Effect of reperfusion on O2 supply/consumption balance in ischemic canine left ventricle

This study was designed to assess the effects of reperfusion on regional O2 supply and O2 consumption of ischemic areas of the myocardium in 15 anesthetized open-chested dogs. The left anterior descending coronary artery (LAD) was occluded for 6 h (n = 8), 2 h (n = 5), 2-h occlusion followed by 4-h period of reperfusion (n = 7), and 10-min occlusion followed by 90-min period of reperfusion (n = 3). Small artery and vein O2 saturations obtained microspectrophotometrically were combined with regional flow measurements using radioactive microspheres to determine regional myocardial O2 consumption. Coronary occlusion for 2 or 6 h significantly reduced mean flow to 15 +/- 8 and 13 +/- 14 ml/min/100 g (mean +/- SD), respectively, in the affected LAD areas as compared to 128 +/- 26 and 113 +/- 46 ml/min/100 g in the non-ischemic areas. In the 4-h reperfusion group, reperfusion increased the average flow (60 +/- 42 ml/min/100 g). O2 extraction was greater in the ischemic area than in the unaffected area after both occlusion and 4-h reperfusion. In the affected area, O2 consumption was reduced by 84% after 6-h occlusion. Reperfusion for 4 h increased O2 consumption toward normal values. Coronary artery occlusion produced an increase in the number of arteries and veins with reduced O2 saturations and this was not affected by reperfusion. Short-term occlusion had no significant O2 supply effects after 90 min of reperfusion. It can be concluded that even though there was an increased O2 consumption as a consequence of reperfusion, O2 consumption still appeared to be flow-limited as indicated by the microregions of low O2 supply and/or high O2 extraction.     

Hepatic and splanchnic oxygen consumption during acute hypoxemic hypoxia in anesthetized pigs

OBJECTIVE: To compare the hepatosplanchnic oxygen consumption (VO2) with the hepatic and splanchnic VO2 and to calculate the critical oxygen delivery (DO2crit) below which VO2 decreases in the hepatic, splanchnic, and hepatosplanchnic regions in a model of hypoxemic hypoxia. DESIGN: Prospective animal study. SETTING: University research laboratory. SUBJECTS: Anesthetized and ventilated pigs (n = 7). INTERVENTIONS: The right carotid artery was cannulated to measure mean arterial pressure. A pulmonary artery catheter was inserted to measure mean pulmonary arterial pressure and cardiac output. After a midline abdominal incision, two flow probes were positioned around the portal vein and the hepatic artery to measure portal vein blood flow and hepatic artery blood flow. Oxygen and lactate contents in the carotid artery, the portal vein, and the hepatic vein were measured in blood samples obtained from the appropriate catheters. MEASUREMENTS AND MAIN RESULTS: After a 2-hr stabilization period, hemodynamic and biological variables were recorded during acute hypoxemic hypoxia (FIO2 = 0.5, 0.4, 0.3, 0.21, 0.15, 0.10, and 0.07). VO2, DO2, and DO2crit were determined in the hepatic, splanchnic, and hepatosplanchnic regions. The hepatosplanchnic VO2 was 48 +/- 5 mL/min at high FIO2 (40% for the liver and 60% for the splanchnic organs) and decreased below FIO2 of 0.15. Lactate uptake in the whole hepatosplanchnic region remained steady at FIO2 values of 0.5 to 0.15 and then switched to a lactate release at low FIO2. However, the splanchnic region released lactate, whereas lactate was taken up by the liver. DO2crit in the hepatic, splanchnic, and hepatosplanchnic regions was 24 +/- 3, 38 +/- 2, and 49 +/- 4 mL/min, but the systemic DO2crit, below which regional VO2 became oxygen supply dependent, did not differ in the liver, splanchnic, and hepatosplanchnic regions. CONCLUSIONS: The variables of oxygenation and lactate flux measured in the hepatosplanchnic region summarize the metabolic changes of various organs that may vary in different ways during hypoxemic hypoxia.     

