17-Beta estradiol regulation of myocardial glutathione and its role in protection against myocardial stunning in dogs.

We studied the effect of 2-week treatment with estradiol 17beta on myocardial glutathione concentration in dogs and isolated perfused rat heart subjected to brief coronary ischemia and reperfusion. Estradiol protected against ischemia/reperfusion-induced myocardial systolic shortening and malonylaldehyde production and increased myocardial glutathione concentration and glucose-6-phosphate dehydrogenase enzyme activity. Reduction of myocardial glutathione with buthionine sulfoximine to levels seen in the absence of estrogen reversed the protective effect of estradiol against myocardial dysfunction and lipid peroxidation associated with ischemia/reperfusion. These results suggest that the antioxidant effect of estradiol in ischemia/reperfusion may be mediated by regulation of myocardial glutathione metabolism.

17 beta-Estradiol prevents dysfunction of canine coronary endothelium and myocardium and reperfusion arrhythmias after brief ischemia/reperfusion.

BACKGROUND: Brief myocardial ischemia is associated with myocardial and coronary endothelial dysfunction caused by oxygen free radicals released during reperfusion. Estrogen, known to have antioxidant activity, may prevent these complications. METHODS AND RESULTS: We assessed the effect of 2 weeks of treatment with 17 beta-estradiol (E, 100 micrograms.kg-1.d-1, n = 12) or placebo (P, n = 15) on myocardial and coronary endothelial function during the first 2 hours of reperfusion in dogs subjected to 15 minutes of ischemia induced by occlusion of the left anterior descending coronary artery (LAD). Our results show that the incidence of ventricular arrhythmias significantly decreased in E (3 of 12) compared with P (11 of 15). Systolic shortening, significantly depressed in P during early reperfusion, was maintained at preischemic levels in E. During reperfusion, the increase in LAD flow to acetylcholine, attenuated in P (60 +/- 6%), was preserved in E endothelium. (151 +/- 28%) and was associated with increased serum nitrite/nitrate concentration. n-Pentane in exhaled gas in vivo, an index of lipid peroxidation, increased significantly during early reperfusion in P (from 9.1 +/- 1.9 to 41.6 +/- 13.0 ppb, P < .05) but not in E (23.0 +/- 6.9 ppb). In vitro, arterial segments from E generated significantly less superoxide anion after hypoxia/reoxygenation than those from P. Ischemic/reperfused LAD segments from E also revealed a better preservation of endothelium-dependent relaxation in vitro (maximum relaxation, 42 +/- 4% versus 24 +/- 4% in P; P < .05). CONCLUSIONS: Estrogen protects against endothelial and myocardial dysfunction resulting from brief ischemia/reperfusion. This protection may relate to an antioxidant effect of estrogen.

Accurate assessment of right ventricular function in acute respiratory failure.

