Visceral lipid peroxidation occurs at reperfusion after supraceliac aortic cross-clamping

Purpose: Recently, we have reported that lipid peroxidation specific to oxygen free radical – mediated injury increased immediately after reperfusion of human liver allografts. However, in the human liver transplantation setting it was impossible to disassociate the contributions to lipid peroxidation caused by the warm and cold ischemic phases from those caused by reperfusion. Therefore we now have studied lipid peroxidation at reperfusion after supraceliac aortic cross-clamping in patients with normal livers.Methods: Ethane, a noninvasive biomarker of lipid peroxidation, was measured in exhaled breath of patients before and during cross-clamping of the thoracic aorta and at sequential time intervals after visceral reperfusion.Results: Approximately a two-fold transient increase in the ethane level was observed at around 15 minutes after reperfusion in those patients whose aortas were cross-clamped for more than 18 minutes.Conclusions: These results indicate that free radical–mediated lipid peroxidation occurs at reperfusion of warm ischemic viscera in the clinical setting of aortic repair. This observation supports the hypothesis that substantial lipid peroxidation occurs when tissues are subjected to cold or warm ischemia followed by reperfusion. (J VASC SURG 1994;19:473-7.)     

Beneficial effects of potassium cardioplegia during intermittent aortic cross-clamping and reperfusion

Aortic cross-clamping is an essential adjunct to a variety of cardiac surgical procedures requiring a quiet flaccid heart and avoidance of systemic air embolism. The consequences of excluding the heart from perfusion, oxygen, and substrate are time dependent and lead ultimately to irreversible damage of the myocardium. The goal of complete preservation of myocardial function and metabolism during ischemia has not been realized even with the best clinically applicable techniques. The present study was designed to evaluate the effects of sequential aortic cross-clamping interrupted by reperfusion similar to that used in clinical practice. The advantages of induced cardiac arrest with potassium chloride solution at the onset of aortic cross-clamping were assessed in a second group of animals. A total of 27 mongrel dogs supported by normothermic cardiopulmonary bypass was subjected to four aortic cross-clamp periods interrupted by 5-min reper-fusion periods. The study included an evaluation of left ventricular performance using an isovolumic balloon technique and an assessment of myocardial metabolism using “stop-freeze” biopsies and biochemical assay for ATP, ADP, AMP, and creatine phosphate. The data demonstrate that repeated induction of ischemic arrest results in profound depletion of adenine nucleo-tides and severe depression of contractility. Using potassium-induced cardiac arrest, normal contractile function is preserved along with conservation of adenine nucleo-tides, suggesting that even at normothermia, preservation of the heart during ischemia can be achieved.     

The reason for cardiac output reduction after aortic cross-clamping

The hypothesis that a decrease in cardiac output during infrarenal aortic cross-clamping is related to a decrease in oxygen consumption in the perfused tissues (cross-clamp-adapted oxygen consumption) rather than to deterioration of myocardial performance has been tested. Twenty-two patients undergoing excision of an aortic abdominal aneurysm were randomly divided into two groups of equal number. During aortic cross-clamping, Group 1 patients received nitroglycerin infusion, 1 to 2 micrograms.kg-1.min-1, whereas Group 2 patients did not receive a nitroglycerin infusion. During aortic cross-clamping, cross-clamp-adapted body oxygen consumption decreased equally in both groups by 40 to 42 percent of baseline values, whereas cardiac output decreased by 17 percent in Group 2 but did not change significantly in Group 1. Mixed venous oxygen content increased significantly after induction of anesthesia and prior to aortic cross-clamping in both groups. During cross-clamping, the values of mixed venous oxygen content remained increased in Group 2 and increased further in Group 1. The data support our hypothesis since a decrease in cardiac output was not associated with an increase in filling pressures during aortic cross-clamping, but was instead associated with an increase in mixed venous oxygen content and a decrease in the arteriovenous oxygen content difference. Nitroglycerin infusion was associated with a further increase in mixed venous oxygen content during aortic cross-clamping and a decrease in the arteriovenous oxygen content difference, without a concomitant increase in oxygen utilization.     

Potassium-induced cardiac resetting technique for persistent ventricular tachycardia and fibrillation after aortic declamping

We report a technique of injecting a high concentration of potassium chloride into the aorta root to resolve refractory ventricular tachycardia after aortic declamping, which occurs occasionally in open heart surgeries. Using this technique, normal sinus rhythm can be restored without the need for defibrillation and aortic clamping.     

