Gordon Ross

Ultrastructural and fluorescence histochemical studies on the innervation of the tracheo bronchial muscle of normal cats and cats treated with 6-hydroxydopamine.

Ultrastructural and fluorescence histochemical studies have shown that the tracheobronchial muscle of the cat receives an extensive autonomic innervation. A rich plexus of nerves is present on the surface of the trachealis muscle and on the surface of the muscle of the large, medium, and small bronchi and the bronchioles. From this plexus nerve fasciculi pass between bundles of smooth muscle as well as between the muscle cells. Nerve fibers containing small (300–600 A) and large vesicles, and specific green fluorescence indicative of catecholamines usually associated with adrenergic nerves were seen in these nerve bundles. In the animals treated with 6-OHDA, the surviving nerves presumed to be cholinergic had the same distribution as the adrenergic nerves. No specific fluorescence was seen in the animals treated with 6-OHDA. The significance of these findings is discussed. The tracheobronchial glands contained cholinergic nerves. In addition adrenergic nerves were seen passing in between and close to the glands. The trachealis muscle tendon junction was examined, and this showed some regions of direct contact between the elastica and the plasma membrane of the smooth muscle cells as well as regions in which the plasma membrane was separated from the elastica by a basement membrane.

Acetylcholine vasodilation of resistance vessels in vivo may not entirely depend on newly synthesized nitric oxide

Blood flow was measured in denervated hind limbs of pentobarbital-anesthetized cats. Intravenous NG-methyl-L-arginine, 3-30 mg/kg did not affect the magnitude or duration of vasodilation produced by intra-arterial acetylcholine. Intra-arterial NG-methyl-L-arginine induced hind limb vasoconstriction and reduced the duration but not the magnitude of the acetylcholine vasodilator response. The results suggest that acetylcholine-induced hind limb vasodilation may not entirely depend on newly synthesized nitric oxide.

An Electromagnetic Catheter-Flowmeter

An electromagnetic flowmeter incorporated into a catheter is described. The catheter is introduced into the aorta via the femoral artery. The flow sensor is located some distance below the catheter tip and is sensitive to flow at right angles to the catheter. A crater-like elevation at one end of the transducer lumen permits funnel-like connection of the transducer to the ostium of an aortic branch. The transducer thus measures the blood flow through a selected branch of the aorta. It is pressed against the branch artery by arching the catheter by means of a pull-wire. A reliable and readily reproducible zero-flow baseline is obtained by slightly withdrawing the lumen of the transducer from the branch ostium, thus closing the lumen by the aortic wall. Records of phasic blood flow in the left renal and superior mesenteric arteries of a dog are presented. The calibration was accomplished by comparison with a calibrated noncannulating electromagnetic flow transducer. Reliable calibration can also be performed in vitro.

Blood Flow in Turtles

;\ LTHOUGH of great interest to the comparative rl.. physiologist, the circulation of the blood in reptiles has received little study. There is no information on blood flow in the great vessels, cardiac output or the factors affecting its distribution between systemic and pulmonary circuits in intact animals. This article reports the electromagnetic determination of blood flow in the aorta, subclavian and pulmonary arteries of intact unanaesthetized turtles and illustrates the instantaneous flow patterns in these arteries and &!so tho changes resulting from temperature variation, respiration, and painful stimuli. Turtles (Ps3udemys scripta) weighing 2-3 kg were refrigerated for several hours at 5° C and then transferred to a tray of ice. A portion of the plastron (8 em x 8 em) was removed and 1-cm lengths of the arteries to be studied were separated from adjacent connective tissue. Flow was measured with the gated sine-wave electromagnetic flowmeter using non-cannulating probes1 •2 • In some animals indwelling polyethylene catheters were inserted into an aorta and pulmonary artery for pressure determination. The excised plastron was then replaced and secured with stainless steel sutures and sealed with acrylic denture material. The flow probe cables and pressure leads were strapped to the carapace after removing the turtle from the ice tray. The investigations reported here wore performed during the first 4--7 post-operative days, during which time the animals behaviour was identical to that before operation. The turtles usually died within 10 days of operation and autopsy invariably showed a large blood clot at the operation site but no evidence of damage or obstruction to the arteries carrying the probes. Calibration was performed by allowing saline to flow from a gravity feed through tho flow probes into a graduated cylinder. In some experiments, for example during forced diving, very low heart rates of l-2 per min wore observed. The portion of the flow trace immediately preceding one of these infrequent boats was considered to

