The relation between arterial oxygen tension and cerebral blood flow during cardiopulmonary bypass

BACKGROUND: The precise mechanisms involved in islet xenograft rejection remain unknown. The purpose of the present study was to determine cellular mechanisms responsible for islet xenograft rejection in the liver to facilitate finding a procedure for prevention of immune rejection. METHODS: Hepatic mononuclear cells (MNC) as well as splenocytes, peripheral blood MNC, and thymocytes from streptozotocin-induced diabetic mice (BALB/c) rejecting the intrahepatic rat (Lewis) islet xenografts were isolated and examined by two-color FACS analysis. RESULTS: The characteristic finding of the hepatic MNC from the mice rejecting islet xenografts compared with mice receiving isografts was a significant increase in the yield as well as in the percentage of the cells expressing CD3+ interleukin-2 receptor (IL-2R) alpha- beta+, CD3+ CD8alpha+ beta+, and T cell receptor (TCR) alphabeta+ lymphocyte function-associated antigen-1+. The expression of CD3 and TCR alphabeta of these T cells was found to be of intermediate intensity (TCR(int) cells). The expansion of these TCR(int) cells occurred predominantly in the liver. There was no significant difference in the cells expressing CD3+ IL-2R alpha+, CD3+ CD4+, CD3+ TCRgammadelta+, CD3- IL-2Rbeta+ (natural killer cells), and B220+ (B cells). In vivo administration of anti-IL-2Rbeta monoclonal antibody directed to the expanded cells produced a prevention of rejection. CONCLUSIONS: These findings suggest that islet xenograft rejection in the liver from rat to mouse is an event for which the TCR(int) cells are responsible.     

The effects of hemodilution on cerebral hemodynamics and oxygen consumption during nonpulsatile hypothermic cardiopulmonary bypass

The effects of hemodilution on cerebral hemodynamics and oxygen consumption during nonpulsatile hypothermic cardiopulmonary bypass (CPB) were investigated in 16 patients undergoing elective open heart surgery under CPB. They were divided into 2 groups; high (25%) (H) and low hematocrit (15%) (L) groups according to the hematocrit values during CPB. Simultaneous measurements of blood flow velocity in the middle cerebral artery (VMCA) and oxygen tension in the jugular venous bulb (PjvbO2) were performed at prebypass, bypass, and post bypass periods. There were no significant differences in nasopharyngeal temperature (NPT), cerebral perfusion pressure, pump flow rate, and PaCO2 between the two groups at any period. VMCA changed in correlation with NPT in both groups, and VMCA in the L group was faster than that in the H group at any period. PjvbO2 increased during aortic cross clamp, and decreased on rewarming in both groups. However, there were no significant differences in VMCA and PjvbO2 between the two groups at any period. These findings suggest that increased cerebral blood flow may compensate the decreased oxygen content due to the hemodilution during CPB. Therefore, the profound hemodilution up to 15% of hematocrit is considered to be a safe technique during CPB.     

Measurement of cerebral blood flow during cardiopulmonary bypass with near-infrared spectroscopy

