrhythmias : solvent 3/8; R 68070 2/7; ST changes : solvent 7/8; R 68070 1/7, p < 0.05) and the decrease in coronary blood flow after electrical stimulation (solvent : from 13 to 6.5 ml/min; R 68070 : from 13 to 11 ml/min median values, p < 0.05). Serum TXB2 levels were reduced by 92 % at 100 min after the injection of the active compound (median value, n = 7).Heart rate and coronary blood flow measured before the induction of the endothelial injury were not modified by R 68070.The present study thus demostrates that R 68070 exerts a potent anti-thrombotic effect in canine coronary arteries. The relative contributions to this effect of TXA2 synthetase inhibition and of TXA2/prostaglandin endoperoxide receptor blockade exerted by the compound are being investigated.

scholarly journals To Balloon or Not to Balloon? The Effects of an Intra-Aortic Balloon-Pump on Coronary Artery Flow during Extracorporeal Circulation Simulating Normal and Low Cardiac Output Syndromes

2021 ◽  
Vol 10 (22) ◽  
pp. 5333
Author(s):  
Philippe Reymond ◽  
Karim Bendjelid ◽  
Raphaël Giraud ◽  
Gérald Richard ◽  
Nicolas Murith ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Blood Flow ◽  
Cardiac Output ◽  
Coronary Artery ◽  
Coronary Blood Flow ◽  
Low Cardiac Output ◽  
Coronary Artery Flow ◽  
Artery Flow

ECMO is the most frequently used mechanical support for patients suffering from low cardiac output syndrome. Combining IABP with ECMO is believed to increase coronary artery blood flow, decrease high afterload, and restore systemic pulsatile flow conditions. This study evaluates that combined effect on coronary artery flow during various load conditions using an in vitro circuit. In doing so, different clinical scenarios were simulated, such as normal cardiac output and moderate-to-severe heart failure. In the heart failure scenarios, we used peripheral ECMO support to compensate for the lowered cardiac output value and reach a default normal value. The increase in coronary blood flow using the combined IABP-ECMO setup was more noticeable in low heart rate conditions. At baseline, intermediate and severe LV failure levels, adding IABP increased coronary mean flow by 16%, 7.5%, and 3.4% (HR 60 bpm) and by 6%, 4.5%, and 2.5% (HR 100 bpm) respectively. Based on our in vitro study results, combining ECMO and IABP in a heart failure setup further improves coronary blood flow. This effect was more pronounced at a lower heart rate and decreased with heart failure, which might positively impact recovery from cardiac failure.

Electrical stimulation in perifornical lateral hypothalamus decreases coronary blood flow in cats

1987 ◽  
Vol 252 (3) ◽  
pp. H474-H484 ◽  
Author(s):  
A. C. Bonham ◽  
D. D. Gutterman ◽  
J. M. Arthur ◽  
M. L. Marcus ◽  
G. F. Gebhart ◽  
...  
Keyword(s):  
Blood Flow ◽  
Electrical Stimulation ◽  
Flow Velocity ◽  
Coronary Blood Flow ◽  
Nerve Stimulation ◽  
Lateral Hypothalamus ◽  
Blood Flow Velocity ◽  
Adrenergic Receptor ◽  
Receptor Blockade ◽  
Coronary Vasoconstriction

Based on evidence implicating the central nervous system in the regulation of coronary vascular resistance and the knowledge that the hypothalamus is a central site for integration of cardiovascular control, studies were undertaken to determine if electrical stimulation in the hypothalamus produced coronary vasoconstriction. In anesthetized cats, following beta-adrenergic receptor blockade, stimulation in perifornical lateral hypothalamus produced a transient decrease in coronary blood flow velocity (30 +/- 5%), a small pressor effect (7 +/- 2 mmHg), and an initial decrease in hindquarter blood flow velocity (51 +/- 5%). The decrease in coronary flow velocity, which had an onset latency of 1-3 s and a duration of 5-15 s, was abolished by ipsilateral stellate ganglionectomy and by intravenous and intracoronary prazosin. The coronary vasoconstriction produced by hypothalamic stimulation was not different from that produced by cardioaccelerator nerve stimulation. These results suggest that electrical stimulation of a hypothalamic site produces an alpha-adrenergic receptor-mediated decrease in coronary blood flow that is unmasked by beta-adrenergic receptor blockade, requires the integrity of ipsilateral cardiac sympathetic innervation, and mimics the coronary response to cardioaccelerator nerve stimulation.

