Association of age and packed red blood cell transfusion to 1-year survival--an observational study of ICU patients.

OBJECTIVES: To compare the 1-year survival for different age strata of intensive care unit (ICU) patients after receipt of packed red blood cell (PRBC) transfusions. BACKGROUND: Despite guidelines documenting risks of PRBC transfusion and data showing that increasing age is associated with ICU mortality, little data exist on whether age alters the transfusion-related risk of decreased survival. METHODS: We retrospectively examined data on 2393 consecutive male ICU patients admitted to a tertiary-care hospital from 2003 to 2009 in age strata: 21-50, 51-60, 61-70, 71-80 and >80 years. We calculated Cox regression models to determine the modifying effect of age on the impact of PRBC transfusion on 1-year survival by using interaction terms between receipt of transfusion and age strata, controlling for type of admission and Charlson co-morbidity indices. We also examined the distribution of admission haematocrit and whether transfusion rates differed by age strata. RESULTS: All age strata experienced statistically similar risks of decreased 1-year survival after receipt of PRBC transfusions. However, patients age >80 were more likely than younger cohorts to have haematocrits of 25-30% at admission and were transfused at approximately twice the rate of each of the younger age strata. DISCUSSION: We found no significant interaction between receipt of red cell transfusion and age, as variables, and survival at 1 year as an outcome.

Colchicine inhibits isoflurane-induced preconditioning.

BACKGROUND: When administered before prolonged myocardial ischemia and reperfusion, isoflurane exerts potent cardioprotective effects similar to those inferred by ischemic preconditioning. To determine whether an intact cytoskeleton is critically important in isoflurane-induced preconditioning, the authors used a rabbit model in which isoflurane-induced myocardial preconditioning decreases myocardial infarct size (IS) substantially. In this model, the authors tested whether the microtubule depolymerizing agent, colchicine, would inhibit isoflurane-induced myocardial preconditioning. METHODS: Myocardial IS was measured in four groups of propofol-anesthetized rabbits, each subjected to 30 min of anterolateral coronary occlusion followed by 3 h of reperfusion. Groups differed only in the pretreatments given, and only the control group received no pretreatment. An isoflurane-preconditioned group was pretreated with 15 min of end-tidal isoflurane, 1.1%, and then 15 min of washout. An isoflurane-plus-colchicine group was administered 2 mg/kg colchicine intravenously before isoflurane pretreatment. A colchicine-control group was administered 2 mg/kg colchicine but no isoflurane pretreatment. Myocardial IS and area at risk (AR) were defined by staining. Data were analyzed by analysis of variance or covariance. RESULTS: Infarct size, expressed as a percentage of AR (IS:AR) was 33.6%+/-8.8% (SD) in the control group. Isoflurane preexposure reduced myocardial IS:AR significantly, to 11.8%+/-9.1%. Colchicine pretreatment eliminated the preconditioning-like effect of isoflurane (IS:AR = 32.6%+/-8.7%). Colchicine alone did not alter IS (IS:AR = 27.6%+/-7.1%; P = not significant). CONCLUSIONS: Colchicine abolished the preconditioning effect of isoflurane but did not increase IS when administered alone. An intact microtubular cytoskeleton is critically important in the process of volatile anesthetic-induced preconditioning.

Mechanisms of isoflurane-induced myocardial preconditioning in rabbits.