OBJECTIVES: We sought to assess the incidence and clinical relevance of examination data to recurrent ischemia within an international randomized trial. BACKGROUND: Ischemic symptoms commonly recur after thrombolysis for acute myocardial infarction. METHODS: Patients (n = 40,848) were prospectively evaluated for recurrent angina and transient electrocardiographic (ECG) or hemodynamic changes. Five groups were developed: Group 1, patients with no signs or symptoms of recurrent ischemia; Group 2, patients with angina only; Group 3, patients with angina and ST segment changes; Group 4, patients with angina and hemodynamic abnormalities; and Group 5, patients with angina, ST segment changes and hemodynamic abnormalities. Baseline clinical and outcome variables were compared among the five groups. RESULTS: Group 1 comprised 32,717 patients, and Groups 2 to 5 comprised 20% of patients (4,488 in Group 2; 3,021 in Group 3; 337 in Group 4; and 285 in Group 5). Patients with recurrent ischemia were more often female, had more cardiovascular risk factors and less often received intravenous heparin. Significantly more extensive and more severe coronary disease, antianginal treatment, angioplasty and coronary bypass surgery were observed as a function of ischemic severity. The 30-day reinfarction rate was 1.6% in Group 1, 6.5% in Group 2, 21.7% in Group 3, 13.1% in Group 4 and 36.5% in Group 5 (p < 0.0001); in contrast, the 30-day mortality rate was significantly lower (p < 0.0001) in Groups 1, 2 and 3 (6.6%, 5.4% and 7.7%, respectively) than in Groups 4 and 5 (21.8% and 29.1%). CONCLUSIONS: Postinfarction angina greatly increases the risk of reinfarction, especially when accompanied by transient ECG changes. However, mortality is markedly increased only in the presence of concomitant hemodynamic abnormalities.     

Renal blood flow velocity in acute renal failure following cardiopulmonary bypass surgery

Two lysosomal storage diseases, aspartylglucosaminuria and mannosidosis, are associated with highly elevated serum dolichol concentrations. To elucidate possible mechanisms leading to elevated serum dolichols, we studied the effects of Triton WR 1339 (known to increase serum cholesterol) and orotic acid (known to decrease serum cholesterol) on blood and biliary dolichol and beta-hexosaminidase levels in rats. In Triton WR 1339-treated rats, serum dolichol was markedly increased compared with saline-treated controls 1 (400 +/- 70 ng/mL, n = 7 v 85 +/- 11 ng/mL, n = 8, P < .001), 4 (789 +/- 70 ng/mL, n = 10 v 110 +/- 10 ng/mL, n = 7, P < .0001), and 8 (549 +/- 43 ng/mL, n = 8 v 87 +/- 8 ng/mL, n = 7, P < .001) days after administration of the drug. By contrast, serum dolichol was decreased (64 +/- 5 ng/mL, n = 8 v 119 +/- 7 ng/mL, n = 8, P < .0001) after a 7-day orotic acid feeding compared with controls. Serum beta-hexosaminidase was unaffected by both treatments. Orotic acid also increased biliary dolichol (280 +/- 47 ng/100 g body weight [BW]/h, n = 7 v 83 +/- 15 ng/100 g BW/h, n = 7, P < .01) and beta-hexosaminidase (21 +/- 3 mU/100 g BW/h, n = 7 v 8.3 +/- 2 mU/100 g BW/h, n = 9, P < .01) excretion compared with controls. Thus, both Triton WR 1339 and orotic acid have an effect on dolichol metabolism, and it is conceivable--based on our results--that serum dolichol concentrations are regulated, at least in part, by a mechanism similar to that for serum cholesterol levels.     

Gut mucosal ischemia during normothermic cardiopulmonary bypass results from blood flow redistribution and increased oxygen demand