Dilation and constriction of large coronary arteries in conscious dogs by endothelin

1991 ◽  
Vol 261 (5) ◽  
pp. H1379-H1386 ◽  
Author(s):  
J. Wang ◽  
G. A. Zeballos ◽  
G. Kaley ◽  
T. H. Hintze
Keyword(s):  
Blood Flow ◽  
Coronary Artery ◽  
Coronary Blood Flow ◽  
Coronary Arteries ◽  
Cardiovascular Effects ◽  
Left Ventricular ◽  
Conscious Dogs ◽  
Control Value ◽  
Coronary Artery Diameter ◽  
The Relationship

This study examined the effects of endothelin on coronary circulation and the relationship between the plasma concentration of endothelin and cardiovascular function in conscious dogs. The injection of a low dose (50 ng/kg) of endothelin increased coronary artery diameter by 2.17 +/- 0.49% and then decreased coronary artery diameter by 1.13 +/- 0.17% (P less than 0.01) from 3.51 +/- 0.14 mm. This dose increased coronary blood flow by 39 +/- 8.5% and then decreased coronary blood flow by 14 +/- 3.5% (P less than 0.01) from 25 +/- 1.6 ml/min, respectively. Four doses of endothelin (1, 10, 20, and 50 ng.kg-1.min-1) were infused for 20 min each as a cumulative dose response and blood samples were taken to assay endothelin. Significant changes in systemic and coronary dynamics were observed at infusions of 10 and 20 ng.kg-1.min-1. For instance, at 10 ng.kg-1.min-1 there was a significant (P less than 0.05) increase in mean arterial pressure (10 +/- 2.7%), left ventricular (LV) end-diastolic (32 +/- 11%), and LV systolic (8 +/- 3%) pressures and late diastolic coronary resistance (12 +/- 3.0%). This was accompanied by a reduction in large coronary artery diameter (2.0 +/- 0.5%) and coronary blood flow (22 +/- 6.0%; P less than 0.05). At this infusion rate, plasma endothelin reached 70 pg/ml when compared with a control value of 4 +/- 1 pg/ml. Thus the bolus injections of endothelin evoked a biphasic response of large and small coronary arteries, whereas during infusion we observed only vasoconstriction. The levels of circulating endothelin necessary to cause significant cardiovascular effects are much higher than expected.

Thromboxane A2 and serotonin mediate coronary blood flow reductions in unsedated dogs

1989 ◽  
Vol 257 (3) ◽  
pp. H873-H882 ◽  
Author(s):  
J. F. Eidt ◽  
J. Ashton ◽  
P. Golino ◽  
J. McNatt ◽  
L. M. Buja ◽  
...  
Keyword(s):  
Blood Flow ◽  
Coronary Artery ◽  
Receptor Antagonist ◽  
Coronary Blood Flow ◽  
Serotonin Receptor ◽  
Thromboxane A2 ◽  
Endothelial Injury ◽  
Low Flow ◽  
Closed Chest ◽  
Coronary Artery Stenoses

We have shown in anesthetized open-chest dogs that recurrent platelet aggregation at the site of coronary artery stenosis and endothelial injury results in a pattern of cyclical variations in coronary blood flow (CFVs) and that serotonin and thromboxane A2 are important mediators of CFVs. In the present study, we tested the following hypotheses: 1) severe spontaneous reductions in coronary blood flow occur in awake closed-chest dogs with coronary artery stenoses and endothelial injury; 2) there is a progression from CFVs to persistent low coronary blood flow; and 3) serotonin and thromboxane A2 are important mediators of coronary blood flow reductions in this model. In 17 of 20 awake closed-chest unsedated dogs with experimental coronary artery stenoses and endothelial injury, either intermittent CFVs (n = 3), persistent low flow (n = 4), or progression from CFVs to low flow (n = 10) occurred during the first postoperative week. A serotonin receptor antagonist (ketanserin or LY 53857) or a thromboxane synthesis inhibitor (dazoxiben) or receptor antagonist (SQ 29548) abolished platelet-dependent CFVs in 80% of dogs. Thus 1) severe spontaneous reductions in coronary blood flow occur in awake closed-chest unsedated dogs with coronary artery stenoses and endothelial injury; 2) there is a progression from CFVs to persistent low coronary blood flow and final coronary artery occlusion; and 3) serotonin and thromboxane A2 are important mediators of coronary blood flow reductions in this experimental model.

Local endogenous opiate activity in dog myocardium: receptor blockade with naloxone

1985 ◽  
Vol 248 (3) ◽  
pp. H382-H388 ◽  
Author(s):  
J. L. Caffrey ◽  
J. F. Gaugl ◽  
C. E. Jones
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Coronary Blood Flow ◽  
Opiate Receptor ◽  
Rapid Onset ◽  
Contractile Force ◽  
Left Ventricular ◽  
Right Atrial ◽  
Receptor Blockade ◽  
Endogenous Opiates

