Mean Arterial PO2 Research Articles

Time window of fibroblast growth factor-18-mediated neuroprotection after occlusion of the middle cerebral artery in rats.

To assess the time window for fibroblast growth factor-18 (FGF18)-mediated neuroprotection, FGF18 was administered by intravenous infusion at various times after transient occlusion of the middle cerebral artery (MCAO) in rats. Vehicle or FGF18 (100 microg x kg(-1) x h(-1)) was infused at 0.25, 0.5, 1.0, 2.0, 4.0, or 8.0 hours after MCAO with infarct volumes and behavioral deficits measured at 24.0 hours after MCAO. A separate group of animals received the infusions 24 hours after MCAO with endpoints measured at 48 hours after MCAO. Infusion of FGF18 reduced infarct volumes and improved scores in tests of reference and working memory, motor ability, and exploratory behavior. FGF18 was most efficacious when infused within 2 hours after MCAO. Significant reductions in infarct volumes and reductions in deficits of reference memory and motor activity were also observed with FGF18 infused 24 hours after MCAO. Measurements taken at infusion times before 2 hours after MCAO showed that regional cerebral blood flow was increased by FGF18. Administration of vehicle or FGF18 had no significant effect on mean arterial blood pressure, heart rate, brain temperature, blood pH, Pco2, or Po2. These results demonstrate that FGF18 is an effective neuroprotective agent when administered early after transient MCAO in rats. Efficacy observed with infusions at later times suggests an expanded time window for FGF18-mediated neuroprotection.

Hemodynamic changes during complete umbilical cord occlusion in fetal sheep related to hippocampal neuronal damage

Objectives: The purpose of our study was to examine the physiologic changes caused by 10 minutes of umbilical cord occlusion in fetal sheep and to determine the correlation between fetal acidemia or cerebral ischemia and hippocampal neuronal damage. Study design: Thirteen fetal sheep were instrumented and catheterized. Carotid artery blood flow (CaF), fetal mean arterial blood pressure (FMABP), pH, PCO2, base excess, oxygen saturation (SatO2), and PO2 were monitored throughout the occlusion study. Brain sections were examined for the hippocampal neuronal damage. Results: Our data showed severe ischemia (CaF: 10 ± 7 mL/min; FMABP: 29 ± 8 mm Hg) and acidemia (pH: 7.0 ± 0.05; base excess: −9.9 ± 2.4 mEq/L) at the end of occlusion. The neuronal damage score had significant correlations with ischemia and also with reperfusion, but not with the acidemic or hypoxic parameters. Conclusion: We demonstrated that the degree of hippocampal damage was correlated with the degree of ischemia and reperfusion. (Am J Obstet Gynecol 2003;188:413-8.)

Placental Restriction Increases the Expression of Prostaglandin Endoperoxide G/H Synthase-2 and EP2 mRNA in the Fetal Sheep Kidney during Late Gestation

There is evidence that fetal growth restriction is associated with impaired nephrogenesis and reduced numbers of mature nephrons at birth. It has been proposed that such impairment of renal growth may contribute to increased blood pressure in later life. Although prostaglandins (PG) play a key role in kidney development, it is unknown whether a poor fetal substrate supply alters the synthesis or actions of PG within the fetal kidney. Using real-time reverse transcriptase PCR, we have measured the effect of chronic placental restriction (PR) on the renal expression of PG endoperoxide G/H synthase-2 (PGHS-2), PGE2 receptors EP2 and EP4, and renin mRNA in the sheep fetus in late gestation. Restriction of placental growth reduced fetal body weight (PR: 3.2 ± 0.2 kg, control: 4.8 ± 0.2 kg) and total kidney weight (PR: 19.7 ± 1.8 g, control: 25.1 ± 1.3 g). Mean fetal arterial Po2 was reduced by PR (PR: 15.03 ± 0.67 mm Hg, control: 21.3 ± 0.87 mm Hg). Renal PGHS-2 mRNA was increased in the PR group (PR: 2.26 ± 0.38, control: 1.20 ± 0.31) and was inversely related to mean fetal arterial Po2 in the PR and control groups [PGHS-2: −0.17 (Po2) + 4.69, r2 = 0.26]. PR also increased renal EP2 (PR: 1.57 + 0.24, control: 0.82 + 0.13) but not EP4 mRNA. Renin mRNA was directly related to renal EP2 [renin = 0.37 (EP2) + 0.97, r2 = 0.29] and EP4, [renin = 0.75 (EP4) + 0.44, r2 = 0.38] mRNA expression. Thus, the restriction of placental growth and associated chronic hypoxemia appear to increase the renal capacity to synthesize and respond to PG, which may play an important role in maintaining renin mRNA expression in the growth-restricted fetus.

