Enkephalin lowers vascular resistance in dog hindlimb via a peripheral nonlimb site

1991 ◽  
Vol 260 (2) ◽  
pp. H386-H392 ◽  
Author(s):  
J. L. Caffrey ◽  
H. Gu ◽  
B. A. Barron ◽  
J. F. Gaugl
Keyword(s):  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Vascular Resistance ◽  
Opiate Receptors ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Sharp Decline ◽  
Descending Aorta ◽  
A Site

The intravenous administration of methionine enkephalin in anesthetized dogs produces an abrupt decline in mean arterial pressure, left ventricular pressure, and the maximal rate of left ventricular pressure development. All of these changes are prevented by receptor blockade with the opiate antagonist, naloxone. To evaluate peripheral vascular contributions to these responses, experiments were conducted in a constant pressure-isolated perfused hindlimb. In this model, the sharp decline in mean arterial pressure associated with enkephalin injection (5 micrograms/kg iv) coincided with an equally sharp decline in vascular resistance (rise in blood flow) in the hindlimb. Both were blocked by naloxone pretreatment (1 mg/kg). When equal doses of enkephalin were administered directly into the femoral inflow (external iliac artery), both arterial pressure and hindlimb flow responses were all but eliminated. This observation ruled out significant direct vascular interactions in the response and indicated a site of action outside the hindlimb. Additional catheters were placed in the bracheocephalic artery and descending aorta to permit the comparison of arterial injections conducted, respectively, into the cerebral or abdominal circulations. Injections introduced into the descending aorta consistently produced the greatest response, followed by injections (in descending order of effectiveness) into the jugular, the brachiocephalic, and external iliac. The response in the hindlimb vasculature was initiated at a site somewhere between the diaphragm and terminal aorta. The vascular response to enkephalin was subsequently eliminated by blocking ganglionic transmission with the nicotinic antagonist mecamylamine. These observations suggest that the opioids probably interrupt local vasomotor traffic via opiate receptors in regional sympathetic ganglia or in the spinal cord.

Clonidine Modulation of Hemodynamic and Catecholamine Responses Associated with Hypoxia or Hypercapnia in Dogs

1996 ◽  
Vol 84 (3) ◽  
pp. 672-685 ◽  
Author(s):  
Toshiaki Nishikawa ◽  
Hiroshi Naito
Keyword(s):  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Bolus Injection ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Control Group ◽  
Plasma Norepinephrine ◽  
Plasma Catecholamine ◽  
Anesthetized Dogs ◽  
Plasma Catecholamine Concentrations

Background Hypoxia or hypercapnia elicits cardiovascular responses associated with increased plasma catecholamine concentrations, whereas clonidine, an alpha(2)- adrenergic agonist, decreases plasma catecholamine concentrations. The authors examined whether systemic clonidine administration would alter the hemodynamic and catecholamine responses to hypoxia or hypercapnia in anesthetized dogs. Methods Pentobarbital-anesthetized dogs whose lungs were mechanically ventilated were instrumented for measurement of mean arterial pressure, heart rate, mean pulmonary artery pressure, right atrial pressure, cardiac output, left ventricular end-diastolic pressure, and the peak of first derivative of left ventricular pressure. The dogs were randomly assigned to receive an intravenous bolus injection of 10 microg/kg clonidine followed by continous infusion at a rate of 1 microg. kg (-1). min (-1)(clonidine-10 group, n = 7), an intravenous bolus injection of microg/kg clonidine followed by continuous infusion at a rate of 0.5 micro.kg(-).min(-1)(clonidine-5 group, n = 7), or an equivalent volume of 0.9% saline (control group = 7). Each dog underwent random challenges of hypoxia (PaO2 30, 40, and 50 mmHg) and hypercapnia (PaCO2 60, 80, and 120 mmHg). Measurements of hemodynamic and plasma norepinephrine and epinephrine concentrations were made after the loading dose of clonidine and the first and the second exposure of hypoxia or hypercapnia. Results Although significant increases from prehypoxic values in mean arterial pressure (39 +/- 10 mmHg) and plasma norepinephrine (291 +/- 66 pg/ml) and epinephrine (45 +/- 22 pg/ml) concentrations were noted during hypoxia of PaO2 30, mmHg in the control group (P<0.05), such changes were absent in both clonidine groups. During hypercapnia of PaCo2 120 mmHg, changes from prehypercapnic values in mean arterial pressure, mean pulmonary artery pressure, the peak of first derivative of left ventricular pressure, and plasma norepinephrine and epinephrine concentrations in the clonidine-10 and clonidine-5 groups were significantly less than those in the control group. Plasma clonidine concentrations in the clonidine-10 and clonidine-5 groups were 16.8 +/- 1.7 and 8.9 =/- 1.0, 42.5 =/- 2.9 and 21.5 +/- 1.5, and 51.1 +/- 3.2 and 26.7 +/- 1.0 ng/ml after the loading dose of clonidine and the first and the second exposure of hypoxia or hypercapnia, respectively. Conclusions Systemic clonidine administration alter the hemodynamic changes associated with hypoxia or hypercapnia and suppresses plasma catecholamine responses in anesthetized dogs when a larger dose of clonidine is administered. catecholamines: epinephrine; norepinephrine.)

