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.

Defective endothelium-mediated control of coronary circulation in conscious dogs after heart failure

1994 ◽  
Vol 266 (2) ◽  
pp. H670-H680 ◽  
Author(s):  
J. Wang ◽  
N. Seyedi ◽  
X. B. Xu ◽  
M. S. Wolin ◽  
T. H. Hintze
Keyword(s):  
Nitric Oxide ◽  
Heart Failure ◽  
Blood Flow ◽  
Coronary Artery ◽  
Coronary Arteries ◽  
Coronary Circulation ◽  
Clinical Signs ◽  
Left Ventricular ◽  
Conscious Dogs ◽  
Large Coronary Arteries

The goal of this study was to determine whether coronary endothelial function was altered after pacing-induced heart failure in conscious dogs. Fourteen mongrel dogs were chronically instrumented for measurements of systemic hemodynamics, left circumflex coronary artery diameter (CD) and blood flow, and for left ventricular pacing for 4 wk. Heart failure developed during this pacing regimen and was characterized by a significant reduction in arterial pressure, an increase in left atrial pressure, a resting tachycardia, a depression of left ventricular dP/dt to isoproterenol injection, a significant reduction of the slope of the end-systolic pressure-diameter relationship, and all of the characteristic clinical signs. During heart failure, the dilation of CD after release of a brief coronary artery occlusion, acetylcholine, and arachidonic acid was attenuated, whereas prostaglandin (PG) I2- and nitroglycerin-induced dilations of CD were unchanged. The coronary blood flow responses to occlusion, acetylcholine, and nitroglycerin were depressed, but not to PG. Large coronary arteries and microvessels were isolated from normal and failing hearts. Both isolated large coronary arteries and microvessels from failing hearts produced significantly less nitrite, the immediate metabolite of nitric oxide in aqueous solution, than those of normal hearts. Thus endothelium-mediated control of the coronary circulation was depressed during heart failure. A decrease in the production of nitric oxide-endothelium-derived relaxing factor was most likely responsible for this depression.

alpha-Adrenergic control of oxygen delivery to myocardium during exercise in conscious dogs

1982 ◽  
Vol 242 (5) ◽  
pp. H805-H809 ◽  
Author(s):  
G. R. Heyndrickx ◽  
P. Muylaert ◽  
J. L. Pannier
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Oxygen Consumption ◽  
Coronary Blood Flow ◽  
Coronary Sinus ◽  
Oxygen Delivery ◽  
Left Ventricular ◽  
Conscious Dogs ◽  
Adrenergic Blockade ◽  
Adrenergic Control

alpha-Adrenergic control of the oxygen delivery to the myocardium during exercise was investigated in eight conscious dogs instrumented for chronic measurements of coronary blood flow, left ventricular (LV) pressure, aortic blood pressure, and heart rate and sampling of arterial and coronary sinus blood. After alpha-adrenergic receptor blockade a standard exercise load elicited a significantly greater increase in heart rate, rate of change of LV pressure (LV dP/dt), LV dP/dt/P, and coronary blood flow than was elicited in the unblocked state. In contrast to the response pattern during control exercise, there was no significant change in coronary sinus oxygen tension (PO2), myocardial arteriovenous oxygen difference, and myocardial oxygen delivery-to-oxygen consumption ratio. It is concluded that the normal relationship between myocardial oxygen supply and oxygen demand is modified during exercise after alpha-adrenergic blockade, whereby oxygen delivery is better matched to oxygen consumption. These results indicate that the increase in coronary blood flow and oxygen delivery to the myocardium during normal exercise is limited by alpha-adrenergic vasoconstriction.

Ventricular remodeling induced by acute nonocclusive constriction of coronary artery in rats

1989 ◽  
Vol 257 (6) ◽  
pp. H1983-H1993 ◽  
Author(s):  
J. M. Capasso ◽  
M. W. Jeanty ◽  
T. Palackal ◽  
G. Olivetti ◽  
P. Anversa
Keyword(s):  
Blood Flow ◽  
Coronary Artery ◽  
Coronary Blood Flow ◽  
Wall Thickness ◽  
Ventricular Remodeling ◽  
Diastolic Pressure ◽  
Cell Damage ◽  
Left Ventricular ◽  
Consistent Difference ◽  
Luminal Diameter

To determine the consequence of acute nonocclusive constriction of the epicardial coronary artery on the adaptation of the left ventricle and its impact as a function of age, the left main coronary artery was narrowed in rats 4 and 12 mo of age, and the animals were killed 45 min later. Similar reductions in the luminal diameter, averaging 4%, were obtained in both groups of animals, and this change resulted in an increase in left ventricular end-diastolic pressure and a decrease in positive and negative change in pressure overtime (dP/dt) and in peak-developed ventricular pressure. Left ventricular volume increased by 66% and 56% at 4 and 12 mo because of increases in both the longitudinal and transverse chamber diameters. In contrast, wall thickness decreased by 27% and 35%, whereas sarcomere length increased only by 8.0% and 6.0%, respectively. These changes implied the occurrence of side-to-side slippage of myocytes within the wall to accommodate the larger chamber volume. The alterations in myocardial performance combined with the variations in ventricular size and wall thickness produced a marked elevation in diastolic and systolic wall stress. Moreover, myocyte cell damage in the form of contraction bands and disorganization of the intercalated disc region was seen. No consistent difference was found in any of the parameters measured as a function of age. Measurements of resting coronary blood flow across the left ventricular wall before coronary artery narrowing were comparable with those obtained 45 min after constriction. In conclusion, acute nonocclusive coronary artery stenosis has profound detrimental effects on the function and structure of the myocardium in the absence of an impairment of resting coronary blood flow.

