Cold spinoplegia and transvertebral cooling pad reduce spinal cord injury during thoracoabdominal aortic surgery

OBJECTIVE: We examined the protective effects of the new selective spinal cord cooling by using cold saline infusion into the cross-clamped aorta and a transvertebral cooling pad placed over the lumbar vertebral column from paraplegia caused by ischemic spinal cord injury on thoracoabdominal aortic surgery. METHODS: Eighteen rabbits were divided into three groups: groups I, II, and III (n = 6 for each group). In group I (37 degrees C; 5 mL) and group II (3 degrees C; 5 mL), saline was infused into the isolated aortic segment twice, at 0 and 5 minutes after aortic cross clamping. In group III, a 3 degrees C saline solution plus cooling pads placed just after cross clamping were combined. The infrarenal aorta was then isolated proximally and distally by vascular clamps for 12 minutes. In our preliminary study, only the abdominal aorta just distal to the left renal artery was clamped. At 48 hours after reperfusion, the groups clamped for 12 and 15 minutes were all paraplegic. The time of clamping the aorta was set at 12 minutes as the critical point when paraplegia occurred upon simple clamping of the infrarenal aorta only. The spinal cord temperature was monitored at the L4 level continuously during the procedures in all three groups. At 8, 24, and 48 hours after the operation, hind limb function was estimated by using the Tarlov score, which is often used for evaluating motor function in animals. A histopathologic study using hematoxylin and eosin stains was also performed. RESULTS: At 48 hours after the operation, the Tarlov scores in groups I, II, and III were 0 +/- 0, 2.0 +/- 1.9, and 4.0 +/- 0 (mean +/- SD), respectively. The Tarlov score and histopathologic analysis in group III were significantly superior to those of groups I (P < .01) and II (P < .05). The spinal cord temperature in groups II and III decreased by -1.8 degrees C and -4.3 degrees C at its minimum. The rabbits in group III were also protected from paraplegia. CONCLUSIONS: Selective spinal cord cooling with cold saline infusion into the isolated aortic segment and transvertebral regional cooling can reduce the neurologic damage of spinal cord ischemia.     

Paraplegia after thoracic aortic occlusion: influence of cerebrospinal fluid drainage. Experimental and early clinical results

Paraplegia occurs in 6.5% to 40% of patients after repair of extensive thoracoabdominal aortic aneurysms requiring aortic clamping. This study aimed to determine whether drainage of cerebrospinal fluid (CSF) done before aortic cross-clamping could decrease the incidence of paraplegia in dogs. The descending thoracic aorta was clamped distal to the left subclavian artery for either 40 minutes (group I) or 60 minutes (group II). All control animals in group I (10) and group II (10) showed evidence of spinal cord injury with paraparesis or paraplegia. In contrast, 9 of 10 animals (90%) in group I and 7 of 10 animals (70%) in group II that had CSF drainage before aortic cross-clamping were neurologically normal (p less than 0.001 and p less than 0.01, respectively). Aortic pressure distal to the aortic cross clamp was the same in all groups; however, spinal cord perfusion pressure (distal aortic pressure minus CSF pressure) was significantly higher in neurologically normal animals (34 +/- 5 mm Hg, n = 15) compared with those with paraparesis (26 +/- 4 mm Hg, n = 8) or paraplegia (19 +/- 5 mm Hg, n = 8) (r = 0.871, p less than 0.001). This study demonstrates that drainage of CSF before thoracic aortic occlusion significantly increases spinal cord perfusion pressure and decreases the incidence of paraplegia. Limited early clinical experience suggests that CSF drainage may be a useful adjunct to prevent paraplegia in patients who are having repair of thoracoabdominal aortic aneurysms.     

The role of prostaglandin E in the hemodynamic response to aortic clamping and declamping.