The participation of endogenous opiates in myocardial performance and coronary blood flow was investigated. Heart rate, left ventricular contractile force (LVCF), left coronary blood flow (LCBF), and left ventricular oxygen extraction were monitored in anesthetized dogs before and after intracoronary opiate receptor blockade with naloxone. LVCF consistently increased in a dose-dependent fashion following intracoronary naloxone. The increasing LVCF was accompanied by significant increases in LCBF and myocardial oxygen consumption, without changes in heart rate. Rapid onset of responses suggested the presence of endogenous opiates operating locally within the myocardium. Similar effects did not follow right atrial injection of naloxone, ruling out a systemic mechanism. Furthermore, naloxone injected into the isolated left anterior descending artery selectively increased contractile force in that perfusion territory while the adjacent untreated circumflex territory showed no change. The administration of dynorphin into the coronaries produced a depression of LVCF qualitatively consistent with these effects. The effect of dynorphin was subsequently reversed with naloxone. These results support the concept that endogenous opiates participate in the regulation of myocardial function through local mechanisms at the myocardial level.

scholarly journals Magnesium causes nitric oxide independent coronary artery vasodilation in humans

Heart ◽  
2001 ◽  
Vol 86 (2) ◽  
pp. 212-216
Author(s):  
H Teragawa ◽  
M Kato ◽  
T Yamagata ◽  
H Matsuura ◽  
G Kajiyama
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Coronary Artery ◽  
Coronary Blood Flow ◽  
Coronary Arteries ◽  
Quantitative Coronary Angiography ◽  
University Hospital ◽  
Nitric Oxide Synthase Inhibitor ◽  
Before And After ◽  
Synthase Inhibitor

OBJECTIVETo determine how magnesium affects human coronary arteries and whether endothelium derived nitric oxide (EDNO) is involved in the coronary arterial response to magnesium.DESIGNQuantitative coronary angiography and Doppler flow velocity measurements were used to determine the effects of the nitric oxide synthase inhibitorNG-monomethyl-L-arginine (L-NMMA) on magnesium induced dilation of the epicardial and resistance coronary arteries.SETTINGHiroshima University Hospital a tertiary cardiology centre.PATIENTS17 patients with angiographically normal coronary arteries.INTERVENTIONSMagnesium sulfate (MgSO4) (0.02 mmol/min and 0.2 mmol/min) was infused for two minutes into the left coronary ostium before and after intracoronary infusion of L-NMMA.MAIN OUTCOME MEASURESDiameter of the proximal and distal segments of the epicardial coronary arteries and coronary blood flow.RESULTSAt a dose of 0.02 mmol/min, MgSO4 did not affect the coronary arteries. At a dose of 0.2 mmol/min, MgSO4 caused coronary artery dilation (mean (SEM) proximal diameter 3.00 (0.09) to 3.11 (0.09) mm; distal 1.64 (0.06) to 1.77 (0.07) mm) and increased coronary blood flow (79.3 (7.5) to 101.4 (9.9) ml/min, p < 0.001 vbaseline for all). MgSO4 increased the changes in these parameters after the infusion of L-NMMA (p < 0.001v baseline).CONCLUSIONSMagnesium dilates both the epicardial and resistance coronary arteries in humans. Furthermore, the coronary arterial response to magnesium is dose dependent and independent of EDNO.

Adenosine is not responsible for local metabolic control of coronary blood flow in dogs during exercise

2000 ◽  
Vol 278 (1) ◽  
pp. H74-H84 ◽  
Author(s):  
Johnathan D. Tune ◽  
Keith Neu Richmond ◽  
Mark W. Gorman ◽  
Ray A. Olsson ◽  
Eric O. Feigl
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Oxygen Consumption ◽  
Metabolic Control ◽  
Coronary Blood Flow ◽  
Myocardial Oxygen Consumption ◽  
Aortic Pressure ◽  
Receptor Blockade ◽  
Adenosine Concentration ◽  
Venous Plasma

The purpose of this investigation was to quantitatively evaluate the role of adenosine in coronary exercise hyperemia. Dogs ( n = 10) were chronically instrumented with catheters in the aorta and coronary sinus, and a flow probe on the circumflex coronary artery. Cardiac interstitial adenosine concentration was estimated from arterial and coronary venous plasma concentrations using a previously tested mathematical model. Coronary blood flow, myocardial oxygen consumption, heart rate, and aortic pressure were measured at rest and during graded treadmill exercise with and without adenosine receptor blockade with either 8-phenyltheophylline (8-PT) or 8- p-sulfophenyltheophylline (8-PST). In control vehicle dogs, exercise increased myocardial oxygen consumption 4.2-fold, coronary blood flow 3.8-fold, and heart rate 2.5-fold, whereas mean aortic pressure was unchanged. Coronary venous plasma adenosine concentration was little changed with exercise, and the estimated interstitial adenosine concentration remained well below the threshold for coronary vasodilation. Adenosine receptor blockade did not significantly alter myocardial oxygen consumption or coronary blood flow at rest or during exercise. Coronary venous and estimated interstitial adenosine concentration did not increase to overcome the receptor blockade with either 8-PT or 8-PST as would be predicted if adenosine were part of a high-gain, negative-feedback, local metabolic control mechanism. These results demonstrate that adenosine is not responsible for local metabolic control of coronary blood flow in dogs during exercise.

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