Coronary smooth muscle reactivity to muscarinic stimulation after ischemia-reperfusion in porcine myocardial infarction

2003 ◽  
Vol 95 (1) ◽  
pp. 81-88 ◽  
Author(s):  
Antonio Rodríguez-Sinovas ◽  
Josep Bis ◽  
Inocencio Anivarro ◽  
Javier de la Torre ◽  
Antoni Bayés-Genís ◽  
...  
Keyword(s):  
Blood Flow ◽  
Smooth Muscle ◽  
Coronary Artery ◽  
Coronary Blood Flow ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Severe Left Ventricular Dysfunction ◽  
Coronary Smooth Muscle

This study tested whether ischemia-reperfusion alters coronary smooth muscle reactivity to vasoconstrictor stimuli such as those elicited by an adventitial stimulation with methacholine. In vitro studies were performed to assess the reactivity of endothelium-denuded infarct-related coronary arteries to methacholine ( n = 18). In addition, the vasoconstrictor effects of adventitial application of methacholine to left anterior descending (LAD) coronary artery was assessed in vivo in pigs submitted to 2 h of LAD occlusion followed by reperfusion ( n = 12), LAD deendothelization ( n = 11), or a sham operation ( n = 6). Endothelial-dependent vasodilator capacity of infarct-related LAD was assessed by intracoronary injection of bradykinin ( n = 13). In vitro, smooth muscle reactivity to methacholine was unaffected by ischemia-reperfusion. In vivo, baseline methacholine administration induced a transient and reversible drop in coronary blood flow (9.6 ± 4.6 to 1.9 ± 2.6 ml/min, P < 0.01), accompanied by severe left ventricular dysfunction. After ischemia-reperfusion, methacholine induced a prolonged and severe coronary blood flow drop (9.7 ± 7.0 to 3.4 ± 3.9 ml/min), with a significant delay in recovery ( P < 0.001). Endothelial denudation mimics in part the effects of methacholine after ischemia-reperfusion, and intracoronary bradykinin confirmed the existence of endothelial dysfunction. Infarct-related epicardial coronary artery shows a delayed recovery after vasoconstrictor stimuli, because of appropriate smooth muscle reactivity and impairment of endothelial-dependent vasodilator capacity.

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.

Cardiovascular Response to Glucagon in Hypovolemic Dogs

1975 ◽  
Vol 53 (2) ◽  
pp. 211-216
Author(s):  
G. Pinardi ◽  
E. Santiago ◽  
J. V. Vasquez
Keyword(s):  
Blood Flow ◽  
Coronary Blood Flow ◽  
Myocardial Metabolism ◽  
Cardiovascular Response ◽  
Cardiovascular Effects ◽  
Aortic Blood Flow ◽  
Vascular Effects ◽  
Control Value ◽  
Cardiac Depression ◽  
Short Time

Glucagon in a dose of 50 μg/kg body weight was studied for its cardiovascular effects in hypovolemic dogs in which coronary blood flow was reduced to an average of 40% of its control value and cardiac depression was evident. Myocardial contractility, as judged mainly by dP/dt and acceleration of aortic blood flow, was brought to a normal level for a short time. Systemic and coronary vascular resistances were markedly reduced. These effects were similar in normovolemic dogs. The inotropic, chronotropic, and peripheral vascular effects of glucagon can be evoked also in hypovolemic dogs in which coronary blood flow is less than normal and myocardial metabolism is impaired.

scholarly journals The human coronary vasodilatory response to acute mental stress is mediated by neuronal nitric oxide synthase

2017 ◽  
Vol 313 (3) ◽  
pp. H578-H583 ◽  
Author(s):  
Sitara G. Khan ◽  
Narbeh Melikian ◽  
Husain Shabeeh ◽  
Ana R. Cabaco ◽  
Katherine Martin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Coronary Artery ◽  
Nitric Oxide Synthase ◽  
Coronary Blood Flow ◽  
Mental Stress ◽  
Coronary Flow ◽  
Neuronal Nitric Oxide Synthase ◽  
Coronary Artery Diameter ◽  
Oxide Synthase