Bradykinin contributes to the exercise pressor reflex: mechanism of action

1993 ◽  
Vol 75 (5) ◽  
pp. 2061-2068 ◽  
Author(s):  
H. L. Pan ◽  
C. L. Stebbins ◽  
J. C. Longhurst
Keyword(s):  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Left Ventricular Pressure ◽  
Muscle Afferents ◽  
Left Ventricular ◽  
Receptor Blockade ◽  
Exercise Pressor Reflex ◽  
Pressor Reflex ◽  
Over Time

This study determined the receptors responsible for mediating bradykinin's effect on skeletal muscle afferents that cause the pressor reflex in anesthetized cats. In eight cats, 1 microgram of bradykinin was injected intra-arterially into the gracilis muscle before and after intravenous injection of a kinin B2-receptor antagonist (NPC 17731, 20 micrograms/kg). Initial injection of bradykinin reflexly increased mean arterial pressure by 23 +/- 7 mmHg, maximal change in pressure over time by 439 +/- 272 mmHg/s, and heart rate by 11 +/- 4 beats/min. The hemodynamic response to bradykinin was abolished by kinin B2-receptor blockade. Similar injection of the kinin B1-receptor agonist des-Arg9-bradykinin caused no cardiovascular responses (n = 6). In eight different animals, mean arterial pressure, maximal change in left ventricular pressure over time, and heart rate responses to 30 s of electrically stimulated hindlimb contraction were attenuated by 50 +/- 6, 55 +/- 7, and 41 +/- 8%, respectively, after kinin B2-receptor blockade. In eight other animals, mean arterial pressure, maximal change in left ventricular pressure over time, and heart rate responses were reduced by 58 +/- 8, 66 +/- 6, and 40 +/- 12%, respectively, after inhibition of prostaglandin synthesis with indomethacin (2.5–3 mg/kg iv) and were then abolished by subsequent B2-receptor blockade. These data suggest that bradykinin contributes to the exercise pressor reflex through its action on kinin B2 receptors located on the nerve endings of the muscle afferents.(ABSTRACT TRUNCATED AT 250 WORDS)

Stopped-flow epicardial lymph pressure is affected by left ventricular pressure in anesthetized goats

1993 ◽  
Vol 264 (5) ◽  
pp. H1624-H1628 ◽  
Author(s):  
Y. Han ◽  
I. Vergroesen ◽  
J. A. Spaan
Keyword(s):  
Control Level ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Beating Heart ◽  
Ventricular Pressure ◽  
Stopped Flow ◽  
Pressure Waveform ◽  
Descending Aorta ◽  
Aortic Clamping ◽  
The Relationship

We measured epicardial lymph pressure (Plymph) in the anesthetized goat (n = 5 goats). To study the transmission of systolic left ventricular pressure (PLV) to Plymph, the effect of an increase in PLV caused by clamping of the descending aorta on Plymph was evaluated. Peak systolic PLV was 131 +/- 4 (+/- SE) mmHg during control (43 beats) and 188 +/- 4 mmHg when elevated due to aortic clamping (157 beats). Peak systolic Plymph was 24.8 +/- 1.0 and 34.8 +/- 1.1 mmHg during control and elevated PLV, respectively. In the first beat of elevated PLV, peak Plymph did not change, although the pressure waveform did. In the subsequent beats, Plymph increased proportionally with increased PLV. When PLV was decreased back to control, Plymph also decreased but did not reach control level until after three beats. The relationship between normalized Plymph and normalized PLV is given by Plymph = 0.70 x PLV + 0.09. The results show that PLV does affect Plymph in a normal beating heart.