Impaired gut mucosal perfusion has been reported during cardiopulmonary bypass. To better define the adequacy of gut blood flow and oxygenation during cardiopulmonary bypass, we measured overall gut blood flow and ileal mucosal flow and their relationship to mucosal pH, mesenteric oxygen delivery and oxygen consumption in immature pigs (n = 8). Normothermic, noncross-clamped, right atrium-to-aorta cardiopulmonary bypass was maintained at 100 ml/kg per minute for 120 minutes. Animals were instrumented with an ultrasonic Doppler flow probe on the superior mesenteric artery, a mucosal laser Doppler flow probe in the ileum, and pH tonometers in the stomach, ileum, and rectum. Radioactive microspheres were injected before and at 5, 60, and 120 minutes of cardiopulmonary bypass for tissue blood flow measurements. Overall gut blood flow significantly increased during cardiopulmonary bypass as evidenced by increases in superior mesenteric arterial flow to 134.1% +/- 8.0%, 137.1% +/- 7.5%, 130.3% +/- 11.2%, and 130.2% +/- 12.7% of baseline values at 30, 60, 90, and 120 minutes of bypass, respectively. Conversely, ileal mucosal blood flow significantly decreased to 53.6% +/- 6.4%, 49.5% +/- 6.8%, 58.9% +/- 11.6%, and 47.8% +/- 10.0% of baseline values, respectively. Blood flow measured with microspheres was significantly increased to proximal portions of the gut, duodenum and jejunum, during cardiopulmonary bypass, whereas blood flow to distal portions, ileum and colon, was unchanged. Gut mucosal pH decreased progressively during cardiopulmonary bypass and paralleled the decrease in ileal mucosal blood flow. Mesenteric oxygen delivery decreased significantly from 67.0 +/- 10.0 ml/min per square meter at baseline to 42.4 +/- 4.6, 44.9 +/- 3.5, 46.0 +/- 3.6, and 42.9 +/- 3.9 ml/min per square meter at 30, 60, 90, and 120 minutes of bypass. Despite the decrease in mesenteric oxygen delivery, mesenteric oxygen consumption increased progressively from 10.8 +/- 1.4 ml/min per square meter at baseline to 13.4 +/- 1.2, 15.9 +/- 1.2, 16.7 +/- 1.4, and 16.6 +/- 1.54 ml/min per square meter, respectively. We conclude that gut mucosal ischemia during normothermic cardiopulmonary bypass results from a combination of redistribution of blood flow away from mucosa and an increased oxygen demand.     

The effect of remifentanil on cerebral blood flow velocity

High concentrations of lidocaine induce irreversible conduction block with little effect on resting membrane potential (Em). We assumed the mechanism of persistent neurologic deficit caused by local anesthetics may result from neural death, as represented by the loss of Em. We investigated the effects of lidocaine on Em and action potential (AP) in single crayfish giant axons in vitro. Axons were perfused with two doses of lidocaine for either 15 or 30 min, and they were continuously washed. No axons exposed to 80 mM lidocaine for 30 min showed recovery of AP and Em. Those exposed to 40 mM for 30 min and 80 mM for 15 min showed a return to baseline for Em, but no recovery of AP. Those exposed to 40 mM lidocaine for 15 min showed full recovery of Em and AP immediately after washing. The membrane depolarization was significantly greater during exposure to 80 mM lidocaine for 30 min than in other groups. We conclude that lidocaine has a direct neurotoxic effect on crayfish giant axons and that the generation of AP is more vulnerable than the maintenance of Em. The irreversibility of AP and Em is dose- and time-dependent. IMPLICATIONS: Highly concentrated lidocaine induced an irreversible conduction block and a complete loss of resting membrane potential in crayfish giant axons in vitro. Our results may represent a possible explanation for various grades of local anesthetic-induced neurotoxicity in clinical cases if the same toxicity occurs in mammalian nerves in vivo.     

Hepato-splanchnic blood flow and oxygen extraction capabilities during experimental tamponade: effects of endotoxin

We studied the hepato-splanchnic vascular response and changes in O2 extraction capabilities to a reduction in blood flow following endotoxemia. Fourteen anesthetized and mechanically ventilated dogs were divided into two groups of seven each. Group 1 received 2 mg/kg of E. coli endotoxin, and group 2 served as a control. After initial fluid resuscitation following endotoxic shock, regional blood flow estimated by an ultrasonic technique increased similarly in the hepatic artery, portal vein, and mesenteric artery, but microvascular blood flow estimated by a laser Doppler technique was lower in the liver than in the intestinal mucosa. When blood flow was reduced by cardiac tamponade, endotoxin-treated animals had greater whole body and regional critical O2 delivery (DO2crit) and lower whole body, liver, and intestinal critical O2 extraction ratios (O2ERcrit). DO2crit was higher in the liver than in intestine but O2ERcrit was similar in the two organs. Whole body DO2crit at the onset of organ O2 supply dependency was similar under control (9.4 +/- 1.9 mL/kg. min for whole body, 10.3 +/- 4.7 mL/kg. min for liver, and 10.0 +/- 2.6 mL/kg. min for intestine) and endotoxic conditions (13.6 +/- 3.2 mL/kg. min for whole body, 15.6 +/- 2.7 mL/kg. min for liver, and 15.4 +/- 8.7 mL/kg. min for intestine). We conclude that fluid-resuscitated endotoxic shock in dogs is characterized by blood flow redistribution within the liver and intestine. Microvascular depression may be more severe in the liver than in the intestinal mucosa, although the whole body, the liver, and the intestine became O2 supply-dependent simultaneously.     

