In conscious pigs, arteriovenous anastomoses (AVAs) are in a constricted state so that < 5% of intra-atrially injected radioactive (15-microns-diam) microspheres are shunted to the lungs. Many of the anesthetic regimens frequently used in cardiovascular research dilate AVAs, thereby greatly increasing the percentage of microspheres reaching the lungs. This may seriously limit extrapolation of results obtained under anesthesia to the conscious state. We now describe that anesthesia with a combination of fentanyl and thiopental preserves the tone of AVAs, maintaining shunting under 4% of cardiac output. Furthermore, we studied in the carotid circulation of this model whether norepinephrine or 5-hydroxy-tryptamine (5-HT), both contained in perivascular nerves, is responsible for this tone. Consecutive antagonism of alpha 1-, alpha 2-, 5-HT1, and 5-HT2 receptors was obtained by sequential injection of prazosin, phentolamine, ketanserin, and methiothepin. Prazosin increased AVA blood flow, partly at the expense of extracerebral tissue blood flow, but preserved cerebral blood flow. None of the other antagonists had any additional significant effect. Therefore, in this model the tone in AVAs seems to be maintained by sympathetic norepinephrine-containing nerves via alpha 1-adrenoceptors.

1 We investigated the presence of dopamine D1 receptors in the myocardium of anaesthetized pigs using intravenous infusions of dopamine, alone and after a-and fl-adrenoceptor blockade and intracoronary infusions of the selective D, receptor agonist, fenoldopam. 2 Intravenous infusion of dopamine (2.5, 5 and lOpgkg1 min1 for 10min, n = 6) caused dosedependent changes in heart rate (from 94 + 6 to 132 + 10 beats min-', P < 0.05), the maximal rate of rise of left ventricular pressure (LVdP/dt,,..,X; from 2280 + 170 to 4800 + 410 mmHgs-r', P < 0.05), mean arterial blood pressure (from 87 + 5 to 62 + 3 mmHg) and systemic vascular resistance (from 40 + 4 to 28 + 2 mmHgP1 min, P < 0.05). The increases in heart rate and LVdP/dt, were abolished when dopa-.mine was infused after x-and /J-adrenoceptor blockade. The vasodilator response was, however, only minimally affected. 3 Intravenous infusions of dopamine decreased coronary vascular resistance from 0.90 + 0.06 to 0.53 + 0.07 mmHg mlP 1 min 100 g (P < 0.05). This action of dopamine was not observed when dopamine was infused after blockade of the a-and fi-adrenoceptors. 4 Pretreatment with cx-and fi-adrenoceptor blockade had no effect or only slightly attenuated the dopamine-induced decrease in vascular resistance of the brain, kidneys, adrenals and small intestine. 5 In 7 animals, intracoronary doses of 0.04, 0.1, 0.2 and 0.4g kg1-min 1 of fenoldopam had no effect on coronary venous oxygen content, local myocardial oxygen consumption, coronary blood flow or coronary vascular resistance. However, systemic effects were observed at the highest two doses, as manifested by a drop in mean arterial blood pressure from 82 + 4 to 72 + 4 mmHg (P < 0.05) due to peripheral vasodilatation (e.g. cerebral vascular bed). Heart rate, LVdP/dt,.,, regional myocardial segment length shortening and left ventricular end-diastolic pressure were not affected at these doses. In 2 animals the infusion rate was increased to 4jug kg1 min 1, but again there was no evidence for coronary vasodilatation. 6 We conclude that the intravenous infusion of dopamine after ac-and fi-adrenoceptor blockade and the intracoronary infusion of fenoldopam provided no evidence for a major role of D1 receptors in the coronary circulation of pigs. The absence of any effect of the employed doses of fenoldopam on LVdP/dt.mx and on regional myocardial segment length shortening also indicates that fenoldopam does not exhibit any inotropic action in this species.

Background. Intracoronary stents may be effective when used as "bail-out" devices for acute complications after percutaneous transluminal coronary angioplasty. Furthermore, preliminary reports have demonstrated some promising results with stents with regard to the reduction of restenosis. Several stent devices are available for preclinical and clinical evaluation. The use of these stainless-steel stents has been limited by poor visibility during fluoroscopy and thrombogenicity during the first days to weeks after implantation. We therefore investigated the immediate and short-term effects on arterial patency of a new, radiopaque, balloon-expandable coil stent in normal coronary arteries of pigs.Methods and Results. In 10 animals, a stent was placed in two of the three epicardial coronary arteries. During the implantation procedure, the animals received heparin; after the procedure, no antithrombotic drugs were administered. After 1 week (five animals and 10 stents) or 4 weeks (five animals and 10 stents), repeat angiography was performed, followed by pressurefixation of the coronary arteries for light and electron microscopic examination. Angiographic analysis revealed that all stented coronary segments were patent and without signs of intraluminal defects. Scanning electron microscopy showed complete endothelial covering of all stents within 7 days. Light microscopy showed a reduced tunica media locally under the stent wires, which resulted from exerted pressure. The neointima on top of the stent wires measured 56 ,m (range, ,um) after 1 week and 139 ,um (range, 84-250 jum) after 4 weeks.Conclusions. Results from this study show that this radiopaque endoprosthesis can be safely placed in normal coronary arteries of pigs. After 4 weeks, all stents were patent and there was no need for additional antithrombotic treatment, whereas neointimal proliferation was limited.

The effects of the butyrophenone, azaperone 5 mg kg-1 i.m. alone and after addition of the imidazole derivative metomidate 6 mg kg-1 i.v. were studied in eight conscious pigs. Fifteen minutes after administration of azaperone, systemic arterial pressure was reduced by 35% as a result of a 45% increase in systemic vascular conductance and 10% decrease in cardiac output (Q). After azaperone, 23% of the radioactive labelled microspheres (15 (SD 1) microns) injected into the left atrium were detected in the lungs as a result of opening of arteriovenous anastomoses (baseline 3%). The increase in arteriovenous anastomotic blood flow was at the expense of the nutritional (= capillary) channels. Flow to the brain was maintained, but that to the left ventricle decreased in parallel with the reduction in arterial pressure. Vascular conductance of most other organs, except the skin, increased or was maintained. The addition of metomidate had no effect on Q because an increase in stroke volume (by 30%) compensated for the decrease in heart rate. Systemic vascular conductance decreased, most noticeably in the brain, left ventricle and skeletal muscle. We conclude that azaperone alone and in combination with metomidate had only a moderate effect on Q, but caused a redistribution in favour of arteriovenous anastomoses.

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