Uso do óxido nítrico inalatório no tratamento da crise hipertensiva pulmonar no pós-operatório de transplante cardíaco

OBJETIVO: Este trabalho relata a experiência no manuseio da crise hipertensiva pulmonar (CHP) refratária, com o uso do óxido nítrico inalatório (NOi) no pós-operatório imediato do transplante cardíaco (TC) ortotópico. MÉTODOS: De outubro/1997 a fevereiro/2002 foram realizados 31 TC em adultos, sendo incluídos pacientes com RVP < 6uW, ou < 2,5uW na prova farmacológica. Após o período de circulação extracorpórea (CEC) (M=101±21 minutos), todos fizeram uso de dobutamina, dopamina e milrinona; entretanto, frente à ausência de resposta adequada e CHP, administrou-se NOi em doses crescentes de 20 a 40ppm. Foram utilizados registros das pressões através de cateter no átrio esquerdo e no tronco da artéria pulmonar, gasometria arterial seriada e ecocardiograma transtorácico (ETT). O tempo médio de morte encefálica (ME) do doador foi de 16<FONT FACE=Symbol>±5,1</FONT>horas<FONT FACE=Symbol>.</FONT>RESULTADOS: Cinco pacientes (1 mulher), com idade média de 42 anos, fizeram uso de NOi por apresentarem critérios de CHP, todos com sinais de baixo débito cardíaco. O tempo médio de CEC foi de 150,8±34,3 minutos, a média sistólica arterial pulmonar foi de 87mmHg (75-115) e a PO2 média de 60mmHg (FiO2 100%), sendo evidenciada dilatação moderada a severa do ventrículo direito no ETT. Foi administrado NOi durante uma média 35h (6-96), iniciando-se desmame após estabilização hemodinâmica. O tempo médio de ME do doador foi de 27,6±5,5horas, a internação hospitalar média foi de 63 dias (17-145), uma morte ocorreu por sepse no 17º PO e os demais pacientes estão em CF I (NYHA). CONCLUSÕES: O tempo de CEC superior a 120 minutos e tempo de ME do doador superior a 20 horas sugerem fatores de risco para CHP no período pós-operatório imediato do TC. O NOi é uma ferramenta útil no manuseio desta complicação, refratária ao tratamento convencional no POI de pacientes submetidos ao TC.

Single vital capacity breath for preoxygenation.

The report investigates, in awake patients before induction of anesthesia, the effect of preoxygenation by the single vital capacity breath technique following forced exhalation on the mean arterial PO2 (PaO2). In 10 adult patients undergoing elective surgery, the mean PaO2 values achieved 30 sec after preoxygenation by the single vital capacity breath technique was compared with the mean PaO2 values achieved by preoxygenation by the traditional tidal volume breathing for three minutes. Each patient served as her/his own control. The mean PaO2 following the single vital capacity breath technique was higher (295 +/- 67 mmHg) than that achieved by the traditional tidal volume breathing technique at 30 sec and 60 sec, and was not significantly different from that achieved by the traditional technique after three minutes (307 +/- 70 mmHg). The single vital capacity breath technique following forced exhalation can rapidly provide adequate preoxygenation within 30 sec.

Therapeutic effect of tirilazad mesylate (U-74006F), mannitol, and their combination on experimental ischemia.

