Hypotensive mechanism of [Leu13]motilin in dogs in vivo and in vitro

The effects of [Leu13]motilin were examined in vivo after its intravenous administration into anesthetized dogs and in vitro with isolated preparations of canine mesenteric artery. [Leu13]Motilin (0.1-10 nmol·kg-1, i.v.) induced both strong and clustered phasic contractions in the gastric antrum and duodenum. At doses of over 1 nmol·kg-1, [Leu13]motilin also produced transient decreases in arterial blood pressure, left ventricular pressure, maximum rate of rise of left ventricular pressure, and total peripheral resistance, and an increase in aortic blood flow and heart rate. A selective motilin antagonist, GM-109 (Phe-cyclo[Lys-Tyr(3-tBu)-betaAla]betatrifluoroacetate), completely abolished the gastric antrum and duodenal motor responses induced by [Leu13]motilin. In contrast, hypotension induced by [Leu13]motilin (1 nmol·kg-1) was unchanged in the presence of GM-109. In isolated mesenteric artery preparations precontracted with U-46619 (10-7 M), [Leu13]motilin (10-8-10-5 M) induced an endothelium-dependent relaxation, and this was inhibited by a pretreatment with Nomega-nitro-L-arginine, a competitive inhibitor of NO synthase (10-4 M). A high dose (10-4 M) of GM-109 slightly decreased [Leu13]motilin-induced relaxation, and shifted the concentration-response curve of [Leu13]motilin to the right. However, the pA2 value (4.09) of GM-109 for [Leu13]motilin in the present study was conspicuously lower than that previously demonstrated in the rabbit duodenum (7.37). These results suggest that [Leu13]motilin induces hypotension via the endothelial NO-dependent relaxation mechanism and not through the receptor type that causes upper gastrointestinal contractions.Key words: motilin, gastrointestinal motility, hypotension, hemodynamics, anesthetized dog, mesenteric artery, endothelium, nitric oxide.

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Malignant Hyperthermia Phenotype

Anesthesiology ◽

10.1097/00000542-200006000-00038 ◽

2000 ◽

Vol 92 (6) ◽

pp. 1777-1788 ◽

Cited By ~ 8

Author(s):

Daniel C. Sigg ◽

Paul A. Iaizzo

Keyword(s):

Malignant Hyperthermia ◽

Right Ventricular ◽

Left Ventricular Pressure ◽

Left Ventricular ◽

Ventricular Pressure ◽

High Dose ◽

Central Venous ◽

Induced Hypotension ◽

Arterial Blood ◽

Left And Right

Background Succinylcholine causes immediate and severe arterial hypotension in swine with the malignant hyperthermia phenotype. The underlying mechanisms are unknown. Methods Malignant hyperthermia-susceptible (MHS; n = 10) and normal swine (n = 5) were anesthetized with thiopental. The following were monitored: electrocardiogram; arterial blood pressure; pulmonary artery, central venous, and left and right ventricular pressure; cardiac output; end-tidal carbon dioxide; core temperature; peripheral-blood flows; and arterial blood gases. After a control period, 2 mg/kg succinylcholine was given intravenously. Three MHS animals received 1 mg/kg vecuronium and two MHS animals received 2.5 mg/kg dantrolene intravenously. The effects of succinylcholine on left and right ventricular pressure and contractility were analyzed in isolated hearts. The effects of 0.06 mm succinylcholine on isometric tension development were recorded in isolated femoral artery rings. Results Succinylcholine caused an early, severe decrease in blood pressure, cardiac output, left ventricular pressure, and left ventricular contractility in MHS swine but not in normal swine; no significant differences were found in heart rate, right ventricular parameters, systemic vascular resistance, and preload (pulmonary diastolic pressure, central venous pressure). The succinylcholine-induced hypotension and associated effects were not prevented by dantrolene. However, pretreatment with high-dose vecuronium prevented not only the cardiovascular depression, but also MH. In addition, no phenotypic differences of succinylcholine on contractility or left ventricular pressure were observed in the isolated working hearts. Similary, succinylcholine did not cause a significantly different relaxation in rings in either phenotype. Conclusion Succinylcholine-induced hypotension occurred before muscle hypermetabolism in MHS swine. Succinylcholine had no differential physiologic effects on either the isolated heart or on isolated arteries. This hypotension could not be prevented by dantrolene but was prevented by pretreatment with high-dose vecuronium. Thus, an indirect mechanism such as the release of a cardiac depressant from skeletal muscle may have caused this hypotensive response.

