Increased Oxygen Extraction Research Articles

Limitation of exercise capacity in nucleoside‐treated HIV‐infected patients with hyperlactataemia

Inhibition of DNA polymerase gamma by nucleoside reverse transcriptase inhibitors (NRTIs) can cause mitochondrial dysfunction and cellular toxicity. Hyperlactataemia, which is a consequence of a shift in the metabolism of pyruvate, is an indicator of nucleoside-related mitochondrial toxicity. We evaluated exercise and oxidative capacities as well as circulatory and ventilatory responses to exercise in 24 HIV-infected patients on NRTIs presenting hyperlactataemia [mean (+/-standard deviation) fasted lactate=3.5+/-1.1 mmol/L]; 27 NRTI-treated patients with normal baseline lactate concentrations were used as controls (mean fasted lactate=1.6+/-0.3 mmol/L). In the patients with hyperlactataemia, the average peak work capacity (1.7+/-0.6 W/kg) and peak oxygen consumption (VO(2)) (21+/-4 mL/kg/min) were significantly lower (P<0.01) than in control subjects (work, 2.1+/-0.4 W/kg; VO(2), 25+/-4 mL/kg/min). The capacity to increase oxygen extraction during exercise was significantly diminished in the hyperlactataemia group, as shown by a low peak systemic arteriovenous oxygen difference (a-vO(2)) difference compared with controls (11+/-3 vs 14+/-3 mL/dL; P=0.008), and as indicated by a linear correlation between VO(2) and systemic a-vO(2) difference (r(2)=0.76). During exercise, the increases in cardiac output relative to VO(2) (mean Delta cardiac output (Q)/DeltaVO(2)=8+/-3.6) and ventilation (mean Delta ventilation (VE)/DeltaVO(2)=48.6+/-13.2) were significantly higher in hyperlactataemia patients compared with controls (mean cardiac output Delta(Q)/DeltaVO(2)=6+/-2; mean DeltaVE/DeltaVO(2)=42+/-12.7; P=0.03). The degree of exercise limitation in patients with nucleoside-related mitochondrial toxicity correlates directly with the severity of impaired muscle oxidative phosphorylation, as indicated by the capacity for muscle oxygen extraction. Exaggerated circulatory and ventilatory responses to exercise are direct consequences of the level of impaired muscle oxidative phosphorylation.

脳動脈硬化と脳循環障害

The 32nd Annual Meeting of Japan Stroke Society was held in Fukuoka city during March 22-23, 2007. The main thema was “Resure the brain and keep up with the given life span”. Finally 766 papers were accepted, and 7 symposia, 12 luncheon and 8 evening seminors were convened altogether. Professor Heistad and professor Donnan presented their outstanding works, respectively.Athersclerosis is most responsible for the development of circulatory disturbance in the brain. Hypertension is the major factor to precipitate atherosclerosis of cerebral arteries. In recent years, the prevalence of diabete mellitus is increased, and atherosclerosis in the extra- and intracranial arteries in normotensives with diabetes mellitus has become more severe than ever.In hypertensives, cerebral blood flow (CBF) is reduced, and cerebral metabolic rate of oxygen (CMR2) are maitained by increased oxygen extraction fraction (OEF). In cases with severe atherosclerosis, perfusion pressure in the brain is decreased and both CBF and CMRO2 are reduced despite of the elevated OEF. Prevention of the developmenet of cerebral and carotid atherosclerosis are of great use to protect patients against ischemic stroke.

Comparative cardiovascular and pulmonary effects of sedatives and anesthetic agents and anesthetic drug selection for the trauma patient

