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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although preischemic hyperglycemia is known to aggravate damage due to transient ischemia, it is a matter of controversy whether or not this is a result of the exaggerated acidosis. It has recently been reported that although tissue acidosis of a comparable severity could be induced in normoglycemic dogs by an excessive rise in arterial CO2 tension, short-term functional recovery was improved, rather than compromised. In the present experiments we induced excessive hypercapnia (PaCO2, approximately 300 mm Hg) in normoglycemic rats before inducing forebrain ischemia of 10-min duration. This reduced the brain extracellular pH to values normally encountered in hyperglycemic rats subjected to ischemia. The events induced by hypercapnia clearly enhanced ischemic brain damage, as assessed histologically after 7 days of recovery. We hypothesize that the decisive event was an exaggerated decrease in extra- and intracellular pH and that the results thus demonstrate an adverse effect of acidosis. However, since postischemic seizures did not occur in the hypercapnic ischemic rats, the results also demonstrate that changes in intra-extracellular pH and bicarbonate concentrations modulated ischemic damage in an unexpected way.
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PMID:Acidosis induced by hypercapnia exaggerates ischemic brain damage. 811 21

From the time animals became dependent upon molecular oxygen as an integral part of their energy-producing processes, they have remained in the shadow of acute asphyxial threat--the blocking of respiratory exchange resulting in the intracellular triad of hypoxia, hypercapnia and acidosis. The most commonly occurring precipitant of acute asphyxia has always been the transfer between air and water environments. Over the last one hundred years studies on a wide range of living organisms, from single cells to complex multicellular organisms like mammals, have demonstrated the presence of well-defined metabolic and cardiovascular-respiratory mechanisms for protecting living things against acute asphyxia. Single-celled animals depend upon anaerobiosis and secondarily hypometabolism. In addition to these processes, animals with gills or lungs utilize "passive" protection such as increased oxygen storage and the "dynamic" cardiovascular adjustments of bradycardia and selective ischemia. These latter changes decrease overall oxygen consumption and hence utilize the oxygen stores in the most economical way to protect the cardiac and cerebral tissue, which are most sensitive to hypoxia and vital to continued survival of the organism. In this article an attempt is made to place these processes into an evolutionary context. As through a glass darkly we glimpse asphyxial defense running like a paleophysiological thread through hundreds of millions of years, being accentuated here and muted there, depending upon the particular needs of individual species.
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PMID:The evolution of asphyxial defense. 811 77

Testing vasoreactivity with CO2 or Diamox is a common diagnostic procedure for the study of haemodynamics in stroke patients. CO2 reactivity (CO2R) was tested in 5 baboons six hours after permanent occlusion of the left middle cerebral artery (MCA) in order to attain new insights into interpretation of vasoreactivity tests. Using the microsphere method, cerebral blood flow (CBF) was determined in the various vascular territories as well as in the centre of the ischemia, the penumbra and the remaining MCA-tissue. CBF decreased significantly in the affected MCA in all animals and in addition in the contralateral cerebellum in one animal (p < 0.05). In addition, the left anterior cerebral artery (ACA) demonstrated a similar decrease. During hypercapnia CBF increased in all areas with the exception of the left, occluded MCA territory. Thus CO2 enhanced the difference between ischaemic and non-ischaemic tissue (i.e., tissue with diaschisis). Mean CO2 R was 3.37 ml/100 g/min/mmHg in the right MCA, 0.16 in the left. While the left ACA demonstrated a decreased perfusion during normocapnia in a similar range to the MCA territory, only CO2R was able to identify precisely the territory of the occluded vessel. CO2 R was zero or negative in the ischaemic core, close to zero in the penumbra and profoundly decreased in the remaining MCA tissue. The overall CO2 R of the MCA was almost zero, suggesting vasoparalysis in response to hypercapnia in the core and penumbra and exhausted CO2 R even in non-infarcted, non-penumbral tissue. One animal displayed a negative CO2 R equivalent to an intracerebral steal-phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:CO2 reactivity in the ischaemic core, penumbra, and normal tissue 6 hours after acute MCA-occlusion in primates. 812 41