Pulsatile versus nonpulsatile flow. No difference in cerebral blood flow or metabolism during normothermic cardiopulmonary bypass in rabbits

BACKGROUND: Although pulsatile and nonpulsatile cardiopulmonary bypass (CPB) do not differentially affect cerebral blood flow (CBF) or metabolism during hypothermia, studies suggest pulsatile CPB may result in greater CBF than nonpulsatile CPB under normothermic conditions. Consequently, nonpulsatile flow may contribute to poorer neurologic outcome observed in some studies of normothermic CPB. This study compared CBF and cerebral metabolic rate for oxygen (CMRO2) between pulsatile and nonpulsatile CPB at 37 degrees C. METHODS: In experiment A, 16 anesthetized New Zealand white rabbits were randomized to one of two pulsatile CPB groups based on pump systolic ejection period (100 and 140 ms, respectively). Each animal was perfused at 37 degrees C for 30 min at each of two pulse rates (150 and 250 pulse/min, respectively). This scheme created four different arterial pressure waveforms. At the end of each perfusion period, arterial pressure waveform, arterial and cerebral venous oxygen content, CBF (microspheres), and CMRO2 (Fick) were measured. In experiment B, 22 rabbits were randomized to pulsatile (100-ms ejection period, 250 pulse/min) or nonpulsatile CPB at 37 degrees C. At 30 and 60 min of CPB, physiologic measurements were made as before. RESULTS: In experiment A, CBF and CMRO2 were independent of ejection period and pulse rate. Thus, all four waveforms were physiologically equivalent. In experiment B, CBF did not differ between pulsatile and nonpulsatile CPB (72 +/- 6 vs. 77 +/- 9 ml.100 g-1.min-1, respectively (median +/- quartile deviation)). CMRO2 did not differ between pulsatile and nonpulsatile CPB (4.7 +/- 0.5 vs. 4.1 +/- 0.6 ml O2.100 g-1.min-1, respectively) and decreased slightly (0.4 +/- 0.4 ml O2.100 g-1.min-1) between measurements. CONCLUSIONS: During CPB in rabbits at 37 degrees C, neither CBF nor CMRO2 is affected by arterial pulsation. The absence of pulsation per se is not responsible for the small decreases in CMRO2 observed during CPB.     

Comparative effects of propofol, pentobarbital, and isoflurane on cerebral blood flow and blood volume

While intravenous and volatile anesthetics have widely differing effects on cerebral blood flow (CBF), clinical studies suggest that the relative differences in their effects on intracranial pressure (ICP) may be smaller. Because acute changes in ICP are determined primarily by changes in cerebral blood volume (CBV), we compared the impact of propofol, pentobarbital, and isoflurane on CBF and CBV in rats. Equipotent doses of the three agents were determined by tail-clamp studies. Animals were then anesthetized with propofol (20 mg/kg load, 38 mg.kg-1.h-1 infusion), pentobarbital (30 mg/kg load, 20 mg.kg-1.h-1 infusion), or isoflurane 1.6-1.8%. Two hours later, CBF and CBV were measured using 3H-nicotine as a CBF tracer, and 14C-dextran and 99mTc-labeled red cells as markers for cerebral plasma and red blood cell volumes (CPV and CRBCV), respectively. Total CBV was the sum of CPV and CRBCV. CBF was 2.0-2.6 times greater with isoflurane than with propofol or pentobarbital (137 vs. 67 and 52 ml.100 g-1.min-1, respectively). By contrast, while CBV was greater in the isoflurane group than in either the propofol or pentobarbital groups, the magnitude of the intergroup differences were much smaller (propofol = 2.49 +/- 0.28 ml/100 g; pentobarbital = 2.27 +/- 0.15 ml/100 g; isoflurane = 2.77 +/- 0.24 ml/100 g, mean +/- SD). These results suggest that the simple measurement of CBF may not adequately describe the cerebrovascular effects of an anesthetic, at least with respect to predicting the magnitude of the agents likely effects on ICP.     