Effect of Nω-nitro-L-arginine methyl ester on arterial pressure and on vasodilator and vasoconstrictor responses: influence of initial vascular tone

Intravenous N omega-nitro-L-arginine methyl ester (L-NAME) 0.3, 3 and 30 mg/kg produced a dose-dependent increase of blood pressure in urethane-anesthetized rats. Similar pressure responses occurred in rats after ganglionic or adrenergic blockade, hemorrhage or acetylcholine infusion. L-NAME potentiated the pressor response to phenylephrine in pentolinium-treated rats. L-NAME increased the depressor effect of acetylcholine and sodium nitroprusside and shortened the acetylcholine response. Phenylephrine potentiated the magnitude but not the duration of the acetylcholine response and had no effect on the duration or magnitude of sodium nitroprusside-induced hypotension. L-NAME potentiated the initial fall of blood pressure induced by a 5 min acetylcholine infusion but had no effect on the pressure drop at the end of infusion. These results suggest that basal production of nitric oxide (NO) is not related to vascular tone and do not support the view that acetylcholine releases NO from resistance vessels in vivo.

Effects of iproveratril and nitroglycerin in the heart and coronary circulation of dogs

A lthough iproveratril (ar-isopropyl-a-[ (Nmethyl-N-homoveratryl) y -aminopropyl] 3,4 dimethoxyphenylacetonitrile; IsoptinR) has been shown to increase coronary flow in animals1z2 and has been used successfully in the treatment of angina pectoris,3-6 information concerning some of its cardiovascular actions is incomplete. For example, there have been no direct measurements of the effect of the agent on instantaneous coronary inflow, myocardial contractile force, or cardiac output in the intact animal. In the present study, noncannulating electromagnetic flowmeters were used to measure blood flow in the ascending aorta and coronary arteries of anesthetized open-chest dogs. hlyocardial contractile force was determined by a Walton-Brodie strain-gauge arch. The effects of both intracoronary and intravenous iproveratril were observed and were compared with those of nitroglycerin.

The effect of nicotine on the coronary circulation of dogs

A lthough the effects of nicotine on coronary blood flow have been extensively investigated, most of the studies have been concerned with average flow determinations and with coronary venous outflow rather than coronary arterial inflow. The present study reports the action of nicotine on instantaneous coronary arterial flow in anesthetized dogs. Instantaneous coronary flow measurements provide much more information than average flow and permit a better assessment of some of the important determinants of coronary flow which might be altered by the drug, e.g., extravascular compression, relative duration of systole and diastole, and end-diastolic vascular resistance.‘v2 In order to avoid the complex systemic actions of nicotine, injections were made directly into the coronary arterial system in doses insufficient to produce systemic responses. Because of the reported liberation of catecholamines in the heart by nicotine3 the effects of this drug were examined before and after the induction of beta-adrenergic blockade with propranolol. venous pentobarbital sodium, 40 mg. per kilogram, and intubated. The chest was opened in the fifth left intercostal space, while ventilation was maintained with a Bird Mark 8 respirator. After incising the pericardium, the anterior descending branch of the left coronary artery was carefully dissected over a distance of approximately 1 cm. and a noncannulating flow probe was placed on the vessel. Flow was determined by means of a Biotronex BL-610 flowmeter. The zero reference point was frequently determined during each experiment by mechanically occluding the vessel distal to its probe. Calibration was performed by placing the probe on a branch of the femoral artery and withdrawing a known amount of blood from this vessel at rates from 5 to 80 ml. per minute with a Harvard infusion-withdrawal pump. Aortic pressure was determined with a Statham P23Db transducer via a polyethylene tube (PE200) approximately twelve artery inches long inserted into the carotid and advanced into the arch of the aorta. The frequency response of both the flow and pressure measuring systems was 25 Hz (-3 db). Methods

Effects of norepinephrine infusions on mesenteric arterial blood flow and its tissue distribution.

