Local factors controlling coronary circulation

Wilcken, D. E. L.

doi:10.1016/0002-9149(83)90171-6

Cited by 12 publications

(2 citation statements)

References 46 publications

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“…Failure of autoregulation of medial tonal decreases during ZD6169 exposure likely leads to poor perfusion of susceptible vascular beds during diastole such as in subendocardial and papillary muscles due to coronary steal, leading to ischemic myocardial necrosis. The lesser degree of arterial dilatation and gradual onset of minor coronary vascular flow and resistance changes with potential accommodation of flow due to other mechanisms (Wilcken 1983) may account for the absence of ischemic myocardial necrosis following ZD1611 infusion, while being of sufficient magnitude to induce multiple coronary arterial lesions. ZD6169 administration resulted in decreased peripheral cardiovascular resistance associated with reduced BP, tachycardia, increased cardiac output, and coronary arterial dilatation, which, taken together, indicate that coronary arterial flow is likely to be significantly perturbed, with vessels dilating during diastole, retaining an abnormal blood volume such that the systolic reflection wave results in an abnormal reversed flow of blood.…”

Section: Discussionmentioning

confidence: 99%

Coronary and Systemic Arterial Physiology and Immunohistochemical Markers Related to Early Coronary Arterial Lesions in Beagle Dogs Given the Potassium Channel Opener, ZD6169, or the Endothelin Receptor Antagonist, ZD1611

2012

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We evaluated immunohistochemistry (von Willebrand Factor [vWF] or fibrinogen) and systemic and coronary arterial physiological parameters in beagle dogs to investigate early arterial lesions induced by the potassium channel opener, ZD6169, or the endothelin receptor antagonist, ZD1611. Dogs given an oral dose of ZD6169 (experiment 1) were terminated 1 day later and showed arterial and myocardial lesions. Minimal arterial lesions exhibited few condensed medial smooth muscle cells only, with others showing segmental medial necrosis occasionally with medial/adventitial acute inflammation. Intercellular immunostaining was seen in ostensibly normal tissue, where no pathology was present in conventionally stained sections. vWF and fibrinogen are valuable tools for detecting disruption of arterial integrity. In experiment 2, 2 dogs were given a single high dose of ZD6169 or ZD1611 and BP/HR monitored by conventional measures or telemetry. Substantially reduced systolic/diastolic BP and increased HR occurred within 10 min of ZD6169 infusion: ZD1611 caused minor BP decrease and HR increase. In experiment 3, both drugs given to anaesthetized dogs induced markedly exaggerated systolic phasic forward and reverse flow in left descending and right coronary arteries. Diastolic coronary artery flows were unaffected with ZD1611 and increased slightly with ZD6169. In both coronary arteries, the ZD1611-induced increase in flows paralleled decreased resistance.

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Section: Discussionmentioning

confidence: 99%

Coronary and Systemic Arterial Physiology and Immunohistochemical Markers Related to Early Coronary Arterial Lesions in Beagle Dogs Given the Potassium Channel Opener, ZD6169, or the Endothelin Receptor Antagonist, ZD1611

2012

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“…Both of these have been shown to increase myocardial oxygen demand (43). Adenosine, a metabolic product of ATP breakdown that relaxes vascular smooth muscle, appears to be the local mediator for coronary vasodilatation in conditions of increased oxygen consumption (44).…”

Section: Effects Of Dopumine Infusionmentioning

confidence: 99%

The Effects of Dopamine Infusion on Regional Blood Flow in Newborn Lambs

et al. 1987

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ABSTRACT. The purpose of this project was to investigate the effects of high rates of dopamine infusion on cardiac output and regional blood flow in the lamb. We studied eight unanesthetized newborn lambs (mean age 7 + 2 days) during a 15-min baseline period and while infusing dopamine at 5-, 20-, 80-, and 160 pg/kg/min. We measured cardiac output and mean aortic, pulmonary arterial and left atrial pressures, and organ blood flow using radionuclidelabeled microspheres at each rate of dopamine infusion. Cardiac output increased significantly with increasing rates of infusion up to 80 pg/kg/min but decreased at 160 pg/kg/ min. Aortic, pulmonary arterial, and left atrial pressures increased at rates of infusion above 5 pg/kg/min. Blood flow to all organs was unchanged at the 5 pg/kg/min rate of infusion of dopamine while blood flow to the brain and heart increased at the 80 pg/kg/min rate of infusion and blood flow to the gut and kidney decreased. We conclude that dopamine is an effective inotropic agent in the newborn lamb but that an inotropic:afterload mismatch exists at high infusion rates. Despite an increase in cardiac output at low rates of infusion, dopamine did not selectively vasodilate the vascular bed of any organs tested. Furthermore, at high rates of infusion dopamine actually impaired blood flow to the gut and kidney. (Pediatr Res 21: 131-136, 1987) Dopamine remains an extensively used catecholamine in the management of shock in critically ill infants and children (1). We recently studied the effects of dopamine on hemodynamics in 2-to 3-wk-old lambs and found it to be an effective inotropic agent (2). However, inherent properties of neonatal myocardium may render it relatively unresponsive to the inotropic actions of dopamine and the same effects may not occur in the younger lamb. In the clinical setting, myocardial immaturity may prompt the use of rates of infusion of dopamine in excess of those currently recommended (1). The effects of high rates of infusion on regional blood flow in the newborn are unknown.The purpose of our study was to investigate the effects of dopamine on regional blood flow in newborn lambs over a wide range of infusion rates. We hypothesized that in the newborn lamb dopamine would not increase cardiac output at conventionally used rates of infusion but might at higher rates. At these higher rates, however, we anticipated that the a-adrenergic effect of dopamine would compromise blood flow to vital organs. MATERIALS AND METHODSSurgical preparations. We operated on eight lambs using halothane and nitrous oxide anesthesia delivered by a piston type ventilator. From a left hindlimb cutdown we inserted polyvinyl catheters into a peripheral artery and vein and advanced them into the descending aorta and inferior vena cava, respectively. We also inserted a 3.5 Fr thermistor wire (Edwards Laboratories, Inc., Irvine, CA) into a peripheral artery by separate hindlimb cutdown and advanced it into the descending aorta. Finally, we placed a polyvinyl catheter in a forelimb artery and ad...

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Cardiovascular Anatomy and Physiology

Lake

1985

Cardiovascular Anesthesia

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Local factors controlling coronary circulation

Cited by 12 publications

References 46 publications

Coronary and Systemic Arterial Physiology and Immunohistochemical Markers Related to Early Coronary Arterial Lesions in Beagle Dogs Given the Potassium Channel Opener, ZD6169, or the Endothelin Receptor Antagonist, ZD1611

Coronary and Systemic Arterial Physiology and Immunohistochemical Markers Related to Early Coronary Arterial Lesions in Beagle Dogs Given the Potassium Channel Opener, ZD6169, or the Endothelin Receptor Antagonist, ZD1611

The Effects of Dopamine Infusion on Regional Blood Flow in Newborn Lambs

Cardiovascular Anatomy and Physiology

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