The effect of tirilazad mesylate (U-74006F), mannitol, and their combination was investigated on focal cerebral ischemia induced by permanent middle cerebral artery (MCA) occlusion in rabbits. Rabbits were divided into four groups receiving vehicle, U-74006F, mannitol, and U-74006F plus mannitol. Hematocrit (hct), glucose, mean arterial blood pressure (MABP), pH, PCO2, and PO2 were measured both before and after occlusion. Seventy-two hours following the permanent MCA occlusion, the neurological outcome was assessed and a quantitative neuropathologic examination was performed in all rabbits. The neurological outcome was better in the rabbits treated with U-74006F plus mannitol than in the other groups. The size of infarction of the affected hemisphere following MCA occlusion was 49.7% in the control group, 30.6% in the U-74006F group, 47.6% in the mannitol group, and 24.1% in the U-74006F plus mannitol group. There was a statistically significant reduction in infarct size in the U-74006F plus mannitol group compared with the other groups (P < 0.05). The ratio of ischemic neurons to total neurons in the cortex was smaller in the U-74006F plus mannitol group than in the other groups. The ratio of ischemic neurons to total neurons in the subcortex was significantly lower in the U-74006F plus mannitol group than in the other groups (P < 0.05). Our data provide evidence for the beneficial effects of both U-74006F and U-74006F plus mannitol in promoting neurological recovery and preservation of the ischemic area.

Restriction of placental and fetal growth in sheep alters fetal blood pressure responses to angiotensin II and captopril.

1. We have measured arterial blood pressure between 115 and 145 days gestation in normally grown fetal sheep (control group; n = 16) and in fetal sheep in which growth was restricted by experimental restriction of placental growth and development (PR group; n = 13). There was no significant difference in the mean gestational arterial blood pressure between the PR (42.7 +/- 2.6 mmHg) and control groups (37.7 +/- 2.3 mmHg). Mean arterial blood pressure and arterial PO2 were significantly correlated in control animals (r = 0.53, P < 0.05, n = 16), but not in the PR group. 2. There were no changes in mean arterial blood pressure in either the PR or control groups in response to captopril (7.5 microg captopril min-1; PR group n = 7, control group n = 6) between 115 and 125 days gestation. After 135 days gestation, there was a significant decrease (P < 0.05) in the fetal arterial blood pressure in the PR group but not in the control group during the captopril infusion (15 microg captopril min-1; PR group n = 7, control group n = 6). 3. There was a significant effect (F = 14.75; P < 0.001) of increasing doses of angiotensin II on fetal diastolic blood pressure in the PR and control groups. The effects of angiotensin II were different (F = 8.67; P < 0.05) in the PR and control groups at both gestational age ranges. 4. These data indicate that arterial blood pressure may be maintained by different mechanisms in growth restricted fetuses and normally grown counterparts and suggests a role for the fetal renin-angiotensin system in the maintenance of blood pressure in growth restricted fetuses.

Differential effects of increasing gestational age and placental restriction on tyrosine hydroxylase, phenylethanolamine N-methyltransferase, and proenkephalin A mRNA levels in the fetal sheep adrenal.

We have demonstrated that there are differential changes in the levels of tyrosine hydroxylase (TH), phenylethanolamine N-methyltransferase (PNMT), and proenkephalin A (Pro Enk A) mRNA in the fetal sheep adrenal during late gestation. Adrenal TH mRNA:18S rRNA ratios increased between gestational days 100 (0.98 +/- 0.13; n = 6) and 125 (1.40 +/- 0.15; n = 6) and then decreased, whereas adrenal PNMT mRNA:18S rRNA ratios increased regularly between gestational days 100 (0.08 +/- 0.01) and 146 (0.17 +/- 0.03). The ratio of adrenal Pro Enk A mRNA to 18S rRNA was higher at gestational day 125 (0.085 +/- 0.005) than at either 80-100 days (0.038 +/- 0.007) or 140-146 days of gestation (0.055 +/- 0.013). In 12 ewes, the growth and development of the placenta were restricted (placental restriction group) from conception. The ratio of adrenal PNMT mRNA to 18S rRNA was significantly reduced in the placental restriction group of fetal sheep (0.003 +/- 0.002) compared with controls (0.011 +/- 0.002), and there was a significant correlation between the ratio of adrenal PNMT mRNA to 18S rRNA and the mean arterial PO2 (r = 0.88, p < 0.0005). In contrast, TH mRNA and Pro Enk mRNA were unaffected by placental restriction. Adrenaline and noradrenaline syntheses are therefore differentially regulated in the adrenal during late gestation and in response to chronic intrauterine hypoxemia.

Physiological implications of hyperbaric oxygen tensions in isolated limb perfusion using melphalan: a pilot study.