AbstractObjective: To integrate and compare the effects of tranquilizer/sedatives and anesthetic drugs on various parameters of cardiovascular function in normal dogs and in dogs stressed by hypovolemia, anemia, and endotoxemia, and to discuss the relative merits and appropriate precautions of anesthetic drugs with respect to specific patient physiologic complications.Data sources: Personal data and experiences in conjunction with veterinary and human clinical and research studies.Human and veterinary data synthesis: Drugs that produce calming, sedation, muscle relaxation, analgesia, and loss of consciousness have the potential to produce marked cardiorespiratory effects particularly in hemorrhaged, hypovolemic‐traumatized animals. Acute but key cardiovascular components that are affected by sedative and anesthetic drugs include heart rate and rhythm, venous return (preload), systemic vascular resistance (afterload), and myocardial contractile (inotropic) and relaxation (lusitropic) properties. In addition, all sedative and anesthetic drugs alter or depress normal baroreceptor reflex activity, thereby inhibiting or eliminating the animal's normal physiologic response to decreases in arterial blood pressure and predisposing to tissue hypoperfusion, decreased oxygen delivery, and oxygenation. Oxygen delivery needs to be adequate to meet the metabolic (oxygen) requirements of the patient. Decreases in oxygen delivery to tissues increases oxygen extraction, thereby maintaining tissue oxygenation (supply‐independent oxygen consumption phase) until compensatory processes reach their limit and any further decrease in oxygen delivery causes a decrease in oxygen consumption (supply‐dependent oxygen consumption phase). The critical oxygen delivery that defines the transition between these 2 phases is generally higher in the anesthetized state than in the awake state. The effect of anesthetics on critical oxygen delivery at comparable anesthetic dosages is pentobarbital=ketamine&gt;alfentanil&gt;etomidate=propofol&gt;inhalational anesthetics. Anesthetics generally decrease oxygen consumption from the awake, baseline state; exceptions are ketamine and ether. Ketamine, however, increases oxygen delivery and oxygen extraction.Conclusions: The transition from the awake to the anesthetized state is a huge imposition on the physiology of animals and, therefore, should be accomplished with great care and proper vigilance. Rapid, ‘crash’ induction of anesthesia should be avoided in hypotension‐prone animals and slow, prolonged induction should be avoided in animals with respiratory disorders. It is not recommended to implement an unfamiliar protocol in critical patients, even if it might be pharmacologically preferable. Familiarity with an anesthetic drug is a very important reason for its selection.

Water conservation in fasting northern elephant seals (Mirounga angustirostris).

Prolonged terrestrial fasting is a key element in the life history of elephant seals. While on land seals typically fast without access to fresh water, and thus must maintain positive water balance by reductions in water loss such that they can subsist primarily on metabolic water production (MWP). The terrestrial apnea demonstrated by seals may reduce respiratory evaporative water loss (REWL) to levels that allow seals to make a net gain of water from MWP. We empirically measured REWL in 13 fasting northern elephant seal pups and determined the effects on water conservation of a breathing mode that incorporates a regular pattern of apneas, of > or =1 min in duration, followed by eupneic recovery, compared with a breathing mode with no apneas longer than 20 s and resembling typical breathing patterns in other mammals (normative breathing). Overall REWL fell 41% from 0.075+/-0.013 g min(-1) (mean +/- s.d.) during normative breathing to 0.044+/-0.006 g min(-1) during apneic breathing. The decline in REWL is attributed to a decrease in overall ventilation rate, made possible by a decline in metabolic rate along with an increase in oxygen extraction that would occur during apneic breathing. Data on the range of ambient humidity conditions at the local breeding site were collected and used to bound the range of environmental conditions used in laboratory measurements. Our data showed that the observed variations in ambient humidity had no significant effect on REWL. A combination of apneic breathing and the complex nasal turbinates allows fasting elephant seals to reduce REWL well below the rate of MWP so that they can maintain water balance during the fast.

Systemic and regional hemodynamic effects of enalaprilat infusion in experimental normotensive sepsis