BACKGROUND: Isoflurane has cardioprotective effects that mimic the ischemic preconditioning phenomenon. Because adenosine triphosphate-sensitive potassium channels and adenosine receptors are implicated in ischemic preconditioning, the authors wanted to determine whether the preconditioning effect of isoflurane is mediated through these pathways. METHODS: Myocardial infarct size was measured in seven groups of propofol-anesthetized rabbits, each subjected to 30 min of anterolateral coronary occlusion followed by 3 h of reperfusion. Groups differed only in the pretreatments given, and controls received no pretreatment. An ischemia-preconditioned group was pretreated with 5 min of coronary occlusion and 15 min of reperfusion. An isoflurane-preconditioned group was pretreated with 15 min end-tidal isoflurane, 1.1%, and then 15 min of washout. An isoflurane-plus-glyburide group was administered 0.33 mg/kg glyburide intravenously before isoflurane pretreatment. An isoflurane plus 8-(p-sulfophenyl)-theophylline (SPT) group received 7.5 mg/kg SPT intravenously before isoflurane. Additional groups were administered identical doses of glyburide or SPT, but they were not pretreated with isoflurane. Infarct size and area at risk were defined by staining. Data were analyzed by analysis of variance or covariance. RESULTS: Infarct size, expressed as a percentage of the area at risk (IS:AR) was 30.2+/-11% (SD) in controls. Ischemic preconditioning and isoflurane preexposure reduced myocardial infarct size significantly, to 8.3+/-5% and 13.4+/-8.2% (P<0.05), respectively. Both glyburide and SPT pretreatment eliminated the preconditioning-like effect of isoflurane (IS:AR = 30.0+/-9.1% and 29.2+/-12.6%, respectively; P = not significant). Neither glyburide nor SPF alone increased infarct size (IS:AR = 33.9+/-7.6% and 31.8+/-12.7%, respectively; P = not significant). CONCLUSIONS: Glyburide and SPT abolished the preconditioning-like effects of isoflurane but did not increase infarct size when administered in the absence of isoflurane. Isoflurane-induced preconditioning and ischemia-induced preconditioning share similar mechanisms, which include activation of adenosine triphosphate-sensitive potassium channels and adenosine receptors.

Anesthetic-induced preconditioning: previous administration of isoflurane decreases myocardial infarct size in rabbits.

BACKGROUND: Experimental evidence suggests that ATP-sensitive potassium channels are involved in myocardial ischemic preconditioning. Because some pharmacologic effects of isoflurane are mediated by K(ATP) channels, the authors tested the hypothesis: Isoflurane administration, before myocardial ischemia, can induce or mimic myocardial preconditioning. METHODS: Myocardial infarct size was measured in three groups of propofol-anesthetized rabbits, each subjected to 30 min of anterolateral coronary occlusion followed by 3 h of reperfusion. Groups differed in their pretreatment: Group 1 (control, N = 13) no pretreatment, Group 2 (ischemic preconditioning, N = 8), 5 min of coronary occlusion and 15 min of reperfusion; Group 3 (isoflurane pretreatment; N = 15), 15 min of isoflurane (1.1% end-tidal) and 15 min of washout. Hemodynamics were monitored serially. Myocardial infarct size and the area at risk were defined using triphenyltetrazolium chloride staining and fluorescent microspheres, respectively, and both were measured using computerized planimetry. RESULTS: Infarct size expressed as a percentage of area at risk was 23.4 +/- 8.5% (mean +/- SD) in the isoflurane group compared with 33.1 +/- 13.3% in controls, and 8.7 +/- 6.2% in the ischemia-preconditioned group. Analysis for coincidental regressions, followed by tests for equality of slope and elevation, showed that the linear relationship between infarct size and area at risk was significantly (P < 0.05) different in all three groups because of differences in line elevation. Minor differences in hemodynamic variables were found between groups, which were unlikely to account for the significant differences in infarct size. CONCLUSION: Preadministration of isoflurane, before myocardial ischemia, reduces myocardial infarct size, and mimics myocardial preconditioning.

Timing of tracheal extubation in adult cardiac surgery patients.

In this article, we examine 14 studies conducted from 1974 to 1994 on "early" endotracheal extubation (0 to 12 hours postoperatively) in adult cardiac surgery patients. Aspects reviewed include: criteria for patient selection; criteria for extubation; analyses of feasibility and safety; effects of anesthetic technique; and patient morbidity. Advantages and disadvantages of early or "fast-track" extubation are discussed as are directions for future research. Selection criteria varied among studies; patients were most commonly excluded because of severe, preexisting pulmonary disease or ventricular dysfunction. Based on the studies examined, however, at least 70% to 80% of adult patients would meet selection criteria. Three universal criteria were applied in all studies: (1) patient is awake and responsive; (2) adequate gas exchange while breathing spontaneously; and (3) cardiovascular stability. To facilitate early extubation in appropriately selected patients, the choice of anesthetic technique and postoperative sedation technique appears to be important. Anesthetic techniques based on inhalational anesthetic agents, supplemented by moderate doses of narcotics, are more appropriate than high-dose narcotic anesthesia for early extubation protocols. Postoperative sedation with propofol, which has a rapid offset of action, may be particularly advantageous. Every published investigation has concluded that early extubation is safe, feasible, and desirable. Morbidity and mortality have not been shown to be affected by early extubation. Anesthetic technique and the patient's medical condition are the two major factors to consider in accomplishing early extubation.

