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Biomedical subjects

D J Duncker

Publications and source records attributed to D J Duncker.

115 records · Page 7Linked to original sources
PubMed1986

Usefulness of pimobendan in the treatment of heart failure.

The effects of the benzimidazole-pyridazinone pimobendan (UD-CG 115 BS) on systemic haemodynamics, myocardial performance and the distribution of cardiac output were studied in open-chest anaesthetized pigs. After intravenous bolus injections (0.1-0.5 mg X kg-1, n = 7) increases in heart rate (up to 37%), LVdP/dtmax (up to 54%) and decreases in systemic vascular resistance (up to 33%) and left ventricular filling pressure (up to 50%) were observed, while cardiac output was unchanged. Vasodilation occurred in nearly all regional vascular beds, but was most pronounced in the adrenals (200%), followed by stomach (150%), small intestines (130%), heart (125%) and brain (110%). O2-consumption was not affected in spite of the increases in heart rate and myocardial inotropy. To evaluate the direct effects on the myocardial, pimobendan was also infused (1-5 micrograms X kg-1 X min-1, n = 7) directly into the left anterior descending coronary artery. In addition to a marked vasodilation of the coronary bed (140%), also a lowering of the left ventricular filling pressure (up to 20%) and cardiac output (15%) was observed, but no changes in regional myocardial function, LVdP/dtmax and systemic vascular resistance occurred. Immediately after intracoronary bolus injections (1 mg X kg-1, n = 4), vasodilation of the coronary vessels was apparent, but myocardial contractility was not affected. This may explain that cyclic AMP content, determined in biopsies excised 30 s after injection, was unaltered. It may be concluded that pimobendan exerts actions on the cardiovascular system which may be useful in the treatment of heart failure.

Animals↗
PubMed1984

Redistribution of carotid artery blood flow by 5-HT: effects of the 5-HT2 receptor antagonists ketanserin and Wal 1307.

The study concerned effects of ketanserin and a new 5-HT2 receptor antagonist, Wal 1307, on the responses to 5-hydroxytryptamine (5-HT) in the porcine common carotid vascular bed. More than 80% of the total carotid blood flow (208 +/- 18 ml; n = 12) bypassed the tissues via arteriovenous anastomoses. Intracarotid infusions of 5-HT (2 micrograms X kg-1 X min-1) reduced the total carotid blood flow by about 50% and arteriovenous anastomotic flow by 85% but extracerebral tissue (nutrient) blood flow more than tripled. The cerebral component did not change. Thus, 5-HT appears to constrict large conducting arteries and arteriovenous anastomoses but dilates arterioles. Ketanserin and Wal 1307 did not affect carotid blood flow distribution but completely blocked the amine-induced reduction of total carotid blood flow. The constriction of arteriovenous anastomoses was only slightly reduced but the 5-HT-induced arteriolar, vasodilation was enhanced. We conclude that vasoconstriction in the main trunk of the carotid artery and, to a smaller degree, in the arteriovenous anastomoses and arterioles, is mediated by mediated by 5-HT2 receptors. The major part of the constriction of arteriovenous anastomoses and arteriolar dilation elicited by 5-HT is, however, not mediated by 5-HT2 receptors. It is argued that these 'atypical' 5-HT receptors may be related to 5-HT1 binding sites.

Animals↗
PubMed1984

Poor vasoconstrictor response to adrenergic stimulation in the arteriovenous anastomoses present in the carotid vascular bed of young Yorkshire pigs.

Studies using electromagnetic flowmeters and radioactive labeled microspheres (15 +/- 1 micron) have revealed that about 80% of the total common carotid artery blood flow in young domestic pigs (12-14 weeks) is shunted through arteriovenous anastomoses (AVAs). To investigate the influence of the sympathetic nervous system we measured the distribution of carotid blood flow before and after cervical sympathetic nerve stimulation (2-16 Hz), intracarotid infusions of noradrenaline (0.025-0.2 micrograms X kg-1 X min-1) or intracarotid bolus injections of noradrenaline (0.3 and 1.0 micrograms X kg-1) and clonidine (1 and 5 micrograms X kg-1). The first two interventions did not exert any effect, but bolus injections of noradrenaline and clonidine, achieving high local concentrations temporarily, caused a short-lasting decrease in AVA-flow, which was attenuated by phentolamine (1 mg X kg-1). It is concluded that the sympathetic nervous system in the carotid vascular bed of young Yorkshire pigs is poorly developed.

Animals↗
PubMedDate not supplied

Impaired endothelium-dependent vasodilation of coronary resistance vessels in severely stunned porcine myocardium.