Angiotensin-converting enzyme inhibitors have been shown to improve splanchnic perfusion in distinct shock states. We hypothesized that enalaprilat potentiates the benefits of early fluid resuscitation in severe experimental sepsis, particularly in the splanchnic region. Anesthetized and mechanically ventilated mongrel dogs received an intravenous infusion of live Escherichia coli over a period of 30 min. Thereafter, two interventions were performed: fluid infusion (normal saline, 32 mL/kg over 30 min) and enalaprilat infusion (0.02 mg kg(-1) min(-1) for 60 min) in randomized groups. The following groups were studied: controls (fluid infusion, N = 4), E1 (enalaprilat infusion followed by fluid infusion, N = 5) and E2 (fluid infusion followed by enalaprilat infusion, N = 5). All animals were observed for a 120 min after bacterial infusion. Mean arterial pressure, cardiac output (CO), portal vein blood flow (PVBF), systemic and regional oxygen-derived variables, and lactate levels were measured. Rapid and progressive reductions in CO and PVBF were induced by the infusion of live bacteria, while minor changes were observed in mean arterial pressure. Systemic and regional territories showed a significant increase in oxygen extraction and lactate levels. Widening venous-arterial and portal-arterial pCO2 gradients were also detected. Fluid replacement promoted transient benefits in CO and PVBF. Enalaprilat after fluid resuscitation did not affect systemic or regional hemodynamic variables. We conclude that in this model of normotensive sepsis inhibition of angiotensin-converting enzyme did not interfere with the course of systemic or regional hemodynamic and oxygen-derived variables.

Systemic and regional hemodynamic effects of enalaprilat infusion in experimental normotensive sepsis

Angiotensin-converting enzyme inhibitors have been shown to improve splanchnic perfusion in distinct shock states. We hypothesized that enalaprilat potentiates the benefits of early fluid resuscitation in severe experimental sepsis, particularly in the splanchnic region. Anesthetized and mechanically ventilated mongrel dogs received an intravenous infusion of live Escherichia coli over a period of 30 min. Thereafter, two interventions were performed: fluid infusion (normal saline, 32 mL/kg over 30 min) and enalaprilat infusion (0.02 mg kg-1 min-1 for 60 min) in randomized groups. The following groups were studied: controls (fluid infusion, N = 4), E1 (enalaprilat infusion followed by fluid infusion, N = 5) and E2 (fluid infusion followed by enalaprilat infusion, N = 5). All animals were observed for a 120 min after bacterial infusion. Mean arterial pressure, cardiac output (CO), portal vein blood flow (PVBF), systemic and regional oxygen-derived variables, and lactate levels were measured. Rapid and progressive reductions in CO and PVBF were induced by the infusion of live bacteria, while minor changes were observed in mean arterial pressure. Systemic and regional territories showed a significant increase in oxygen extraction and lactate levels. Widening venous-arterial and portal-arterial pCO2 gradients were also detected. Fluid replacement promoted transient benefits in CO and PVBF. Enalaprilat after fluid resuscitation did not affect systemic or regional hemodynamic variables. We conclude that in this model of normotensive sepsis inhibition of angiotensin-converting enzyme did not interfere with the course of systemic or regional hemodynamic and oxygen-derived variables.

Near-infrared spectroscopy in the detection of regional tissue oxygenation during hypoxic events in preterm infants undergoing critical care

To determine whether pulse oximetry-detected episodes of desaturation are associated with impairment of cerebral and somatic (renal) tissue oxygenation in mechanically ventilated preterm neonates. Observational cross-sectional study. Neonatal intensive care unit of a university-affiliated children's hospital. Ten mechanically ventilated preterm (gestational age 24-32 wks) infants. In addition to the traditional monitoring of hemodynamic variables that included pulse oximetry (Sao2), near-infrared spectroscopy (NIRS) was used to evaluate the cerebral and somatic (renal) tissue oxygen saturation (rSO2C and rSO2R, respectively). A total of 40 rSO2C and rSO2R measurements were simultaneously recorded: 20 during hypoxic events when the Sao2 was </=80% for >/=4 secs (cases) and generally ranged between 70% and 80%, and 20 measurements when the Sao2 was >/=85% (paired controls). Additionally, the fractional oxygen extraction (FOE) from the cerebral (FOEC) and renal (FOER) tissue was calculated. All the measurements were made under steady conditions during a 2-hr period. The rSO2C, rSO2R, FOEC, and FOER among the cases (Sao2 </= 80%) and controls (Sao2 >/= 85%) were compared using the paired Student's t-test. Both rSO2C and rSO2R during the desaturation episodes were lower than in the controls (51.6 +/- 6.3% vs. 66.2 +/- 10.2%, p < .0001 and 61.1 +/- 6.8% vs. 80.1 +/- 10.0%, p < .0001, respectively). The FOEC during the hypoxic episodes was comparable with control levels but increased in renal tissue. However, during two of the desaturation episodes (10%), the rSO2C and FOEC levels (which were <44% and >0.47, respectively) may reflect compromised tissue oxygen supply. In the majority of mechanically ventilated preterm neonates, the reduction in cerebral and renal tissue oxygenation associated with short periods of decreased arterial saturation to 70-80% does not significantly compromise oxygen utilization in the cerebral tissue but increases oxygen extraction in the renal tissue, which might cause ischemic tissue injury following a further reduction in oxygen delivery.