Effect of neuromuscular blockade on oxygen consumption and energy expenditure in sedated, mechanically ventilated children

OBJECTIVE: To quantify the effects of neuromuscular blockade (NMB) on energy expenditure for intubated, mechanically ventilated, critically ill children. DESIGN: A prospective, unblinded clinical study. Each subject was studied twice, before and after establishment of NMB. SETTING: A tertiary care pediatric intensive care unit. PATIENTS: Critically ill children undergoing mechanical ventilation and receiving ongoing sedation were eligible, if they had a cuffed endotracheal tube and were physiologically stable. INTERVENTIONS: A total of 20 children (age, 1 to 15 yrs) were studied in an unblinded, crossover fashion. All were mechanically ventilated via a cuffed endotracheal tube, with ventilator rate and tidal volume adequate to provide complete ventilation, and F(IO2) <0.6. Absence of gas leak around the endotracheal tube was assured, and all patients were sedated using continuous infusions of midazolam and/or fentanyl; no changes in ventilator settings, nutritional input, or inotropic drug dose were permitted during the study period. Each patient underwent indirect calorimetry immediately before establishment of NMB. NMB was then induced, and indirect calorimetry was repeated. Complete blockade was verified using a peripheral nerve stimulator. In each case, the two sets of measurements were completed within a 1-hr period. MEASUREMENTS AND MAIN RESULTS: Data analyzed included identifying and diagnostic information, oxygen consumption, and carbon dioxide production. Energy expenditure was calculated using standard formulas. Oxygen consumption and energy expenditure values obtained before and after the establishment of NMB were compared by using paired Student's t-test. NMB reduced oxygen consumption from 6.54+/-0.49 mL/kg/min to 5.90+/-0.40 ml/kg/min, and energy expenditure was reduced from 46.5+/-3.7 kcal/kg/24 hrs to 41.0+/-2.8 kcal/kg/24 hrs (p < .001 in each case). The reduction in oxygen consumption was 8.7+/-1.7%, and that in energy expenditure 10.3+/-1.8%, of pre-NMB values, respectively. CONCLUSION: NMB significantly reduces oxygen consumption and energy expenditure in critically ill children who are sedated and mechanically ventilated; the degree of reduction is small.     

Effect of arteriovenous shunting on plasma vasopressin levels in the anesthetized dog

Studies were performed in dogs anesthetized with chloralose to establish the plasma arginine vasopressin (AVP) response to 30-minute periods of femoral arteriovenous (AV) shunting at levels of either 10%, 30%, or 50% of control cardiac output. Significant increases in cardiac output, heart rate, and total body peripheral resistance (shunt resistance excluded), suggesting decreased sinoaortic baroreceptor activity, occurred at shunt fractions greater than 10%. There were no significant changes in plasma concentrations of AVP at any level of AV shunting. In separate studies, significant elevations in plasma AVP levels were observed in vagotomized dogs during AV shunting of 50% of control cardiac output. These results indicate that AV shunting less than or equal to 50% of cardiac output does not acutely alter plasma AVP levels in the intact dog and that cardiopulmonary receptors with vagal afferents suppress AVP release that might otherwise occur in this canine model of AV shunting.     

Intracoronary infusion of bradykinin: effects on noradrenaline overflow following reperfusion of ischemic myocardium in the anesthetized dog

Summary— Objective: The aim of this study was to investigate the effects of intracoronary bradykinin (BK) infusion on noradrenaline release and ventricular arrhythmias induced by coronary occlusion and reperfusion in the anesthetized dog. Methods: 14 anesthetized adult mongrel dogs of either sex underwent a 60 min occlusion of the left anterior descending coronary artery (LAD) followed by a 30-min reperfusion period. BK (1 ng.kg⁻¹·min⁻¹, n = 7), or its vehicle (Lactate Ringer, n = 7), infusions just distal to the left coronary ostium started 15 min before the LAD occlusion and were maintained throughout the experimental period. An epicardial vein, running parallel to the LAD was cannulated to enable the biochemical determinations. The effects of BK on ventricular arrhythmias, cardiac noradrenaline and lactate releases and creatine kinase activity were assessed. Results: BK significantly reduced the amount of noradrenaline released at reperfusion by ischemic myocardium (from 82.1 ± 31.7 to 11.9 ± 9.6 ng·min⁻¹), as well as plasma creatine kinase activity at 30 min of reperfusion. This is accompanied by a significant reduction in the incidence of reperfusion-induced sustained ventricular tachycardia. Conclusion: This suggests that the protective effect of bradykinin against reperfusion-induced sustained ventricular tachycardia could be associated with a reduction in cardiac noradrenaline release.     