This study examined the effect of hypercarbia on cerebral agonal glycolytic rates and brain lactate accumulation after complete ischemia induced by cardiac arrest. Before cardiac arrest, the blood plasma glucose concentration in seven newborn (113 d postconception; normal gestation, 115 d) and seven 1-mo-old (144 d postconception) piglets was adjusted to a specific value (range, 1 to 64 mM), and then inspired ventilation gases were changed to 10:50:40 CO2:O2:N2 for 20 min. The agonal glycolytic rate was measured by monitoring the rate of cerebral lactate formation in vivo using proton nuclear magnetic resonance spectroscopy, and postmortem brain lactate concentrations were measured biochemically in tissue extracts obtained 40 to 45 min after cardiac arrest. These data were compared with 21 normocarbic piglets of similar age, nine examined as part of the present study and 12 examined previously (Corbett RJT, Laptook AR, Ruley JI, Garcia D: Pediatr Res 30:579-586, 1991). There was a nonlinear relationship between the final postmortem brain lactate concentration and preischemia blood plasma glucose concentration that was most prominent in newborn piglets and previously had gone unnoticed. When analyzed using a steady-state model for glucose transport, this relationship revealed that normocarbic newborns had a lower preischemia affinity constant for the transport mechanism for glucose (2.8 +/- 1.5 mM) and lower cerebral glucose utilization rate relative to transport rate (0.12 +/- 0.04), compared with 1-mo-olds (4.5 +/- 1.4 mM and 0.30 +/- 0.03, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of hypercarbia on age-related changes in cerebral glucose transport and glucose-modulated agonal glycolytic rates. 813 81

We tested the hypothesis that administering polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) either before global cerebral ischemia or at the time of reperfusion would alter recovery of cerebral blood flow (CBF; microspheres) response to alteration in arterial PCO2 in pentobarbital-anesthetized, mechanically ventilated piglets (1 to 2-wk old). CBF was measured at an arterial PCO2 of approximately 3.3, 5.3, and 8.7 kPa before and 2 h after ischemia (10 min aortic cross clamp). To determine the effect of preischemic versus postischemic treatment with PEG-SOD, each piglet received two i.v. drug injections of either 30,000 U PEG-SOD or an equal volume of PEG diluent in a randomized, blinded fashion before ischemia and just before reperfusion. Cerebral oxygen consumption and somatosensory evoked potentials were measured during reperfusion as an assessment of brain function. During reperfusion, no group demonstrated delayed hypoperfusion. Hypercapnic CBF was less during reperfusion (48 +/- 6 mL/min/100 g) compared with preischemia (69 +/- 10 mL/min/100 g) in PEG/PEG-treated piglets. However, hypercapnic CBF during reperfusion was not different from preischemic values with either preischemic or postischemic PEG-SOD treatment. Improved return of hypercapnic CBF in PEG-SOD-treated piglets was not attributable to improved postischemic cerebral oxygen consumption. Somatosensory evoked potential amplitude was decreased similarly during reperfusion (approximately 25% of preischemic values) in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Polyethylene glycol-conjugated superoxide dismutase improves recovery of postischemic hypercapnic cerebral blood flow in piglets. 825 89

Piglet brains generate superoxide during postischemic reperfusion, and topical application of activated oxygen species alters pial arteriolar responses. We investigated effects of pretreatment with scavengers of superoxide and H2O2 on ischemia-induced alterations of pial arteriolar responses in anesthetized newborn pigs. Four groups were studied: 1) time control, 2) untreated ischemia, 3) ischemia pretreated topically and systemically (conjugated to polyethylene glycol) with superoxide dismutase (SOD) and catalase, and 4) ischemia pretreated with Tiron. Pretreatment with SOD conjugated to polyethylene glycol alone during postischemic reperfusion effectively removed superoxide from its site of generation during postischemic reperfusion, but topical SOD was used also an insurance. Piglets were studied before and after 20 min of total cerebral ischemia caused by maintaining intracranial pressure above mean arterial pressure. As reported previously, before ischemia, hypercapnia and isoproterenol dilated pial arteries and arterioles and hypercapnia but not isoproterenol increased cortical periarachnoid cerebrospinal fluid 6-keto-prostaglandin F1 alpha, measured as an index of cerebral cortical prostacyclin synthesis. After cerebral ischemia, pial arterioles did not dilate in response to hypercapnia and 6-keto-prostaglandin F1 alpha did not increase, but dilation to isoproterenol was unchanged. The present study found that treatment with SOD/catalase or Tiron did not prevent loss of vasodilation to hypercapnia or the loss of hypercapnia-induced cerebral 6-keto-prostaglandin F1 alpha synthesis after cerebral ischemia. The postischemic loss of cerebral vasodilation to hypercapnia does not appear to involve superoxide or a subsequent reduced form of oxygen.
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PMID:Superoxide scavengers do not prevent ischemia-induced alteration of cerebral vasodilation in piglets. 838 55