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In vivo safety and accuracy of a clinically applicable telemetered left ventricular pressure module: intermediate-term results

Journal of Cardiac Failure ◽

10.1016/j.cardfail.2004.06.179 ◽

2004 ◽

Vol 10 (4) ◽

pp. S67 ◽

Cited By ~ 2

Author(s):

Patrick I. McConnell ◽

Daise de Cunha ◽

Tanya Shipkowitz ◽

Justin Van Hee ◽

Phillip H. Long ◽

...

Keyword(s):

Left Ventricular Pressure ◽

Left Ventricular ◽

Ventricular Pressure

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Possible mechanism of the cardio-renal protective effects of AVE-0991, a non-peptide Mas-receptor agonist, in diabetic rats

Journal of the Renin-Angiotensin-Aldosterone System ◽

10.1177/1470320311435534 ◽

2012 ◽

Vol 13 (3) ◽

pp. 334-340 ◽

Cited By ~ 14

Author(s):

Kulwinder Singh ◽

Kuldeepak Sharma ◽

Manjeet Singh ◽

PL Sharma

Keyword(s):

Blood Pressure ◽

Receptor Agonist ◽

Diastolic Pressure ◽

Left Ventricular Pressure ◽

Diabetic Rats ◽

Left Ventricular ◽

Ventricular Pressure ◽

Protective Effects ◽

Mas Receptor ◽

Arterial Blood

Hypothesis: This study was designed to investigate the cardio-renal protective effect of AVE-0991, a non-peptide Mas-receptor agonist, and A-779, a Mas-receptor antagonist, in diabetic rats. Materials and methods: Wistar rats treated with streptozotocin (50 mg/kg, i.p., once), developed diabetes mellitus after 1 week. After 8 weeks, myocardial functions were assessed by measuring left ventricular developed pressure (LVDP), rate of left ventricular pressure development (d p/d tmax), rate of left ventricular pressure decay (d p/d tmin) and left ventricular end diastolic pressure (LVEDP) on an isolated Langendorff’s heart preparation. Further, mean arterial blood pressure (MABP) was measured by using the tail-cuff method. Assessment of renal functions and lipid profile was carried out using a spectrophotometer. Results: The administration of streptozotocin to rats produced persistent hyperglycaemia, dyslipidaemia and hypertension which consequently produced cardiac and renal dysfunction in 8 weeks. AVE0991 treatment produced cardio-renal protective effects, as evidenced by a significant increase in LVDP, d p/d tmax, d p/d tmin and a significant decrease in LVEDP, BUN, and protein urea. Further, AVE-0991 treatment for the first time has been shown to reduce dyslipidaemia and produced antihyperglycaemic activity in streptozotocin-treated rats. However, MABP and creatinine clearance remained unaffected with AVE-0991 treatment. Conclusions: AVE-0991 produced cardio-renal protection possibly by improving glucose and lipid metabolism in diabetic rats, independent of its blood pressure lowering action.

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Stability of cardiodynamic and some blood parameters in the baboon following intravenous anaesthesia with ketamine and diazepam

Journal of the South African Veterinary Association ◽

10.4102/jsava.v69i1.803 ◽

1998 ◽

Vol 69 (1) ◽

Cited By ~ 7

Author(s):

W.J. Du Plooy ◽

P.J. Schutte ◽

J. Still ◽

L. Hay ◽

C.P. Kahler

Keyword(s):

Blood Pressure ◽

Continuous Infusion ◽

Total Duration ◽

Systolic Pressure ◽

Left Ventricular Pressure ◽

Blood Parameters ◽

Left Ventricular ◽

Ventricular Pressure ◽

Pressure Curve ◽

Arterial Blood

The stability of cardiodynamic and some blood parameters during a slow, continuous infusion of a combination of ketamine and diazepam is reported. Contractility (dP/dt), myocardial relaxation (Tln), left ventricular end-diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), arterial blood pressure and certain blood parameters were assessed in 3 male and 3 female juvenile baboons (Papio ursinus). Anaesthesia was induced with 15 mg/kg ketamine IM and maintained with a continuous IV infusion (40-60 mℓ/h) of ketamine and diazepam. The mixture consisted of 2 mℓ ketamine (100 mg/mℓ), 2 mℓ diazepam (5 mg/mℓ) and 50 mℓ saline. A period of 75 + 10 min was allowed for preparation of the animals, after which lead II of the ECG, femoral artery blood pressure and left ventricular pressure were recorded at 15-min intervals for a period of 2 h: the total duration of anaesthesia was 195 min. Arterial blood samples were analysed at 30-min intervals for blood gases, electrolytes, glucose and insulin. Left ventricular parameters were derived from the left ventricular pressure curve. Tln, LVSP and LVEDP showed small fluctuations. Contractility decreased (p < 0.037) at the 195-min interval. No arrhythmias or ECG changes were seen, while blood pressure decreased gradually. Serum calcium concentration decreased and blood glucose levels increased gradually over time. Anaesthesia and analgesia were sufficient and no other drugs were necessary. The animals appeared sedated and dazed 60-80 min after the procedure. A continuous infusion of a combination of ketamine and diazepam for a duration of 150 min can provide stable anaesthesia for cardiodynamic measurements.