Infusions of norepinephrine into the superior mesenteric artery or stimulation of the mesenteric periarterial nerves of cats or dogs produces a transient reduction in mesenteric blood flow but, as stimulation or infusion continues, flow returns to near control values (1-3). Studies based on India ink injections, changes in capillary filtration coefficient and isotope clearances suggested that a redistribution of intestinal blood flow occurred during the “escape” from the vasoconstrictor influence (4, 5). Vasoconstriction in the mucosa appeared to be well maintained throughout whereas blood flow in the submucosa increased. However, other observations (6, 7) have indicated that escape may be due to relaxation of the same vascular elements which were initially constricted. The purpose of the present investigation was to determine whether norepinephrine escape occurred in animals other than the dog and cat and to reexamine the possibility that escape is associated with a redistribution of blood flow among the intestinal layers. Methods. Two Sprague-Dawley rats, two rabbits, two monkeys (Macaca mulatta and Aotus trivirgatus) and 18 cats were used in the study. The rats, rabbits, and cats were anesthetized with intraperitoneal sodium pentobarbital and the monkeys with intravenous sodium pentobarbital 30 mg/kg after premedication with intramuscular Sernylan 5 mg/kg. Catheters were inserted into a common carotid artery and external jugular vein for arterial pressure measurement and intravenous administration of supplemental anesthesia, respectively. The abdomen was opened in the mid-line. Anastomotic connections between the superior and inferior mesenteric arteries were divided. The superior mesenteric artery was dissected free from the enveloping nerves which were cut. A non-cannulating electromagnetic flow probe was placed on the vessel, and flow was determined with a Biotronex BL-610 flowmeter used in conjunction with a Beckman S11 Dynograph recorder.

Cholinergic mechanisms on the heart and coronary circulation

1 The effects of rapid intracoronary injection of acetylcholine (ACh) were studied in anaesthetized open chest dogs. Changes in phasic coronary blood flow were followed with non‐cannulating electromagnetic flow probes and in contractile force with isometric strain gauges. 2 Increasing doses of ACh from 0.01 to 100 μg produced progressively larger increases in systolic and diastolic coronary blood flow and progressive decreases in end‐diastolic vascular resistance which were blocked by atropine but not by propranolol. 3 Contractile force showed both negative and positive responses. The negative inotropic effect was small and was blocked by atropine but not by propranolol. The threshold for the negative inotropic response was higher than for the coronary vasodilator effect and the dose response curve was flatter. The positive inotropic response usually showed two components. One component reached its maximum 13 to 18 s after injection, had a high threshold (over 1 μg), was potentiated by atropine and blocked by propranolol. The other reached its maximum 25 to 60 s after the injection, had a threshold between 0.01 and 0.1 μg, and was blocked by atropine but not by propranolol. 4 These results suggest that the coronary dilator response, the negative inotropic response and part of the positive inotropic response are mediated through “muscarinic” receptors. The remaining component of the positive inotropic response appears to involve catecholamine release.

Hemodynamics of Endotoxin Shock in the Rat and the Effects of Phenoxybenzamine.

Summary We have investigated the hemo-dynamics of endotoxin shock in the rat and the influence of phenoxybenzamine. Within a few minutes after injecting endotoxin there was a marked rise in portal venous pressure and a fall in both arterial pressure and mesen-teric blood flow. Considerable recovery of these values toward control occurred within 30 minutes after administration of endotoxin, following which there was a gradual decline in measured parameters till death. Animals pretreated with phenoxybenzamine had lower portal and arterial pressures and mesenteric blood flow before injection of endotoxin. The magnitude and direction of the early vascular responses to endotoxin were the same as in rats not administered the adrenergic blocking agent; however, arterial pressure and mesenteric perfusion failed to recover from the early effects of endotoxin in rats receiving phenoxybenzamine. Furthermore, prior treatment with phenoxybenzamine conferred no protection against the lethality of endotoxin although it reduced the severity of the intestinal lesions.