The effect of stunning on endothelium-dependent responses of resistance vessels in vivo remains of interest. We utilized the coronary pressure-flow relationship during maximal vasodilation in anesthetized swine to identify subtle changes in flow reserve within stunned myocardium. Prior to and following stunning, the coronary pressure-flow relationship during maximal doses of intracoronary adenosine was compared with that of the endothelium-dependent vasodilator ATP. In 11 anesthetized swine, 30 min of partial LAD occlusion and 40 min of reperfusion reduced fractional shortening from 16 +/- 4% to 6 +/- 5% (p < 0.05). This caused a rightward shift of the coronary pressure-flow relationships during infusions of either adenosine or ATP, suggestive of increased extra vascular compressive forces. With adenosine, the slope of the linear portion of the relationship (i.e., coronary pressures > 30 mmHg) was 1.31 +/- 0.54 ml/min-mmHg at baseline and 1.30 +/- 0.55 ml/min-mmHg following stunning (NS). With ATP however, the slope decreased from 1.34 +/- 0.48 ml/min-mmHg at baseline to 1.08 +/- 0.47 ml/min-mmHg following reperfusion (p < 0.05), indicating an attenuation of endothelium-dependent vasodilator capacity. In five of the animals, the slope of the pressure-flow relationship during intracoronary nitroprusside was unchanged post-stunning, which is similar to the adenosine results. In conclusion, the data support the hypothesis that endothelium-dependent vasodilation of resistance vessels in the intact animal is altered within severely stunned myocardium. The rightward shift of the coronary pressure-flow relationships with both classes of vasodilators suggest that extra vascular factors may also play a role in limiting coronary flow reserve.

Adenosine↗
PubMedDate not supplied

Alpha 1-adrenergic tone does not influence the transmural distribution of myocardial blood flow during exercise in dogs with pressure overload left ventricular hypertrophy.

This study was carried out to test the hypothesis that alpha 1-adrenergic activation during exercise causes preferential vasoconstriction of subepicardial coronary resistance vessels, thereby augmenting blood flow to the subendocardium. Studies were performed in 7 dogs in which left ventricular hypertrophy was produced by banding the ascending aorta at 6-9 weeks of age. Animals were studied at approximately 1 year of age when the left ventricular/body weight ratio was 7.7 +/- 0.3 g/kg (mean +/- SE). Left anterior descending (LAD) coronary artery flow was measured with a Doppler velocity flow probe at rest and during a three-stage graded treadmill exercise protocol. The transmural distribution of myocardial blood flow was assessed with radioactive microspheres. Coronary blood flow increased progressively as a function of heart rate and rate-pressure product in response to exercise. In contrast to normal dogs which maintain preferential blood flow to the subendocardium (ENDO) relative to the subepicardium (EPI) during exercise, the ENDO/EPI flow ratio in the hypertrophied left ventricles was 0.88 +/- 0.10 during exercise. Selective alpha 1-adrenergic blockade by infusion of prazosin (10 micrograms/kg) into the LAD decreased mean aortic pressure during exercise from 86 +/- 6 to 76 +/- 4 mmHg (p < 0.05), but did not change coronary pressure, heart rate, left ventricular systolic or enddiastolic pressures, or LVdP/dtmax. Coronary blood flow was not significantly altered by prazosin at rest, but was progressively increased during increasing levels of exercise levels. During the heaviest level of exercise prazosin caused a 22 +/- 3% increase in mean myocardial blood flow which was similar in all transmural layers, with no change in the transmural distribution of perfusion (ENDO/EPI = 0.85 +/- 0.09). These findings demonstrate that alpha 1-adrenergic vasoconstrictor tone limits blood flow during exercise in the hypertrophied left ventricle, but do not support the concept that alpha 1-adrenergic activation augments perfusion of the subendocardium during exercise.

Animals↗
PubMedDate not supplied

Actions of nisoldipine in cardiovascular disease.

The potent systemic and coronary vasodilatory properties of nisoldipine have been demonstrated in several studies in patients with cardiovascular disease. The increase in cardiac output results from enhancements of both stroke volume and heart rate, while coronary blood supply increases in excess of demand. There is evidence that nisoldipine favourably affects several indicators of myocardial ischemia during exercise such as time to onset of anginal complaints and ST segment changes. Furthermore, in patients with elevated left ventricular filling pressures and reduced cardiac pump function the drug tends to normalize these parameters, thus opening new avenues for the treatment of patients with heart failure. The effect of nisoldipine on the incidence of ventricular arrhythmias has not yet been studied in patients, but experimental evidence shows an antifibrillatory activity at doses which may, however, not be clinically applicable. Finally, in healthy men, nisoldipine partially inhibits platelet aggregation. This, together with a potential antiatherosclerotic effect, could be of additional benefit to patients with coronary artery disease.

Calcium Channel Blockers↗