The effects of alinidine, an N-allyl derivative of clonidine, on regional myocardial perfusion and performance in the pig with or without atrial pacing

Verdouw, Pieter D.; Saxena, Pramod R.; Schamhardt, H. C.; Hoek, Teunis M. Van Der; Rutteman, A. M.

doi:10.1016/0014-2999(80)90228-9

Cited by 21 publications

(13 citation statements)

References 12 publications

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“…More than 20 years ago, Kaihara et al (1968) showed that anaesthesia may open AVA, but relatively little attention has been paid to the effects of pharmacological agents on the fractionation of cardiac output into arteriovenous anastomotic and capillary blood flow (Verdouw et al, 1980;Hof & Hof, 1989). The latter group studied the effect of several antihypertensive drugs on nutritional and non-nutritional blood flow and concluded that isradipine, a related compound to elgodipine, which decreased mean arterial blood pressure from 75 to 50 mmHg, also decreased AVA blood flow, but slightly increased the resistance of the AVA, probably due to sympathetic reflex activation (Hof & Hof, 1989).…”

Section: Arteriovenous Anastomotic Bloodflowmentioning

confidence: 99%

“…As a calcium antagonist may have differential effects on skeletal muscles of different regions (Duncker et al, 1986a), we also estimated elgodipine-induced changes in blood flow in six different muscle groups. Since it has been well established that, in anaesthetized animals, a large fraction of the cardiac output is shunted through arteriovenous anastomoses (AVA: Kaihara et al, 1968;Verdouw et al, 1980;Saxena & Verdouw, 1985a), which are abundantly present in the skin (Hales & Cliff, 1977;Saxena & Verdouw, 1985b), and that antihypertensive drugs may exert differential effects on the flow through these anastomoses (Hof & Hof, 1989), we paid special attention to the effects of elgodipine on the division of cardiac output into its nutritional and non-nutritional fractions using the radioactive microsphere technique. As the microspheres (of 15.pm diameter), which pass through the AVA, will be trapped by the lungs, this non-nutritional fraction can be determined by counting the radioactivity in the lungs (Saxena & Verdouw, 1982;Hof & Hof, 1989).…”

Section: Introductionmentioning

confidence: 99%

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The central and regional cardiovascular responses to intravenous and intracoronary administration of the phenyldihydropyridine elgodipine in anaesthetized pigs

Sassen¹,

Soei²,

Koning³

et al. 1990

British J Pharmacology

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1 The central and regional cardiovascular responses to intravenous (0.3, 1.0, 3.0 and 10.Oygkg-1 min 1) and intracoronary (0.3, 0.9, 3.0 and 4.5.pg kg 1min 1) infusions of elgodipine, a phenyldihydropyridine, and its solvent were studied in anaesthetized pigs. 2 Elgodipine (i.v.) caused dose-dependent decreases in arterial blood pressure (up to 44%) and systemic vascular resistance (up to 48%), whereas heart rate, LV dP/dt,,.., left ventricular filling pressure, cardiac output and segment length shortening did not change. The absence of a negative inotropic effect with the employed doses was confirmed by the intracoronary infusions; with the lowest dose (0.3pg kg-1 min -) both LV dP/dt,,,, and segment length shortening decreased by less than 10%. With 0.9pgkg-1min-' (intracoronary) the negative inotropic properties of the drug became apparent as LV dP/dt.. and segment length shortening decreased by 20% and 33%, respectively, whereas heart rate and left ventricular filling pressure were not affected. 3 Transmural myocardial blood flow did not change during intravenous infusion of elgodipine, as vasodilatation, more pronounced in the subepicardial than in the subendocardial layers, compensated for the decrease in arterial perfusion pressure. The intracoronary infusions revealed that the decrease in normalized subendocardial/subepicardial blood flow ratio was not secondary to the fall in arterial blood pressure. 4 Myocardial oxygen consumption decreased during both the i.v. and the intracoronary administration of elgodipine. With the i.v. administration the decrease was secondary to the hypotensive action of the drug, whereas with the intracoronary administration the negative inotropic properties played the dominant role.5 Elgodipine (i.v.), although not affecting total cardiac output, caused a redistribution in favour of the nutritional blood flow at the expense of the arteriovenous anastomotic (AVA) blood flow. Up to an infusion rate of 3.0upg kg -I min-1 the decrease in AVA-flow was due to a fall in arterial blood pressure, but at the highest infusion rate both the decrease in arterial perfusion pressure and an increase in their resistance contributed to a further decrease in AVA blood flow. 6 The skeletal muscles benefited most from the elgodipine(i.v.)-induced increase in nutritional blood flow, but vasodilatation was not uniform for all muscle groups. Up to an infusion rate of 3 yg kg -' min-1 the vasodilatation in the renal vascular bed was more pronounced in the inner than in the outer cortex, but, at 0 pyg kg-1 min-, vascular resistances of both cortical layers returned to baseline values. In all regions of the brain, blood flow was maintained until the highest infusion rate was given. With 10 yg kg-I min -' only flow to the vital parts of the brain (diencephalon and brain stem) was maintained. Blood flows to the skin and various abdominal organs were well maintained up to 3 pg kg'-min -1 but, at the highest dose, a decrease was observed in blood flow to the adrenals and spleen. Vascular resistances of...

