Parasympathetic control of transmural coronary blood flow in dogs.

The transmural distribution of coronary blood flow was studied during vagal stimulation in closed-chest, morphine- and alpha-chloralose-anesthetized dogs. The left main coronary artery was cannulated and perfused at constant pressure. Bradycardia during vagal stimulation was prevented by atrioventricular heart block and ventricular pacing. Beta-adrenergic receptors were blocked with propranolol (1 mg/kg iv), and aortic pressure was stabilized by means of a pressure reservoir. Regional myocardial blood flow was measured with 9-micron radioactive microspheres during vagal stimulation and during intracoronary acetylcholine infusion. Vagal stimulation increased coronary blood flow uniformly across the left ventricular wall. In contrast, intracoronary acetylcholine infusion, at a rate selected to increase total flow to the same degree, vasodilated the subendocardium more than the subepicardium, increasing the inner/outer blood flow ratio. It is concluded that both vagal activation and acetylcholine produce coronary vasodilation that is independent of left ventricular preload, afterload, and heart rate. Acetylcholine vasodilation preferentially vasodilates the subendocardium, increasing the inner/outer flow ratio, but vagal stimulation produces uniform vasodilation across the left ventricular wall.

Histochemical localization of acetylcholinesterase in the wall of cardiac blood vessels in the baboon, dog and vervet monkey.

Histochemical methods were used to demonstrate acetylcholinesterase in the wall of cardiac blood vessels in the baboon, dog and vervet monkey. To remove cholinesterase-containing sympathetic nerves, some of the animals were treated with guanethidine for four weeks prior to being sacrificed. In cardiac muscle from the dog and the vervet monkey, cholinergic nerves were histochemically visualized in both small and large vessels. On the other hand, in cardiac muscle from baboons, cholinergic nerves were not seen in branches of the coronary artery with diameters between 0.6 mm to 1 mm and very few fibres were seen around smaller vessels of diameter less than 0.3 mm. The few fibres seen did not appear to penetrate the media of the vessels. These results support physiological findings that the baboon coronary vasculature is not innervated by parasympathetic cholinergic nerves.

Baroreflex control of coronary conductance in normotensive and renal hypertensive conscious dogs with complete heart block.

1. The autonomic and local control of the circumflex coronary bed evoked through acute rises in aortic pressure (aortic balloon inflation) was analysed in conscious, normotensive and hypertensive dogs in complete heart block with ventricles paced at 100 beats/min. 2. In normotensive dogs there was an initial rise (6-12 s) in circumflex conductance preceding a fall in conductance as aortic pressure increased and was sustained. The initial rise, but not the later fall, in circumflex conductance was partly due to a cholinoreceptor and partly due to alpha-adrenoreceptor mechanisms. Local constrictor mechanisms were responsible for the later fall in conductance. 3. The initial cholinoreceptor component of the rise in circumflex conductance is initiated through arterial baroreflex mechanisms. 4. The initial autonomic mechanisms regulating circumflex conductance appear to be absent in renal hypertension. 5. The absence of the transient autonomic rise in circumflex flow and conductance in response to rapid elevations in aortic pressure in certain forms of hypertension, e.g; during tachyarrhythmias and behavioural disturbances, may result in myocardial ischaemia when it is least appropriate.

Differential effect of right and left vagal stimulation on right and left circumflex coronary arteries.

In anasthetised, closed-chest dogs in complete heart block that were paced at a ventricular rate of 100 beats/min, vagal stimulation increased right coronary (RC) flow by 46% and conductance by 59%, but these increases were less than those measured in the left circumflex coronary (LCC) flow (66%) and conductance (80%). Both the right and left vagus nerves affected RC and LCC flow, the left vagus having the greater effect. The response to vagal stimulation is not limited at higher ventricular rates.

Depressed cell-mediated immunity in megaloblastic anemia due to folic acid deficiency.

Cell-mediated immunity has been studied in patients with 1) megaloblastic anemia of folic acid deficiency, 2)megaloblastic anemia of pregnancy, or 3) iron-deficiency anemia. Using dinitrochlorobenzene skin tests, phytohemagglutinin-stimulated lymphocyte transformation, and rosette inhibition by antilymphocyte globulin, we have shown that cell-mediated immunity is depressed in megaloblastic anemia due to folate deficiency; this depression was reversed by folate treatment. Cell-mediated immunity was not impaired by iron-deficiency anemia. Suggested interactions between iron deficiency and folate metabolism were not clarified by these studies.

Effect on coronary flow of atrial contraction.

The transient decrease in coronary conductance and flow that is seen when the atria contract has been studied in 6 anaesthetized, open-chest dogs in heart block, paced via epicardial pacemaker leads. Left circumflex and anterior descending coronary flows were recorded via Doppler ultrasonic flow probes; aortic and left ventricular pressures and electrocardiogram were recorded simultaneously. The transient conductance and flow decrease in diastole were found from linear regression to be consistent with the left ventricular pressure rise caused by atrial contraction, in the case of the anterior descending coronary artery, which also showed no decrease in peak systolic conductance or flow when atria and ventricles contracted simultaneously. Circumflex conductance and flow were decreased by an atrial contraction to an extent greater than could be accounted for by the rise in left ventricular diastolic pressure. Peak circumflex flow and conductance were also decreased in systole, by 12 per cent, when atrial and ventricular contractions were exactly synchronous so that the atria could not discharge into the ventricles. The systolic effect and the excessive diastolic effect are ascribed to compression of atrial branches of the circumflex artery. This artrial compression mechanism accounted for 37-75 per cent of the effect of an atrial contraction on conductance in diastole. Values from 5 dogs of systolic and diastolic conductance changes due to atrial compression were linearly related. Calculation of atrial flow by applying this percentage to the transient flow decrease indicated that 17 per cent of circumflex diastolic flow was atrial, and that this percentage stayed constant throughout diastole.