The role of ATP sensitive potassium channels in myocardial protection.

Several factors have pointed to a potential link between ATP sensitive potassium channel activation in ventricular myocytes and the phenomenon of myocardial preconditioning. Preconditioning can be blocked by adenosine antagonists, and is mimicked by adenosine A1-receptor agonists. A portion of the physiological action of adenosine is, however attributable to adenosine actions on KATP channels. The adenosine A1 receptor is reported to be linked to the KATP channel in rat ventricular myocytes by a G-protein mechanism. This article will review the current status of work regarding the role of KATP channels in myocardial preconditioning and will highlight recent work addressing the role of anesthetic effects in these studies. Recent reports and work from our laboratory reveal that several commonly used anesthetic drugs either have direct effects on KATP channels (barbiturates) or have prominent physiological effects that are modulated in large part by KATP channels (volatile anesthetics halothane and isoflurane).

Dichloroacetate stimulates carbohydrate metabolism but does not improve systolic function in ischemic pig heart.

Increased carbohydrate utilization may protect the heart during ischemia and reperfusion. Dichloroacetate (DCA) stimulates pyruvate dehydrogenase, which is the rate-limiting step in oxidation of lactate and pyruvate. The purpose of this study was to determine if the myocardial metabolic changes induced by intracoronary DCA during myocardial ischemia were accompanied by improvement in systolic function. A perfusion circuit was created from the carotid to left anterior descending coronary artery (LAD) in 11 anesthetized Yorkshire swine. Data were obtained under strict hemodynamic control at baseline, after 15 min of moderate (30%) LAD flow reduction, and after an additional 15 min of ischemia with either intracoronary DCA (3 mM, n = 6) or saline (n = 5) infusion. DCA decreased lactate release and increased lactate uptake during ischemia as measured by glucose and lactate carbon-labeled tracers. Despite these metabolic changes, no improvement in systolic shortening, microsphere blood flow, or oxygen consumption occurred. Thus, although DCA stimulated carbohydrate metabolism during myocardial ischemia, it did not directly improve systolic function.

Blockade of adenosine triphosphate-sensitive potassium channels eliminates isoflurane-induced coronary artery vasodilation.

BACKGROUND: The mechanisms by which volatile anesthetics induce vasodilation are unknown. Recent studies of adenosine triphosphate-sensitive potassium channels (KATP channels) in the vascular smooth muscle of the coronary circulation suggest that these channels play a role in the coronary artery dilation produced by hypoxemia, the coronary blood flow (CBF) reactive hyperemic response, and in CBF auto regulation. We therefore conducted this study to determine the role of KATP channels in isoflurane-induced coronary vasodilation. METHODS: Studies were conducted in six open-chest, anesthetized swine. The left anterior descending coronary artery was cannulated and perfused by blood passed through a membrane oxygenator. This preparation allowed us to administer drugs and volatile anesthetics regionally to the perfused myocardium, minimizing systemic effects. Regional CBF response to 1.5% and 3.0% isoflurane administered via the membrane oxygenator was measured before and after blockade of KATP channels, and was compared to the vasodilation produced by regional administration of several doses of sodium nitroprusside and adenosine. Blockade of KATP channels was achieved by regional intracoronary administration of glibenclamide (1-22 micrograms.kg-1.min-1), a specific blocker of these channels. RESULTS: Administration of 1.5 and 3.0 percent isoflurane increased regional CBF by 29 +/- 29% and by 62 +/- 28%, respectively. Under control conditions, blockade of KATP channels decreased mean CBF by 18%, but did not cause ischemia. KATP channel blockade totally eliminated the vasodilator response to both doses of isoflurane. During KATP channel blockade the response to 3% isoflurane was converted to net vasoconstriction: mean delta CBF = -5% +/- 6%, P = < 0.05 versus control. Negative inotropic effects of isoflurane were not eliminated by glibenclamide. Because KATP channel blockade was so effective in eliminating isoflurane-induced coronary vasodilation, the dose of glibenclamide was decreased in sequential experiments, but total blockade of isoflurane vasodilation was achieved even at the smallest dose of glibenclamide studied (1 microgram.kg-1.min-1). The vasodilator response to nitroprusside was not affected, and the vasodilator response to adenosine was partially inhibited (consistent with their known mechanisms of action). CONCLUSIONS: Blockade of KATP channels by glibenclamide completely inhibits isoflurane-induced coronary vasodilation in the regionally perfused swine myocardium. The response to sodium nitroprusside, a drug that induces vasodilation via a different mechanism, was unaffected. The response to adenosine, a drug whose vasodilation is partially mediated via KATP channels, was partially inhibited. These results suggest that in vivo isoflurane-induced coronary artery vasodilation is predominantly mediated by KATP channels.