Successful use of intravenous amiodarone for refractory ventricular fibrillation just after releasing aortic cross-clamp

Amiodarone is widely used in Europe and the United States for refractory ventricular fibrillation (VF) in various situations, such as VF after myocardial infarction or out-of-hospital cardiac arrest. We report a case of successful treatment with amiodarone of refractory VF immediately after releasing aortic cross-clamp in cardiac surgery. A 66-year-old man suffering from severe aortic stenosis underwent aortic valve replacement (AVR). General anesthesia was induced with propofol and remifentanil, and subsequently AVR was performed under cardiopulmonary bypass. Just after releasing aortic cross-clamp, VF occurred, and it continued despite multiple trials of cardioversion with direct current (DC) shocks of 20 J or 30 J. Furthermore, some DC shocks of 30 J or 50 J after administering lidocaine 60 mg and 0.5 mol x l(-1) magnesium sulfate 20 ml were also ineffective. Then, nifekalant 20 mg was administered and DC shocks of 50 J were repeated intermittently, but VF still persisted. Eventually, VF disappeared after a final DC shock of 50 J with intravenous amiodarone 125 mg. Overall duration of VF was 60 minutes. The patient's trachea was extubated three days after the surgery without any complications. Intravenous amiodarone may be one of the most useful remedies for some types of arrhythmias including persistent VE.     

Myocardial blood flow and oxygen consumption after aortic cross-clamping

The effect of four repetitive periods of 10 min global ischemia, followed by 15 min of reperfusion on myocardial blood flow and oxygen consumption at 34 degrees C (group N) and 25 degrees C (group H) were studied in comparison with that of 60 min continuous ischemia combined with multidose St. Thomas Cardioplegia (group C) in dogs on cardiopulmonary bypass (CPB). Two groups, in which a protocol comparable to the groups N and H, respectively, but without repetitive periods of ischemia was followed, served as control. In all groups a hyperemic response was observed after release of aortic cross-clamping (AC). Myocardial blood flow was not diminished at the end of CPB as compared to the values at the start of CPB. We conclude that the no-reflow phenomenon did not occur after these procedures of intermittent or continuous AC. Immediately following release of AC the arterial-coronary sinus difference of oxygen content reached a peak value in groups N and H indicating rapid replenishment of the low tissue oxygen content. These peak values appeared to be much smaller after cardioplegia. After 10 min of reperfusion a significant lower oxygen consumption was observed at 25 degrees C (0.2 mumole.g-1.min-1 O2) as compared to 34 degrees C (1.5 mumole.g-1.min-1 O2). This difference cannot be explained by temperature alone because oxygen consumption did not decrease below 0.5 mumole.g-1.min-1 in the control group of dogs put on CPB at 25 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intestinal injury after thoracic aortic cross-clamping in the pig

BACKGROUND: The mucosal surface epithelium is an essential part of the functional intestinal barrier, but its structural response to ischemia/reperfusion is only partly characterized. The purpose of this study was to provide a detailed morphological evaluation of intestinal surface epithelium after aortic cross-clamping. MATERIAL AND METHODS: Pigs were subjected to thoracic aortic cross-clamping for 60 min and subsequent reperfusion for 120 min. Tissue blood flow and high-energy phosphates were measured with microspheres and HPLC, respectively. Urinary excretion of (14)C polyethylene glycol (MW 4000 Da) (PEG-4000), loaded into an intestinal loop, provided an index of intestinal permeability. RESULTS: Jejunal blood flow was restored at 10 min after aortic declamping. Denudation of the basement membrane of the intestinal villi tips, as a consequence of epithelial shedding, increased markedly during the initial 60 min of reperfusion (P = 0.002). During the following 45 min, the denuded basement membrane was partly covered with low cuboidal and squamous-shaped cells extending lamellipodia over a wavy basement membrane. Restoration of ATP at 60 min after aortic declamping correlated inversely to the extent of denuded basement membrane (r = 0.75, P = 0.032). Permeability of PEG-4000 increased markedly after aortic declamping and was linearly correlated to the area of denuded basement membrane (r = 0.87, P = 0.01). CONCLUSIONS: Reperfusion for 2 h after aortic cross-clamping is associated with initial aggravation of ischemia-induced injury in the porcine jejunum, but thereafter with restitution of the surface epithelium. Restoration of ATP may be important to avoid intestinal injury after ischemia. Increased permeability of a macromolecule in response to reperfusion is closely correlated to injury of the surface epithelium.     