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In vivo murine left ventricular pressure-volume relations by miniaturized conductance micromanometry

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1998.274.4.h1416 ◽

1998 ◽

Vol 274 (4) ◽

pp. H1416-H1422 ◽

Cited By ~ 102

Author(s):

Dimitrios Georgakopoulos ◽

Wayne A. Mitzner ◽

Chen-Huan Chen ◽

Barry J. Byrne ◽

Huntly D. Millar ◽

...

Keyword(s):

Left Ventricular Pressure ◽

Left Ventricular ◽

Genetically Engineered ◽

Ventricular Pressure ◽

Stroke Work ◽

Time Varying ◽

End Diastolic Volume ◽

Novel Approach ◽

Preload Reduction

The mouse is the species of choice for creating genetically engineered models of human disease. To study detailed systolic and diastolic left ventricular (LV) chamber mechanics in mice in vivo, we developed a miniaturized conductance-manometer system. α-Chloralose-urethan-anesthetized animals were instrumented with a two-electrode pressure-volume catheter advanced via the LV apex to the aortic root. Custom electronics provided time-varying conductances related to cavity volume. Baseline hemodynamics were similar to values in conscious animals: 634 ± 14 beats/min, 112 ± 4 mmHg, 5.3 ± 0.8 mmHg, and 11,777 ± 732 mmHg/s for heart rate, end-systolic and end-diastolic pressures, and maximum first derivative of ventricular pressure with respect to time (dP/d t max), respectively. Catheter stroke volume during preload reduction by inferior vena caval occlusion correlated with that by ultrasound aortic flow probe ( r 2 = 0.98). This maneuver yielded end-systolic elastances of 79 ± 21 mmHg/μl, preload-recruitable stroke work of 82 ± 5.6 mmHg, and slope of dP/d t max-end-diastolic volume relation of 699 ± 100 mmHg ⋅ s−1 ⋅ μl−1, and these relations varied predictably with acute inotropic interventions. The control normalized time-varying elastance curve was similar to human data, further supporting comparable chamber mechanics between species. This novel approach should greatly help assess cardiovascular function in the blood-perfused murine heart.

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Inconstancy Of PGI2 Administration In Preventing Attacks Of Prinzmetal Angina

10.1055/s-0038-1652795 ◽

1981 ◽

Author(s):

S Chierchia ◽

R De Caterina ◽

F Crea ◽

W Bernini ◽

A Distante ◽

...

Keyword(s):

Healthy Volunteers ◽

Pulmonary Arterial Pressure ◽

Left Ventricular Pressure ◽

Left Ventricular ◽

Right Atrial ◽

Arterial Blood ◽

Pulmonary Arterial ◽

Local Defects ◽

Ecg Leads

It has been proposed that vasospastic angina, eventually due to local defects of PGI2 production, might benefit from PGI2 administration. We therefore investigated the effects of PGI2 in healthy volunteers and, then, in patients with frequent ischemic episodes (IE) of Prinzmetal angina, to detennine 1. hemodynamic, antiplatelet and possible side effects of the drug and 2. its possible therapeutic usefulness in the management of IE. In 6 healthy volunteers PGI2 was infused i.v. at doses of 2.5,5,10 and 20 ng/kg/min during consecutive periods of 30 min each. Heart rate (HR) and right atrial pressure were monitored continuously; cardiac output (thermodilution in 2 subjects, indirectly by a Doppler technique in all), arterial blood pressure (BP) and in-vitro platelet aggre- gability (PA) by ADP (Born), intermittently. In 2 subjects we also measured pulmonary arterial pressure and, in one, left ventricular pressure, during the infusion and in control conditions. PGI2 was then infused in 6 pts with frequent IE at maximal well tolerable rate (6-26 ng/kg/min) for periods of 3 hours alternated with equal periods of placebo (P), continuosly recording 2 ECG leads to detect ST-T changes, and sampling blood for PA as before. In all healthy volunteers PGI2, at the highest rates of infusion, decreased significantly (p < .001) both systolic BP (-10 ± 3%, mean ± SD) and diastolic BP (-19 ± 5%) increasing HR (+ 21 ± 5%); no significant changes were observed in the other hemodynamic parameters. The maximal decrease in PA was 58 ± 30%(p <. 001). Skin flushing, restlessness and headache, sometimes observed at the highest doses, rapidly disappeared decreasing the infusion rate. In the 6 pts the same trend in BP, HR and PA was evident. 106 IE were observed. PGI2 did not affect severity, duration and number of IE (44 during P, 62 during PGI2 infusion). One of the pts, however,not clinically different from the others, showed a reduction at 10 ng/ kg/min (6 IE during P, 2 during PGI2) and a complete abolition in the 3 following periods at 20 ng/kg/min (4,3,5 IE during P vs. none duringPGI2). We conclude that 1. PGI2 can be safely administered to humans and 2. it may prevent IE is some vasospastic pts, but not in others. Different pathogenetic mechanisms are perhaps involved in apparently similar Prinzmetal anginas.

