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.

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.

Alteration in myocardial oxygen balance during exercise after beta-adrenergic blockade in dogs

1980 ◽  
Vol 49 (1) ◽  
pp. 28-33 ◽  
Author(s):  
G. R. Heyndrickx ◽  
J. L. Pannier ◽  
P. Muylaert ◽  
C. Mabilde ◽  
I. Leusen
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Oxygen Consumption ◽  
Myocardial Blood Flow ◽  
Coronary Blood Flow ◽  
Coronary Sinus ◽  
Myocardial Oxygen Consumption ◽  
Left Ventricular ◽  
Adrenergic Blockade ◽  
Oxygen Balance

The effects of beta-adrenergic blockade upon myocardial blood flow and oxygen balance during exercise were evaluated in eight conscious dogs, instrumented for chronic measurements of coronary blood flow, left ventricular pressure, aortic blood pressure, heart rate, and sampling of arterial and coronary sinus venous blood. The administration of propranolol (1.5 mg/kg iv) produced a decrease in heart rate, peak left ventricular (LV) dP/dt, LV (dP/dt/P, and an increase in LV end-diastolic pressure during exercise. Mean coronary blood flow and myocardial oxygen consumption were lower after propranolol than at the same exercise intensity in control conditions. The oxygen delivery-to-oxygen consumption ratio and the coronary sinus oxygen content were also significantly lower. It is concluded that the relationship between myocardial oxygen supply and demand is modified during exercise after propranolol, so that a given level of myocardial oxygen consumption is achieved with a proportionally lower myocardial blood flow and a higher oxygen extraction.

Positive inotropic response to inosine in the in situ canine heart

1977 ◽  
Vol 233 (4) ◽  
pp. H438-H443 ◽  
Author(s):  
C. E. Jones ◽  
J. X. Thomas ◽  
M. D. Devous ◽  
C. P. Norris ◽  
E. E. Smith
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Arterial Pressure ◽  
Substantial Effect ◽  
Contractile Force ◽  
Left Ventricular ◽  
Canine Heart ◽  
Inotropic State ◽  
Arterial Blood ◽  
The Right

Effects of inosine on left ventricular contractile force, circumflex blood flow, heart rate, and arterial pressure were investigated in mongrel dogs. Infusion of 50 ml of 10, 25, or 50 mM inosine into the right atrium over 5 min produced arterial blood inosine concentrations of 20-120 microM. Infusion of inosine concentrations of 10 mM or greater produced statistically significant increases in contractile force and circumflex blood flow (P less than 0.05). The increases in contractile force and circumflex blood flow caused by 50 inosine were approximately 40% and 110%, respectively. No statistically significant increases in heart rate or arterial pressure were observed during infusion of inosine at any concentration. Administration of propranolol (2 mg/kg) in no way altered the effects of inosine on contractile force or circumflex blood flow. Thus, the present study suggests that inosine in concentrations which may be produced in the myocardium during stressful conditions causes a substantial effect on the inotropic state of the heart and that the effects of inosine are not mediated through adrenergic mechanisms.

Augmented catecholamine uptake by the heart during hemorrhage in the conscious dog

1986 ◽  
Vol 250 (1) ◽  
pp. H76-H81 ◽  
Author(s):  
O. L. Woodman ◽  
J. Amano ◽  
T. H. Hintze ◽  
S. F. Vatner
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Coronary Blood Flow ◽  
Coronary Sinus ◽  
Nerve Stimulation ◽  
Left Ventricular ◽  
Sympathetic Nerve Stimulation ◽  
Net Release

Changes in arterial and coronary sinus concentrations of norepinephrine (NE) and epinephrine (E) in response to hemorrhage were examined in conscious dogs. Hemorrhage (45 +/- 3.2 ml/kg) decreased mean arterial pressure by 47 +/- 6%, left ventricular (LV) dP/dt by 38 +/- 6%, and mean left circumflex coronary blood flow by 47 +/- 6%, while heart rate increased by 44 +/- 13%. Increases in concentrations of arterial NE (5,050 +/- 1,080 from 190 +/- 20 pg/ml) and E (12,700 +/- 3,280 from 110 +/- 20 pg/ml) were far greater than increases in coronary sinus NE (1,700 +/- 780 from 270 +/- 50 pg/ml) and E (4,300 +/- 2,590 from 90 +/- 10 pg/ml). Net release of NE from the heart at rest was converted to a fractional extraction of 66 +/- 9% after hemorrhage. Fractional extraction of E increased from 16 +/- 6% at rest to 73 +/- 8% after hemorrhage. In cardiac-denervated dogs, hemorrhage (46 +/- 2.8 ml/kg) decreased mean arterial pressure by 39 +/- 15%, LV dP/dt by 36 +/- 10%, and mean left circumflex coronary blood flow by 36 +/- 13%, while heart rate increased by 24 +/- 10%. Hemorrhage increased arterial NE (1,740 +/- 150 from 210 +/- 30 pg/ml) and E (3,050 +/- 880 from 140 +/- 20 pg/ml) more than it increased coronary sinus NE (460 +/- 50 from 150 +/- 30 pg/ml) and E (660 +/- 160 from 90 +/- 20 pg/ml) but significantly less (P less than 0.05) than observed in intact dogs. These experiments indicate that hemorrhage, unlike exercise and sympathetic nerve stimulation, does not induce net overflow of NE from the heart.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Coronary pressure-flow relationship and exercise: contributions of heart rate, contractility, and alpha 1-adrenergic tone