艾司洛尔在体外循环主动脉开放后顽固性室颤中的应用

目的 评价艾司洛尔应用于体外循环主动脉开放后顽固性室颤的临床效果.方法 主动脉开放后出现顽固性室颤的瓣膜置换术患者40例,数字表法随机分为艾司洛尔组和对照组,每组20例.两组患者按照1 mg/kg分别静脉推注艾司洛尔(10 mg/ml)或利多卡因(10 mg/ml),2 min后继续除颤.2次除颤后仍不能复跳者,采取临床其他常月方法处理,直至心脏复跳.记录开放前主动脉阻断时间、肛温、平均动脉压、血乳酸值、血钾值、pH值;给予艾司洛尔或等浓度利多卡因后记录干预后除颤次数、复跳5 min后心律、心率,停机后记录体外循环时间及正性肌力药物用量.结果 两组相比较,艾司洛尔组除颤成功率高,复跳5 min后心率低,体外循环时间短,正性肌力药物用量少,差异均有统计学意义(P＜0.05).结论体外循环升主动脉开放后复跳困难的患者,给予艾司洛尔可明显减少除颤次数,提高除颤成功率.同时还可以改善复跳后心脏功能,减少正性肌力药物依赖,缩短体外循环时间.     

Lidocaine increases the ventricular fibrillation threshold during bupivacaine-induced cardiotoxicity in pigs

Ventricular fibrillation (VF) is a cause of death in bupivacaine- induced cardiovascular toxicity. We have examined the therapeutic effects of lidocaine on the threshold for bupivacaine-induced VF in in situ beating swine hearts. Twenty-four animals were allocated to one of three groups: 0.25% bupivacaine, 1% lidocaine or 0.25% bupivacaine with 1% lidocaine were infused into the left anterior descending coronary artery in increasing doses of 0, 1, 2, 4, 8 and 16 ml h-1 for 15 min, respectively. ECG and haemodynamic variables were monitored continuously during infusion. Regional myocardial function in the area supplied by the left anterior descending coronary artery was assessed using the sonomicrometry technique. VF did not occur in the lidocaine group. VF developed at higher infusion rates in animals given bupivacaine with lidocaine (in one animal at an infusion rate of 8 ml h- 1 and in seven at 16 ml h-1) compared with animals given bupivacaine alone (in one at an infusion rate of 4 and in seven at 8 ml h-1). Although regional myocardial function decreased with increases in the infusion rate in each group, the depressant effects of the bupivacaine solution (medial inhibitory infusion rate of systolic shortening: IR50 = 2.43 (0.43) ml h-1) were significantly greater than those of the lidocaine solution (IR50 = 5.83 (0.87) ml h-1), but did not differ from those of the bupivacaine with lidocaine solution (IR50 = 3.54 (0.56) ml h-1). This study indicates that a combination of lidocaine and bupivacaine increased the threshold for bupivacaine-induced VF without further depressing myocardial contractility.      

Ischemic spinal cord injury induced by aortic cross-clamping: prevention by riluzole.

OBJECTIVE: Recent studies confirmed the deleterious role of glutamate in the pathophysiology of spinal cord ischemia induced by aortic cross-clamping. We investigated the effect of riluzole, an anti-glutamate drug, in a rat model of spinal cord ischemia. MATERIALS AND METHODS: Spinal cord ischemia was induced in normothermia for 14 min in Sprague-Dawley rats using direct aortic arch plus left subclavian artery cross-clamping through a limited thoracotomy. Experimental groups were as follows: sham-operation (n=15), control (n=15) receiving only vehicle, riluzole (n=15) receiving riluzole (4 mg/kg) before clamping and at the onset of reperfusion. Separate animals were used for monitoring physiologic parameters in the sham-operation (n=3), control (n=5), and riluzole (n=5) groups. Neurologic status was assessed at 6, 24 h, and then daily up to 96 h. Rats were randomly killed at 24, 48, or 96 h (n=5 for each time). Spinal cords were harvested for histopathology, immunohistochemistry for microtubule-associated protein 2 (MAP-2), TUNEL staining, and analysis of DNA fragmentation by agarose gel electrophoresis. RESULTS: All sham-operated rats had a normal neurologic outcome, whereas all control rats suffered severe and definitive paraplegia. Riluzole-treated rats had significantly better neurologic function compared to the control. Histopathology disclosed severe neuronal necrosis in the lumbar gray matter of control rats, whereas riluzole-treated rats suffered usually mild to moderate injury. Riluzole particularly prevented motor neurons injury. MAP-2 immunoreactivity was completely lost in control rats, whereas it was preserved either completely or partly in riluzole-treated rats. TUNEL staining revealed numerous apoptotic neurons scattered within the whole gray matter of control rats. Riluzole prevented or dramatically attenuated apoptotic neuronal death in treated rats. DNA extracted from lumbar spinal cords of sham-operated and riluzole-treated rats exhibited no laddering, whereas spinal cords from control rats showed DNA laddering with fragmentation into approximately 180 multiples of base pairs. CONCLUSIONS: Riluzole may protect the spinal cord in a setting of severe ischemia by preventing neuronal necrosis and apoptosis. This drug may therefore be considered for clinical use during 'high risk' surgical procedures on the thoracoabdominal aorta.     