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Inhibition of vascular peroxidase alleviates cardiac dysfunction and apoptosis induced by ischemia–reperfusion

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y2012-066 ◽

2012 ◽

Vol 90 (7) ◽

pp. 851-862 ◽

Cited By ~ 4

Author(s):

Ting-Ting Li ◽

Yi-Shuai Zhang ◽

Lan He ◽

Bin Liu ◽

Rui-Zheng Shi ◽

...

Keyword(s):

Cardiac Function ◽

Cardiac Dysfunction ◽

Isolated Heart ◽

Ischemia Reperfusion ◽

Left Ventricular Pressure ◽

Left Ventricular ◽

Ventricular Pressure ◽

Clinical Value ◽

Pharmacologic Inhibition

Myeloperoxidase (MPO) is involved in myocardial ischemia–reperfusion (IR) injury and vascular peroxidase (VPO) is a newly identified isoform of MPO. This study was conducted to explore whether VPO is involved in IR-induced cardiac dysfunction and apoptosis. In a rat Langendorff model of myocardial IR, the cardiac function parameters (left ventricular pressure and the maximum derivatives of left ventricular pressure and coronary flow), creatine kinase (CK) activity, apoptosis, VPO1 activity were measured. In a cell (rat-heart-derived H9c2 cells) model of hypoxia–reoxygenation (HR), apoptosis, VPO activity, and VPO1 mRNA expression were examined. In isolated heart, IR caused a marked decrease in cardiac function and a significant increase in apoptosis, CK, and VPO activity. These effects were attenuated by pharmacologic inhibition of VPO. In vitro, pharmacologic inhibition of VPO activity or silencing of VPO1 expression significantly suppressed HR-induced cellular apoptosis. Our results suggest that increased VPO activity contributes to IR-induced cardiac dysfunction and inhibition of VPO activity may have the potential clinical value in protecting the myocardium against IR injury.

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Experimental study of the detrimental effect of dopamine/glucagon combination in d,l- propranolol intoxication

Human & Experimental Toxicology ◽

10.1177/096032719601500509 ◽

1996 ◽

Vol 15 (5) ◽

pp. 411-421 ◽

Cited By ~ 10

Author(s):

AE Toet ◽

J. Wemer ◽

W. Vleeming ◽

JD te Biesebeek ◽

J. Meulenbelt ◽

...

Keyword(s):

Survival Time ◽

Detrimental Effect ◽

Left Ventricular Pressure ◽

Respiratory Arrest ◽

Left Ventricular ◽

Ventricular Pressure ◽

Cardiovascular Failure ◽

Arterial Blood ◽

Β Blocker ◽

Spontaneously Breathing

1 Respiratory and cardiovascular failure are the princi ple toxic effects of β-blocker overdose. Respiratory arrest is the primary cause of death in β-blocker intoxicated rats. 2 The effect of glucagon, dopamine and the combination of glucagon/dopamine on respiratory and cardiovas cular function and survival time in β-blocker overdose was investigated in a model of acute d, l-propranolol (resp. 30 and 15 mg kg-1 h-1 in rat and rabbit) intoxication in spontaneously breathing rats and artifically ventilated rats and rabbits. 3 Glucagon (initial dose of 100 μg kg-1 (bolus), followed by 1 μg kg -1 min-1), dopamine (25 μg kg-1 min-1 ) or the combination of glucagon/dopamine did not im prove survival time (ST) in d, l-propranolol intoxicated spontaneously breathing rats and artificially venti lated rats and rabbits, although some haemodynamic variables i.e. heart rate (HR), mean arterial blood pressure (MAP), left ventricular pressure (LVPmax) and the differentiated left ventricular pressure (LVdp/ dtmax) temporarily improved. 4 Survival time was considerably reduced in d,l- propranolol intoxicated spontaneously breathing and artifically ventilated rats treated with a combination of glucagon /dopamine, which induced a decrease in PaO2 and pH and an increase in PaCO2 partly due to ventilation/perfusion mismatch. 5 The combination of glucagon/dopamine should be used carefully in the treatment of β-blocker overdose in man.

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