Hemodynamic effects of periodic obstructive apneas in sedated pigs with congestive heart failure

2000 ◽  
Vol 88 (3) ◽  
pp. 1051-1060 ◽  
Author(s):  
Ling Chen ◽  
Quihu Shi ◽  
Steven M. Scharf
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Systemic Vascular Resistance ◽  
Vascular Resistance ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Air Breathing ◽  
Obstructive Sleep

Because of similar physiological changes such as increased left ventricular (LV) afterload and sympathetic tone, an exaggerated depression in cardiac output (CO) could be expected in patients with coexisting obstructive sleep apnea and congestive heart failure (CHF). To determine cardiovascular effects and mechanisms of periodic obstructive apnea in the presence of CHF, 11 sedated and chronically instrumented pigs with CHF (rapid pacing) were tested with upper airway occlusion under room air breathing (RA), O2 breathing (O2), and room air breathing after hexamethonium (Hex). All conditions led to large negative swings in intrathoracic pressure (−30 to −39 Torr) and hypercapnia ([Formula: see text] ∼60 Torr), and RA and Hex also caused hypoxia (to ∼42 Torr). Relative to baseline, RA increased mean arterial pressure (from 97.5 ± 5.0 to 107.3 ± 5.7 Torr, P < 0.01), systemic vascular resistance, LV end-diastolic pressure, and LV end-systolic length while it decreased CO (from 2.17 ± 0.27 to 1.52 ± 0.31 l/min, P < 0.01), stroke volume (SV; from 23.5 ± 2.4 to 16.0 ± 4.0 ml, P < 0.01), and LV end-diastolic length (LVEDL). O2 and Hex decreased mean arterial pressure [from 102.3 ± 4.1 to 16.0 ± 4.0 Torr ( P < 0.01) with O2 and from 86.0 ± 8.5 to 78.1 ± 8.7 Torr ( P < 0.05) with Hex] and blunted the reduction in CO [from 2.09 ± 0.15 to 1.78 ± 0.18 l/ml for O2 and from 2.91 ± 0.43 to 2.50 ± 0.35 l/ml for Hex (both P< 0.05)] and SV. However, the reduction in LVEDL and LV end-diastolic pressure was the same as with RA. There was no change in systemic vascular resistance and LVEDL during O2 and Hex relative to baseline. In the CHF pigs during apnea, there was an exaggerated reduction in CO and SV relative to our previously published data from normal sedated pigs under similar conditions. The primary difference between CHF (present study) and the normal animals is that, in addition to increased LV afterload, there was a decrease in LV preload in CHF contributing to SV depression not seen in normal animals. The decrease in LV preload during apneas in CHF may be related to effects of ventricular interdependence.

scholarly journals Pharmacodynamics and Pharmacokinetics of Injectable Pimobendan and Its Metabolite, O-Desmethyl-Pimobendan, in Healthy Dogs

2021 ◽  
Vol 8 ◽  
Author(s):  
Poonavit Pichayapaiboon ◽  
Lalida Tantisuwat ◽  
Pakit Boonpala ◽  
Nakkawee Saengklub ◽  
Tussapon Boonyarattanasoonthorn ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Vascular Resistance ◽  
Maximum Rate ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Cardiac Contraction ◽  
Ventricular Pressure ◽  
Right Atrial ◽  
Pulmonary Capillary ◽  
Pulmonary Arterial

Objectives: This study was designed to thoroughly evaluate the effects of bolus pimobendan at a dose of 0.15 mg/kg on cardiac functions, hemodynamics, and electrocardiographic parameters together with the pharmacokinetic profile of pimobendan and its active metabolite, o-desmethyl-pimobendan (ODMP), in anesthetized dogs.Methods: Nine beagle dogs were anesthetized and instrumented to obtain left ventricular pressures, aortic pressures, cardiac outputs, right atrial pressures, pulmonary arterial pressures, pulmonary capillary wedge pressures, electrocardiograms. After baseline data were collected, dogs were given a single bolus of pimobendan, and the pharmacodynamic parameters were obtained at 10, 20, 30, 60, and 120 min. Meanwhile, the venous blood was collected at baseline and 2, 5, 10, 20, 30, 60, 120, 180, 360, and 1,440 min after administration for the determination of pharmacokinetic parameters.Results: Compared with baseline measurements, the left ventricular inotropic indices significantly increased in response to intravenous pimobendan, as inferred from the maximum rate of rise in the left ventricular pressure and the contractility index. Conversely, the left ventricular lusitropic parameters significantly decreased, as inferred from the maximum rate of fall in the left ventricular pressure and the left ventricular relaxation time constant. Significant increases were also noted in cardiac output and systolic blood pressure. Decreases were observed in the systemic vascular resistance, pulmonary vascular resistance, left ventricular end-diastolic pressure, pulmonary capillary wedge pressure, right atrial pressure, and pulmonary arterial pressure. The heart rate increased, but the PQ interval decreased. There was no arrhythmia during the observed period (2 h). The mean maximum plasma concentration (in μg/L) for ODMP was 30.0 ± 8.8. Pimobendan exerted large volume of distribution ~9 L/kg.Conclusions: Intravenous pimobendan at the recommended dose for dogs increased cardiac contraction and cardiac output, accelerated cardiac relaxation but decreased both vascular resistances. These mechanisms support the use of injectable pimobendan in acute heart failure.