1994 ◽  
Vol 266 (2) ◽  
pp. H795-H810 ◽  
Author(s):  
D. J. Duncker ◽  
N. S. Van Zon ◽  
M. Crampton ◽  
S. Herrlinger ◽  
D. C. Homans ◽  
...  
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Coronary Blood Flow ◽  
Left Ventricular ◽  
Filling Pressure ◽  
Pressure Flow ◽  
Coronary Pressure ◽  
Ventricular Filling Pressure ◽  
Exercise Induced ◽  
Ventricular Filling

We examined the impeding effects of exercise on coronary blood flow by analyzing exercise-induced changes in the pressure-flow relationship during maximal coronary vasodilation with adenosine in chronically instrumented dogs and assessed the individual contributions produced by heart rate, contractility, and alpha 1-adrenergic vasoconstriction. Treadmill exercise that increased heart rate from 118 +/- 6 beats/min at rest to 213 +/- 8 beats/min (P < 0.01) decreased maximum coronary blood flows by decreasing the slope of the linear part of the pressure-flow relationship for coronary pressures > or = 30 mmHg (slopeP > or = 30) from 12.3 +/- 0.9 to 10.9 +/- 0.9 ml.min-1 x g-1 x mmHg-1 (P < 0.01) and increasing the measured coronary pressure at zero flow (P zf,measured) from 12.6 +/- 1.2 to 23.3 +/- 2.0 mmHg (P < 0.01). Atrial pacing at 200 beats/min caused an increase of P zf,measured from 15.0 +/- 1.6 to 18.3 +/- 2.1 mmHg (P < 0.05) with no change in slopeP > or = 30. While pacing continued, infusion of dobutamine (20 micrograms.kg-1 x min-1 i.v.) increased contractility to levels similar to those during exercise but caused no significant change in coronary blood flow, as a decrease of the slopeP > or = 30 was compensated for by a slight decrease in P zf,measured. alpha 1-Adrenergic blockade with intracoronary prazosin (10 micrograms/kg) did not prevent the exercise-induced increase of P zf,measured but abolished the decrease of the slopeP > or = 30. When the increases in heart rate, contractility, and alpha 1-adrenergic vasoconstriction were prevented, exercise still increased P zf,measured from 15.8 +/- 2.1 to 21.8 +/- 2.6 mmHg (P < 0.05) but had no effect on the slopeP > or = 30. This residual increase in P zf,measured correlated with the concomitant increase in left ventricular filling pressure. In conclusion, exercise-induced decreases of maximum coronary blood flow were explained by increases in heart rate, alpha 1-adrenergic vasoconstriction, and left ventricular filling pressure, with a minimal contribution of contractility.

Effects of aminophylline on behaviorally induced coronary blood flow increases

1987 ◽  
Vol 253 (3) ◽  
pp. H548-H555
Author(s):  
G. E. Billman
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Coronary Blood Flow ◽  
Left Ventricular Pressure ◽  
Aversive Conditioning ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Adenosine Antagonist ◽  
Blood Flow Increase ◽  
Myocardial Oxygen Supply

It has been proposed that adenosine is a metabolic vasodilator that matches myocardial oxygen supply to demand by regulating coronary blood flow. In the present study, the adenosine antagonist aminophylline (Am) was used to evaluate the role adenosine plays in the coronary blood flow increase elicited by a controlled aversive stress, namely, classical aversive conditioning (a 30-s tone reinforced with a 1-s shock). Fifteen mongrel dogs were chronically instrumented to measure left circumflex coronary blood flow (CBF), left ventricular pressure (LVP), and heart rate. Am significantly (P greater than 0.01) attenuated the CBF response to the aversive stress without affecting the prestress levels (pre-Am control 40.9 +/- 2.4, peak 64.6 +/- 3.3 ml/min; post-Am control 41.7 +/- 2.2, peak 55.0 +/- 2.5 ml/min). The maximal CBF increase was reduced by 38.9 +/- 6.7% when compared with the control (no drug) condition. In a similar manner, neither heart rate nor LVP was affected by Am. However, Am significantly increased prestress level of first derivative of left ventricular pressure with reference to time [LV dP/dt] (pre-Am control 3,793.5 +/- 289.8 and Am 4,599.6 +/- 331.2 mmHg/s, respectively). These data suggest that adenosine contributes significantly to the regulation of CBF during a controlled emotional stress.

