THE USE OF RADIOACTIVE MICROSPHERES TO COMPARE THE EFFECTS OF HYDRALAZINE, GUANETHIDINE AND SK&amp;F 24260 ON THE REDISTRIBUTION OF CARDIAC OUTPUT IN ANAESTHETIZED RABBITS

Johnston, Barbara M.

doi:10.1111/j.1476-5381.1975.tb06943.x

Cited by 28 publications

(12 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Alternatively, the increase in venous return due to the decreased venous resistance would be masked by the increased venous capacitance. The increase in venous return alone by SK&F 24260 can be well understood if one takes into account of the finding by Fielden et al (14) and by Johnston (24) that SK&F 24260 dilates preferentially precapillary sphincter vessels to reduce resistance but does little to capacitance vessels. Although the decreased venous return was a main feature of the effect of nitroglycerin, a transient but overt increase preceded the decrease.…”

Section: Discussionmentioning

confidence: 99%

Differential effects of nitroglycerin, trimetazidine, verapamil and SK&F 24260 on venous return as revealed by the open-loop method in the dog.

1980

View full text Add to dashboard Cite

Abstract-To obtain detailed information concerning the effects of different vaso dilators on venous return, experiments were carried out on 28 dogs by the use of the open-loop method. Blood from the superior and inferior venae cavae was drained at the level of the tricuspid valve into a reservoir, from which blood was pumped into the right atrium at a constant flow rate. Changes in reservoir volume reflected a total blood shift from the experimental dog and indicated changes in venous return. Drugs were administered into the ascending aorta. Nitroglycerin (1-10 pg/kg) decreased systemic blood pressure, total peripheral resistance and venous return but scarcely altered heart rate. Trimetazidine (0.3-3 mg/kg) decreased systemic blood pressure, total peripheral resistance, venous return and heart rate. Verapamil (10-100 ug/kg) decreased systemic blood pressure, total peripheral resistance and heart rate, and increased venous return. SK&F 24260 (1-10 fig/kg) decreased systemic blood pres sure, total peripheral resistance and increased venous return. Only high doses (10 30 pg/kg) of SK&F 24260 reduced heart rate. Rigorous measurements of systemic output showed that nitroglycerin (10 pg/kg), trimetazidine (3 mg/kg), verapamil (100 pg/kg), SK&F 24260 (10 pg/kg) produced no change in this parameter. SK&F 24260 increased venous return even when sino-aortic baroreceptor reflex was eliminated, ruling out reflex venoconstriction as a possible cause of the increased venous return. The results suggest the following: [1] Vasodilators like SK&F 24260 and verapamil increase venous return by decreasing arterial and/or venous resistance. [2] If the effect which increases venous capacitance prevails over the effect which decreases ar terial and/or venous resistance, venous return is reduced as is the case of nitroglycerin and trimetazidine.Nitroglycerin reduces the left ventricular end-diastolic pressure and volume (1-4), and such is considered to be one of mechanisms responsible for the antianginal action of nitro glycerin (1, 2, 4-6). The reduction in these 2 parameters is thought to be due mainly to a decrease in venous return (3, 4). Thus, it was of interest to investigate the effect on venous return of other vasodilators used for prevention of attacks of angina pectoris. In previous studies (7,8) we demonstrated that some of vasodilators increased venous return whereas others decreased it. However, in those studies we measured venous return by noncannulating type flow probes of electromagnetic flow meters placed at the superior and the inferior vena cava in anesthetized open-chest dogs and did not control cardiac input (the closed-loop method). Thus, it was hardly discernible whether the observed change in venous return by a certain vasodilator would be due to its effect on vasculature or on the heart. Most

show abstract

Section: Discussionmentioning

confidence: 99%

Differential effects of nitroglycerin, trimetazidine, verapamil and SK&F 24260 on venous return as revealed by the open-loop method in the dog.