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Section: Arteriovenous Anastomotic Bloodflowmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The central and regional cardiovascular responses to intravenous and intracoronary administration of the phenyldihydropyridine elgodipine in anaesthetized pigs

Sassen¹,

Soei²,

Koning³

et al. 1990

British J Pharmacology

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“…each to both ipsilateral and contralateral brain structures (total weight: 82 + 1P5 g, n = 22) -seems to be adequate. Total cerebral blood flow in pigs, measured either by xenon infusion (van Duyl, 1978) or by microsphere method (Lauchlin, Burns & Loxsom, 1979;Verdouw, Saxena, Schamhardt, Van der Hoek & Rutteman, 1980;Dhasmana, Verdouw, Prakash & Saxena, 1982), is in the order of 0-25-0-35 ml. min-' g-1 (equivalent to about 20-28 ml.…”

Section: Distribution Of Carotid Blood Flowmentioning

confidence: 99%

Redistribution by 5‐hydroxytryptamine of carotid arterial blood at the expense of arteriovenous anastomotic blood flow

Saxena

Verdouw

1982

The Journal of Physiology

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101

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SUMMARY1. The effects of 5-hydroxytryptamine by intravenous (1, 5 and 10 ,ug kg-' min' in cats) and intracarotid (0 5 and 2 jug kg-' min' in pigs) routes were studied on the complete distribution ofcommon carotid artery blood flow, measured with radioactive microspheres (15 ,um). In addition, the amine was also infused (0-75-3 ,ug kg-' min-') into the carotid artery of cats to observe its influence on the shunting of microspheres in the jugular venous blood.2. The basal total common carotid blood flow was distributed ipsilaterally mainly to extracerebral tissues and only little blood entered the brain. As shown by the presence of microspheres in the lungs after injection into the carotid artery (52 % in cats; 82 % in pigs), a major fraction of the carotid blood by-passed the capillary bed through arteriovenous anastomoses in the head (non-nutrient fraction).3. 5-Hydroxytryptamine redistributed the blood in favour of the nutrient compartment at the expense of arteriovenous anastomotic fraction. In cats, tissue blood flow did not significantly change but, in the pig, blood flow to all tissues, particularly to skin and ears, was substantially increased despite a reduction in total carotid blood flow. This reduction was entirely due to a change in the non-nutrient fraction.4. Intracarotid infusion of 5-hydroxytryptamine in vagosympathectomized intact or spinal cats decreased the number of microspheres appearing in the jugular venous blood, again indicating a reduction in arteriovenous anastomotic flow due to a constriction of these non-nutrient vessels.5. Cyproheptadine (1 mg kg-') completely reversed the effect of 5-hydroxytryptamine on the total carotid blood flow. However, the vasoconstriction of arteriovenous anastomoses was only partially attenuated and the vasodilatatory response was either unchanged (muscle) or even enhanced (skin, ear and bones).6. It is suggested that 5-hydroxytryptamine causes vasoconstriction of the large arteries via D-receptors which are only partly involved in the constriction of arteriovenous anastomoses. A part of the vasoconstriction in these non-nutrient vessels and the vasodilatation in extracerebral tissues are mediated by atypical 5-hydroxytryptamine receptors that are yet to be fully characterized.

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“…The segments were excised and weighed. Details of the analysis of the regional myocardial blood flow and myocardial wall thickness data were described earlier (41).…”

Section: Complete Ligation Of the Ladmentioning

confidence: 99%

Decreased incidence of ventricular fibrillation after an acute coronary artery ligation in exercised pigs

Scheffer

Verdouw

1983

Basic Res Cardiol

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Evidence has been presented that regular physical activity may be associated with a decreased incidence of sudden cardiac death. It has been suggested that self-selection of those engaging in regular exercise rather than the physical activity itself is a major factor in explaining these results. We therefore studied the effects of a two-month exercise program on the incidence of ventricular fibrillation after an acute ligation of the left anterior descending (LAD) coronary artery in domestic Yorkshire pigs. At the end of the exercise program, the exercised group (EG, n = 17) had a lower heart rate (10%), a 5 times higher maximum exercise capacity, a 10% larger left ventricular mass and a thicker myocardial wall during end-diastole than a sedentary group (SG, n = 13). After the animals were anesthetized, the LAD artery was occluded at one third of its distal end. Ventricular fibrillation (VF) occurred in 92% of the SG (12 out of 13) against only 30% of the EG (5 out of 17) within 1 hour after occlusion. Percentage of the area at risk was the same (9-10% of total left ventricular mass) in both the EG and SG. Transmural myocardial perfusion after coronary artery ligation was slightly larger in EG than in SG (30 vs 21 ml . min-1 . 100 g-1, p less than 0.05). Although the improvement in perfusion of the ischemic zone of the EG may have contributed to the reduced occurrence of ventricular fibrillation, other mechanisms cannot be excluded.

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The effects of alinidine, an N-allyl derivative of clonidine, on regional myocardial perfusion and performance in the pig with or without atrial pacing

Cited by 21 publications

References 12 publications

The central and regional cardiovascular responses to intravenous and intracoronary administration of the phenyldihydropyridine elgodipine in anaesthetized pigs

The central and regional cardiovascular responses to intravenous and intracoronary administration of the phenyldihydropyridine elgodipine in anaesthetized pigs

Redistribution by 5‐hydroxytryptamine of carotid arterial blood at the expense of arteriovenous anastomotic blood flow

Decreased incidence of ventricular fibrillation after an acute coronary artery ligation in exercised pigs

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