The infrarenal aorta was occluded for one hour in 11 control dogs and in eight dogs in which biosynthesis of prostaglandin E (PGE) was inhibited by administration of indomethacin (2.5 mg. per kilogram). The mean arterial pressure (MAP) in the indomethacin group was significantly (p less than 0.001) higher than in the control group at the end of 60 minutes of aortic occlusion (187 +/- 3 vs. 137 +/- 4 mm. Hg, mean +/- S.E.M.) and remained higher (p less than 0.001) after declamping. However, the decline in MAP at the time of aortic declamping was essentially the same for both groups. Total peripheral resistance (TPR) was higher in the indomethacin group than in the control group at the end of one hour of occlusion (159 +/- 13 vs. 124 +/- 12%, p less than 0.001) and remainded higher throughout the period following occlusion. The plasma concentration of PGE in the control group increased significantly (p less than 0.05) above control (630 +/- 110 to 1,299 +/- 261 pg. per milliliter) during the 60 minute period of occlusion with further increases to 1,447 +/- 389 and 1,523 +/- 256 pg. per milliliter (p less than 0.001) at 10 and 60 seconds after declamping, respectively. In the indomethacin group, PGE remained essentially unchanged throughout the clamping and declamping period and therefore was significantly (p less than 0.05) lower than in the control group. A similar pattern was observed in the tissue levels of PGE. This study suggests that PGE is released during and after infrarenal aortic occlusion and may be responsible for maintaining reduced TPR and MAP. However, hypotension after declamping is not affected by inhibition of PGE biosynthesis.     

The effect of direct lidocaine injection into the clamped aortic segment on the spinal evoked potential: early diagnosis for spinal cord ischemia.

PURPOSE: The aim of this study was to identify a method to determine whether segmental artery reconstruction was indicated during aortic clamping. METHOD: Spinal cord evoked potential (SCEP) and regional spinal blood flow were studied in 24 adult dogs. Using the left heart bypass technique, aortic clamping divided the aorta into thoracic, abdominal, and terminal segments. After the occlusion of the descending aorta and discontinuation of the perfusion to the abdominal segment, animals were assigned to four groups: no treatment with perfusion to the terminal aorta (group IA), no treatment with cessation of bypass (group IB), 5% lidocaine administration (5 mg/kg) into the abdominal segment with perfusion to the terminal aorta (group IIA), and lidocaine administration with cessation of bypass (group IIB). RESULTS: Cessation of bypass reduced spinal blood flow and SCEP amplitude. Lidocaine injection allowed for a significant rapid decrease in SCEP amplitude in group IIB compared with group IB (24.2% +/- 13.4% versus 92.3% +/- 33.2%; p = 0.0039). The degree of spinal blood supply was reflected immediately in the magnitude of SCEP amplitude change by the direct lidocaine injection. (group IB versus group IIB; p = 0.023). CONCLUSION: The direct injection of lidocaine into the clamped aorta results in a rapidly change in SCEP in the threat of ischemia and can be used to make an early detection of the segmental arteries perfusing to the spinal cord.     

Separate grafts or en bloc anastomosis for arch vessels reimplantation to the aortic arch