Coronary blood flow autoregulation and flow heterogeneity in the stunned heart.

We used an anesthetized swine model of regionally "stunned" myocardium to determine the effect of stunning on coronary autoregulation and blood flow heterogeneity. In 18 domestic swine, stunning was accomplished by reducing blood flow to the left anterior descending coronary artery (LAD) by approximately 75% of baseline for 15 min and restoring it to normal for 1 hour. We quantified coronary autoregulation using both the slope of coronary pressure-flow curves and an autoregulation index. We quantified blood flow heterogeneity using radioactive microspheres to determine the variability in flow (dispersion index) among forty 200 mg segments of myocardium from the center of the stunned, LAD-perfused left ventricle. Before and after stunning, we measured autoregulation, myocardial blood flow and flow heterogeneity, as well as hemodynamic indices of myocardial oxygen demand. Fifteen min of ischemia and 1 hour of reperfusion produced both a 46% reduction in mechanical function, and a 7% drop in systemic arterial pressure, but not change in heart rate or rate pressure product. Myocardial oxygen consumption was 15% reduced and myocardial blood flow 16% reduced in the stunned myocardium when measured at one hour of reperfusion. Fifteen min after reperfusion, the slope of the coronary pressure flow plots and the coronary venous oxygenation were increased whereas the autoregulation index decreased. These findings all indicate reduced autoregulation during early reperfusion. However, after one hour of reperfusion, the slope of the coronary pressure-flow relation (0.41 +/- 0.19 vs. 0.48 +/- 0.26 ml.100 g-1.min-1.mmHg-1) and the autoregulation index (0.43 +/- 0.16 vs. 0.30 +/- 0.32) were unchanged from control measurements (p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Regional vasodilating properties of isoflurane in stunned swine myocardium.

Studies about the coronary vasodilating properties of isoflurane indicate that this drug induces coronary vasodilation. No work has examined isoflurane-induced vasodilation in known stunned myocardium. This study was conducted to determine isoflurane's coronary vasodilation potency in stunned myocardium and to compare the results obtained with normal myocardium. We determined the vasodilating properties of isoflurane in regionally perfused swine myocardium. Six domestic swine were anesthetized with pentobarbital and fentanyl. The left anterior descending artery (LAD) was cannulated and perfused with blood drawn from the carotid artery and passed thorough a membrane oxygenator. LAD arterial flow was controlled by a calibrated roller pump with continuous digital readout, and LAD arterial pressure was measured directly. The anterior interventricular vein was cannulated and dimension crystals placed in the LAD-perfused myocardium. Myocardial stunning was induced by reduction of coronary blood flow (CBF) to 30% of control flow for 20 minutes. One hour after reperfusion, the vasodilatory response to 0%, 1%, and 2% isoflurane administered via the membrane oxygenator was determined and compared to maximum vasodilatation produced by regional intracoronary administration of adenosine. Systemic blood pressure and heart rate remained constant throughout the experiment. At 2% isoflurane, systolic shortening and regional myocardial oxygen consumption decreased 53% and 17%, respectively. The same concentration increased CBF by 33% and reduced coronary vascular resistance (CVR) by 25%. One percent isoflurane affected neither CBF nor CVR. Regional coronary administration of adenosine produced much greater changes in CBF (+509) and CVR (-89.5%).(ABSTRACT TRUNCATED AT 250 WORDS)

Therapeutic hyperoxia diminishes myocardial stunning.