OBJECTIVE: Since right ventricular ejection fraction is highly dependent on afterload, right ventricular ejection fraction may not reflect right ventricular contractile function in acute respiratory failure. Despite a severe reduction in right ventricular ejection fraction, the right ventricle may be able to generate pressure output that is sufficient enough to maintain an adequate distribution of pulmonary perfusion. We tested this hypothesis by assessing the correlation between the right ventricular ejection fraction and the right ventricular end-systolic pressure-volume relationship, and by assessing the correlations between right ventricular ejection fraction and the physiologic deadspace/tidal volume ratio and between the physiologic deadspace/tidal volume ratio and the right ventricular end-systolic pressure-volume relationship. DESIGN: Prospective study. SETTING: University hospital intensive care unit (ICU). PATIENTS: Twenty-one patients with acute respiratory failure. MEASUREMENTS AND MAIN RESULTS: The physiologic deadspace/tidal volume ratio was used as an index of the distribution of pulmonary perfusion. Right ventricular ejection fraction was measured by the thermodilution method. Right ventricular end-diastolic volume index was obtained from the stroke volume index divided by the right ventricular ejection fraction. Right ventricular end-systolic volume index was calculated as the difference between the right ventricular end-diastolic volume index and the stroke volume index. Pulmonary arterial dicrotic notch pressure was used as an estimate of right ventricular end-systolic pressure. Data were collected at baseline and after one or two alterations in preload to define the right ventricular end-systolic pressure-volume relationship. There was no correlation between the right ventricular ejection fraction and the slope of the right ventricular end-systolic pressure-volume relationship line. No correlation was found between the right ventricular ejection fraction and the physiologic deadspace/tidal volume ratio. There was a hyperbolic curvilinear relationship between the physiologic deadspace/tidal volume ratio and the slope of the right ventricular end-systolic pressure-volume relationship line (r2 = .82, p < .0001). When the patients were divided into two groups based on the slope of the right ventricular end-systolic pressure-volume relationship line, the physiologic deadspace/tidal volume ratio was lower in the group with a high slope of the right ventricular end-systolic pressure-volume relationship line (p < .0001). There was no difference in other hemodynamic data between the two groups. CONCLUSIONS: These data suggest that in acute respiratory failure, the right ventricular ejection fraction does not reflect right ventricular performance.

Constriction of canine coronary arteries by platelet activating factor after brief ischemia.

Platelet activating factor (PAF) has been suggested as a mediator of coronary spasm and acute myocardial ischemia. However, PAF can have either vasodilator or vasoconstrictor activities according to various reports. Because of the importance of endothelium in regulating vascular tone, we hypothesized that changes in endothelial function could modulate some of the observed differences in the activities of PAF. To test this hypothesis, PAF was infused directly into the left anterior descending coronary artery (LAD) of dogs at a rate of 0.3 microgram/min before and after 20 min of LAD ligation followed by reperfusion. Coronary blood flow (CBF) was measured continuously via a Doppler flow probe. Likewise, responses to the endothelium dependent vasodilator, acetylcholine (ACh) were measured before and after the LAD ligation. Before ligation, PAF produced a vasodilatory response in the LAD, resulting in 28.4 +/- 11.0% increase in CBF and a 21.5 +/- 5.8% decrease in coronary vascular resistance (CVR). However, after ligation and subsequent reperfusion, 0.3 microgram/min PAF produced vasoconstriction, resulting in a 10.2 +/- 8.7% decrease in CBF (p < 0.01 compared to pre-infusion change in (CBF), and a 27.8 +/- 23.2% increase in CVR (p = 0.05) compared to pre-infusion change in CVR). The vasodilator response to ACh was markedly blunted by ischemia. These results suggest that the coronary vascular response to PAF may depend upon the functional integrity of the endothelium, with endothelial damage resulting in constrictor responses to PAF.(ABSTRACT TRUNCATED AT 250 WORDS)

Elevated pulmonary artery systolic storage volume associated with improved ventilation-to-perfusion ratios in acute respiratory failure.

The possibility that an elevated pulmonary artery systolic storage volume (PASSV) correlates with improved overall ratios of ventilation-to-perfusion and hence benefits gas exchange in acute respiratory failure was examined. We examined this by assessing the correlation between PASSV and both the physiologic dead space to tidal volume ratio (VD/VT) and intrapulmonary shunt fraction (Qsp/Qt). The VD/VT and Qsp/Qt were used as an index of distribution of ventilation-to-perfusion as well as efficiency of pulmonary gas exchange. Twenty-eight patients suffering from acute respiratory failure were included. All required mechanical ventilation. PASSV was calculated from the pulmonary artery (PA) compliance and mean PA systolic distending pressure. Pulmonary arteriolar pressures were computed by Fourier analysis. PA compliance was derived from the PA time constant and the PA resistance. Storage volume fraction of stroke volume index (PASSV/SVI) was used to compare individual variations. There were inverse linear relationships between PASSV/SVI and VD/VT (r = 0.693, p less than 0.0001), and between PASSV/SVI and Qsp/Qt (r = 0.427, p = 0.012). Also, a direct correlation was found between VD/VT and PA time constant (r = 0.503, p = 0.002). The patients were divided into two groups based on PASSV/SVI to evaluate the effect of other hemodynamic data on PASSV. Comparison of the two groups revealed that VD/VT and Qsp/Qt were lower (p less than 0.0001, and p = 0.018, respectively), PA time constant was higher (p less than 0.001), and right ventricular stroke-work index was higher (p = 0.005) in the group with a high PASSV/SVI. There were no differences in other hemodynamic data between the two groups. These data suggest that an elevated PASSV may indeed benefit gas exchange in acute respiratory failure.