Autologous blood transfusion during cardiopulmonary bypass

Immediately prior to cardiopulmonary bypass, two units of blood were removed from each of 25 patients undergoing open-heart surgery, and the autologous blood was reinfused after cessation of support with the pump oxygenator. Pertinent data on blood balance and hematologic measurements were compared to a matched group of control subjects. There were no significant differences in the amount of operative or postoperative bleeding, the requirements for homologous blood and blood products, or the amount of protamine needed for neutralization of heparin.     

Cerebral blood flow velocity in relation to cerebral blood flow, cerebral metabolic rate for oxygen, and electroencephalogram analysis during isoflurane anesthesia in dogs

The purpose of this study was to correlate changes in cerebral blood flow velocity (Vmean) with cerebral blood flow (CBF) during isoflurane anesthesia in dogs. The relation between cerebral oxygen consumption (CMRO2) and electroencephalogram (EEG) analysis also was investigated. Blood flow velocity was measured in the middle cerebral artery using a pulsed transcranial Doppler (TCD). CBF was measured with radioactive microspheres. EEG was measured over both hemispheres and median EEG frequency (median frequency) was calculated after fast Fourier transformation. Baseline anesthesia was maintained with 50% nitrous oxide in oxygen and 50 micrograms.kg-1 x h-1 fentanyl. Animals of Group I (control, n = 6) were not given isoflurane. Data were recorded at baseline, and at 30, 60, and 90 min. There was no significant change in any variable over time. In Group II (n = 7), data were recorded at baseline and at 1%, 2%, and 3% end-tidal isoflurane. Mean arterial pressure was maintained at baseline levels by phenylephrine infusion. CBF increased from 70.8 +/- 10.6 mL.100g-1 x min-1 at baseline to 146.1 +/- 36.9 mL.100 g-1 x min-1 with 3% isoflurane (P < 0.01). Vmean increased from 38.3 +/- 6.7 cm/s to 65.6 +/- 9.7 cm/s (P < 0.01). The correlation between relative changes in CBF and Vmean was r = 0.94 (P < 0.01). With 1% isoflurane the EEG shifted to slow-wave, high-voltage activity, and median frequency decreased from 5.9 +/- 0.7 Hz to 1.4 +/- 0.4 Hz (P < 0.05). Median frequency was not decreased further during 2% and 3% isoflurane anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regional blood flow during pulsatile cardiopulmonary bypass and after circulatory arrest in an infant model

BACKGROUND: Pulsatile perfusion systems have been proposed as a means of improving end-organ perfusion during and after cardiopulmonary bypass. Few attempts have been made to study this issue in an infant model. METHODS: Neonatal piglets were subjected to nonpulsatile (n = 6) or pulsatile (n = 7) cardiopulmonary bypass and 60 minutes of circulatory arrest. Cerebral, renal, and myocardial blood flow measurements were obtained at baseline, on bypass before and after circulatory arrest, and after bypass. RESULTS: Cerebral blood flow did not differ between groups at any time and was diminished equally in both groups after circulatory arrest. Renal blood flow was diminished in both groups during bypass but was significantly better in the pulsatile group than in the nonpulsatile group prior to, but not after, circulatory arrest. Myocardial blood flow was maintained at or above baseline in the pulsatile group throughout the study, but in the nonpulsatile group, it was significantly lower than baseline during CPB prior to circulatory arrest and lower compared with baseline and with the pulsatile group 60 minutes after CPB. CONCLUSIONS: Pulsatile bypass does not improve recovery of cerebral blood flow after circulatory arrest, may improve renal perfusion during bypass but does not improve its recovery after ischemia, and may have beneficial effects on myocardial blood flow during bypass and after ischemia compared with nonpulsatile bypass in this infant model.     