UNLABELLED: We used a model of isolated coronary perfusion to answer the question: Does high PO2 during low flow myocardial ischemia diminish postischemic myocardial contractile dysfunction? In 12 anesthetized, open chest swine, the left anterior descending (LAD) coronary artery was cannulated and perfused via an extracorporeal circuit. Normoxic arterial blood was pumped through a pediatric membrane oxygenator, which was used to control arterial PO2 in the perfusion bed. Myocardial stunning was created by reducing LAD coronary artery flow to 40% of control values for 30 minutes. After 5 minutes of ischemia, swine were randomized to either continued coronary normoxia or to coronary hyperoxia. In the hyperoxic group, oxygen was substituted for nitrogen in the oxygenator, thus increasing coronary PO2 to 382 +/- 32 mmHg. After 30 minutes of ischemia, all swine were reperfused with normoxic blood. RESULTS: There were no significant baseline differences between the two groups with regard to baseline hemodynamics, myocardial blood flow, or oxygen delivery parameters. Preischemic systolic shortening was comparable in the normoxic and hyperoxic groups: 23.6 +/- 6.8% and 24.9 +/- 3.9%, respectively. Increasing coronary arterial PO2 to 382 mmHg during ischemia led to a significant decrease in myocardial stunning in the hyperoxic group. Postischemic systolic shortening in the hyperoxic treatment group, measured at 15, 30, 45, and 60 minutes of reperfusion, was 14.8% +/- 6.3% (p < 0.05), 13.4% +/- 6.4% (p < 0.05), 13.8% +/- 6.7% (p < 0.05), and 14.3% +/- 5.8% (p < 0.05) compared to comparable measurements in the normoxic control group of 9.0% +/- 5.4%, 7.8% +/- 5.0%, 7.8% +/- 5.2%, and 7.2% +/- 5.1%.(ABSTRACT TRUNCATED AT 250 WORDS)

Regional vasodilating properties of isoflurane in normal swine myocardium.

BACKGROUND: Studies of the coronary vasodilating properties of isoflurane have produced inconsistent results. Isoflurane has been reported to cause minimal or no coronary vasodilation, mild dose-related vasodilation, or even near-maximal coronary vasodilation. The current study was performed to clarify the direct coronary vasodilating potency of isoflurane. METHODS: We determined the vasodilating properties of isoflurane in regionally perfused swine myocardium. Six domestic swine were anesthetized with pentobarbital and fentanyl. The left anterior descending artery (LAD) was cannulated and perfused with blood drawn from the carotid artery and passed thorough a membrane oxygenator. LAD arterial flow was controlled by a calibrated roller pump with continuous digital readout, and LAD arterial pressure was measured directly. The anterior interventricular vein was cannulated and dimension crystals placed in the LAD-perfused myocardium. The vasodilation response to 0, 1, 2, and 3% isoflurane administered via the membrane oxygenator was determined and compared to maximal vasodilation produced by regional intracoronary administration of adenosine. RESULTS: Systemic blood pressure and heart rate remained constant throughout the experiment. With 3% isoflurane, systolic shortening and regional myocardial oxygen consumption decreased by 60 and 20%, respectively. The same concentration increased coronary blood flow by 51 +/- 34% and reduced coronary vascular resistance by 32.9 +/- 11.0%. Neither coronary blood flow nor coronary vascular resistance was affected with 1% isoflurane. Regional coronary administration of adenosine produced much greater changes in both coronary blood flow (+591%) and coronary vascular resistance (-92.5%). Isoflurane increased the venous oxygen content of the anterior interventricular vein in a dose-dependent fashion from 4.85 vol% at control to 6.17, 7.01, and 8.63 vol% at 1, 2, and 3% isoflurane, respectively. CONCLUSIONS: We conclude that isoflurane is a mild dose-dependent coronary vasodilator. At a 1% concentration, the coronary vasodilating properties of isoflurane are minimal.

Coronary pressure-flow regulation in the stunned myocardium.