Urotensin II causes fatal circulatory collapse in anesthesized monkeys in vivo: a “vasoconstrictor” with a unique hemodynamic profile

2004 ◽  
Vol 286 (3) ◽  
pp. H830-H836 ◽  
Author(s):  
Yi Zhun Zhu ◽  
Zhong Jing Wang ◽  
Yi Chun Zhu ◽  
Li Zhang ◽  
Reida M. E. Oakley ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Blood Flow ◽  
Coronary Blood Flow ◽  
Nonhuman Primates ◽  
Peripheral Resistance ◽  
Left Ventricular ◽  
Circulatory Collapse ◽  
Urotensin Ii

Urotensin II (UII) is a vasoactive peptide that has recently emerged as a likely contributor to cardiovascular physiology and pathology. Acute infusion of UII into nonhuman primates results in circulatory collapse and death; however, the exact cause of death is not well understood. This study was undertaken to elucidate the mechanism underlying the fatal cardiovascular event on UII application in vivo in nonhuman primates. To this end, cynomolgus monkeys ( n = 4) were anesthetized and tracheal intubation was performed. One internal jugular vein was cannulated for administration of drugs, and one femoral artery for recording of blood pressure and heart rate using a transonic pressure transducer. Cardiac parameters were not significantly changed after administration of 0.003 nmol/kg human UII. A bolus of human UII (0.03 nmol/kg) caused a decrease of heart rate (HR) (13%), mean blood pressure (MBP) (18%), and first-order derivative of left ventricular pressure (dP/d t) (11%). Carotid and coronary blood flow were reduced by 9% and 7%, respectively; 0.3 nmol/kg of human UII resulted in a further reduction of HR (50.3%), MBP (65%), dP/d t (45%), carotid (38%), and coronary blood flow (30%), ultimately leading to cardiovascular breakdown and death. Pulmonary pressure, however, was increased by 30%. Plasma histamine levels were found to be unaffected by administration of UII. Our results indicate that systemic administration of human UII has negative inotropic and chronotropic effects and reduces total peripheral resistance ultimately leading to severe myocardial depression, pulmonary hypertension, and fatal circulation collapse in nonhuman primates. We suggest that successful design of UII antagonists might offer a new therapeutic principle in treating cardiovascular diseases.

Regional oxygen consumption and supply in heart: effect of methoxamine-induced pressure rise

1981 ◽  
Vol 241 (3) ◽  
pp. H370-H375 ◽  
Author(s):  
H. R. Weiss
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Coronary Blood Flow ◽  
Regional Differences ◽  
Pressure Rise ◽  
Left Ventricular ◽  
Atrial Pacing ◽  
O2 Consumption ◽  
Regional Flow ◽  
Arterial Blood

The effect of raising arterial blood pressure 50 mmHg with methoxamine on regional left ventricular O2 supply and consumption was studied in 27 pentobarbital-anesthetized open-chest rabbits. Three groups of animals were studied: 1) control, 2) methoxamine infusion sufficient to raise pressure 50 mmHg, and 3) methoxamine infusion sufficient to raise pressure 50 mmHg with atrial pacing to maintain heart rate. Subepicardial (epi) and subendocardial (endo) O2 saturations were determined with a microspectrophotometric technique. Regional flow was determined with radioactive microspheres and regional O2 consumption by the Fick principle. In the control group, endo venous O2 saturation [31 +/- 3% (SE)] was lower than epi (42 +/- 2%). There were no significant regional differences in blood flow (avg 128 +/- 2 ml . min-1 . 100 g-1). With methoxamine when heart rate fell, there were no differences in regional flow or consumption when compared to control. During methoxamine infusion, when heart rate was maintained, there was higher coronary blood flow (361 +/- 52 ml . min-1 . 100 g-1) and O2 consumption (27 +/- 4 ml O2 . min-1 . 100 g-1). No regional differences, epi vs. endo, were found in this group. After a 50-mmHg pressure rise, the endo region of the left ventricle had an increased O2 consumption mediated by an increased coronary blood flow without a significant rise in O2 extraction, similarly to epi.

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