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.

scholarly journals Distinct hemodynamic responses to (pyr)apelin-13 in large animal models

2020 ◽  
Vol 318 (4) ◽  
pp. H747-H755
Author(s):  
Johnathan D. Tune ◽  
Hana E. Baker ◽  
Zachary Berwick ◽  
Steven P. Moberly ◽  
Eli D. Casalini ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Blood Flow ◽  
Stroke Volume ◽  
Coronary Blood Flow ◽  
Myocardial Contractility ◽  
Left Ventricular ◽  
Large Animal ◽  
Hemodynamic Responses ◽  
End Diastolic Volume

This study tested the hypothesis that (pyr)apelin-13 dose-dependently augments myocardial contractility and coronary blood flow, irrespective of changes in systemic hemodynamics. Acute effects of intravenous (pyr)apelin-13 administration (10 to 1,000 nM) on blood pressure, heart rate, left ventricular pressure and volume, and coronary parameters were measured in dogs and pigs. Administration of (pyr)apelin-13 did not influence blood pressure ( P = 0.59), dP/d tmax ( P = 0.26), or dP/d tmin ( P = 0.85) in dogs. However, heart rate dose-dependently increased > 70% ( P < 0.01), which was accompanied by a significant increase in coronary blood flow ( P < 0.05) and reductions in left ventricular end-diastolic volume and stroke volume ( P < 0.001). In contrast, (pyr)apelin-13 did not significantly affect hemodynamics, coronary blood flow, or indexes of contractile function in pigs. Furthermore, swine studies found no effect of intracoronary (pyr)apelin-13 administration on coronary blood flow ( P = 0.83) or vasorelaxation in isolated, endothelium-intact ( P = 0.89) or denuded ( P = 0.38) coronary artery rings. Examination of all data across (pyr)apelin-13 concentrations revealed an exponential increase in cardiac output as peripheral resistance decreased across pigs and dogs ( P < 0.001; R2 = 0.78). Assessment of the Frank-Starling relationship demonstrated a significant linear relationship between left ventricular end-diastolic volume and stroke volume across species ( P < 0.001; R2 = 0.70). Taken together, these findings demonstrate that (pyr)apelin-13 does not directly influence myocardial contractility or coronary blood flow in either dogs or pigs. NEW & NOTEWORTHY Our findings provide much needed insight regarding the pharmacological cardiac and coronary effects of (pyr)apelin-13 in larger animal preparations. In particular, data highlight distinct hemodynamic responses of apelin across species, which are independent of any direct effect on myocardial contractility or perfusion.

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.

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.

Epicardial Coronary Blood Flow Including the Presence of Stenoses and Aorto-Coronary Bypasses—I: Model and Numerical Method

1985 ◽  
Vol 107 (4) ◽  
pp. 361-367 ◽  
Author(s):  
E. Rooz ◽  
T. F. Wiesner ◽  
R. M. Nerem
Keyword(s):  
Blood Flow ◽  
Numerical Method ◽  
Coronary Blood Flow ◽  
Wave Speed ◽  
Peripheral Resistance ◽  
Left Ventricular Pressure ◽  
Systematic Investigation ◽  
Left Ventricular ◽  
Resistive Component ◽  
The One

A computer model and numerical method for calculating left epicardial coronary blood flow has been developed. This model employs a finite-branching geometry of the coronary vasculature and the one-dimensional, unsteady equations for flow with friction. The epicardial coronary geometry includes the left main and its bifurcation, the left anterior descending and left circumflex coronary arteries, and a selected number of small branches. Each of the latter terminate in an impedance, whose resistive component is related to intramyocardial compression through a linear dependence on left ventricular pressure. The elastic properties of the epicardial arteries are taken to be non-linear and are prescribed by specifying the local small-disturbance wave speed. The model allows for the incorporation of multiple stenoses as well as aorto-coronary bypasses. Calculations using this model predict pressure and flow waveform development and allow for the systematic investigation of the dependence of coronary flow on various parameters, e.g., peripheral resistance, wall properties, and branching pattern, as well as the presence of stenoses and bypass grafts. Reasonable comparison between calculations and earlier experiments in horses has been obtained.

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)

scholarly journals The ocular cardiac reflex effect study on cardiac hemodynamic parameters in healthy young mans.

2019 ◽  
Vol 40 (1) ◽  
pp. 17-24
Author(s):  
A. I. Palamarchuk
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Blood Flow ◽  
Cardiovascular System ◽  
Peripheral Resistance ◽  
Blood Flow Rate ◽  
Effect Study ◽  
Nonlinear Dependence ◽  
System Response ◽  
Hemodynamic Parameters

Purpose of the study. Investigate changes of cardiac hemodynamic parameters caused by ocular cardiac reflex triggering in healthy men’s in youthful age.Material and methods. 120 healthy male volunteers in youthful age were examined. The mean age was (19,2 ± 0,93 years). For ocular-cardiac reflex (OCR) triggering we used a patented model «Device for dosed compression effects on the eyeballs» and «The method of ocular cardiac reflex triggering». On the basis of the obtained parameters of systolic (SBP) and diastolic (DBP) blood pressure, by arithmetic operations, pulse pressure (PP) and average flow pressure (AFP) and integrative parameters of cardiohemodynamics (CHD) – systolic blood volume (SBV), minute blood flow volume (MBFV), volumetric blood flow rate (V), total peripheral resistance (TPR) were determined. Results. Three main types of cardiovascular system response on OCR triggering were identified. The first type – hypertensive (n = 30 (25%) of the total number of examined subjects) was characterized by a significant (p < 0,05) increase in heart rate, SBP, DBP, PP, AFP and other integrative parameters of CHD. The second, hypotonic type of the response (62 subjects; 51,7%) was characterized by a significant (p < 0,05) decrease in SBP, DBP, PP, AFP. Patients with third, dystonic type, of response (n = 28 (23,3%) of the total number examined subjects) showed significant bilateral changes of blood pressure parameters in a nonlinear dependence of compression power on the eyeballs. Determination CHD parameters directly after and 3 and 5 minutes after decompression of the air in the compression device we enabled to determine the subtype of the mobility of the nervous centers as a feature that complements the basic type. The subtype of normal mobility was revealed in 63,3% (n = 19) of subjects with the main hypertensive type of response, 69,3% (n = 43) of subjects with the main hypotonic and 60,7 % (n = 17) with the main dystonic type of response of the cardiovascular system. The inert subtype in the mobility of the cardiovascular system were identified in 36,7% (n = 11) individuals with hypertension is the main type of response, at 30,7% (n = 19) of individuals with primary hypotonic type of response and 39,3 % (n = 11) – distancing. The obtained typological changes in blood pressure parameters caused by OCR triggering allowed to reveal predisposition to hypertension, hypotension, dystonia and to predict the development of hypertension in patients with hypertensive type of response usin appropriate primary prevention changes in life style. The highest risk of hypertension development may be in persons with hypertensive inert type of reaction of the system of regulation of blood pressure on OCR triggering. Further studies are being conducted to confirm this assumption. Keywords: oculo-cardiac reflex, blood pressure, heart rate, young age.

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.

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