DOSE RESPONSE OF INTRAVENOUS SILDENAFIL ON SYSTEMIC AND REGIONAL HEMODYNAMICS IN HYPOXIC NEONATAL PIGLETS

In neonates with acute pulmonary hypertension (PHT), the dose-response effect of sildenafil citrate, a selective phosphodiesterase-5 inhibitor that can alleviate PHT, has not been detailedly examined. We tested the hypothesis that the treatment of hypoxia-induced acute PHT with sildenafil would dose-dependently reduce the elevated pulmonary and systemic arterial pressures (PAP and SAP, respectively) with no effect on the oxygenation in newborn animals. We also examined the regional hemodynamic responses. Using a randomized controlled design, piglets (age range, 1-3 days; weight range, 1.5-2.1 kg) were anesthetized and acutely instrumented to measure cardiac index, left common carotid, superior mesenteric and left renal arterial flow indexes, SAP, and PAP. After stabilization, hypoxia was induced with fractional inspired oxygen concentration at 0.15 and, subsequently, piglets were randomized to receive i.v. sildenafil at 0.06, 0.2, or 2.0 mg/kg per hour or normal saline (controls) for 90 min (n = 6 each). Within 30 min of hypoxia (PaO2, 31 +/- 5 mmHg), the piglets developed PHT (PAP, 33 +/- 5 vs. 26 +/- 4 mmHg at baseline; P < 0.05. Sildenafil dose-dependently reduced the hypoxia-induced PHT (PAP at 90 min: 33 +/- 6, 29 +/- 6, and 26 +/- 6 mmHg of 0.06, 0.2, and 2.0 mg/kg per hour, respectively, vs. 44 +/- 8 mmHg of controls; P < 0.05. Sildenafil at 2.0 mg/kg per hour had the greatest decrease in SAP (P < 0.05) with no significant change at 0.06 and 0.2 mg/kg per hour. Pulmonary selectivity (PAP:SAP ratio) was best in the group treated with 0.2 mg/kg per hour dosage of sildenafil (P < 0.05). There were no differences in cardiac index and regional flow indexes between groups. Although hypoxia decreased oxygen delivery and increased oxygen extraction with no significant effect on oxygen consumption, the administration of sildenafil did not affect the oxygen metabolism (vs. controls). In neonatal piglets, i.v. sildenafil dose-dependently alleviates the hypoxia-induced acute PHT, with the best pulmonary selectivity at 0.2 mg/kg per hour, and shows no significant effect on regional circulation and oxygen metabolism.

Surgical closure of patent ductus arteriosus reduces the cerebral tissue oxygenation index in preterm infants: a near‐infrared spectroscopy and Doppler study

The aim of this study was to investigate the effects of patent ductus arteriosus (PDA) ligature on cerebral oxygen saturation, cerebral blood volume (CBV) and cerebral blood flow velocity by means of near-infrared spectroscopy (NIRS) and transcranial Doppler simultaneous examinations. This is an observational study considering 16 babies of gestational age 24-34 weeks diagnosed with PDA who underwent surgical ligation. The cerebral oxygen saturation, CBV and blood gases values were obtained 35 min before ligation, so also around the 14th and 27th min after the clip's insertion. Cerebral oxygen saturation, measured as tissue oxygenation index (TOI), decreased significantly after PDA ligation from a basal value of 61.1 (3.8) before surgery to 56.6 (3.3) and 55.8 (2.6)%, for the 14th and 27th min, respectively (P<0.04). CBV before and after clipping was unvaried. A negative correlation was found between DeltapH and DeltaCBV after ligation (R=0.52, P=0.03), whilst a positive correlation was found between DeltaCBV and DeltaP(aCO2) (R=0.62, P=0.009). pH increased at the 27th min post-ligation. NIRS is a tool for obtaining information on cerebral oxygen saturation and CBV changes during surgical PDA ligation at the bedside. A fall in TOI suggests an increased oxygen extraction during PDA surgery. The lack of increase in DeltaCBV or in diastolic flow velocity show that the PDA before the clipping did not limit cerebral blood flow, the drop in TOI suggests increased oxygen consumption over the clip and the need for accurate monitoring of oxygen utilization after the surgical treatment.