1980

View full text Add to dashboard Cite

show abstract

“…The frequency response of this system was measured according to the method of Fry (1960) Johnston (1975) and Johnston & Owen (1977 Following preparation of the skin, two parallel incisions were made in the neck, 4cm apart, starting at the level of the manubrium and running cranially for approximately 10cm, one on the mid-line the other distal to the right jugular vein. The skin between the two incisions was carefully dissected from the underlying tissues and wrapped in saline dampened swabs.…”

Section: Anaesthetized Catsmentioning

confidence: 99%

In vivo pharmacological studies with SK&F 94836, a potent inotrope/vasodilator with a sustained duration of action

Gristwood¹,

Comer²,

Eden³

et al. 1988

British J Pharmacology

View full text Add to dashboard Cite

4 The inodilator activity of SK&F 94836 in conscious and anaesthetized animals occurred in association with minimal changes in either blood pressure or heart rate. 5 Detailed studies carried out on anaesthetized cats indicated that SK&F 94836 caused a balanced dilatation of both resistance and capacitance blood vessels. 6 Haemodynamic studies in anaesthetized cats indicated that as a consequence of the inotropic/ vasodilator actions, SK&F 94836 caused significant increases in cardiac output and stroke volume. 7 Detailed studies in anaesthetized dogs indicated that significant inodilator activity occurred in the absence of an increase in myocardial oxygen consumption. 8 The duration of action of SK&F 94836 was sustained following both i.v. and oral administration. 9 We conclude that SK&F 94836, as an orally active inotropic/vasodilator agent with a sustained duration in vivo, has potential utility in the treatment of congestive heart failure.

show abstract

“…The principles and validation of the technique have been described in detail elsewhere (for example Rudolph & Heymann, 1967;Neutze, Wyler & Rudolph 1968;Wagner, Rhodes, Sasaki & Ryan, 1969;Warren & Ledingham, 1974;Johnston, 1975).…”

Section: Methodsmentioning

confidence: 99%

“…Tissue blood flows were calculated from knowledge of cardiac output and the distribution of microspheres to tissues. Details of the calculations have been described by Johnston (1975).…”

Section: Calculationsmentioning

confidence: 99%

Tissue Blood Flow and Distribution of Cardiac Output in Cats: Changes Caused by Intravenous Infusions of Histamine and Histamine Receptor Agonists

Johnston¹,

Owen²

1977

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

The effects of infusions of histamine on blood pressure, cardiac output, heart rate, total peripheral resistance, stroke volume and tissue blood flow have been determined in anaesthetized cats using radio‐active microspheres to measure cardiac output and tissue blood flow. Histamine caused dose‐dependent falls in blood pressure and total peripheral resistance over the dose‐range 1 × 10−8 to 3.3 × 10−7 mol kg−1 min−1. Histamine had no effect on cardiac output, heart rate or stroke volume. Histamine caused vasodilatation in the heart and stomach, with increased blood flow through these organs, and in the small and large intestine where blood flow was maintained despite the falls in arterial blood pressure. Blood flow to the brain, kidneys, liver, adrenal glands, skeletal muscle, spleen and skin was reduced when arterial blood pressure fell. Vascular resistance increased in the skin and spleen, presumably due to reflex vasoconstriction when blood pressure fell. The selective H1‐receptor agonist 2‐(2‐aminoethyl)pyridine lowered blood pressure and decreased total peripheral resistance but did not change cardiac output, heart rate or stroke volume. 2‐(2‐Aminoethyl)pyridine caused vasodilatation in the heart, small and large intestine and kidneys. Vascular resistance was increased in the spleen and skin. The selective H2‐receptor agonist 4‐methylhistamine also lowered blood pressure and decreased total peripheral resistance but did not change cardiac output, heart rate or stroke volume. 4‐Methylhistamine caused vasodilatation in the heart, stomach, small and large intestines and skeletal muscle. Vascular resistance was increased in the skin.

show abstract

THE USE OF RADIOACTIVE MICROSPHERES TO COMPARE THE EFFECTS OF HYDRALAZINE, GUANETHIDINE AND SK&F 24260 ON THE REDISTRIBUTION OF CARDIAC OUTPUT IN ANAESTHETIZED RABBITS

Cited by 28 publications

References 26 publications

Differential effects of nitroglycerin, trimetazidine, verapamil and SK&F 24260 on venous return as revealed by the open-loop method in the dog.

Differential effects of nitroglycerin, trimetazidine, verapamil and SK&F 24260 on venous return as revealed by the open-loop method in the dog.

In vivo pharmacological studies with SK&F 94836, a potent inotrope/vasodilator with a sustained duration of action

Tissue Blood Flow and Distribution of Cardiac Output in Cats: Changes Caused by Intravenous Infusions of Histamine and Histamine Receptor Agonists

Contact Info

Product

Resources

About