BACKGROUND: This study compares the results of the separated graft technique and the en bloc technique as a method of arch vessels reimplantation during surgery of the aortic arch and determines the predictive risk factors associated with hospital mortality and adverse neurologic outcome during aortic arch repair. METHODS: Between October 1995 and March 2002, 352 patients (mean age 64.9 +/- 11.3 years; urgent status: 49/352 [13.9%]) underwent surgery of the aortic arch using the separated graft technique (group A: n = 230 [65.3%]) and the en bloc technique (group B: n = 122 [34.7%]) to reimplant the arch vessels. An aortic arch replacement was performed in 32 patients (9.1%), an ascending aorta and arch replacement in 222 patients (53.1%), an aortic arch and descending aorta replacement in 16 patients (4.5%), and a complete replacement of the thoracic aorta in 82 patients (23.3%). Brain protection was achieved by means of antegrade selective cerebral perfusion in all patients. The mean cardiopulmonary bypass time was 204.8 +/- 61.9 minutes (group A: 199.7 +/- 57.0 minutes; group B: 214.5 +/- 69.4 minutes; p = 0.033), the mean myocardial ischemic time was 121.5 +/- 43.2 minutes (group A: 116.7 +/- 38.9 minutes; group B: 130.80 +/- 49.4 minutes; p = 0.003), and the mean antegrade selective cerebral perfusion time was 84.5 +/- 36.4 (group A: separated graft technique 91.3 +/- 36.3 minutes; group B: 70.6 +/- 32.7 minutes; p = 0.000). RESULTS: Overall hospital mortality was 6.8% (group A: 6.5%; group B: 7.4%; p = not significant [NS]). The permanent neurologic dysfunction rate was 3.5% (group A: 4.0%; group B: 2.5%; p = NS). The transient neurologic dysfunction rate was 5.4% (group A: 5.5%; group B: 5.2%, p = NS). Postoperative systemic morbidity was similar in the two groups. A logistic regression analysis revealed preoperative cardiac tamponade (p = 0.011; odds ratio [OR] = 5.9) and cardiopulmonary bypass time (p = 0.010; OR = 1.01/min) to be independent predictors of hospital mortality. None of the analyzed preoperative variables were associated with an increased risk of permanent neurologic dysfunction. Age more than 70 years old (p = 0.029, OR = 5.7), myocardial revascularization (p = 0.001, OR = 2.9), and pump time (p = 0.013, OR = 1.01/min) were indicated as independent predictors of transient neurologic dysfunction by logistic regression. CONCLUSIONS: Antegrade selective cerebral perfusion was confirmed to be a safe method of cerebral protection allowing complex aortic arch operations to be performed with acceptable results in terms of hospital mortality and neurologic outcome. The separated graft technique had no adverse impact on hospital mortality and morbidity.     

The mechanisms and prevention of intravascular fluid loss after occlusion of the supraceliac aorta in dogs

Mechanisms of intravascular fluid depletion after temporary occlusion of the supraceliac aorta were investigated in a canine model. During ischemia and reperfusion, hemodynamic parameters, superior mesenteric artery flow, intestinal mucosal perfusion, and mucosal permeability were monitored. After 12 hours of reperfusion, the volumes of intravenous electrolyte fluid required to maintain hemodynamic stability and fluid lost into the gastrointestinal tract and peritoneal cavity were measured. The distribution of total body water was analyzed by use of radionuclide dilution techniques. Group A animals underwent laparotomy only, group B had the supraceliac aorta occluded for 45 minutes, group C had superoxide dismutase administered after 45 minutes of aortic occlusion, and group D animals were exposed to mild hypothermia during a similar ischemia and reperfusion period. No significant difference was found in mean superior mesenteric artery flow or mucosal perfusion during ischemia among groups B, C, and D. During reperfusion superior mesenteric artery flow returned to values similar to control in all groups. Aortic occlusion increased mucosal permeability most significantly in group B (p less than 0.01). Mean intravenous fluid requirements (ml/mg) were the following: group A, 80 +/- 5; group B, 201 +/- 9 (p less than 0.01); group C, 116 +/- 7 (p less than 0.05); group D, 245 +/- 24 (p less than 0.05). Mean gastrointestinal fluid loss was highest in the hypothermic group and smallest if superoxide dismutase was given. Mean intracellular fluid volume was increased in groups B and D compared with group A (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hypothermia relieves oxidative stress in reperfused skeletal muscle following partial ischemia.

The impact of hypothermia on reperfusion-associated oxidative stress in postischemic skeletal muscle was evaluated in a small animal model of high-grade partial ischemia. The infrarenal aorta of heparinized Sprague-Dawley rats was clamped for 90 min, declamped, and then reperfused for 60 min. Previous characterization of this model with 51Cr-tagged microspheres revealed that hindlimb perfusion during aortic clamping continued at 16.6% of baseline values. Resting transmembrane potential difference (Em) and tissue malondialdehyde (MDA), lactate and high-energy phosphate content were determined in hindlimb skeletal muscle at baseline, during ischemia, and upon reperfusion. Four experimental groups (N = 7 in each group) were studied: control animals underwent aortic clamping and declamping; hypothermia animals underwent topical cooling of hindlimbs prior to aortic clamping, with muscle temperatures maintained between 5 and 15 degrees C during ischemia; sham animals underwent midline laparotomy only; and hypothermia-sham animals underwent cooling and midline laparotomy only. During ischemia, resting Em (-mV) was significantly depolarized (P < 0.05 versus baseline) in control (74.9 +/- 0.8 from 91.0 +/- 0.1), hypothermia (64.4 +/- 1.1 from 90.9 +/- 0.3), and hypothermia-sham (67.2 +/- 1.4 from 90.9 +/- 0.4) animals. Upon reperfusion, resting Em remained depolarized in control animals (74.7 +/- 1.6), while repolarization occurred in hypothermia (88.8 +/- 1.1) and hypothermia-sham (90.7 +/- 0.3) animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Total arch replacement using prior selective cerebral perfusion