Mental stress-induced ischemia approximately doubles the risk of cardiac events in patients with coronary artery disease, yet the mechanisms underlying changes in coronary blood flow in response to mental stress are poorly characterized. Neuronal nitric oxide synthase (nNOS) regulates basal coronary blood flow in healthy humans and mediates mental stress-induced vasodilation in the forearm. However, its possible role in mental stress-induced increases in coronary blood flow is unknown. We studied 11 patients (6 men and 5 women, mean age: 58 ± 14 yr) undergoing elective diagnostic cardiac catheterization and assessed the vasodilator response to mental stress elicited by the Stroop color-word test. Intracoronary substance P (20 pmol/min) and isosorbide dinitrate (1 mg) were used to assess endothelium-dependent and -independent vasodilation, respectively. Coronary blood flow was estimated using intracoronary Doppler recordings and quantitative coronary angiography to measure coronary artery diameter. Mental stress increased coronary flow by 34 ± 7.0% over the preceding baseline during saline infusion ( P < 0.01), and this was reduced to 26 ± 7.0% in the presence of the selective nNOS inhibitor S-methyl-l-thiocitrulline (0.625 µmol/min, P < 0.001). Mental stress increased coronary artery diameter by 6.9 ± 3.7% ( P = 0.02) and 0.5 ± 2.8% ( P = 0.51) in the presence of S-methyl-l-thiocitrulline. The response to substance P did not predict the response to mental stress ( r2 = −0.22, P = 0.83). nNOS mediates the human coronary vasodilator response to mental stress, predominantly through actions at the level of coronary resistance vessels. NEW & NOTEWORTHY Acute mental stress induces vasodilation of the coronary microvasculature. Here, we show that this response involves neuronal nitric oxide synthase in the human coronary circulation. Listen to this article’s corresponding podcast at http://ajpheart.podbean.com/e/nnos-and-coronary-flow-during-mental-stress/ .

Reactive dilation and late-hyperemic constriction of epicardial coronary artery after short coronary occlusion

1986 ◽  
Vol 251 (3) ◽  
pp. H554-H561
Author(s):  
H. Yamamoto ◽  
H. Tomoike ◽  
K. Hisano ◽  
T. Inoue ◽  
M. Mohri ◽  
...  
Keyword(s):  
Blood Flow ◽  
Coronary Artery ◽  
Coronary Blood Flow ◽  
Coronary Occlusion ◽  
Reactive Hyperemia ◽  
Beta Blockade ◽  
Adrenergic Blockade ◽  
Epicardial Coronary Artery ◽  
Dependent Change ◽  
Coronary Artery Diameter

Coronary blood flow and epicardial coronary artery diameter were simultaneously measured by an electromagnetic or Doppler flow probe and a pair of ultrasonic crystals, respectively, during reactive hyperemia in conscious dogs. Reactive dilation appeared after the full appearance of reactive hyperemia and lasted for a period of 4-20 times the duration of the coronary occlusion. beta-Receptor blockade (propranolol, 1 mg/kg iv) attenuated both the reactive hyperemia in volume by 21-22% (P less than 0.01) and dilative responses of the epicardial coronary diameter by 27-28% (P less than 0.01), despite a nonsignificant attenuation of the resting or peak hyperemic coronary blood flow. When coronary blood flow was held constant during reperfusion, by an occluder distal to the ultrasonic crystals, the reactive dilation disappeared. A peculiar reactive constriction was noted when coronary occlusion was performed proximal to the site of the ultrasonic crystals. Appearance of this constriction was at 149 and 385 s after the release of 5 and 60 s of coronary occlusion, respectively. This late reactive constriction disappeared after pretreatment with alpha- (phentolamine, 1 mg/kg iv) and/or alpha- + beta-blockade, but not with beta-blockade alone, and it was not observed when the coronary diameter was measured proximal to the occluder. Thus reactive dilation of the epicardial coronary artery derives from an increase in coronary flow and is reduced by propranolol via a reduction in the hyperemic flow, suggesting a flow-dependent change in the diameter of the epicardial coronary artery. Reactive constriction is a local phenomenon following marked reduction in the coronary diameter and is abolished by alpha-adrenergic blockade with phentolamine.

Hypothermic Myocardial Oxygenation

1957 ◽  
Vol 190 (1) ◽  
pp. 57-62 ◽  
Author(s):  
James R. Jude ◽  
L. M. Haroutunian ◽  
Roland Folse
Keyword(s):  
Blood Flow ◽  
Oxygen Consumption ◽  
Coronary Blood Flow ◽  
Vascular Resistance ◽  
Peripheral Resistance ◽  
Left Ventricular ◽  
Control Value ◽  
Myocardial Oxygenation ◽  
Total Body Oxygen ◽  
Oxygen Difference

Coronary blood flow together with corollary functions were determined in 11 anesthetized dogs at normal body temperature and in 9 of these animals after cooling to 20°C. The arterial ph was kept in the normal range by controlled ventilation. At 20°C coronary blood flow/100 gm left ventricle decreased to 29% of the normothermic control value. Myocardial oxygen consumption decreased to 24%, coronary A-V oxygen difference to 82%, total body oxygen consumption to 24%, cardiac output to 21%, and calculated left ventricular work to 10.7%. Systemic A-V oxygen difference did not vary significantly. Pulmonary vascular resistance increased to 306% of the normothermic control, peripheral resistance to 304% and coronary vascular resistance to 193%. Coronary blood flow appeared to be sufficient to maintain an adequate supply of oxygen to the myocardium for the work performed by it at 20°C.

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