Controversy exists concerning the optimal pO2 of the perfusate during isolated limb perfusion (ILP) with melphalan. Therefore we studied the implications of hyperbaric oxygen tensions in the perfusate. In 12 consecutive patients, subcutaneous pO2 (Continucath 1000), tissue and tumor pH, and blood gas values were monitored throughout the ILP procedure. ILP started with an oxygen flow through the bubble oxygenator which was set routinely at one half of the flow of the perfusate; 30 min before the end of ILP, the oxygen flow was tripled. Mean arterial pO2 before and during ILP (before and after increasing the oxygen supply) was 19.4, 25.5 and 49.4 kPa, respectively. Mean subcutaneous pO2 values before, during (before and after increasing the oxygen supply), and post-ILP, were 7.4, 10.1, 16.3, and 9.1 kPa, respectively. Tissue pH values in the subcutis and muscle decreased during routine oxygen supply (p = 0.001); muscle pH moved towards starting values after increase of the oxygen supply (p = 0.011). In 4 patients, tumor pH was recorded showing a rise after increasing the oxygen supply (from 7.10 to 7.22; p = 0.11). In conclusion, high pO2 in the perfusate improves muscle pH during ILP. However, a concomitant rise in tumor pH may unfavorably influence the therapeutic effect of ILP, as it has been shown that low pH increases the cytotoxicity of melphalan.

Dopexamine hydrochloride in septic shock: Effects on oxygen delivery and oxygenation of gut, liver, and muscle: J Trauma Inj Infect Crit Care 1995; 38/5: 767–775

It has been suggested that septic shock is a disorder of microvascular autoregulation. Tissue blood flow is modulated by the state of activation of upstream endothelial receptors controlling the vascular smooth muscle tone. Because vascular receptor populations vary between organs, it should be expected that vasoactive drugs affect tissue oxygenation differently in different organs. We studied the effects of dopexamine HCl (a novel inotrope) and septic shock on oxygen delivery as well as tissue Po2 in gut, liver, and skeletal muscle in anesthetized rabbits. Employing the thermodilution technique, cardiac output was measured across the pulmonary bed and used to calculate oxygen delivery. Three eight-channel Mehrdraht Dortmund Oberflache oxygen electrodes were placed on gut serosa, liver, and skeletal muscle surfaces, respectively, and sufficient readings were obtained to calculate tissue Po2 distributions. During septic shock mean arterial pressure, cardiac output, oxygen delivery, and mean tissue Po2 decreased in all organs. Our results suggest that the observed changes in tissue oxygenation during septic shock were caused by defective regulation of microvascular blood flow. In conclusion, during baseline conditions dopexamine HCl caused no statistically significant changes in tissue oxygenation in any organ, except in skeletal muscle at 10 micrograms/kg/min when tissue Po2 increased. During septic shock, however, dopexamine HCl improved oxygenation in all three organs in a dose-dependent manner.

Does Hypoxia or Hypercarbia Independently Affect Resuscitation From Cardiac Arrest?

In a previous cardiopulmonary resuscitation (CPR) study in swine, ventilation was associated with improved rate of return of spontaneous circulation (ROSC) compared with nonventilated animals, which had greater hypoxia and hypercarbic acidosis. We used the same model to determine the independent effect of hypoxia and hypercarbic acidosis on ROSC after cardiac arrest. Laboratory model of cardiac arrest. University teaching hospital laboratory. Domestic swine (23 to 61 kg). Twenty-four swine were randomly assigned to three groups receiving ventilation during CPR with 85% O2/15% N2 (control), 95% O2/5% CO2 (hypercarbia), or 10% O2/90% N2 (hypoxia). All animals had ventricular fibrillation for 6 min without CPR, then CPR with one of the ventilation gases for 10 min, then defibrillation. Animals without ROSC received epinephrine, 85% O2, CPR for another 3 min, and defibrillation. During the tenth minute of CPR, the hypercarbic group had more mean (SD) arterial hypercarbia than the control group (PCO2, 47 +/- 6, compared with 34 +/- 6; p < 0.01), and greater mixed venous hypercarbia (PCO2, 72 +/- 14, compared with 59 +/- 8; p < 0.05), while mean arterial and mixed venous PO2 was not significantly different. The hypoxic group had significantly less mean arterial (43 +/- 9 compared with 228 +/- 103 mm Hg) and mixed venous (22 +/- 5 compared with 35 +/- 7 mm Hg) PO2 when compared with the control group (p < 0.01), while mean arterial and mixed venous PCO2 were not significantly different. Thus, the model succeeded in producing isolated hypercarbia without hypoxia in the hypercarbic group and isolated hypoxia without hypercarbia in the hypoxic group. The rate of ROSC was 6/8 (75%) for the control group, 1/8 (13%) for the hypercarbic group, and 1/8 (13%) for the hypoxic group (p < 0.02). Both hypoxia and hypercarbia independently had an adverse effect on resuscitation from cardiac arrest. In this model with a prolonged interval of untreated cardiac arrest, adequate ventilation was important for resuscitation.

