Ralph R. Sonnenschein

Cerebrovascular Anatomy and Blood Flow Measurements in the Rabbit

The arterial supply and venous drainage of the rabbits brain were characterized by intravascular injection of casting material and intra-arterial administration of markers (crystal violet or dissolved hydrogen gas). The internal carotid artery supplies the homolateral cerebral cortex and subcortical structures except for the thalamus and the posterior portion of the nucleus caudatus; it also supplies the homolateral retina and optic nerve. No noncerebral structures are supplied by this artery. The dorsal sagittal sinus drains the dorsal and lateral parts of the frontal and parietal areas of the cerebral cortex, with no detectable extracerebral contamination. Electromagnetic measurement of flow in the internal carotid artery (ICBF), volumetric or H2-clearance measurement of flow in the dorsal sagittal sinus (SSBF), and H2-clearance determination in cerebral cortex yield comparable results on the cerebrovascular response to hyper- and hypocapnia. ICBF and SSBF are reliable and valid estimates of average blood flow through the homolateral cerebral hemisphere and the cerebral cortex, respectively.

Visceral and behavioral responses to intraduodenal fat.

Introduction of milk or corn oil into the duodenum of the cat evokes an increase in superior mesenteric blood flow (blocked by atropine), an inhibition of gastric and duodenal motility, and sedation. Cholecystokinin-pancreozymin mimics the mesenteric vascular effect of intraduodenal fat and seems to have a sedating action.

Cholinergic Cerebral Vasodilatation in the Rabbit: Absence of Concomitant Metabolic Activation

Cerebral blood flow (CBF) was estimated from measurements of internal carotid blood flow and sagittal sinus blood flow in mechanically ventilated rabbits under 70% N2O–30% O2. Intravenously administered physostigmine, a cholinesterase inhibitor, increased CBF under normocapnia and enhanced the cerebral vasodilatation of hypercapnia, but did not alter the cerebral metabolic rate of oxygen (CMRO2). The cerebrovascular effects of physostigmine were antagonized by atropine but not by dihydro-beta-erythroidine, a nicotinic blocker. Neostigmine, a quaternary cholinesterase inhibitor that does not cross the blood-brain barrier, showed no cerebrovascular effects, It is concluded that the cholinergic cerebral vasodilatation does not depend on cerebral metabolic activation, and that the cholinergic receptors involved are muscarinic and located beyond the blood-brain barrier.

The Electroencephalogram, Blood Flow, and Oxygen Uptake in Rabbit Cerebrum

In the present study, the relationships among electroencephalographic (EEG) amplitude shifts, cerebral blood flow (CBF), and cerebral oxygen uptake (CMRO2) have been characterized in halothane-anesthetized rabbits. CBF was measured by timed collection of venous effluent from the superior sagittal sinus. CMRO2 was calculated as the product of CBF and the arteriovenous difference in oxygen content. The depth of anesthesia in the first series of experiments was maintained at a constant level that was characterized by spontaneous EEG shifts from high- to low-voltage states (HV-LV shifts). These shifts were associated with transient decreases in mean arterial pressure (MAP), which averaged 23 ± 2 mm Hg (n = 17). Ninety seconds after spontaneous HV-LV shifts, MAP had returned to its original value, CBF had increased by 26 ± 7% (n = 8), and CMRO2 had increased 22 ± 4% (n = 7). In a second series of experiments, HV-LV shifts were induced by a 90-s application of a standardized nociceptive stimulus (n = 13). Following these stimulation-induced HV-LV shifts, CBF increased 28 ± 5% and CMRO2 increased 27 ± 4%. Under scopolamine (0.35 mg/kg, i.v., n = 8), no change in CBF was observed following HV-LV shifts induced by 90-s of stimulation, although CMRO2 increased significantly by 14 ± 3%. After 300 s of post-scopolamine stimulation, however, both CBF and CMRO2 had significantly increased by 12 ± 3 and 15 ± 3% (n = 8) of control, respectively. These results demonstrate that HV-LV shifts, whether spontaneous or stimulation-induced, are associated with significant increases in both CBF and CMRO2. Because the early (90-s) increases in CBF but not those in CMRO2 could be blocked by scopolamine, we suggest that the cerebral vasodilatation that occurs during the early phase of HV-LV shifts involves cholinergic mechanisms. Because scopolamine could not block the increase in CBF observed after 300 s of stimulation, we suggest that the final value of CBF obtained after an HV-LV shift is determined by a combination of both cholinergic and noncholinergic factors.