Effect of exercise intensity on oxygen consumption kinetics in non-exercising muscle during exercise

This study examined the effect of exercise intensity on the kinetics of muscle oxygen consumption in non-exercising forearm flexor muscles (VO(2mf)) during exercise. Seven healthy male subjects performed cycling exercise for 60 min at 30% of maximal oxygen consumption (%VO(2max)) and 30 min at 50% VO(2max) on separate days. The VO(2mf) values at rest and during exercise were measured by near-infrared spectroscopy. The VO(2mf) at 30% VO(2max) significantly increased to 1·2 ± 0·1-fold over resting value at 20 min after the beginning of exercise (P<0·05) and remained constant within 1·2- to 1·3-fold over resting value until 60 min during exercise. The VO(2mf) at 50% VO(2max) significantly increased to 1·2 ± 0·1-fold over resting value at 15 min after the beginning of exercise (P<0·05). Subsequently, the VO(2mf) at 50% VO(2max) increased with time to 1·3 ± 0·1-fold over resting value at 20 min after the beginning of exercise and to 1·5 ± 0·2-fold over resting value at 30 min. The VO(2mf) 15-30 min of exercise at 50% VO(2max) was significantly higher than that at 30% VO(2max) (P<0·05). These data suggest that the increase in VO(2mf) has a time lag from the beginning of exercise, and the kinetics of VO(2mf) during exercise differs with exercise intensity. Therefore, we conclude that the kinetics of VO(2mf) during exercise is dependent on exercise intensity.     

Increased oxygen consumption in the somatosensory cortex of alpha-chloralose anesthetized rats during forepaw stimulation determined using MRS at 11.7 Tesla

The significance of changes in cerebral oxygen consumption in focally activated brain tissue is still controversial. Since the rate of cerebral oxygen consumption is tightly coupled to that of tricarboxylic acid cycle which can be measured from the turnover kinetics of [4-(13)C]glutamate using in vivo (1)H{(13)C} magnetic resonance spectroscopy, changes in tricarboxylic acid cycle flux rate were assessed in primary somatosensory cortex of alpha-chloralose anesthetized rats during electrical forepaw stimulation. With markedly improved (1)H{(13)C} magnetic resonance spectroscopy technique and the use of high magnetic field strength of 11.7 T accessible to the current study, [4-(13)C]glutamate at 2.35 ppm was spectrally resolved from overlapping resonances of [4-(13)C]glutamine at 2.46 ppm and [2-(13)C]GABA at 2.28 ppm as well as the more distal [3-(13)C]glutamate and [3-(13)C]glutamine. The results showed a significantly increased V(TCA) in focally activated primary somatosensory cortex during forepaw stimulation, corresponding to approximately 51 +/- 27% (n = 6, mean +/- SD) increase in cerebral oxygen consumption rate. Considering the high efficiency in producing adenosine triphosphate by oxidative metabolism of glucose, the results demonstrate that aerobic oxidative metabolism provides the majority of energy required for cerebral focal activation in alpha-chloralose anesthetized rats subjected to forepaw stimulation.     

Effect of thromboxane receptor antagonists on venous thrombosis in rats

The activities of two structurally unrelated thromboxane/prostaglandin endoperoxide receptor antagonists, SQ 30,741 and BM 13,505, were compared to heparin in a model of venous thrombosis. A combination of blood stasis with osmotic and pressure stress was used to induce thrombus formation in the vena cava of anesthetized rats. Intravenous infusions of SQ 30,741 (500 micrograms/kg/min) and BM 13,505 (50 micrograms/kg/min) produced significant (P less than .01) and equivalent reductions in thrombus mass of 58 and 56%, respectively. Thrombus reduction in response to heparin (50 U/kg) was greater (95%; P less than .001) than in response to the thromboxane antagonists. Either lower doses of SQ 30,741 (50 and 100 micrograms/kg/min) or aspirin (30 and 60 mg/kg) were ineffective in altering thrombus formation. However, a subthreshold dose of SQ 30,741 (100 micrograms/kg/min) increased (P less than .01) the antithrombotic activity obtained with both threshold (0.5 U/kg) and subthreshold (0.3 U/kg) doses of heparin. SQ 30,741 (500 micrograms/kg/min) did not change activated partial thromboplastin times or inhibit platelet loss induced by contact activation in response to kaolin in vivo. This suggests that SQ 30,741 does not interfere with components of the coagulation cascade that are not dependent on platelet factors. The extent of thromboxane antagonism achieved with SQ 30,741 (50 and 500 micrograms/kg/min) and BM 13,505 (50 micrograms/kg/min) was determined from parallel shifts in dose-dependent U-46,619-induced vasoconstriction in vivo (approximately 200- and 1300-fold, respectively, for SQ 30,741 and 200-fold for BM 13,505). These data demonstrate that thromboxane antagonists inhibit venous thrombosis partially, but only at doses producing near complete receptor inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)     