Major Ongoing Stroke Trials

Major Ongoing Stroke Trials

Oxygen consumption following trauma: a reappraisal in severely injured patients requiring mechanical ventilation.

Oxygen consumption (VO2) immediately following major injury in man has been said to be reduced. The evidence for this is poor. We have therefore measured VO2 soon after major injury in 16 patients. VO2 was reduced in only two patients, within the normal range in four and increased in ten. VO2 was maintained by increased oxygen extraction in six patients leading to low levels of mixed venous oxygen saturation. There is no evidence for an 'ebb phase' response in man.

Enhanced central organ oxygenation after application of bovine cell-free hemoglobin HBOC-201

While the effects of dilutional anemia or isovolemic hemodilution (IHD) on the oxygen extraction and tissue oxygenation in peripheral organs after application of hemoglobin-based oxygen carriers like HBOC-201 have been studied intensively, little is known about tissue oxygenation properties of hemoglobin solutions in central organs like the liver.Twelve Foxhounds were anesthetized and then randomized to either a control group without hemodilution (Group 1) or underwent first step isovolemic hemodilution (pulmonary artery occlusion pressure constant) with Ringer's solution (Group 2) to a hematocrit of 25% with second step infusion of HBOC-201 until a hemoglobin concentration of +0.6 g.dL(-1) was reached. Tissue oxygen tensions (tpO2) were measured in the gastrocnemius muscle using a polarographic needle probe, and in the liver using a flexible polarographic electrode.While arterial oxygen content and oxygen delivery decreased with hemodilution in Group 2, global liver and muscle oxygen extraction ratio increased after hemodilution and additional application of HBOC-201. Hemodilution and application of HBOC-201 provided augmentation of the mean liver tpO2 (baseline: 48 +/- 9, 20 min: 53 +/- 10, 60 min: 67 +/- 11*, 100 min: 68 +/- 7*; *P < 0.05 vs baseline and Group 1), while oxygen tensions in Group 1 remained unchanged. Oxygen tension in the skeletal muscle increased after hemodilution and additionally after application of HBOC-201 in comparison to baseline and to the control group (P < 0.05).In the present animal model, IHD with Ringer's solution and additional application of HBOC-201 increased oxygen extraction and tpO(2) in the liver and skeletal muscle, in parallel and in comparison with baseline values and a control group.

Differential cardiovascular responses during weaning failure: effects on tissue oxygenation and lactate

To test the following two hypotheses during weaning failure: (a) mixed venous oxygen saturation (SvO2) does not decrease in patients whose oxygen consumption does not increase, and (b) blood lactate may increase in patients who demonstrate substantial decreases in SvO2. A prospective observational and physiological study in a 30-bed university intensive care unit. 18 patients who failed weaning and 12 patients who succeeded weaning (controls). Hemodynamics, global tissue oxygenation, cardiovascular response (cardiac index/oxygen extraction diagram), and blood lactate were measured in ventilator-supported patients undergoing a spontaneous breathing trial. In patients who failed without having increased their oxygen consumption (n=9) the increase in oxygen delivery was accompanied by a decrease in oxygen extraction (by 15+/-4%). In patients who failed (n=9) having increased their oxygen consumption (by>10%) this increase was met mainly by an increase in oxygen extraction (by 30+/-7%). SvO2 increased by 2+/-1% in the former patients, whereas it decreased by 20+/-5% in the latter. Arterial lactate increased (range 2.3-3.1 mM/l) in only three patients who failed to have increased oxygen consumption and exhibited heart failure and the highest decreases in SvO2 (by 12-39%). Patients whose SvO2 does not decrease during weaning failure do not have increased oxygen consumption probably due to respiratory center depression in some of them. Patients whose SvO2 decreases have increased oxygen consumption.