The effect of phototherapy on cerebral blood flow velocity in preterm infants

Cerebral blood flow velocity was studied with two-dimensional/pulsed Doppler ultrasound before, during and after discontinuation of phototherapy in 22 preterm infants (gestational age < or =32 weeks), who were treated for a minimum of 12h with blue-light phototherapy for non-haemolytic hyperbilirubinaemia. Before the cerebral blood flow velocity measurements, patency of the ductus arteriosus was diagnosed by Doppler echocardiography. All infants had normal brain ultrasound scans. Mean cerebral blood flow velocity increased significantly after initiation of phototherapy in all infants. Only in "healthy" (non-ventilated) infants did cerebral blood flow velocity return to pre-phototherapy values (baseline) after discontinuation of phototherapy, whereas in "unhealthy" (ventilated) infants cerebral blood flow velocity did not return to baseline. In 10 infants the ductus arteriosus reopened during phototherapy. In those infants, mean cerebral blood flow velocity returned to pre-phototherapy values after 2 h of phototherapy prior to its discontinuation.     

Transcranial Doppler sonographic measurements of middle cerebral artery flow velocity during hyperbaric oxygen exposures

In the present study, experimental exposures to hyperbaric oxygen (HBO2) were performed (30-min exposure to 2.8 bar (280 kPa) pure oxygen). During all phases of the experiment, blood flow velocity in the right middle cerebral artery was monitored with transcranial Doppler (TCD) sonography. Time courses of heart rate, blood pressure, respiratory rate, end-tidal CO2, and TCD mean velocity (Vmean) are described for a group of 23 subjects during uncomplicated exposure to HBO2 and for three subjects who showed signs of central nervous system (CNS) O2 toxicity, including one subject with a HBO2-induced generalized tonic-clonic seizure. Hyperbaric oxygen decreased Vmean an effect that could not completely be explained by changes in end-tidal CO2. The findings of the present study are in agreement with the concept that an increase in partial oxygen pressure is the primary factor underlying CNS O2 toxicity. Of the variables analyzed, the TCD Vmean is the most valuable variable for monitoring a HBO2 exposure. The Vmean showed the most pronounced change during HBO2 application, and in one subject a sudden increase in Vmean during HBO2 exposure heralded toxicity before clinical signs. It should be realized, however, that the small series of subjects with toxicity in this study does not allow us to draw definite conclusions.     

Comparison of pH-stat and alpha-stat cardiopulmonary bypass on cerebral oxygenation and blood flow in relation to hypothermic circulatory arrest in piglets

