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Biomedical subjects

J R Parratt

Publications and source records attributed to J R Parratt.

At least 217 records · Page 12Linked to original sources
PubMed1971

Cardiovascular pharmacology of quazodine (MJ-1988), with particular reference to effects of myocardial blood flow and metabolic heat production.

1. The effects of intravenous infusions of quazodine (6,7-dimethoxy-4-ethylquinazoline; MJ-1988) on myocardial blood flow, myocardial metabolic heat production and on general haemodynamics have been studied in cats anaesthetized with sodium pentobarbitone.2. Quazodine (0.25 and 0.5 (mg/kg)/min for 10 min) decreased diastolic blood pressure, peripheral vascular resistance, systolic ejection time and left ventricular end-diastolic pressure. Heart rate, cardiac effort, output and external work and left ventricular dP/dt were markedly increased. These changes are indicative of increased myocardial contractility and peripheral vasodilatation.3. In a dose of (1.0 mg/kg)/min, quazodine had a more marked hypotensive effect, systolic pressure being significantly reduced, and had less effect on left ventricular dP/dt and cardiac effort. Calculated external cardiac work was slightly reduced and there were very occasional nodal arrhythmias.4. Changes in heart rate, aortic dP/dt and diastolic blood pressure induced by quazodine were unaffected by the previous administration of the beta-adrenoceptor blocking agent alprenolol in a dose (1.0 mg/kg) which abolished the effects of isoprenaline.5. In all doses, quazodine markedly increased local blood flow (by 70-540%) around an implanted myocardial heated thermocouple recorder. ;Corrected temperature', an index of local myocardial metabolic heat production, was almost unchanged and it is suggested that increased myocardial contractility, occurring with unchanged metabolic heat production and oxygen consumption, probably results from a concomitant decrease in intramural wall tension.

Adrenergic beta-Antagonists↗
PubMed1971

Actions of quazodine (MJ1988) on smooth muscle.

1. Quazodine (MJ1988; 6,7-dimethoxy-4-ethyl-quinazoline) relaxed a variety of vascular and extravascular smooth muscle preparations and antagonized, non-competitively, several substances which contract smooth muscle.2. This activity was not due to beta-adrenoceptor stimulation or to alpha-adrenoceptor blockade.3. On the rabbit duodenum, the inhibitory effect was qualitatively similar to that of theophylline and was antagonized by the phosphodiesterase potentiator, imidazole.4. The activity of quazodine was similar to, but up to 18 times greater than, that of theophylline and it is suggested that at least part of its activity on vascular and extravascular smooth muscle is due to inhibition of phosphodiesterase.

Animals↗
PubMed1971

Myocardial and haemodynamic effects of phentolamine.

1. In cats anaesthetized with pentobarbitone, intravenous infusions of phentolamine ((10-50 mug/kg)/min for 5 min) increased heart rate, left ventricular dp/dt max (without increasing end-diastolic pressure), aortic dp/dt, cardiac output, myocardial blood flow and metabolic heat production.2. Phentolamine-induced increases in myocardial contractility occurred irrespective of the direction or magnitude of the blood pressure change and were maintained well beyond the actual infusion period.3. In cats treated with alprenolol, bretylium or reserpine there was no evidence of increased cardiac contractility following phentolamine administration.4. It is concluded that phentolamine, in doses less than those required to produce significant alpha-adrenoceptor blockade, increased myocardial contractility through an effect on the sympathetic nervous system.

Adrenergic beta-Antagonists↗
PubMed1970

The effect of catecholamine infusions on myocardial blood flow, metabolic heat production and on general haemodynamics, before and after alprenolol (H56-28), in anaesthetized cats.

1. In cats anaesthetized with pentobarbitone sodium, infusions of adrenaline, noradrenaline (0.5 mug/kg per min) and isoprenaline (0.25 mug/kg per min) increased myocardial blood flow, myocardial heat production, left ventricular systolic and end-diastolic pressures, left ventricular +ve and -ve dp/dt max, and calculated cardiac output, effort and oxygen consumption. These effects (apart from the effect of noradrenaline on left ventricular systolic pressure) were markedly reduced by previous administration of alprenolol (0.5 or 1.0 mg/kg).2. Infusions of adrenaline and noradrenaline increased arterial diastolic blood pressure and isoprenaline reduced it. After alprenolol the effects of adrenaline and noradrenaline were potentiated and that of isoprenaline abolished; in some experiments isoprenaline increased arterial diastolic pressure after alprenolol. Alprenolol did not influence the increases in arterial systolic pressure which followed the administration of adrenaline and noradrenaline.3. Isoprenaline-induced tachycardia was markedly reduced and adrenaline tachycardia was converted to bradycardia after alprenolol. The bradycardia which occurred during noradrenaline infusions was unaffected.4. After blockade by alprenolol, recovery of the effects of isoprenaline on left ventricular dp/dt and on heart rate occurred more quickly than recovery of the effects on arterial diastolic pressure. This suggests that alprenolol has a greater affinity for beta(2)- than for beta(1)-adrenoceptors.5. Intravenous administration of acetylcholine decreased arterial blood pressure, left ventricular pressure and +ve and -ve dp/dt max. During recovery from these effects there was a marked increase in +ve dp/dt max. which was absent after the administration of alprenolol (0.5 mg/kg). Because this dose of alprenolol is thus able to block the effects of reflex sympathetic cardiac nerve stimulation but does not completely antagonize the effects of exogenous adrenaline on dp/dt, it is suggested that alprenolol may have some adrenergic neurone blocking activity.6. Increases in liver and myocardial blood flow and heat production produced by noradrenaline, adrenaline and isoprenaline were reduced after alprenolol.7. Isoprenaline reduced air-way resistance and this effect was abolished by alprenolol; increases in air-way resistance produced by adrenaline and nor-adrenaline were augmented. All three amines inhibited intestinal smooth muscle contractions in vivo. Only the effect of isoprenaline was reduced by alprenolol.