Prior selective cerebral perfusion is the method whereby selective cerebral perfusion and systemic perfusion start almost simultaneously, and the arch vessels are clamped. Cerebral circulation is isolated from systemic circulation to avoid cerebral embolization owing to detachment of atherosclerotic material from the aorta, caused by the "sandblasting" effect of high-velocity jets of blood exiting the aortic canula. Twenty-seven consecutive patients underwent total arch replacement for degenerative aortic arch aneurysm using prior selective cerebral perfusion from 1992 to 2001. Surgical death (within 1 month after operation) was 2 cases (7.4%), in-hospital death was 5 cases (18.5%). Systemic circulatory arrest time is almost equal to the time which distal anastomosis takes. The time was 81.4 +/- 24.3 minutes. Selective cerebral perfusion time was 194.9 +/- 30.9 minutes. Extracorporeal circulation time was 280.6 +/- 55.3 minutes. The time for emergence from anesthesia was 6.0 +/- 2.7 hours. Permanent neurologic dysfunction which was thought to occurred within 48 hours after surgery was noted in 1 case (3.7%). Postoperative survival at 8 years was 73.3%. There was 1 arch aneurismal related accident. Prior selective cerebral perfusion may be useful for avoiding cerebral embolization.     

Intrathecal perfusion of an oxygenated perfluorocarbon prevents paraplegia after aortic occlusion.

A canine model was used to evaluate the effects of continuous intrathecal perfusion of an oxygenated perfluorocarbon emulsion on systemic and cerebral hemodynamics and neurologic outcome after 70 minutes of normothermic aortic occlusion. Twelve mongrel dogs were instrumented to monitor proximal and distal arterial blood pressure, cerebrospinal fluid pressure, spinal cord perfusion pressure, and somatosensory evoked potentials. The intrathecal perfusion apparatus consisted of two perfusing catheters, placed in the intrathecal space through a laminectomy, and a draining catheter percutaneously inserted in the cisterna cerebellomedullaris. The aorta was cross-clamped just distal to the left subclavian artery for 70 minutes. Animals were randomized into two groups: group 1 (n = 6) animals were treated with intrathecal perfusion of saline solution, whereas group 2 (n = 6) animals received oxygenated Fluosol-DA 20%. Data were acquired at baseline, during the cross-clamp period, and after reperfusion. Normothermic Fluosol or saline solution was infused at a rate of 15 mL/min beginning 15 minutes before cross-clamping and continued throughout the ischemic interval. There was no difference in proximal arterial blood pressure (97.2 versus 95.4 mm Hg; p > 0.05) or distal arterial blood pressure (14.6 versus 15.0; p > 0.05) between the two groups throughout the cross-clamp interval. Cerebrospinal fluid pressure rose significantly in both groups with the onset of intrathecal perfusion of either saline solution or Fluosol (7 +/- 1 versus 24 +/- 5 and 8 +/- 1 versus 40 +/- 4 mm Hg, respectively; p < 0.05). The rise in cerebrospinal fluid pressure was sustained throughout the perfusion interval in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effective administration method of recombinant superoxide dismutase in acute myocardial ischemia and reperfusion