Melagatran, a new, competitive and rapid inhibitor of thrombin with a molecular mass of 429 Da is described. Melagatran is well tolerated when administered in very high doses, and the oral bioavailability in the dog is relatively high. The aim of the study was to determine, in the preclinical setting, the degree of selectivity against the fibrinolytic system required for entering the clinical development phase. Melagatran was compared with two structurally similar thrombin inhibitors, inogatran and H 317/86. The potent inhibition of thrombin by melagatran was demonstrated by a low inhibition constant (Ki) for thrombin (0.002 micromol/l) and prolongation of clotting time to twice the control value in coagulation assays at low concentrations (0.010, 0.59 and 2.2 micromol/l for thrombin time, activated partial thromboplastin time and prothrombin time, respectively). Furthermore, thrombin-induced platelet aggregation was inhibited at the same concentration (IC50-value 0.002 micromol/l) as the Ki-value for thrombin. In two assays of global fibrinolysis, inhibition was observed at a concentration of 1.1 micromol/l in a euglobulin plasma fraction model, while no inhibition was observed at a concentration of < or = 10 micromol/l in a plasma model. In an in vivo model of endogenous fibrinolysis in the rat, inhibition of fibrinolysis was observed at > or = 1.0 micromol/l. In all assays, except the Ki-ratio determinations, the compounds could be graded with regard to selectivity against the fibrinolytic system: inogatran > melagatran > H 317/86. For melagatran, inhibition of fibrinolysis was not observed at concentrations below the upper limit of the proposed therapeutic plasma concentration interval (< 0.5 micromol/l). Thus, melagatran seems to have a sufficient selectivity against the fibrinolytic system, while H 317/86 was considered to be insufficient for clinical development.     

Effect of the no-flow interval and hypothermia on cerebral blood flow and metabolism during cardiopulmonary resuscitation in dogs

BACKGROUND and PURPOSE: We sought (1) to determine the effect of brief periods of no flow on the subsequent forebrain blood flow during cardiopulmonary resuscitation (CPR) and (2) to test the hypothesis that hypothermia prevents the impact of the no-flow duration on cerebral blood flow (CBF) during CPR. METHODS: No-flow intervals of 1.5, 3, and 6 minutes before CPR at brain temperatures of 28 degreesC and 38 degreesC were compared in 6 groups of anesthetized dogs. Microsphere-determined CBF and metabolism were measured before and during vest CPR adjusted to maintain cerebral perfusion pressure at 25 mm Hg. RESULTS: Increasing the no-flow interval from 1.5 to 6 minutes at 38 degreesC decreased the CBF (18. 6+/-3.6 to 6.1+/-1.7 mL/100 g per minute) and the cerebral metabolic rate (2.1+/-0.3 to 0.7+/-0.2 mL/100 g per minute) during CPR. Cooling to 28 degreesC before and during the arrest eliminated the detrimental effects of increasing the no-flow interval on CBF (16. 8+/-1.0 to 14.8+/-1.9 mL/100 g per minute) and cerebral metabolic rate (1.1+/-0.1 to 1.3+/-0.1 mL/100 g per minute). Unlike the forebrain, 6 minutes of preceding cardiac arrest did not affect brain stem blood flow during CPR. CONCLUSIONS: Increasing the no-flow interval to 6 minutes in normothermic animals decreases the supratentorial blood flow and cerebral metabolic rate during CPR at a cerebral perfusion pressure of 25 mm Hg. Cooling to 28 degreesC eliminates the detrimental impact of the 6-minute no-flow interval on the reflow produced during CPR. The brain-protective effects of hypothermia include improving reflow during CPR after cardiac arrest. The effect of hypothermia and the impact of short durations of no flow on reperfusion indicate that increasing viscosity and reflex vasoconstriction are unlikely causes of the "no-reflow" phenomenon.     

Hypothermic modulation of cerebral ischemic injury during cardiopulmonary bypass in pigs