Postpartum transient blindness probably related to undiagnosed brain tumor.

Nausea and vomiting are so frequent under regional anesthesia during parturition that these symptoms can be misleading and may cause the clinician to overlook a potential intracranial lesion. In the case we have reported, it was not until the onset of blindness that an intracranial lesion was suspected. Although the incidence of brain tumor during pregnancy is low, it does occur with various manifestations and has been associated with blindness. Therefore, prompt neurologic investigation may be warranted in patients complaining of visual changes, even though transient blindness can occur in the absence of a neurologic lesion.

Combined epidural and general anesthesia for abdominal aortic surgery.

The hypothesis that combined epidural and light general anesthesia for infrarenal abdominal aortic surgery is associated with a more stable intraoperative course and less postoperative morbidity than general anesthesia alone was tested. The authors compared intraoperative hemodynamic variables and postoperative morbidity between a group with combined epidural and general anesthesia (n = 30) and a group with general anesthesia (n = 19). Patients who had combined epidural and general anesthesia were given epidural bupivacaine intraoperatively and epidural morphine postoperatively. After cross-clamping of the aorta, cardiac index and pulmonary capillary wedge pressure did not change in the group with combined epidural and general anesthesia, whereas cardiac index decreased (mean change, 0.30 L/min/m2; P = 0.0006) and pulmonary capillary wedge pressure increased (mean change, 1 mm Hg; P = 0.007) in the group with general anesthesia. After unclamping, cardiac index increased in both groups (mean change, 0.26 L/min/m2, P = 0.002, and 0.30 L/min/m2, P = 0.001, respectively). Postoperatively, the necessity for ventilatory support and the incidence of respiratory failure were lower in the combined epidural and general anesthesia group than in the general anesthesia group (P = 0.0002 and P = 0.018, respectively). In addition, vasodilator therapy was required less frequently in the group with combined epidural and general anesthesia (P = 0.002). Duration of intensive care unit stay was shorter in the combined epidural and general anesthesia group (2.7 days v 3.8 days, P = 0.003). These data indicate that for infrarenal abdominal aortic surgery, combined epidural and general anesthesia is associated with more stable intraoperative hemodynamics and significantly less postoperative morbidity than general anesthesia alone.

The changes in brain surface, intracerebral tissue, and transconjunctival oxygen tension during hypo- and hyperventilation.

To evaluate the validity of organ surface oxygen tension monitoring for assessment of cerebral perfusion, the oxygen tension in brain surface (Pbs(O)(2)), intracerebral tissue (Pic(O)(2)), and conjunctiva (Pcj(O)(2)) were measured simultaneously during hypo- and hyperventilation in dogs, and the comparative study was done. Pbs(O)(2) and Pic(O)(2) significantly increased during hypoventilation and decreased during hyperventilation. And the values of Pbs(O)(2) and Pic(O)(2) were correlated to the corresponding Pa(CO)(2) values significantly ( P << 0.001 in each case). On the contrary, Pcj(O)(2) did not change significantly during hypo- and hyperventilation. These findings indicate that Pbs(O)(2) as well as Pic(O)(2) could reflect the changes in cerebral perfusion caused by induced hyper- and hypocapnia but that Pcj(O)(2) could not.