To determine the efficacy of direct versus systemic administration of human recombinant superoxide dismutase (rt-SOD) in acute myocardial ischemia and reperfusion, the following experimental model was applied. Twenty-one dogs were subjected to 30 minutes normothermic global ischemia caused by the occlusion of the ascending aorta followed by 60 minutes reperfusion. To eliminate collateral blood flows during the ischemia, bipulmonary hilus were cross clamped. The dogs were randomly assigned to three groups: group A (n = 7), 12 ml of normal saline was injected through the aortic root into the coronary artery 1 minute prior to reperfusion, in addition to a 30 minute continuous infusion of 50 ml of saline into the cardiopulmonary bypass circuit beginning just after reperfusion; group B (n = 7), rt-SOD (10,000 U/kg) dissolved in 12 ml saline was administered by bolus injection through the aortic root and an additional 30,000 U/kg of rt-SOD dissolved in 50 ml of saline was injected into the cardiopulmonary bypass circuit as the same manner as the group A; group C (n = 7), the treatment was similar to the group B except the bolus injection of rt-SOD was into the cardiopulmonary bypass circuit. The left ventricular stroke work index (LVSWI) was determined by a right heart bypass technique and expressed as a percent recovery of pre-occlusion state. Morphologic structures were observed by the electron microscope. The coronary sinus blood was assessed for malondialdehyde (MDA) measured by TBA method and creatine phosphokinase (CPK). The percent of recovery of LVSWI after 60 minutes reperfusion was superior in group B (121 +/- 82%) than groups A (24 +/- 38%*, *p less than 0.05) and C (52 +/- 21%*). In group B, the myocardial cell structure had a normal appearance in most areas, but swollen mitochondria and disrupted myofibrils were observed in groups A and C. Serum MDA levels did not change in all groups. Increasing CPK levels after reperfusion were less in group b than group A. These results suggest that an adequate concentration of rt-SOD in the interstitial fluid or cell surface at the time of reperfusion may be required to prevent reperfusion injury.     

Comparison of ischemic vulnerability and responsiveness to cardioplegic protection in crystalloid-perfused versus blood-perfused hearts.

The possibility of differences between crystalloid-perfused and blood-perfused hearts in their vulnerability to ischemia and responsiveness to protective interventions has been investigated in isolated rabbit hearts perfused with bicarbonate buffer or arterial blood. In preliminary studies with 165 minutes of aerobic perfusion at constant perfusion pressure (55 +/- 3 mm Hg), the stability of left ventricular developed pressure was significantly better in blood-perfused hearts. In subsequent studies, hearts were subjected to 20 minutes of aerobic perfusion (coronary flow, 2.0 +/- 0.3 ml/min/gm wet weight in blood-perfused hearts versus 11.3 +/- 3.0 ml/min/gm wet weight in crystalloid-perfused hearts; left ventricular developed pressure, 90 +/- 4 and 91 +/- 2 mm Hg, respectively) followed by 30, 45, 60, 75, 90, or 105 minutes of normothermic global ischemia and 40 minutes of reperfusion (n = 4 per group). In the buffer-perfused groups the postischemic recoveries of left ventricular developed pressure were 74% +/- 6%, 45% +/- 7%, 39% +/- 6% 32%, +/- 5%, 27% +/- 4%, and 12% +/- 3% of preischemic control, respectively. In blood-perfused groups they were consistently greater (91% +/- 3%, 55% +/- 5%, 46% +/- 5%, 45% +/- 1%, 33% +/- 2%, and 19% +/- 3%, respectively). In further studies, hearts (n = 5 per group) were perfused with buffer (groups 1 and 2) or blood (groups 3 and 4), and each was subjected to 60 minutes of normothermic global ischemia, with (groups 2 and 4) or without (groups 1 and 3) a 3-minute preischemic infusion of St. Thomas' Hospital cardioplegic solution. After 60 minutes of reperfusion, the postischemic recoveries of left ventricular developed pressure in groups 1, 2, 3, and 4 were 32% +/- 3%, 44% +/- 4%, 43% +/- 7%, and 72% +/- 6%, respectively, with coronary flow recovering to 64% +/- 7%, 82% +/- 4%, 82% +/- 4%, and 110% +/- 5%, respectively. Left ventricular end-diastolic pressures were 20 +/- 5, 24 +/- 7, 15 +/- 4, and 4 +/- 3 mm Hg, and tissue water contents were 4.76 +/- 0.11, 4.87 +/- 0.55, 3.93 +/- 0.05, and 3.68 +/- 0.02 ml/gm dry weight, respectively. In conclusion, compared with crystalloid perfusion, the blood-perfused rabbit heart has a greater resistance to ischemia, a superior response to cardioplegic protection, and a lower tissue water content.     

