Transient analysis of the canine cerebrovascular response to carbon dioxide.

Cerebral venous outflow and carbon dioxide transients were studied during five different transitional states: (1) on and off 10% carbon dioxide breathing, (2) on and off hyperventilation, (3) on 7% carbon dioxide breathing, (4) on 10% carbon dioxide breathing initiated from 7% carbon dioxide breathing, and (5) on 10% carbon dioxide breathing initiated during intracarotid papaverine infusion, in pentobarbital anesthetized, paralyzed, mechanically ventilated dogs. Plots of the temporal relationships between these variables indicated that cerebral blood flow is closely related with cerebral venous carbon dioxide tension but not arterial carbon dioxide tension. The rate at which flow changed upon transition from one steady state to another was phase dependent, in that longer times were required to establish stable conditions in the on phase than in the off phase. The magnitude of the maximum rates of change in cerebral blood flow achieved during transition was influenced both by the size of the forcing function and the level of flow present at the time the response was initiated. Directional changes had no effect upon the maximum rate of the flow change as long as equivalent-sized forcing functions were employed and the initial blood flow levels were similar between responses. However, faster flow transients could be produced by increasing either of the latter two factors. These findings are consistent with the hypothesis that it is either tissue carbon dioxide tension or cerebral venous carbon dioxide tension that is the important variable regulated by cerebral blood flow. The rate-limiting factor in the response appears to be carbon dioxide delivery rate and not the rate of carbon dioxide diffusion.

Analysis of the effect of bilateral sympathetic stimulation of cerebral and cephalic blood flow in the dog.

Unilateral stimulation of the cervical sympathetic in dogs had no effect on cerebral blood flow (CBF) measured by the venous outflow technique. Since this technique measured CBF from both cerebral hemispheres, small changes induced by unilateral stimulation could have been masked by a large constant CBF measured from the contralteral hemisphere. To test this possibility the effect of simultaneous bilateral sympathetic stimulation was studied when the dog was breathing either normal air or a gas mixture of 10%CO2. During normocapnia, no changes in CBF occurred; during hypercapnia CBF increased 19% following passively the increase in blood pressure. These data indicate that bilateral stimulation of extracranial sympathetic nerves does not exert a significant effect on CBF. We show mathematically and experimentally that unoccluded anastomses will cause CBF to appear to decrease in response to sympathetic stimulation. This may explain why others have observed changes in CBF during sympathetic stimulation.

Computer-assisted method for multi-exponential curve fitting for determining cerebral blood flow.

A computer program has been developed for use in determining cerebral blood flow using an inert radioactive gas. The basic algorithm involves the determination of multiple exponential coefficients from the complex concentration-time function. The exponential coefficients are determined by 'peeling' away slower exponentials complex function one at a time. The procedure involves the use of a small laboratory computer in the interactive graphics mode. The method is currently in use analyzing data in a cerebral vascular research laboratory.

Microvascular control in intestinal mucosa of normal and hemorrhaged rats.

The mucosal microcirculation in innervated and denervated small intestine was studied using anesthetized rats. Denervation did not cause significant (P greater than 0.05) diameter changes in the precapillary vasculature; however, venules did constrict significantly. These results indicate minimum neural control in the precapillary vasculature during the resting state. The innervated precapillary vasculature constricted during both the carotid occlusion reflex and hemorrhagic hypotension. The diameter of the denervated precapillary vasculature was unchanged during the carotid occlusion reflex and dilated during hemorrhage. The responses of innervated and denervated precapillary vasculatures were attributed to increased neural activity and autoregulatory mechanisms, respectively. Neither innervated nor denervated venules responded during the carotid occlusion reflex. During hemorrhage, however, innervated venules constricted and denervated vessels dilated. The vasoconstriction of the innervated vasculature during hemorrhage contributed to a stoppage of blood and epithelial detachment; these responses did not occur in the dilated, denervated vasculature. Therefore, neural vasoconstriction, qualitatively similar to that in normal animals during the baroreceptor reflex, is a contributing cause to the vascular and tissue impairment in the intestinal mucosa during hemorrhage.

Effect of sympathetic nerve stimulation on cerebral and cephalic blood flow in dogs.

The effect of sympathetic stimulation (stellate ganglion) on dog cerebral and cephalic blood flows was studied via a cervical or a thoracic approach to the stellate ganglion under sodium pentobarbital or chloralose anesthesia. Two different stimulation voltages (3v and 5v) of monophasic pulses were applied for 1 minute. Venous outflow was measured at the confluence of the sagittal, straight and lateral sinuses with the lateral sinuses occluded and with them patent. When the lateral sinuses were occluded, stellate ganglion stimulation resulted in a marked decrease in common carotid blood flow to 38 plus or minus 2.5% (SE) of control and dilation of the ipsilateral pupil, but cerebral blood flow did not change. Similar effects were observed with each of the anatomic approaches, anesthetics, and voltages used and in dogs with low cerebral vascular tone induced by hypercapnia. When the lateral sinuses were kept patent, sympathetic nerve stimulation decreased the venous outflow to 89 plus or minus 2.9% of control and clamping both of the external jugular veins increased venous outflow to 120 plus or minus 2.7% of control. When the lateral sinuses were kept patent and the extracranial venous pressure was increased by clamping both of the external jugular veins, the decrease in venous outflow in response to sympathetic stimulation was even larger: venous outflow was only 65 plus or minus 4.9% of control. We conclude that stimulation of the stellate ganglion has no effect on the cerebral vasculature. Sympathetic stimulation significantly decreases venous blood flow measured at the confluence of the sinuses only when communications between the intracranial and extracranial venous vasculatures are present.