EVIDENCE FOR MYOCARDIAL DEFECTS UNDER EXTREME ACUTE NORMOVOLEMIC HEMODILUTION WITH HYDROXYETHYL STARCH AND LACTATED RINGER'S SOLUTION

Acute normovolemic hemodilution (ANH) has been proposed to avoid the risks of allogenic transfusion. In reference to its cellular effects, ANH reports in the literature are scarce. Using electron microscopy (EM), we evaluated the effects of ANH on cardiac function and myocardial structure. Twenty-five dogs were prospectively randomized to a control group (n = 5) or to undergo ANH with 6% hydroxyethyl starch (HES; n = 10) or lactated Ringer's solution (LR; n = 10) administered, respectively, at a ratio of 1:1 or 1:3 to the volume of blood removed. Animals were gradually hemodiluted to a hematocrit of 10%, which was accomplished in 80 min. Pulmonary artery catheter and echocardiography were used to evaluate cardiac function. Myocardial samples were taken after the last time point for electron microscopy analysis. Data were obtained during five different stages of ANH, with a mean 20-min interval between each time point. Cardiac index increased significantly in both groups during ANH. A significant decrease in oxygen delivery and oxygen consumption, as well as an increase in oxygen extraction was verified in the LR group. Echocardiography demonstrated a decline in systolic function in the LR group at the end of the experiment. Electron microscopy analysis of the myocardium revealed slight lesions in cardiac cells in the HES group, and moderate-to-significant lesions in the LR group. In this animal species, ANH with HES resulted in better preservation of cardiac function, which was demonstrated by maintenance of systolic function and oxygenation parameters. Minor loss of cellular integrity with HES, in the presence of very low levels of hemoglobin, reinforces these findings.

Post‐operative myocardial dysfunction does not affect the physiological response to early mobilization after coronary artery bypass grafting

An acute increase in oxygen demand can be compensated for either by increased cardiac index (CI) or increased oxygen extraction, resulting in reduced mixed venous oxygen saturation (SvO2). We tested the hypothesis that post-operative cardiac dysfunction may explain why oxygen extraction alone is increased during early mobilization after cardiac surgery. Twenty patients with a pre-operative ejection fraction > 50% were included in an open prospective observational study comparing the changes in SvO2 and hemodynamics during mobilizations immediately prior to surgery and on the first post-operative morning. Mobilization induced an absolute reduction in SvO2 of 17.7 +/- 7.4% pre- and 19.0 +/- 5.5% post-operatively (NS). ANOVA for a series of measurements throughout the mobilization sequence identified no different effect on SvO2 between pre- and post-operative mobilizations (P = 0.567). The SvO2 level was reduced post-operatively resulting in a SvO2 during standing exercise of 55% before and 49% after the surgery (P < 0.01). Mobilization increased the heart rate (HR) and decreased the stroke volume index (SVI), leaving CI unchanged. This response was similar pre- and post-operatively (NS). Compared with pre-operative measurements, CI and HR increased post-operatively while SVI remained unchanged despite elevated cardiac filling pressures and reduced systemic vascular resistance. The left ventricular stroke work index was reduced, indicating reduced myocardial performance. Myocardial function was reduced on the first morning after coronary artery bypass grafting (CABG), but during post-operative mobilization this reduction did not significantly influence the changes in CI or SvO2.

Intensive insulin therapy is associated with reduced extracellular glucose and increased oxygen extraction fraction after severe traumatic brain injury

Intensive Insulin Therapy is Associated with Reduced Extracellular Glucose and Increased Oxygen Extraction Fraction after Severe Traumatic Brain Injury

Short-lasting systemic and regional benefits of early crystalloid infusion after intravenous inoculation of dogs with live Escherichia coli