Influence of isoflurane, fentanyl, thiopental, and alpha-chloralose on formation of brain edema resulting from a focal cryogenic lesion.

The objective of this study was to analyze the effects of various anesthetics on the formation of brain edema resulting from a focal cryogenic lesion. Thirty rabbits (six per group) were anesthetized with isoflurane (1 minimum alveolar anesthetic concentration [MAC] 2.1 vol%), fentanyl (bolus 5 micrograms/kg; infusion rate 1.0-0.5 micrograms.kg-1.min-1), thiopental (32.5 mg.kg-1.h-1), or alpha-chloralose (50 mg/kg). Control animals (sham operation, no lesion) received alpha-chloralose (50 mg/kg). Regional cerebral blood flow (rCBF) in perifocal brain tissue was measured by H2-clearance. Animals anesthetized with isoflurane required support of arterial pressure by angiotensin II (0.15 micrograms.kg-1.min-1). Six hours after trauma the animals were killed. Formation of brain edema was studied by specific gravity of cortical gray matter, white matter, hippocampus, caudate nucleus, putamen, and thalamus. Brain tissue samples were collected at multiple sites close to and distant from the lesion. Mean arterial pressure, arterial PCO2 and PO2, hematocrit, body temperature, and blood glucose were not different between groups during the posttraumatic course (except for an increased arterial pressure with alpha-chloralose compared to thiopental 4-6 h after trauma). The specific gravity of cortical gray matter was significantly reduced up to a distance of 6 mm from the center of the lesion in animals anesthetized with isoflurane, thiopental, or alpha-chloralose and up to 9 mm in animals given fentanyl.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of Isoflurane, Fentanyl, Thiopental, and alpha-Chloralose on Formation of Brain Edema Resulting from a Focal Cryogenic Lesion

The objective of this study was to analyze the effects of various anesthetics on the formation of brain edema resulting from a focal cryogenic lesion.Thirty rabbits (six per group) were anesthetized with isoflurane (1 minimum alveolar anesthetic concentration [MAC] 2.1 vol%), fentanyl (bolus 5 micro gram/kg; infusion rate 1.0-0.5 micro gram centered dot kg-1 centered dot min-1), thiopental (32.5 mg centered dot kg-1 centered dot h-1), or alpha-chloralose (50 mg/kg). Control animals (sham operation, no lesion) received alpha-chloralose (50 mg/kg). Regional cerebral blood flow (rCBF) in perifocal brain tissue was measured by H2-clearance. Animals anesthetized with isoflurane required support of arterial pressure by angiotensin II (0.15 micro gram centered dot kg-1 centered dot min-1). Six hours after trauma the animals were killed. Formation of brain edema was studied by specific gravity of cortical gray matter, white matter, hippocampus, caudate nucleus, putamen, and thalamus. Brain tissue samples were collected at multiple sites close to and distant from the lesion. Mean arterial pressure, arterial PCO2 and PO2, hematocrit, body temperature, and blood glucose were not different between groups during the posttraumatic course (except for an increased arterial pressure with alpha-chloralose compared to thiopental 4-6 h after trauma). The specific gravity of cortical gray matter was significantly reduced up to a distance of 6 mm from the center of the lesion in animals anesthetized with isoflurane, thiopental, or alpha-chloralose and up to 9 mm in animals given fentanyl. In white matter, vasogenic edema extended up to 12 mm from the lesion focus in animals anesthetized with fentanyl, thiopental, or alpha-chloralose. In isoflurane-anesthetized animals, white matter samples in all regions were similar to control. The specific gravity in hippocampus, caudate nucleus, putamen, or thalamus was not altered as compared to the controls. rCBF studied before cryogenic injury had a range of 37-44 mL centered dot 100 g-1 centered dot min-1, except in animals given fentanyl (i.e., 59.9 mL centered dot 100 g-1 centered dot min-1). During the first 3 h after trauma, animals given fentanyl had significantly higher rCBF values than animals with thiopental or the controls. At 4-6 h after trauma, rCBF was decreased in animals with fentanyl or thiopental as compared to the baseline level, although differences were not observed between groups. Regression analyses of data from all experimental groups do not reveal a relationship between the formation of posttraumatic brain edema and mean arterial pressure or rCBF. We conclude that isoflurane anesthesia attenuates cerebral edema from a standard cerebral lesion as compared to fentanyl, thiopental, or alpha-chloralose. (Anesth Analg 1995;80:1108-15)