Perfusion-induced changes in cardiac O2 consumption and contractility are based on different mechanisms

1996 ◽  
Vol 271 (3) ◽  
pp. H984-H989 ◽  
Author(s):  
M. A. Dijkman ◽  
J. W. Heslinga ◽  
P. Sipkema ◽  
N. Westerhof
Keyword(s):  
Shear Stress ◽  
Arterial Pressure ◽  
Coronary Flow ◽  
Isolated Heart ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Cardiac Perfusion ◽  
Induced Changes ◽  
Pressure Measure

Increased cardiac perfusion results in increased oxygen consumption (VO2) and increased contractility (Gregg phenomenon) in the isolated heart. We investigated whether these two aspects of the Gregg phenomenon are related to coronary flow or arterial pressure. Coronary flow and, thus, arterial pressure were changed in the reference state and during vasoconstriction (3 nM vasopressin) in the Langendorff-perfused rat heart contracting isovolumically (ventricular balloon) at 27 degrees C (n = 5). All hearts showed an increase in developed isovolumic left ventricular pressure (measure of contractility) and in VO2 with increased perfusion. Developed left ventricular pressure depended primarily on arterial pressure, so its relationship with coronary flow was shifted by vasoconstriction. Conversely, VO2 primarily depended on coronary flow, so its relationship with arterial pressure was shifted with vasoconstriction. By use of vasoconstriction (decreased vascular radii), the effects of arterial pressure and wall shear stress (proportional to arterial pressure x radius) should be separable, but the results did not reach significance. Thus contractility is related to arterial pressure or shear stress, whereas VO2 is related to coronary flow. We conclude that the two aspects of the Gregg phenomenon are based on different mechanisms.

β2-Microglobulin knockout mice treated with anti-asialoGM1 exhibit improved hemodynamics and cardiac contractile function during acute intra-abdominal sepsis

2004 ◽  
Vol 286 (3) ◽  
pp. R569-R575 ◽  
Author(s):  
Weike Tao ◽  
Edward R. Sherwood
Keyword(s):  
Arterial Pressure ◽  
Systemic Vascular Resistance ◽  
Vascular Resistance ◽  
Knockout Mice ◽  
Contractile Function ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Wild Type ◽  
Cardiac Contractile Function ◽  
Cardiac Contractile

We previously showed that β2-microglobulin knockout mice treated with anti-asialoGM1 (β2M/αAsGM1 mice) exhibit less hypothermia, reduced production of proinflammatory cytokines, less metabolic acidosis, and improved survival after cecal ligation and puncture (CLP) compared with wild-type mice. The present study was designed to assess hemodynamics and left ventricular contractility at 18 h after CLP. Arterial pressure was measured by carotid artery cannulation, and left ventricular pressure-volume loops were obtained by insertion of a 1.4-F conductance catheter into the left ventricle. Heart rate, stroke volume, and cardiac output were not significantly different between wild-type and β2M/αAsGM1 mice after CLP. However, β2M/αAsGM1 mice exhibited improved mean arterial pressure and systemic vascular resistance compared with wild-type mice. Myocardial function was also better preserved in β2M/αAsGM1 mice as indicated by improved left ventricular pressure development over time, time-varying maximum elastance, endsystolic pressure-volume relationship, and preload recruitable stroke work. Overall, this study shows that cardiovascular collapse characterized by hypotension, myocardial depression, and low systemic vascular resistance occurs after CLP in wild-type mice. However, β2M/αAsGM1 mice exhibit improved hemodynamics and cardiac contractile function after CLP that may account, in part, for our previously observed survival benefit.

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