Electrical stimulation of the cerebellar fastigial nucleus (FN) increases CBF and reduces brain damage after focal ischemia. We studied whether FN stimulation "protects" the brain from ischemic damage by increasing blood flow to the ischemic territory. Sprague-Dawley rats were anesthetized (halothane 1-3%) and artificially ventilated through a tracheal cannula inserted transorally. CBF was monitored by a laser-Doppler probe placed over the convexity at a site corresponding to the area spared from infarction by FN stimulation. Arterial pressure (AP), blood gases, and body temperature were controlled, and the electroencephalogram (EEG) was monitored. The stem of the middle cerebral artery (MCA) was occluded. After occlusion, the FN was stimulated for 60 min (100 microA; 50 Hz; 1 s on-1 s off) while AP was maintained at 97 +/- 11 mm Hg (mean +/- SD) by controlled hemorrhage. Rats were then allowed to recover, and infarct volume was determined 24 h later in thionin-stained sections. In unstimulated rats (n = 7), proximal MCA occlusion reduced CBF and the amplitude of the EEG. One day later, these rats had infarcts involving neocortex and striatum. FN stimulation after MCA occlusion (n = 12) enhanced CBF and EEG recovery [61 +/- 34 and 73 +/- 43%, respectively at 60 min; p < 0.05 vs. unstimulated group; analysis of variance (ANOVA)] and reduced the volume of the cortical infarct by 48% (p < 0.05). In contrast, hypercapnia (PCO2 = 64 +/- 4; n = 7) did not affect CBF and EEG recovery or infarct volume (p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fastigial stimulation increases ischemic blood flow and reduces brain damage after focal ischemia. 751 36

We observed previously that 20 min of global cerebral ischemia followed by 45 min of reperfusion selectively blocked cerebral vasodilation to hypercapnia and hypotension. This study determines the effects of pretreatment with transforming growth factor-beta (TGF-beta) on cerebrovascular responses after cerebral ischemia in piglets equipped with closed cranial windows. Hypercapnia-induced pial arteriolar dilation was blocked after cerebral ischemia (20 +/- 1 vs. 2 +/- 1% dilation before and after ischemia, respectively). Similarly, the increases in periarachnoid cortical cerebrospinal fluid 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) and prostaglandin E2 (PGE2) concentration in response to hypercapnia were blocked (2.5 +/- 0.2- vs. 0.2 +/- 0.4-fold and 2.1 +/- 0.1- vs. 0.3 +/- 0.4-fold increase in 6-keto-PGF1 alpha and PGE2, respectively). Treatment with topical TGF-beta (400 ng/ml) before and during ischemia-reperfusion attenuated the loss of hypercapnia-induced cerebrovascular dilation (20 +/- 1 vs. 14 +/- 1% dilation before and after ischemia, respectively) and the loss of associated changes in cerebrospinal fluid prostanoids (2.0 +/- 0.2- vs. 1.7 +/- 0.2-fold and 2.3 +/- 0.2- vs. 2.2 +/- 0.3-fold increase in 6-keto-PGF1 alpha and PGE2 before and after ischemia, respectively). The loss of cerebrovascular dilation in response to hemorrhagic hypotension after ischemia was similarly prevented by TGF-beta. Cerebrovascular dilation to topical isoproterenol was unchanged after ischemia. TGF-beta may preserve endothelial cell function. We conclude that topical TGF-beta can attenuate cerebromicrovascular compromise caused by ischemia-reperfusion in newborn pigs.
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PMID:Transforming growth factor-beta attenuates ischemia-induced alterations in cerebrovascular responses. 844 54