Pathophysiology of aortic cross-clamping and unclamping

Aortic surgery is associated with a high incidence of perioperative complications, affecting virtually every organ system. The development of these complications is influenced by several factors, including whether surgery was emergent or elective, the location and duration of aortic cross-clamping, and the presence of coexisting disease states. The occurrence of end-organ damage reflects two main processes which are set in motion by aortic cross-clamping. The haemodynamic response refers to the changes produced in preload, afterload, and myocardial contractility. The humoral response refers to the formation and release of a series of mediators that both reflect and cause an ischaemia–reperfusion injury process. A clear understanding of the pathophysiological mechanisms involved in these processes will aid the clinician in adopting a rational approach to the care of patients undergoing aortic surgery.     

The mechanism of spinal cord injury after simple and double aortic cross-clamping

Ischemic spinal cord injury after cross-clamping of the descending aorta can occur independently of aortic disease. In a previous study we had shown a precipitous uniform fall of spinal surface oxygen tension downstream to the clamping site irrespective of level. In the present paper, the hemodynamic changes in the spinal and aortic collateral circulation were investigated. Pressures were measured in the proximal, distal, and excluded aortic segments (descending thoracic and lumbar aorta) as well as in the intercostal and the lumbar arterial beds. Before high aortic occlusion, pressures in the intercostal and lumbar arterial beds were lower than aortic pressure. Along with the postclamping fall in distal arterial pressure, intercostal and lumbar arterial bed pressure decreased further but remained above aortic pressure. Exclusion of the thoracic aorta by double clamping restored intercostal bed pressure almost to control, whereas exclusion of the abdominal aorta hardly affected lumbar bed pressure. We conclude that spinal collateral circulation is more highly developed in the thoracic than in the lumbar region. After aortic cross-clamping, blood tends to drain away from the spinal cord rather than supplying it longitudinally. Under clinical conditions, therefore, retrograde bleeding into the opened aorta as well as into the aorta downstream to the distal clamp should be minimized and larger vessels originating from the aorta should promptly be anastomosed to the graft.     

Improvement in thoracic aortic pressure after proximal aortic cross-clamping by balloon occlusion of the distal aorta

Spinal cord hypoperfusion injury is a devastating complication of cross-clamping the proximal thoracic aorta. The collateral circulation around the cross-clamp is generally poorly developed, and the run-off is immense, resulting in extremely low thoracic aortic and spinal cord perfusion pressures. The authors postulated that balloon occlusion of the abdominal aorta might confine this reduced collateral flow around the cross-clamp to the thoracic aorta. In 8 of 16 dogs subjected to aortic cross-clamping of the aorta just beyond the arch vessels, the abdominal aorta was also occluded by a balloon. Thoracic aortic pressure and spinal cord perfusion pressure were significantly higher in the animals with aortic balloon occlusion than in those without balloon occlusion (77 +/- 8 mm Hg versus 26 +/- 1 mm Hg, p less than 0.01, and 67 +/- 8 mm Hg versus 18 +/- 2 mm Hg, p less than 0.01, at 10 minutes after cross-clamping). Abdominal aortic balloon occlusion increases thoracic aortic pressure after the aorta is cross-clamped proximally. Further studies are necessary in primates to assess the effect of this procedure in spinal cord perfusion and the rate of paraplegia.