We investigated the systemic and regional hemodynamic effects of early crystalloid infusion in an experimental model of septic shock induced by intravenous inoculation with live Escherichia coli. Anesthetized dogs received an intravenous infusion of 1.2 x 10(10) cfu/kg live E. coli in 30 min. After 30 min of observation, they were randomized to controls (no fluids; N = 7), or fluid resuscitation with lactated Ringer's solution, 16 ml/kg (N = 7) or 32 ml/kg (N = 7) over 30 min and followed for 120 min. Cardiac index, portal blood flow, mean arterial pressure, systemic and regional oxygen-derived variables, blood lactate, and gastric PCO2 were assessed. Rapid and progressive cardiovascular deterioration with reduction in cardiac output, mean arterial pressure and portal blood flow (approximately 50, approximately 25 and approximately 70%, respectively) was induced by the live bacteria challenge. Systemic and regional territories showed significant increases in oxygen extraction and in lactate levels. Significant increases in venous-arterial (approximately 9.6 mmHg), portal-arterial (approximately 12.1 mmHg) and gastric mucosal-arterial (approximately 18.4 mmHg) PCO2 gradients were also observed. Early fluid replacement, especially with 32 ml/kg volumes of crystalloids, promoted only partial and transient benefits such as increases of approximately 76% in cardiac index, of approximately 50% in portal vein blood flow and decreases in venous-arterial, portal-arterial, gastric mucosal-arterial PCO2 gradients (7.2 +/- 1.0, 7.2 +/- 1.3 and 9.7 +/- 2.5 mmHg, respectively). The fluid infusion promoted only modest and transient benefits, unable to restore the systemic and regional perfusional and metabolic changes in this hypodynamic septic shock model.

MESENTERIC VASCULAR DYSFUNCTION AFTER CARDIOPULMONARY BYPASS WITH CARDIAC ARREST IS AGGRAVATED BY COEXISTENT HEART FAILURE

Although patients suffering from heart failure (HF) have an increased incidence of nonocclusive mesenteric ischemia after opened heart surgery, the impact of cardiopulmonary bypass with cardiac arrest (CPB) on mesenteric vascular circulation in such situation remains unexplored. Therefore, the present study investigates the effects of CPB on mesenteric vascular reactivity, regional metabolism, and oxidative stress in an experimental model of HF. Volume-overload HF was induced in six dogs by bilateral femoral arteriovenous fistula. Six sham-operated dogs were used as controls. Eight weeks later, the short-term effects of 90 min of CPB were assessed in vivo during acute experiments. The significant increase in left ventricular end-diastolic volume in HF animals did not influence the vasodilator response of the superior mesenteric artery to acetylcholine (ACH) and nitroprusside (SNP) under baseline conditions. However, reduced mesenteric oxygen delivery, increased oxygen extraction, and lactate release were found during CPB in the HF group. In addition, an increased free radical production was assessed in the HF group during (89 +/- 23 x 10 relative light units [RLU]) and after CPB (93 +/- 15 x 10 RLU) compared with controls (45 +/- 15 and 49 +/- 7 x 10 RLU, respectively). Finally, 90 min of CPB led to a more pronounced decrease of ACH- (-22% +/- 5% vs. -42% +/- 9%, P < 0.05) and SNP- (-14% +/- 4% vs. -50% +/- 7%, P < 0.002) induced mesenteric vasodilations in the HF group compared with controls. We conclude that coexistent HF significantly enhances the pathological effects of CPB on the mesenteric vascular circulation by additionally altering endothelial and smooth muscle vascular function consequent to augmented oxidative stress.

Hepatosplanchnic blood flow control and oxygen extraction are modified by the underlying mechanism of impaired perfusion