Dopexamine Hydrochloride in Septic Shock

It has been suggested that septic shock is a disorder of microvascular autoregulation. Tissue blood flow is modulated by the state of activation of upstream endothelial receptors controlling the vascular smooth muscle tone. Because vascular receptor populations vary between organs, it should be expected that vasoactive drugs affect tissue oxygenation differently in different organs. We studied the effects of dopexamine HCl (a novel inotrope) and septic shock on oxygen delivery as well as tissue Po2 in gut, liver, and skeletal muscle in anesthetized rabbits. Employing the thermodilution technique, cardiac output was measured across the pulmonary bed and used to calculate oxygen delivery. Three eight-channel Mehrdraht Dortmund Oberfläche oxygen electrodes were placed on gut serosa, liver, and skeletal muscle surfaces, respectively, and sufficient readings were obtained to calculate tissue Po2 distributions. During septic shock mean arterial pressure, cardiac output, oxygen delivery, and mean tissue Po2 decreased in all organs. Our results suggest that the observed changes in tissue oxygenation during septic shock were caused by defective regulation of microvascular blood flow. In conclusion, during baseline conditions dopexamine HCl caused no statistically significant changes in tissue oxygenation in any organ, except in skeletal muscle at 10 micrograms/kg/min when tissue Po2 increased. During septic shock, however, dopexamine HCl improved oxygenation in all three organs in a dose-dependent manner.

Delayed (“Secondary”) Cerebral Energy Failure after Acute Hypoxia-Ischemia in the Newborn Piglet: Continuous 48-Hour Studies by Phosphorus Magnetic Resonance Spectroscopy

Phosphorous (31P) spectra from the brains of severely birth-asphyxiated human infants are commonly normal on the first day of life. Later, cerebral energy failure develops, which carries a serious prognosis. The main purpose of this study was to test the hypothesis that this delayed ("secondary") energy failure could be reproduced in the newborn piglet after a severe acute reversed cerebral hypoxic-ischemic insult. Twelve piglets were subjected to temporary occlusion of the common carotid arteries and hypoxemia [mean arterial PO2 3.1 (SD 0.6) kPa]. Mean cerebral phosphocreatine concentration [PCr]/inorganic orthophosphate concentration [Pi] decreased from 1.40 (SD 0.29) to 0.01 (SD 0.02), and nucleotide triphosphate concentration [NTP]/exchangeable phosphate pool concentration [EPP] decreased from 0.19 (SD 0.02) to 0.06 (SD 0.04) (p < 0.001 for each decrease). On reperfusion and reoxygenation of the brain, mean [PCr]/[Pi] and [NTP]/[EPP] returned to baseline. Observations continuing for the next 48 h showed that [PCr]/[Pi] again decreased, in spite of normal arterial PO2, mean arterial blood pressure, and blood glucose, to 0.62 (SD 0.61) at 24 h (p < 0.01) and 0.49 (SD 0.37) at 48 h (p < 0.001). [NTP]/[EPP] also decreased, but to a lesser degree. Intracellular pH remained unchanged. These findings appeared identical with those seen in birth-asphyxiated human infants. No changes in cerebral metabolite concentrations took place in six control piglets. The severity of secondary energy failure, as judged by the lowest [PCr]/[Pi] recorded at 24-48 h, was directly related to the extent of acute energy depletion, obtained as the time integral of reduction in [NTP]/[EPP] (p < 0.0001). This animal model of secondary energy failure may prove useful for testing cerebroprotective strategies.