Acetylcholine↗
PubMed1970

The effect of "selective" beta-adrenoceptor blocking drugs on the myocardial circulation.

1. A comparison has been made of the effects of a relatively specific beta(1)-adrenoceptor blocking drug (practolol) and a relatively specific beta(2)-adrenoceptor blocking drug (butoxamine) on myocardial and general haemodynamics in anaesthetized cats.2. Practolol, in a dose (10 mg/kg, intravenously) which had little effect on arterial pressure, heart rate, myocardial blood flow or myocardial vascular resistance, markedly reduced the effects of isoprenaline infusions on heart rate, aortic dp/dt, myocardial blood flow, vascular resistance and metabolic heat production, and the cardiac effort index. Isoprenaline induced vasodepression was unaffected.3. Butoxamine (5 mg/kg, intravenously) decreased heart rate, aortic dp/dt, the cardiac effort index and myocardial blood flow and increased myocardial vascular resistance. This is taken as further evidence for the existence of beta(2)-adrenoceptors in the myocardial microcirculation.4. After butoxamine, the effects of isoprenaline on myocardial blood flow, myocardial vascular resistance and heart rate were unaffected but the peripheral vasodilator effect was abolished. The effects on aortic dp/dt and the cardiac effort index were potentiated.5. It is concluded that the effect of isoprenaline in increasing myocardial blood flow is due predominantly to increased cardiac work and oxygen consumption and that practolol, since it has little direct effect on myocardial blood flow yet abolishes the cardiac stimulant and oxygen wasting effects of released catecholamines, has properties which indicate that it should be an effective and safe anti-anginal drug.

Acetanilides↗
PubMed1970

The effect of hypercapnia on myocardial blood flow and metabolism.

1. In closed-chest dogs anaesthetized with trichlorethylene, the inhalation of carbon dioxide sufficient to increase the arterial P(CO2) from 40 to about 100 mm Hg, increased myocardial blood flow (measured using a (133)Xe clearance technique) and right atrial pressure. There were no consistent changes in mean arterial blood pressure, heart rate or cardiac output.2. The effect of hypercapnia on myocardial blood flow was not influenced by the previous administration of atropine and propranolol or of bretylium. It can be concluded, therefore, that the elevated arterial P(CO2) has a direct vasodilator effect on the myocardial microcirculation.3. During hypercapnia the coronary sinus P(O2) was increased and the coronary arteriovenous oxygen content difference, and calculated myocardial oxygen consumption, reduced. It is suggested that this latter effect may be the result of myocardial depression produced by the decrease in arterial blood pH.4. There was no evidence of myocardial glucose uptake either before or during hypercapnia. The myocardial extraction of lactate and pyruvate at rest varied between 0 and 55%. During acute hypercapnia the extraction of lactate usually fell.5. When the arterial P(CO2) was maintained at 100 mm Hg for a period of 1 hr the effects on myocardial blood flow and on oxygen consumption were not sustained.6. Stepwise increments and decrements in arterial P(CO2) of 10-20 mm Hg produced corresponding increases and decreases in myocardial blood flow and demonstrated that changes in arterial P(CO2) of 20-30 mm Hg can markedly affect blood flow in the myocardium.

Animals↗
PubMed1969

Studies on the mode of action of hexobendine, a prospective anti-anginal drug.

1. In cats anaesthetized with pentobarbitone sodium, hexobendine (0.25 mg/kg) markedly increased myocardial blood flow (measured using a heat clearance technique) and usually decreased myocardial metabolic heat production, without influencing cardiac contractility or systemic arterial blood pressure. These effects lasted for about 45 min.2. Larger doses (0.5 and 1.0 mg/kg) decreased systemic arterial blood pressure and the rate of rise of the left ventricular pressure pulse (dp/dt), although left ventricular end-diastolic pressure was usually increased. This is indicative of a decrease in myocardial contractility.3. In a concentration of 5 x 10(-6) g/ml., hexobendine protected isolated rabbit atria against the decrease in contractility that follows the removal of oxygen.4. Hexobendine did not antagonize the systemic and myocardial effects of infusions of adrenaline and noradrenaline, nor (except in concentrations of 10(-5) g/ml.) the increase in contractility induced by these catecholamines on isolated rabbit atria.

Angina Pectoris↗