Elevated pulmonary artery systolic storage volume associated with redistribution of pulmonary perfusion.

The possibility that an increased pulmonary arterial systolic storage volume (PASSV) correlates with a significant redistribution of pulmonary perfusion was examined in 30 surgical patients. Right ventricular stroke work index (RVSWI) was used as an index of distribution of pulmonary perfusion. The systolic storage volume was calculated from the pulmonary arterial compliance and mean pulmonary arterial distending pressure. Pulmonary arteriolar pressures were computed by Fourier analysis. Pulmonary arterial compliance was derived from the pulmonary arterial time constant and pulmonary arterial resistance. There was a linear relationship between PASSV and RVSWI (r = .81, p less than .001). Also, a direct correlation was found between RVSWI and pulmonary arterial time constant (r = .45, p less than .01). When the patients were divided into three groups according to the severity of pre-existing disease, linear relationships between PASSV and RVSWI were present in all groups, and the slopes were not different among the three groups. The patients were also divided into two groups based on a storage volume fraction of stroke volume index, to evaluate the effect of other hemodynamic data on the PASSV. Comparison of the two groups revealed that pulmonary arterial pressure and pulmonary arterial compliance were significantly higher in the group with a high storage volume fraction (p = .05 and p = .01, respectively). RVSWI and time constant were also significantly different between the groups (p less than .01 and p less than .01, respectively). We conclude that the pressure work generated by the right ventricle improved the distribution of pulmonary perfusion by increasing PASSV.

Critical level of oxygen delivery after cardiopulmonary bypass.

The relationship between oxygen uptake (Vo2) and delivery (Do2) was examined in 64 patients immediately after cardiopulmonary bypass. In 44 patients with lactate levels below 2.5 mmol/L, Vo2 decreased proportionally when Do2 decreased below 300 ml/min X m2. At a Do2 over this level, Vo2 plateaued at 105 +/- 13 (SD) ml/min X m2. In a contrasting group of 22 patients with blood lactate levels above 2.5 mmol/L, Vo2 changes depended on changes in Do2 both alone and below 300 ml/min X m2.

Halothane effects on subendocardial oxygen supply-demand balance: estimation from intramyocardial tissue pressure and left ventricular pressure.

We evaluated the effect of halothane on the balance of subendocardial oxygen supply and demand in six dogs by estimating the endocardial viability ratio (EVR) based on the pressure generated within the subendocardium (ENDO-IMP). Concurrently, the conventional EVR based on left ventricular pressure (LVP) was estimated and compared with the EVR based on ENDO-IMP. The subendocardial oxygen supply-demand ratio based on ENDO-IMP (IMP-EVR) was significantly less than EVR based on LVP (LVP-EVR) (0.87 +/- 0.03 vs 1.07 +/- 0.06, P less than 0.05) during the control period. With 0.5% halothane administration, IMP-EVR improved significantly (1.04 +/- 0.07, P less than 0.05) while LVP-EVR remained unchanged (1.08 +/- 0.09). No further changes in EVR (either IMP-EVR or LVP-EVR) were observed with increasing halothane concentrations up to 2%. The relationship between the two indices was weak (r2 = 0.44, P less than 0.001) but statistically significant. Because an estimate of EVR based on direct measurement of subendocardial tissue pressure (IMP-EVR) would reflect more accurately the oxygen supply-demand balance of this region than the LVP-EVR, our results suggest that the oxygen balance of the subendocardium improves with halothane administration. The use of LVP-EVR as a hemodynamic index of subendocardial oxygen balance during halothane anesthesia, therefore, is questionable.

Display adaptor for the Vitatek #511 monitor and the Puritan-Bennett CO2 analyzer.