Effect of ventilation on resuscitation in an animal model of cardiac arrest.

The need for ventilation during the initial management of cardiac arrest is an important public health problem that is being debated. The present study was designed to determine whether ventilation affects return of spontaneous circulation from cardiac arrest in a swine model with an interval of untreated ventricular fibrillation of 6 minutes, as reported in witnessed out-of-hospital human cardiac arrest. Twenty-four animals were randomly assigned to two groups: one that received ventilation during the first 10 minutes of chest compression and one that did not. Coronary perfusion pressure and minute ventilation were continuously recorded. Arterial and mixed venous blood gases were measured at intervals. Return of spontaneous circulation was defined prospectively as an aortic systolic blood pressure of > 80 mm Hg for > 5 minutes and was the primary outcome variable. All animals were anesthetized, paralyzed, and intubated. Ventricular fibrillation was induced and persisted for 6 minutes without chest compression, followed by mechanical chest compression for 10 minutes and then attempted defibrillation. Animals without return of spontaneous circulation were given epinephrine, ventilation, and chest compression for an additional 3 minutes. Defibrillation was again attempted, and animals were assessed for return of spontaneous circulation. There were no significant differences between the two groups in baseline prearrest mean cardiac index, coronary perfusion pressure, or arterial and mixed venous blood gases. However, after 9 minutes of chest compression, significant differences were noted between the ventilated and nonventilated groups. The nonventilated group had significantly (P < .05) lower mean arterial PO2 (38 +/- 17 mm Hg compared with 216 +/- 104 mm Hg) and higher PCO2 (62 +/- 16 mm Hg compared with 35 +/- 8 mm Hg), lower mixed venous PO2 (15 +/- 7 mm Hg compared with 60 +/- 7 mm Hg). Nine of 12 (75%) of the ventilated animals, and only 1 of 12 (8%) of the nonventilated animals had return of spontaneous circulation after cardiac arrest (P < .002). In this animal model of cardiac arrest, ventilation was important for resuscitation. The importance of ventilation could be related to the prolonged duration of untreated ventricular fibrillation and the significantly greater hypoxia and hypercarbic acidosis found in the nonventilated animals.

The effect of sampling technique on measurement of fetal blood pH and gases—An in vitro system

Fetal scalp blood for intrapartum pH monitoring is usually collected aerobically in small volumes and may therefore be affected by the mode of sampling. The effect of specimen collection and handling on measured index values of fetal blood acid-base balance was evaluated in an in vitro simulated system. The system consisted of an air-tight syringe filled with either arterial or venous fresh cord blood and an attached needle with a blunted tip. The rate of blood drop formation at the tip was determined by a variable-speed infusion pump. Two techniques, simulating actual scalp blood sampling, were evaluated: (1) commonly used technique--aspiration of individual drops into a glass tube, transfer into a syringe, and measurement and (2) direct technique--collection as a continuous column of blood into a capillary and subsequent measurement. Control acid-base values obtained before and immediately after completion of each test were not significantly different. Significant changes from control values were noted when sampling by the commonly used technique: mean arterial pH (7.21 to 7.26 and 7.24) and PO2 (19 to 25 and 23 mm Hg) increased, whereas PCO2 decreased (56 to 44 and 47 mm Hg) at slow and fast drop rates, respectively. Changes in venous blood samples were of similar direction and magnitude. Absolute changes from control during sampling by the commonly used technique averaged 21% +/- 2% and 15% +/- 1% (+/- SEM) for slow and fast drop rates, respectively (p < 0.01). On the other hand, sampling by the direct technique did not have a significant effect on measured acid-base values at slow and fast drop rates: absolute changes from control averaged 4.5% +/- 0.4% and 4.7% +/- 1.3% (+/- SEM), respectively. The mode of fetal scalp blood sampling and handling affects measured acid-base index values. Such changes reflect aeration of small blood volumes and may result in falsely elevated capillary scalp pH. This effect may be prominent when blood drops are slow forming or difficult to obtain.