Depression of Contractile Force of Skeletal Muscle by Intra-arterial Vasodilator Drugs

The intra-arterial administration of vasodilator drugs (acetylcholine, histamine, isoproterenol, adenosine triphosphate, bradykinin, and isoxsuprine hydrochloride) induced reversible depression in the maximal contractile force of the intermittently stimulated gastrocnemius-soleus muscles in the cat. In general, blood flow to the muscles was held constant and perfusion pressure was observed. The agents were effective in depressing the muscle at doses the same as those required to produce dilatation in the resting muscle. Increase in blood flow during infusion could reverse the depression. Atropine, in amounts sufficient to block the hypotensive action of intravenously administered acetylcholine, prevented the muscle depressant action of the latter, while leaving unaffected the action of histamine. Further experiments, utilizing mainly acetylcholine as the prototype, were performed to test the hypothesis that the depressant effect on the gastrocnemius was closely related to a vascular action of the drugs. Evidence serving both to exclude neuromuscular blockade and to support a vascular effect was adduced from three sets of observations. 1) In vitro tests of blocking action of acetylcholine and histamine on nerve-muscle preparations indicated that any such action would require doses several hundred times greater than those effective in the cat gastrocnemius. 2) Under conditions where dependency of contractile force on blood flow varied, comparison of the effects of acetylcholine to d-tubocurarine and decamethonium on the cat gastrocnemius showed that when dependency on flow was reduced the effect of acetylcholine was also, while neuromuscular blockade was affected little. 3) A decrease occurred in the I131 clearance rate from the gastrocnemius parallel to the reduction in muscle force from acetylcholine, while a much smaller, or delayed, reduction in rate occurred when force was reduced equally by d-tuboeurarine. A redistribution of blood flow within the muscle and associated connective tissue may account for the results.

Interaction of Three Factors in the Closure of the Ductus Arteriosus

Summary Isolated rings of the ductus arteriosus of the guinea pig developed tension in response to changes in PO2 and transmural electrical stimulation. Increasing the initial tension potentiated the response to elevated PO2. In turn, an increase in PO2 potentiated the responses to transmural stimulation, and also tyramine, norepinephrine and acetylcholine. The three factors, O2, stretch of the vessel wall and autonomic innervation, may potentiate each other in their vasoactive effect during the initiation of ductal closure, secondary to the respiratory and cardiovascular changes occurring at birth.

ROLE OF CENTRAL PATHWAYS AND CRANIAL NERVES IN CEREBRAL CHOLINERGIC VASODILATATION

Publisher Summary A role of neural cholinergic mechanisms in the control of cerebral blood flow (CBF) has been proposed. This idea is supported by the significant increase in CBF and dilatation of pial vessels induced by the direct application of cholinergic agonists to the cerebral cortex; the blockade by atropine of the cerebral vasodilatation associated with low arterial pressure; and the blockade by atropine and enhancement by physostigmine of the hyperemia both of spontaneous cortical arousal and of hypercapnia. These cholinergic effects are not caused by a metabolic or electrical activation of the brain, as cholinergic agonists produce increases of CBF after neuronal electrical activity has been eliminated pharmacologically; the CBF increase induced by physostigmine is not associated with an increase in cerebral O2 consumption. Ascending central pathways originating in the brain stem are involved in the cholinergic cerebrovascular responses. The electrical stimulation of brain stem structures produce increases in CBF that are not explained by the occurrence of blood pressure changes or cortical arousal. The involvement of the brain stem in CBF control is also supported by the blockade of the cerebral vasodilatation of hypercapnia following high decerebration. Theis chapter presents some of the experiments that evaluate the contribution of central versus peripheral routes for cholinergic vasodilator influences on cerebral blood vessels.

Development of the Q2 induced contractions in the ductus arteriosus of the guinea-pig

Die Wirkung von Sauerstoff und Norepinephrin auf die Kontraktionen des isolierten Ductus arteriosus des Meerschweinchens nimmt mit zunehmendem Alter des Feten bis zur Geburt zu und verschwindet kurze Zeit hernach wieder.

Hypoxic tachycardia in the rat.

Awake, freely breathing rats subjected to moderate hypoxia (10% O2) manifest prompt tachycardia which is essentially unaffected by atropine and is blocked by propranolol, and is thus apparently mainly of sympathetic origin.

The tetracaine flare: differences in actions of procaine and tetracaine on peripheral nerve.

Summary 1. Tetracaine hydrochloride, injected intradermally, produces a histaminelike flare which can be blocked hy procaine hydrochloride, 2. On the isolated nerve, tetracaine has much less effect on conduction in C fibers with respect to its effect on A fibers than is the case with procaine. (Preliminary experiments.) 3. In the human skin, tetracaine has much less effect on the threshold for “slow” pain with respect to its effect on “fast” pain than is the case with procaine. 4. These observations suggest that the dare is mediated over C fibers. Tetracaine produces a flare 1) by causing irritation. 2) by failing to block completely the C fibers. 5. The differences in action on conduction of tetracaine and procaine are noted, but no explanation for these differences is available.