Many CO2 infrared analyzers require additional graphics devices for continuous CO2 waveform display. An adaptor was designed to integrate the output of a Puritan-Bennett infrared CO2 analyzer into the display of a Vitatek #511 patient monitor. The adaptor is made with inexpensive off-the-shelf components and proved successful during more than six months of use.

Protamine induced arterial hypoxaemia: the relationship to hypoxic pulmonary vasoconstriction.

Protamine administration may induce arterial hypoxaemia in dogs and humans. However, the responsible mechanism has not been established. Protamine, as it is a pulmonary vasoactive substance, may interfere with normal hypoxic pulmonary vasoconstriction (HPV) and cause arterial hypoxaemia. This possibility was tested in dogs utilizing a one lung hypoxic model. One lung hypoxic ventilation decreased pulmonary blood flow in the hypoxic lung from 1022 +/- 96 ml X min-1 (mean +/- SEM) to 846 +/- 39 ml X min-1 (p less than 0.05) while increasing blood flow from 833 +/- 85 ml X min-1 to 1109 +/- 101 ml X min-1 (p less than 0.05) in the normoxic lung, resulting in 24 per cent effective diversion of blood flow. Protamine infusion, after heparinization, markedly elevated pulmonary vascular resistance in both lungs but preferentially in the normoxic lung (102 +/- 27 per cent increase in normoxic lung, 60 +/- 6.4 per cent increase in hypoxic lung) and significantly reversed the pulmonary blood flow shift induced by one lung hypoxic ventilation (effective diversion of blood flow was reduced to four per cent). Concurrently, arterial PO2 further decreased. Our results demonstrate that protamine interferes with effectiveness of pre-existing HPV and suggest that this mechanism, at least in part, may be responsible for arterial hypoxaemia observed after protamine infusion. The marked generalized pulmonary vasoconstriction with protamine appears to be the direct force that interferes with pre-existing auto-regulatory HPV. In addition to the well known haemodynamic effects of protamine, protamine infusion may also cause arterial hypoxaemia in those patients in whom HPV plays a significant role in maintaining arterial oxygenation.

Resting energy expenditure in controls and cancer patients with localized and diffuse disease.

Resting energy expenditure (REE), nutritional parameters, and substrate levels were measured using a technique to minimize artifacts in 11 control patients, nine patients with localized, and four patients with diffuse neoplastic disease. Patients with diffuse disease had significantly increased percentage preillness weight loss (15.4 +/- 7.0%), decreased arm muscle circumference (21.9 +/- 2.1 vs. 26.2 +/- 3.5 cm), serum albumin (3.6 +/- 0.6 vs. 4.4 +/- 0.2 g/dl), total lymphocyte count (1024 +/- 613 vs. 1796 +/- 495 cells/mm3), and creatinine-height index (0.68 +/- 0.16 vs. 1.18 +/- 0.37) compared to controls. Both groups of cancer patients had significantly increased REE compared to controls: 25.6 +/- 3.7 (diffuse), 21.4 +/- 3.7 (localized), vs. 18.1 +/- 2.9 kcal/kg/d (controls). However, when REE was expressed as a function of metabolic body size, the significant difference persisted only in the patients with diffuse disease compared to controls: 71.8 +/- 16.4 vs. 53.9 +/- 8.1 kcal/kg3/4/d. Patients studied pre- and posttumor resection all had a postoperative drop in their REE, which was significantly correlated with the measured tumor volume. In this homogeneous, select group of patients, the tumor-bearing state exerts a moderate impact on nutritional and metabolic parameters, which are probably related to the extent of disease.

Closing the loop: how near is automated anesthesia?

Technologic advances now make automated anesthesia delivery systems theoretically possible; clinical implementation, however, awaits development and refinement in three areas: (1) adjunctive monitoring, which needs to be extremely sophisticated; (2) automated data collection, which will obviate manual record keeping; (3) automated therapeutic intervention, which will control drug, fluid, and gas administration. Reduced health care costs and increased safety are the primary goals; there is also the possibility, however, of increased costs and new hazards.