BACKGROUND: The aim of this study was to determine whether progressive levels of hypothermia (37, 34, 31, or 28 degrees C) during cardiopulmonary bypass (CPB) in pigs reduce the physiologic and metabolic consequences of global cerebral ischemia. METHODS: Sagittal sinus and cortical microdialysis catheters were inserted into anesthetized pigs. Animals were placed on CPB and randomly assigned to 37 degrees C (n = 10), 34 degrees C (n = 10), 31 degrees C (n = 11), or 28 degrees C (n = 10) management. Next 20 min of global cerebral ischemia was produced by temporarily ligating the innominate and left subclavian arteries, followed by reperfusion, rewarming, and termination of CPB. Cerebral oxygen metabolism (CMRO2) was calculated by cerebral blood flow (radioactive microspheres) and arteriovenous oxygen content gradient. Cortical excitatory amino acids (EAA) by microdialysis were measured using high-performance liquid chromatography. Electroencephalographic (EEG) signals were graded by observers blinded to the protocol. After CPB, cerebrospinal fluid was sampled to test for S-100 protein and the cerebral cortex was biopsied. RESULTS: Cerebral oxygen metabolism increased after rewarming from 28 degrees C, 31 degrees C, and 34 degrees C CPB but not in the 37 degrees animals; CMRO2 remained lower with 37 degrees C (1.8 +/- 0.2 ml x min[-1] x 100 g[-1]) than with 28 degrees C (3.1 +/- 0.1 ml x min[-1] x 100 g[-1]; P < 0.05). The EEG scores after CPB were depressed in all groups and remained significantly lower in the 37 degrees C animals. With 28 degrees C and 31 degrees C CPB, EAA concentrations did not change. In contrast, glutamate increased by sixfold during ischemia at 37 degrees C and remained significantly greater during reperfusion in the 34 degrees C and 37 degrees C groups. Cortical biopsy specimens showed no intergroup differences in energy metabolites except two to three times greater brain lactate in the 37 degrees C animals. S-100 protein in cerebrospinal fluid was greater in the 37 degrees C (6 +/- 0.9 microg/l) and 34 degrees C (3.5 +/- 0.5 microg/l) groups than the 31 degrees C (1.9 +/- 0.1 microg/l) and 28 degrees C (1.7 +/- 0.2 microg/l) animals. CONCLUSIONS: Hypothermia to 28 degrees C and 31 degrees C provides significant cerebral recovery from 20 min of global ischemia during CPB in terms of EAA release, EEG and cerebral metabolic recovery, and S-100 protein release without greater advantage from cooling to 28 degrees C compared with 31 degrees C. In contrast, ischemia during 34 degrees C and particularly 37 degrees C CPB showed greater EAA release and evidence of neurologic morbidity. Cooling to 31 degrees C was necessary to improve acute recovery during global cerebral ischemia on CPB.     

The effects of sevoflurane on cerebral blood flow autoregulation in rats

In all species tested, except humans, biological differences between vitamins D2 and D3 are accepted as fact. To test the presumption of equivalence in humans, we compared the ability of equal molar quantities of vitamin D2 or D3 to increase serum 25-hydroxyvitamin D [25(OH)D], the measure of vitamin D nutrition. Subjects took 260 nmol (approximately 4000 IU) vitamin D2 (n=17) or vitamin D3 (n=55) daily for 14 d. 25(OH)D was assayed with a method that detects both the vitamin D2 and D3 forms. With vitamin D3, mean (+/-SD) serum 25(OH)D increased from 41.3+/-17.7 nmol/L before to 64.6+/-17.2 nmol/L after treatment. With vitamin D2, the 25(OH)D concentration went from 43.7+/-17.7 nmol/L before to 57.4+/-13.0 nmol/L after. The increase in 25(OH)D with vitamin D3 was 23.3+/-15.7 nmol/L, or 1.7 times the increase obtained with vitamin D2 (13.7+/-11.4 nmol/L; P=0.03). There was an inverse relation between the increase in 25(OH)D and the initial 25(OH)D concentration. The lowest 2 tertiles for basal 25(OH)D showed larger increases in 25(OH)D: 30.6 and 25.5 nmol/L, respectively, for the first and second tertiles. In the highest tertile [25(OH)D >49 nmol/L] the mean increase in 25(OH)D was 13.3 nmol/L (P < 0.03 for comparison with each lower tertile). Although the 1.7-times greater efficacy for vitamin D3 shown here may seem small, it is more than what others have shown for 25(OH)D increases when comparing 2-fold differences in vitamin D3 dose. The assumption that vitamins D2 and D3 have equal nutritional value is probably wrong and should be reconsidered.