Ischemia has traditionally been viewed as arising only from abnormalities of oxygen dynamics, namely the cellular hypoxia resulting from the imbalances between oxygen supply, consumption, and demand. Recently, it has become clear that such a view is too restrictive. Hypoperfusion may be caused by both anatomic and functional impediments to either inflow or to outflow from an organ. Furthermore, the pathophysiologic consequences are likely to involve not only cellular hypoxia, but also a restricted supply of nutrients and other important molecules and an abnormal elimination of physiologic wastes such as carbon dioxide. Hence the recommendation that ischemia be defined as a dual defect of oxygen deficit and carbon dioxide excess. AMI is, therefore, a severe anatomic or functional impediment to the splanchnic circulation, resulting in a dual defect of intestinal hypoxia and cellular hypercarbia. Although the functional and structural consequences of cellular hypoxia are well known, the pathophysiology of cellular hypercarbia has only begun to be explored. AMI syndromes include three related processes: occlusive mesenteric ischemia, nonocclusive ischemia, and sepsis-induced SI. Leakage of bacteria or bacterial toxins into the circulation during mesenteric ischemia forms the basis of the systemic components of this syndrome. Striving for an earlier diagnosis, treating the systemic (septic) consequences, and taking measures to promptly restore mucosal oxygen balance through aggressive pharmacologic and appropriate surgical intervention have significantly improved the prognosis. About 80% of patients with acute arterial embolism, 60% of those with nonocclusive ischemia, and only 20% of patients with arterial thrombosis are expected to live without significant residual nutritional deficits. The cause of death is usually sepsis and multisystem organ failure, and therefore, further reductions in mortality are likely to occur with the improved prevention and treatment of sepsis.
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PMID:Acute mesenteric ischemia: pathophysiology, diagnosis, and treatment. 847 15

Currently, no ideal method exists for monitoring the injured brain. Recently, a single, compact, fiberoptic sensor has become available for measuring oxygen, CO2, pH and temperature in blood. We have adapted this instrument for continuous use in brain tissue to measure oxygen tension, carbon dioxide tension (pCO2), pH, and temperature. To evaluate this new technique, we produced hypercapnia, hypocapnia, intracranial pressure increase, and hypoxemia in seven normal cats. In an additional six animals, sensors were placed within a zone of focal brain ischemia induced by occluding the left middle cerebral artery. The sensor readings were compared with cerebral blood flow measurements, intracranial pressure, and brain histological findings. An in vitro experiment was also performed using human blood to test the accuracy of the sensor over a wide range of pCO2 and oxygen tension values. After careful precalibration and rigid cranium fixation, stable measurements could be obtained throughout the 6- to 8-hour experiments. In normal animals, brain oxygen was 42 +/- 9 mm Hg, brain CO2 was 59 +/- 14 mm Hg, brain pH was 7.0 +/- 0.2, and brain temperature was 36.7 +/- 0.7 degrees C. Hypocapnia and hypoxemia produced a significant decline in tissue oxygen (< or = 30 +/- 3 mm Hg; P < 0.001), whereas hypercapnia caused by hypoventilation and intracranial pressure increase produced a significant increase in tissue CO2 (> or = 74 +/- 4 mm Hg; P < 0.001). Focal ischemia produced a rapid 42% decline in brain oxygen (25 +/- 7 mm Hg) and a 25% increase in tissue pCO2 (71 +/- 23 mm Hg). Brain oxygen further decreased to 19 +/- 6 mm Hg toward the end of the experiment, 4 hours later. After middle cerebral artery occlusion, the regional cerebral blood flow decreased to 10 +/- 5 ml per 100 g per minute, within the 1st hour, from a baseline value of 65 +/- 15 ml per 100 g per minute. It then gradually increased to 15 +/- 5 ml per 100 g per minute by the end of the 4-hour experiment. Brain pH was closely and inversely related to brain CO2. The brain temperature in the focally ischemic tissue decreased from 36.7 +/- 0.7 to 35.5 +/- 1.6 degrees C by the end of the experiment. The in vitro experiment demonstrated good linear correlation between the sensor readings and the blood gas analysis. Continuous monitoring of oxygen, CO2, pH, and temperature in damaged or at-risk brain tissue using a single sensor is now feasible and will, thus, allow improved continuous monitoring of neurosurgical patients who are at risk of significant secondary brain damage.
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PMID:Brain oxygen, CO2, pH, and temperature monitoring: evaluation in the feline brain. 858 58


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