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

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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Reduced survival after isoprenaline/ dopamine in d,l-propranolol intoxicated rats

Human & Experimental Toxicology ◽

10.1177/096032719601500204 ◽

1996 ◽

Vol 15 (2) ◽

pp. 120-128 ◽

Cited By ~ 9

Author(s):

AE Toet ◽

JD te Biesebeek ◽

W. Vleeming ◽

J. Wemer ◽

J. Meulenbelt ◽

...

Keyword(s):

Survival Time ◽

Artificial Ventilation ◽

Respiratory Arrest ◽

Favourable Effect ◽

Cardiovascular Failure ◽

Arterial Blood ◽

Adrenoceptor Agonists ◽

Β Blocker ◽

Spontaneously Breathing ◽

Respiratory Variables

1 Respiratory and cardiovascular failure are principle toxic effects of β-blocker overdose. Respiratory arrest is the primary cause of death in β-blocker intoxicated rats. 2 The effect of β-adrenoceptor agonists on respiratory and cardiovascular failure in β-blocker overdose was investigated in a model of acute d,l-propranolol (30 mg kg -1 h-1) intoxication in spontaneously breathing rats. 3 Neither the aselective, hydrophilic β-agonist isoprena line (10, 25, 50 μg kg-1 min-1), nor the β 1-selective, lipophilic β-agonist flerobuterol (1,3,10 μ g kg-1 min-1) and the β2-selective, lipophilic β-agonist clenbuterol (10, 25, 50 μg kg-1 min-1) had any beneficial effect on cardiovascular and respiratory variables or survival time in d,l-propranolol intoxicated spontaneously breathing rats. 4 Isoprenaline (10 μg kg-1 min-1) had no favourable effect on haemodynamic and respiratory variables in artificially ventilated d,l -propranolol intoxicated rats either. 5 Addition of dopamine to isoprenaline resulted in a significant reduction of survival time, primarily caused by a decrease in mean arterial blood pressure, in artificially ventilated d,l-propranolol intoxicated rats. Addition of glucagon to isoprenaline did not affect survival time. 6 Artificial ventilation is the most important supportive measure in d,l-propranolol intoxication in the rat.

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

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y98-138 ◽

1998 ◽

Vol 76 (12) ◽

pp. 1103-1109 ◽

Cited By ~ 6

Author(s):

Takeshi Iwai ◽

Hiroyuki Nakamura ◽

Hisanori Takanashi ◽

Kenji Yogo ◽

Ken-Ichi Ozaki ◽

...

Keyword(s):

Mesenteric Artery ◽

Left Ventricular Pressure ◽

Left Ventricular ◽

Gastric Antrum ◽

Ventricular Pressure ◽

High Dose ◽

Aortic Blood Flow ◽

Arterial Blood

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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Physiologic determinants of left ventricular strength-interval curve of the dog

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1977.233.5.h555 ◽

1977 ◽

Vol 233 (5) ◽

pp. H555-H561 ◽

Cited By ~ 1

Author(s):

A. V. Goodyer ◽

B. Y. Wong

Keyword(s):

Venous Return ◽

Left Ventricular Pressure ◽

Left Ventricular ◽

Ventricular Pressure ◽

High Fidelity ◽

Ventricular Pacing ◽

Arterial Blood ◽

Premature Beats ◽

Straight Lines ◽

Best Fit

Strength-interval curves, relating an index of the contractile vigor of premature beats to their coupling intervals, were elicited in anesthetized, open-chest dogs prepared for atrial or ventricular pacing and the high-fidelity measurement of left ventricular pressure. During inotropic interventions, changes of the curves were evaluated in terms of the parameters (slopes and intercepts) of their straight lines of best fit. These parameters were altered by isoproterenol, propranolol, and heart rate, and were correlated closely with paired values of isovolumic Vmax (of driven beats). The strength-interval curves were reproducible and were not affected by large changes of venous return or arterial blood pressure. These results provide a basis for the use of strength-interval curves for the evaluation of ventricular contractile state, using fluid-filled catheters for the measurement of left ventricular pressure.

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Increased left ventricular pressure attenuates the baroreflex in unanesthetized dogs

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1986.251.1.r23 ◽

1986 ◽

Vol 251 (1) ◽

pp. R23-R31 ◽

Cited By ~ 2

Author(s):

M. J. Holmberg ◽

I. H. Zucker

Keyword(s):

Left Ventricle ◽

Baroreflex Sensitivity ◽

Systolic Pressure ◽

Left Ventricular Pressure ◽

Left Ventricular ◽

Ventricular Pressure ◽

Pulse Interval ◽

Adrenergic Blockade ◽

Baroreflex Control ◽

Arterial Blood

To determine whether stimulation of left ventricular mechanoreceptors alters the baroreflex control of heart rate (HR), dogs were instrumented with a vascular occluder around the ascending aorta and appropriate instrumentation for the recording of left ventricular pressure (LVP), aortic pressure, left atrial pressure, HR, and left ventricular dP/dt. Baroreflex sensitivity (pulse interval or HR vs. aortic systolic pressure linear-regression slopes to infusions of phenylephrine or nitroprusside) was determined in the conscious state a minimum of 7 days postoperatively. After control responses were determined with both phenylephrine and nitroprusside, the experiment was repeated during inflation of the ascending aortic occluder so as to significantly raise left ventricle systolic pressure from 127.9 +/- 8.4 to 178.5 +/- 11.3 mmHg (P less than 0.01) and left ventricle end-diastolic pressure from 3.5 +/- 0.7 to 8.9 +/- 1.0 mmHg (P less than 0.01). There were no changes in mean arterial blood pressure, pulse pressure, or HR during elevation of LVP. The baroreflex sensitivity was reduced only during the infusion of nitroprusside from a control of 11.03 +/- 1.9 to 4.80 +/- 1.2 ms/mmHg (P less than 0.01) for the pulse interval relationship and from -2.51 +/- 0.53 to -1.14 +/- 0.32 beats . min-1 . mmHg-1 (P less than 0.05) for the HR relationship. Cholinergic blockade with atropine abolished the depression in the baroreflex sensitivity during nitroprusside infusion when LVP was increased. beta 1-Adrenergic blockade with metoprolol did not significantly reduce the baroreflex sensitivity during increased LVP.(ABSTRACT TRUNCATED AT 250 WORDS)

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