In this study, we used a swine model to study coronary autoregulation in the stunned myocardium. In 18 domestic swine, the left anterior descending coronary artery was cannulated and flow to this artery controlled via an extracorporeal perfusion circuit. Stunning was induced by reducing pump flow to approximately 25% of the baseline value for 15 minutes followed by 1 hour of reperfusion. This ischemia/reperfusion protocol reduced systolic shortening to approximately 50% of control, at 1 hour of reperfusion. Neither the slope of the coronary pressure-flow relation (0.41 +/- 0.19 vs 0.48 +/- 0.26 mL/100 g per min per mmHg) nor an autoregulation index (0.43 +/- 0.16 vs 0.30 +/- 0.32) was significantly changed at 1 hour reperfusion (p > 0.05) compared to baseline. These findings argue against the hypothesis that the mechanical dysfunction of the stunned myocardium is due to suboptimal perfusion caused by poor coronary autoregulation.

Effects of high arterial oxygen tension on function, blood flow distribution, and metabolism in ischemic myocardium.

BACKGROUND: Although oxygen inhalation therapy has long been used in the treatment of acute myocardial ischemia, experimental evidence that increased arterial PO2 has any beneficial effect in the absence of hypoxemia is equivocal. In this study, we used a swine model of subendocardial myocardial ischemia to determine the effects of arterial hyperoxia on regional myocardial contractile function (sonomicrometry), myocardial blood flow distribution (microspheres), and regional myocardial glycolytic metabolism (carbon isotope-labeled substrates). METHODS AND RESULTS: In 10 domestic swine, the left anterior descending coronary artery was cannulated and flow to this artery was strictly controlled via a roller pump in the perfusion circuit. Arterial PO2 was controlled by manipulating inspired oxygen concentration (FIO2). Low-flow myocardial ischemia was induced by reducing pump flow to 50% of the control value, which diminished regional endocardial systolic shortening to 30-50% of normal. After a 15-minute period of flow stability, each animal was exposed in randomized order to two additional 15-minute experimental periods: coronary normoxia (PO2 = 90-110 mm Hg) and coronary hyperoxia (PO2 greater than 400 mm Hg). At each level of oxygenation, we measured regional myocardial function, regional myocardial blood flow and metabolism, and hemodynamic indexes of myocardial oxygen demand. Myocardial ischemia during normoxia reduced systolic shortening to 10.9 +/- 5.3% in the ischemic zone. Hyperoxia increased ischemic zone systolic shortening substantially to 15.2 +/- 4.6%. During myocardial ischemia, endocardial blood flow was decreased to 0.26 +/- 0.06 ml.g-1.min-1 in the ischemic zone. During hyperoxia, endocardial blood flow rose to 0.34 +/- 0.10 ml.g-1.m-1. The endocardial: epicardial flow ratio was 0.45 +/- 0.18 in the initial ischemia period and rose to 0.61 +/- 0.23 in the hyperoxic period. Myocardial ischemia increased regional uptake of glucose, conversion of glucose to released lactate, and net myocardial lactate release. In the ischemic myocardium, coronary hyperoxia decreased both chemically measured lactate production and isotopically measured lactate release and decreased glucose extraction and the conversion of glucose to lactate. CONCLUSIONS: These data demonstrate for the first time that increasing arterial PO2 to high levels during acute low-flow myocardial ischemia improves both function and flow distribution in the ischemic myocardium and decreases glycolytic metabolism in the ischemic zone. The degree of improvement in contractile function (5% absolute increase in systolic shortening or 25% change normalized to preischemic values) is consistent with the observed increase in subendocardial blood flow.

Isoflurane anesthesia and myocardial ischemia: comparative risk versus sufentanil anesthesia in patients undergoing coronary artery bypass graft surgery. The SPI (Study of Perioperative Ischemia) Research Group.