Is protection of ischemic neonatal myocardium by cardioplegia species dependent?

Hypothermia combined with pharmacologic cardioplegia protects the globally ischemic adult heart, but this benefit may not extend to children, resulting in poor postischemic recovery of function and increased mortality. The relative susceptibilities to ischemia modified by hypothermia alone and by hypothermia plus cardioplegia were assessed in isolated perfused neonatal (3- to 4-day-old) rabbit and pig hearts. Hearts were perfused aerobically with Krebs buffer solution in the working mode for 30 minutes and aortic flow was recorded. This was followed by 3 minutes of hypothermic (14 degrees C) coronary perfusion with either Krebs or St. Thomas' Hospital cardioplegic solution No. 2 followed by hypothermic (14 degrees C) global ischemia (rabbits 2, 4, and 6 hours; pigs 2 and 4 hours). Hearts were reperfused for 15 minutes in the Langendorff mode and 30 minutes in the working mode, and recovery of postischemic aortic flow was measured. Hypothermia alone provided excellent protection of the ischemic neonatal rabbit heart, with recovery of aortic flow after 2 and 4 hours of ischemia at 91% +/- 4% and 87% +/- 5% (mean +/- standard deviation) of its preischemic value. Recovery after 6 hours of ischemia was depressed to 58% +/- 9% of its preischemic value. Ischemic neonatal pig hearts protected with hypothermia alone recovered 94% +/- 3% of preischemic aortic flow after 2 hours; none was able to generate flow after 4 hours. St. Thomas' Hospital solution No. 2 decreased postischemic aortic flow after 4 hours of ischemia in rabbit hearts from 87% +/- 5% to 70% +/- 7% (p less than 0.05, hypothermia alone versus hypothermia plus cardioplegia) but improved postischemic recovery of aortic flow in pig hearts after 4 hours of ischemia from 0 to 73% +/- 13% (p less than 0.0001, hypothermia alone versus hypothermia plus cardioplegia). This effect was dose related in both species. We conclude that the neonatal pig heart is more susceptible to ischemia modified by hypothermia alone than the neonatal rabbit and that St. Thomas' Hospital solution No. 2 improves postischemic recovery of function in the neonatal pig but decreases it in the neonatal rabbit. This species-dependent protection of the neonatal heart may be related to differences in the extent of myocardial maturity at the time of study.     

Should initial clamping for abdominal aortic aneurysm repair be proximal or distal to minimise embolisation?

OBJECTIVES: to determine whether clamping proximally or distally on the infrarenal aorta during abdominal aortic aneurysm (AAA) repair increases the overall embolic potential. MATERIALS AND METHODS: a sheath was placed in the mid-infrarenal aorta of 16 dogs. In eight animals a cross-clamp was placed at the aortic trifurcation, and in another eight animals it was placed in the immediate subrenal position. Under fluoroscopy blood flow within the infrarenal aorta was evaluated by contrast and particle injections. Grey-scale analysis was used to calculate contrast density. Particle distribution was followed fluoroscopically and confirmed pathologically. RESULTS: fifty-seven+/-24% of injected contrast remained within the aorta with distal clamping while 97+/-7% did so with proximal clamping (p<0.01). With distal aortic clamping 6.2+/-1. 3 out of 10 injected particles remained within the aorta after 15 seconds and only 0.8+/-0.8 remained after 5 min. With proximal aortic clamping, all 10 of the particles remained within the aortic lumen for the full 5 minutes (p<0.001). CONCLUSIONS: initial distal clamping minimises distal embolisation, but may result in renal and/or visceral embolisation. Initial proximal clamping prevents proximal embolisation and does not promote distal embolisation. We recommend initial proximal clamping in aortic aneurysm surgery to minimise the overall risk of embolisation.     