To assess the effects of low hepatosplanchnic blood flow on regional blood flow control and oxygenation. Three randomized, controlled animal experiments. Two university experimental research laboratories. Pigs of either gender. Isolated abdominal blood flow reduction: An extracorporeal shunt with reservoir and roller pump was inserted between proximal and distal aorta in 11 pigs. Abdominal aortic blood flow was reduced by 50% by activating the shunt. Mesenteric ischemia: In seven pigs, superior mesenteric arterial flow was reduced to 4 mL.kg.min for 4 hrs. Cardiac tamponade: In 12 pigs, aortic blood flow was reduced by cardiac tamponade to 50 mL (moderate tamponade) and further to 30 mL.kg.min (severe tamponade) for 1 hr each. In each experimental condition, the same number of control animals was used. Abdominal blood flow reduction, acute mesenteric ischemia, and moderate tamponade resulted in a portal venous flow (QPV) reduction to 51 +/- 23%, 52 +/- 18%, and 61 +/- 25% (mean +/- sd) of baseline flow, respectively. During abdominal blood flow reduction, QPV and hepatic arterial flow (QHA) decreased proportionally, whereas in moderate tamponade and acute mesenteric ischemia QPV reduction was associated with an increase in QHA of 30 +/- 39% and 102 +/- 108%, respectively (p = .001 and .018). Prolonged mesenteric ischemia restored total hepatic blood flow (Qliver) completely. During all conditions, decreasing mesenteric oxygen consumption was partly prevented by increased mesenteric oxygen extraction (p < .001 for all conditions). In contrast, decreasing hepatic oxygen delivery was associated with increased oxygen extraction in tamponade (p = .009) but not in abdominal blood flow reduction. Blood flow redistribution can restore Qliver totally when mesenteric blood flow is reduced selectively, partially when cardiac output is reduced, and not at all during abdominal blood flow reduction. Since hepatic oxygen extraction does not increase in abdominal blood flow reduction, hepatic oxygenation is at risk in this condition.

Anaesthesia for the High Risk Patient

This 265-page softcover book has been complied from the effort of some 22 contributors. It aims to provide practical information on the management of high-risk patients by quoting numerous studies and providing sufficient background information to enable an understanding of the principles and rationale behind anesthetic and perioperative management. When I first picked this book up, I expected it to be a “cookbook” of techniques. It is not. This excellent text relies heavily on clinical and scientific studies, and where these studies have weakness the authors readily point them out. This text is not a substitute for major anesthetic texts but concentrates on principles of management of challenging situations. A great deal of emphasis is placed on cardiovascular risk and cardiac disease in general. Many studies are referenced, and one can see how the principles of patient management have actually evolved as the designs of these studies have improved. This book is divided into 17 chapters. These are referenced in the body of the text, and each one concludes with an impressive section entitled “Further Reading” and then “References.” The book relies heavily on the terms reserve, functional capacity, exercise tolerance, and optimization, as well as on implications for the type and site of surgery and its duration. The format is clearly designed to provide easy access to information presented in a concise manner. The actual styles of the chapters vary. Some relate more to basic physiology, medical principles, and pharmacology, whereas others are more practical, discussing the principles of anesthetic techniques for high-risk patients. However, all styles have a firm scientific basis. Almost every body system is considered in this text. The chapters devoted primarily to cardiac risk are especially impressive. Solidly based on scientific and clinical trials, they cover topics such as epidemiology, risk stratification, invasive and noninvasive preoperative testing (especially as these affect outcome), the importance of functional capacity (expressed in terms of metabolic equivalents), concurrent diabetes, and specific cardiovascular lesions, to name only a few. For example, in both animal and human models a coronary stenosis will start to produce flow limitations at rest only when the sectional diameter is reduced by 85–90%. However, under conditions of maximal flow (exercise or pharmacologically induced vasodilatation), stenosis with as little as 45% reduction in cross-sectional diameter will cause flow limitation manifesting as effort induced angina. Thus, the sensitivity of diagnostic physiological tests is markedly improved with increased flow enabling the detection of lesser stenosis. Other chapters cover topics such as respiratory risk, analgesia for the high-risk patient, local anesthetic techniques, the elderly patient, optimization, gastrointestinal considerations, renal considerations, anemia, the role of the cardiology consult, and the actual meaning of risk, again to name only a few. Similarly, considerations with respect to a couple of commonly used outpatient drugs—ketamine and nitrous oxide—are emphasized. For example, ketamine may increase oxygen extraction by tissues, thus helping prevent lactic acidosis, especially in the septic model. In addition, the traditional division of α, β, and dopamine receptor agonist properties on the basis of micrograms per kilogram per minute has now shown that the vasoconstrictor action occurs at much lower doses than what were originally thought. The excellent chapter on the elderly patient goes system-by-system into the changes induced by the aging process. It further emphasizes those factors of importance in preoperative assessment; preparation; anesthetic techniques; and, of course, the principles of optimization. The only so-called flaw I found in this text is the occasional misspelling of arrhythmia. Despite these minor nuances, this book could easily be classified as a must-have text in the reference library of any healthcare professional, especially those providing anesthesia and sedation services.