Concepts of “Tissue PO2” In Relation to O2Delivery

Resistance to O2 diffusion is reflected in the difference in pO2 between O2 reservoirs of hemoglobin (Hb) and myoglobin. The very low normal myocyte pO2 (less than one torr but adequate for optimal oxidative ATP synthesis) compared to venous pO2 indicates that blood does not achieve equilibrium with tissue during its passage through capillaries. In the lung, diffusion rate of O2 from alveolus to capillary is normally sufficient to achieve essential equilibrium. However, system-wide capillary pathology and reduced Hb saturation has been observed with distal local ischemia. In peripheral vascular disease (PVD) patients, we found a mean arterial pO2 of 77 torr (normal over 90 torr). Classical concepts based on "tissue pO2" values derived from venous blood or oxygen electrodes inserted into tissue need re-evaluation. Readings of O2 electrodes moved through tissue range widely from intracapillary levels down toward intracellular levels and do not reflect the pO2 of any particular site. Intravenous pO2 is the result of residual O2 after incomplete diffusion out of capillaries during transit through a tissue, and is not an equilibrium value with some tissue pool. The effect of HbO2 p50 on oxygen release during the passage of blood through a capillary bed, generally judged on the basis of percentage percent saturation at "tissue pO2", should be judged on the basis of the change in pO2 (the diffusion driving force) associated with a particular degree of HbO2 saturation at a particular p50. The thesis that O2 diffusion rate is a major determinant of oxygen delivery is supported by pO2 responses to treatment of PVD that does not alter blood flow or p50.

Simultaneous influence of blood pressure, PCO2, and PO2 on cerebral blood flow velocity in preterm infants of less than 33 weeks' gestation.

In extremely preterm infants, the protective capacity for cerebral blood flow (CBF) autoregulation may be impaired or absent, which increases the risk for developing cerebral lesions. The purpose of this study was to quantify the simultaneous influence of several vital parameters, such as mean arterial blood pressure (MABP), PCO2, and PO2, on cerebral blood flow velocity (CBFv), which is used as a measure for CBF. In 16 mechanically ventilated infants of < 33 wk gestation, the CBFv in the internal carotid artery was measured every minute for 1 h by a computer-controlled pulsed Doppler device. MABP and transcutaneous PCO2 and PO2 were recorded as well. A multiple linear regression analysis was performed in each patient to determine the individual MABP, PCO2, and PO2 reactivities as a measure for CBF autoregulation. The medians (and ranges) of the whole group were an MABP reactivity of 7.5% (-12.5 to 20.1%) rise in CBFv/1 kPa rise in MABP, a PCO2 reactivity of 32.7% (-8.1 to 79.5%) rise in CBFv/1 kPa rise in PCO2, and a PO2 reactivity of -3.1% (-14.2 to 7.9%) fall in CBFv/1 kPa rise in PO2. In preterm infants, the individual's capacity for MABP-, PCO2-, and PO2-dependent CBF autoregulation can be estimated by means of the present method, even if the vital parameters change simultaneously.

Arterial blood gas tensions during breath-hold diving in the Korean ama.

Korean female unassisted divers (cachido ama) breath-hold dive > 100 times to depths of 3-7 m during a work day. We sought to determine the extent of arterial hypoxemia during normal working dives and reasonable time limits for breath-hold diving by measuring radial artery blood gas tensions and pH in five cachido ama who dove to a fixed depth of 4-5 m and then continued to breath hold for various times after their return to the surface. Eighty-two blood samples were withdrawn from indwelling radial artery catheters during 37 ocean dives. We measured compression hyperoxia [arterial PO2 = 141 +/- 24 (SD) Torr] and hypercapnia (arterial PCO2 = 46.6 +/- 2.4 Torr) at depth. Mean arterial PO2 near the end of breath-hold dives lasting 32-95 s (62 +/- 14 s) was decreased (62.6 +/- 13.5 Torr). Mean arterial PCO2 reached 49.9 +/- 5.4 Torr. Complete return of these values to their baseline did not occur until 15-20 s after breathing was resumed. In dives of usual working duration (< 30 s), blood gas tensions remained within normal ranges. Detailed analysis of hemoglobin components and intrinsic oxygenation properties revealed no evidence for adaptive changes that could increase the tolerance of the ama to hypoxic or hypothermic conditions associated with repetitive diving.