Whether isoflurane has the potential to produce coronary artery steal and associated myocardial ischemia is still controversial. Previous studies addressing this issue in humans did not purposefully control hemodynamics or use continuous measures of myocardial ischemia. The authors used transesophageal echocardiography (TEE) and continuous Holter electrocardiography (ECG) to study the relative risk of myocardial ischemia during isoflurane or sufentanil anesthesia under strict control of hemodynamics in 186 high-risk patients undergoing elective coronary artery bypass graft (CABG) surgery. Overall, hemodynamics were well controlled (increased heart rate = 9.8%; increased systolic blood pressure = 7.1%; decreased systolic blood pressure = 10.8% of total prebypass time compared with preoperative baseline values), with no difference between the two anesthetics. In the 162 patients with interpretable TEE recordings, moderate to severe TEE ischemic episodes (grade change greater than or equal to 2) developed in 33 (21%) during the prebypass period, with no difference between isoflurane (12 of 56 = 21%) and sufentanil (21 of 106 = 20%) (P = 0.97). The duration and severity of TEE episodes were not significantly different between the two groups. No correlation was observed between TEE ischemic episodes and isoflurane concentrations (range 0.47-1.75%). In the 181 patients with interpretable ECG recordings, ECG evidence of ischemia developed in 34 (19%) during the prebypass period, with no difference between isoflurane (12 of 59 = 20%) and sufentanil (22 of 122 = 18%) (P = 0.87). The duration and severity of electrocardiographic ischemic episodes were also similar in patients receiving either isoflurane or sufentanil. Four of the 62 patients (6%) who received isoflurane had an adverse cardiac outcome versus 15 of 124 patients (12%) who received sufentanil (P = 0.34). The authors' findings demonstrate that, when hemodynamics are controlled, the incidence of myocardial ischemia (TEE or ECG) during isoflurane and sufentanil anesthesia is similar.

Effects of nitrous oxide on coronary pressure and regional contractile function in experimental myocardial ischemia.

To determine whether nitrous oxide (N2O) worsens myocardial ischemia by diminishing coronary pressure, we performed two sets of experiments using an acutely instrumented swine model of regional coronary ischemia. In constant pressure experiments (n = 11), coronary pressure and heart rate were kept constant as N2O (77%-79%) was substituted for N2 in the inspired gas. Nitrous oxide decreased systolic shortening, measured by sonomicrometry, from 68.0% to 63.6% (P less than 0.05) of preischemic control values in the ischemic zone and from 116.2% to 103.2% (P less than 0.05) of control values in the adjacent normal myocardium. There was no disproportionate effect of N2O on ischemic myocardium, and the N2O-induced depression of contractile function was fully reversible. In a series of constant external stenosis experiments (n = 13), the effects of N2O on heart rate, mean arterial pressure, and the coronary stenosis itself were not controlled. In these experiments, substitution of N2O for N2 induced deterioration in both the ischemic zone (systolic shortening decreased from 68.7% to 58.4% of preischemic control values, P less than 0.05) and in the adjacent normal myocardium (systolic shortening decreased from 113% to 102.9% of preischemic control, P less than 0.05). Nitrous-oxide-induced ischemic zone contractile dysfunction was often not reversible. The pressure gradient across the coronary stenosis did not increase and peripheral coronary pressure did not decrease because of N2O. Diffusion hypoxia was also excluded. This study confirms that N2O has a significant but mild depressant effect on the performance of both normal and ischemic myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperoxemic reperfusion does not increase myocardial infarct size.

We tested the hypothesis that arterial hyperoxia during myocardial reperfusion increases reperfusion injury and infarct size. The anterolateral marginal coronary artery of 35 anesthetized rabbits was occluded for 45 min, then reperfused for 3 h with either normoxic [arterial PO2 (PaO2) = 96.7 +/- 22.9 mmHg)] or hyperoxic (PaO2 = 554.8 +/- 61.7 mmHg) blood. In the hyperoxic group only, PaO2 was adjusted 10 s before the onset of reperfusion by raising inspired oxygen concentration to 100%. The area of infarction (AI) was defined by triphenyltetrazolium staining, and the area at risk (AR) by fluorescent microspheres. These areas were measured by planimetry. Heart rates and blood pressures did not differ between the two groups during occlusion or reperfusion. Infarct size (AI/AR) was 49.1 +/- 16.5% in the normoxic group (n = 17) and 40.8 +/- 16.1% in the hyperoxic group (n = 18). From these data, 90% confidence limits establish that the maximal true increase in AI/AR caused by hyperoxia would be 0%-1%. Hyperoxic reperfusion of ischemic myocardium compared with normoxic reperfusion does not significantly increase myocardial infarct size.