脓毒性休克时大鼠全身氧供给与氧消耗关系的变化

目的：观察脓毒性休克时全身氧供给（ＤＯ２）与氧消耗（ＶＯ２）关系的变化。方法：以改良的盲肠结扎穿孔（ＣＬＰ）方法制备大鼠脓毒性休克模型，观察大鼠休克过程中ＤＯ２、ＶＯ２、氧摄取率（ＥＲＯ２）等变化。结果：ＣＬＰ后５小时已出现平均动脉压明显下降（Ｐ＜０．０５）。在休克早期，ＤＯ２即进行性下降，ＥＲＯ２出现代偿性升高，ＶＯ２维持相对不变，呈非氧供依赖关系；当ＤＯ２降至３４．６０ｍｌ·ｋｇ－１／ｍｉｎ后，ＶＯ２随ＤＯ２线性降低（ｒ＝０．７３３，Ｐ＜０．０１），即呈病理性氧供依赖关系。结论：脓毒性休克时ＤＯ２与ＶＯ２间呈双相变化关系，病理性氧供依赖的出现与组织氧摄取和氧利用功能障碍有关。     

养阴通脑颗粒对麻醉犬血压和心率的影响

背景如何选择中药治疗脑血管病,并且具有既提高脑血流量,又不影响血压和心率的作用,成了极有前途的研究方向.目的观察养阴通脑颗粒对麻醉犬平均血压和心率变化的作用.设计以杂种犬为研究对象,完全随机分组设计,随机对照实验.单位解放军第四军医大学西京医院麻醉科及解放军军第四军医大学基础部药理科.材料实验于2003-03/06在解放军第四军医大学生理教研室心血管实验室完成.实验选用健康杂种犬23只,雌雄不拘.将犬随机分为4组养阴通脑颗粒大剂量(n=8),中剂量(n=6)和小剂量组(n=5)及生理盐水组(n=4).方法模仿人类口服中药方式分别给予养阴通脑颗粒大、中、小剂量组麻醉犬养阴通脑颗粒2.0,1.0,0.5 g/kg.所有用药组按犬体质量计算药量,溶于100 mL生理盐水中,通过胃管灌入胃内,生理盐水组用等量生理盐水灌胃.主动脉平均血压由股动脉插管经晶体压力传感器测量,心率从标准Ⅱ导联心电图的R-R间期测算.记录用药前、用药后0.5,1.0,1.5,2.0,3.0,4.0,5.0,6.0h的平均血压和心率值.主要观察指标各组犬用药前及用药后不同时间点血压和心率的变化.结果纳入结果分析犬29只.血压变化养阴通脑颗粒大、中剂量组平均血压降低,与用药前比较,最大降幅分别为-5.4%和-6.2%,小剂量组的血压有升有降,以降为主,升压的最大变化率为6.6%(P＞0.05),降压最大变化率为-4.1%(P＞0.05).生理盐水组的平均血压最大变化率为-9.6%(P＞0.05).心率变化大、中剂量组的心率随时间延长呈现减慢趋势,与用药前比较,大、中、小剂量组心率减慢的最大变化率分别为-4.4%,-12.2%和-9.5%,变化率数据差异无明显意义(P＞0.05).生理盐水组的心率随时间延长而逐渐减慢.结论养阴通脑颗粒对麻醉犬平均血压和心率无明显的影响.     

Effect of thromboxane receptor antagonists on renal artery thrombosis in the cynomolgus monkey

