Global Ischemia in Dogs: Cerebrovascular CO ₂ Reactivity and Autoregulation

Abstract

Abstract:Global Ischemia in Dogs: Cerebrovascular COi Reactivity and Autoregulation• One hypothesis on the pathogenesis of post-ischemic-anoxic encephalopathy is impaired cerebral perfusion or the no-reflow phenomenon. Therapies aimed at preventing the development of this phenomenon are increased cerebral perfusion pressure (CPP) and hyperventilation or hypercapnia. Using a dog model in which we have described the progressive development of post-ischemic (PI) cerebral hypoperfusion after 15 minutes of global ischemia induced by aortic and vena cavae clamping, our aims in this study were to determine during the PI cerebral hypoperfusion period: (1) cerebrovascular reactivity to CO 2 , and (2) cerebral blood flow (CBF) autoregulation. Post-ischemic cerebral hypoperfusion to about 50% of normal was not accompanied by raised intracranial pressure (ICP) but cerebrovascular CO 2 reactivity was markedly attenuated while maintaining some kind of autoregulatory phenomenon. Cerebral uptake of oxygen was not significantly affected by changing Paco 2 from 20 to 60 torr at constant CPP or by changing CPP from 64 to 104 torr at constant Paco 2 . These results suggest that increasing both CPP and hypocapnia/hypercapnia would not significantly attenuate PI neurological deficit after global cerebral ischemia. However, in two dogs inadvertently hemodiluted in the PI period, increasing CPP from 50 to 200 torr increased CBF by 200%, suggesting that hemodilution plus increased CPP may be effective therapy for amelioration of post-ischemic-anoxic encephalopathy. The significance of our findings on cerebrovascular CO 2 reactivity and autoregulation with respect to the mechanism of the no-reflow phenomenon is discussed.

Cerebral Vascular Autoregulation and CO2 Reactivity following Onset of the Delayed Postischemic Hypoperfusion State in Dogs

“…This can not be ex plained by false autoregulation, as described above, since no meaningful increases in ICP occur with postischemic increases in blood pressure (Table 3). Among these seven studies, the one most compara ble to ours was that by Nemoto et al (1975). Since they used a IS-min period of ischemia we wondered whether the differences in results were accounted for by the different time intervals (12 min vs. 15 min of ischemia).…”

“…Reasons suggested for this inability included vessel vasoparalysis, blood hy perviscosity, and capillary obstruction. Nemoto et al (1975) further noted that in two dogs which were inadvertently hemodiluted in the postischemic hy poperfusion period, increasing CPP from 50 to 200 mm Hg increased CBP by 200%, suggesting that…”

“…We suspect that because CO2 reactivity is so severely attenuated in the postischemic period, it may be detectable only by a method which permits continuous recording of CBP. Isolated intermittent CBP measurements, as used by Nemoto et al (1975), might easily miss the subtle changes in CBP which occur with CO2 manipulation. Nemoto et al (1975) also noted that breakthrough hyperemia did not occur in their dog model after 15 min of complete ischemia, even when the CPP was increased to 200 mm Hg.…”

“…Isolated intermittent CBP measurements, as used by Nemoto et al (1975), might easily miss the subtle changes in CBP which occur with CO2 manipulation. Nemoto et al (1975) also noted that breakthrough hyperemia did not occur in their dog model after 15 min of complete ischemia, even when the CPP was increased to 200 mm Hg. Reasons suggested for this inability included vessel vasoparalysis, blood hy perviscosity, and capillary obstruction.…”

Autoregulation of cerebral blood flow in patients resuscitated from cardiac arrest.

“…4 In experimental studies of global cerebral ischemia, a preserved CBF autoregulation in the delayed hypoperfusion period has been reported. [5][6][7] In patients studied 3 days after resuscitation from cardiac arrest, it has been found that the internal jugular vein oxygen saturation increases when mean arterial pressure (MAP) increases during norepinephrine infusion. 8 Whether this reflects impairment of autoregulation, a decrease in the cerebral metabolic rate of oxygen (CMRO 2 ), or an increase in the perfusion of the extracerebral tissue drained into the internal jugular vein remains to be settled.…”