The effect of the thromboxane (Tx) A2-receptor antagonists SQ 28,668 and SQ 30,741 on platelet function and renal artery thrombosis was studied in the dialurethane-anesthetized cynomolgus monkey. Both antagonists competitively inhibited the aggregation of platelet rich plasma in vitro to arachidonic acid and U-46,619, a Tx-mimetic. SQ 30,741 was 4 to 7 times more potent than SQ 28,668 against either of these agonists. Thrombotic cyclical blood flow reductions (CFRs) were elicited by placing a critical stenosis at a crush injury site on the left renal artery. After allowing 10 consecutive CFRs, of which 95% required shaking of the vessel to restore flow, a single i.v. injection of either SQ 28,668 (1 mg/kg, n = 6), SQ 30,741 (1 mg/kg, n = 8) or vehicle (2 ml of 0.2% Na2CO3 + 10% ethanol, n = 4) was administered. Antithrombotic activity was defined as the spontaneous restoration of flow and was accompanied by a reduction in the rate of flow decline during the CFRs. Spontaneous flow restoration was observed in animals treated with SQ 28,668 (five of six) and SQ 30,741 (six of eight) but not vehicle (zero of four). The rate of flow decline was reduced only with SQ 28,668 (56 +/- 8%) and SQ 30,741 (53 +/- 10%) treatments. The antithrombotic activities of SQ 28,668 and SQ 30,741 lasted 68 +/- 6 and 224 +/- 21 min, respectively. The threshold antithrombotic dose was found to be lower for SQ 30,741 (0.20 +/- 0.03 mg/kg) than SQ 28,668 (0.61 +/- 0.09 mg/kg) in additional experiments.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of the thromboxane A2 receptor antagonist SQ 30,741 on ultimate myocardial infarct size, reperfusion injury and coronary flow reserve

We determined if the thromboxane A2 antagonist SQ 30,741 can reduce ultimate myocardial infarct size and reperfusion injury. Anesthetized dogs were subjected to left circumflex coronary artery occlusion for 90 min at which time reperfusion was instituted. In one study, SQ 30,741 (1 mg/kg + 1 mg/kg/hr) was given either 10 min postocclusion (n = 7) or 2 min (n = 9) before reperfusion along with their appropriate vehicle controls in a model of 90 min of occlusion and 5 hr of reperfusion. Infarct size was reduced 50% (P less than .05) when SQ 30,741 was given 10 min postocclusion and 30% (P less than .05) when given only during reperfusion. Flow reserve using maximally dilating doses of adenosine was determined 3 hr postreperfusion in vehicle (10 min postocclusion, n = 10), SQ 30,741 (10 min postocclusion, n = 6) and nonischemic (n = 5) animals. Maximal subendocardial flow was reduced during reperfusion in ischemic animals, but SQ 30,741 improved this compared to vehicle animals (400 +/- 95, 88 +/- 25 and 208 +/- 48 ml/min/100 g; nonischemic, vehicle, SQ 30,741 groups, respectively). To determine if myocardial salvage can be observed 24 hr postocclusion with SQ 30,741 or the cyclooxygenase inhibitor aspirin, dogs were given vehicle (n = 9), SQ 30,741 (10 min postocclusion up to 4 hr postreperfusion) or aspirin (n = 9, 40 mg/kg 30 min preocclusion) and infarct size was determined 24 hr postocclusion (90 min left circumflex coronary artery occlusion + reperfusion).(ABSTRACT TRUNCATED AT 250 WORDS)     

Absence of supply dependence of oxygen consumption in patients with septic shock

We tested whether oxygen consumption ( o₂) was dependent on oxygen delivery ( o₂) in 10 patients with septic shock when o₂ was changed by the use of the inotropic agent, dobutamine. The mean acute physiology and chronic health evaluation (APACHE) II score of the patients was 27.3 ± 8.1 with a mean blood pressure on entry of 66.8 ± 12.4 mm Hg, and all had been volume resuscitated to a pulmonary artery occlusion pressure of greater than 10 mm Hg. We measured o₂ by analysis of respiratory gases NOW) while calculating o₂ by the Fick equation NOV) at three different OZ deliveries. When the dobutamine infusion rate was increased from 2.5 ± 4.0 to 12.3 ± 6.0 μg/kg/min, thermodilution cardiac output increased from 7.7 ± 2.6 to 10.1 ± 2.7 L/min (P < .01). Accordingly, dobutamine increased o₂ from 13.5 ± 3.8 to 18.2 ± 4.3 mL/min per kg (increase of 36.4% ± 19.7%; P < .01), but o_2G did not increase (3.2 ± 0.5 to 3.2 ± 0.6 mL/ min per kg). During these same interventions, the o_2F tended to increase (2.9 ± 0.7 to 3.4 ± 0.8 mL/min per kg, P < .06), presumably a spurious correlation because of measurement errors shared by the calculation of o_2F and o₂. Neither lactic acidosis nor acute respiratory distress syndrome (ARDS) conferred supply dependence of o_2G, but the presence of ARDS was predictive of death in this cohort. It is concluded that o₂ is independent of o₂ in patients with septic shock and lactic acidosis. These data confirm that maximizing o₂ beyond values achieved by initial fluid and vasoactive drug resuscitation of septic shock does not improve tissue oxygenation as determined by respiratory gas measurement of o₂.