Changes in high-energy phosphates in the myocardium before and after ischemia

Assessment of the level of high-energy phosphates in the myocardium before, during and after ischemia was performed in 19 consecutive patients who underwent cardiac operation. The following results were obtained. 1) The levels of total nucleotides (ATP, ADP, AMP, CP) determined before, during and after aortic cross clamp were 14.94 +/- 4.12, 5.59 +/- 2.16 and 3.58 +/- 1.14 micrograms/mg. protein in the right atrial appendage. Those in the left ventricular myocardium were 18.22 +/- 4.90, 6.99 +/- 1.52 and 4.35 +/- 1.06 micrograms/mg. protein. The latter levels were higher than the former. 2) Rapidly decreasing after aortic cross clamp, the nucleotides dropped to 37-38% of preischemic level during aortic cross clamp and to 23% of preischemic level 30 minutes after reperfusion. At the termination of extracorporeal circulation, when circulatory dynamics stabilized, the nucleotides were only recovered to 50-53% of preischemic level. 3) Negative correlation was observed between the length of aortic cross clamp time and the content of nucleotides in the atrial muscle. (p less than 0.05) 4) Fluctuations in the nucleotide level indicated that the current method of myocardial protection using GIK solution produced unsatisfactory recover from ischemic damage and reperfusion injury.     

Does ischemic preconditioning reduce spinal cord injury because of descending thoracic aortic occlusion?

OBJECTIVE: Ischemic preconditioning has been found to protect various organs from a subsequent longer ischemic insult. We investigated whether the late phase of ischemic preconditioning reduces spinal cord injury from occlusion of the descending thoracic aorta. METHODS: Twenty-four pigs (27 to 30 kg) were randomly divided in four groups: group I (n = 4) underwent a sham operation, group II (n = 4) underwent aortic occlusion for 20 minutes, group III (n = 8) underwent aortic occlusion for 35 minutes, and group IV (n = 8) underwent aortic occlusion for 20 minutes and, 48 hours later, aortic occlusion for 35 minutes. Aortic occlusion was accomplished with two balloon occlusion catheters placed fluoroscopically at T(6) to T(8) above the diaphragm and at the aortic bifurcation. Neurologic evaluation was performed by an independent observer according to Tarlov's scale (0 to 4, with 4 as normal). The lower thoracic and lumbar spinal cords were harvested at 120 hours and examined histologically with hematoxylin and eosin stain. Histologic results (number of neurons and grade of inflammation) were scored 0 to 4 (4, intact spinal cord; 0, no neurons and high inflammation) and were similarly analyzed. Results were expressed as the mean +/- the standard error of the mean, and statistical analysis used the Kruskal-Wallis test. RESULTS: Group IV had a better neurologic outcome at 24, 48, and 120 hours in comparison with group III (P <.001), although 120 hours after the end of the experiment, the neurologic outcome in group IV was worse than at 24 hours (P =.014). The histologic changes were proportional to the neurologic test scores, with the more severe and extensive gray matter damage in the animals of group III (number of neurons, P <.001; and grade of inflammation, P <.001). CONCLUSION: Ischemic preconditioning (late phase, 48 hours after the first occlusion) reduces spinal cord injury after aortic occlusion, as estimated with Tarlov's score and histopathology.     

Dopexamine hydrochloride does not modify hemodynamic response or tissue oxygenation or gut permeability during abdominal aortic surgery

PURPOSE: To assess the effects of intraoperative infusion of dopexamine (a DA-1 and B2 adrenoreceptor agonist) on hemodynamic function, tissue oxygen delivery and consumption, splanchnic perfusion and gut permeability following aortic cross- clamp and release. METHODS: In a randomised double blind controlled trial 24 patients scheduled for elective infrarenal abdominal aortic aneurysm repair were studied in two centres and were assigned to one of two treatment groups. Group I received a dopexamine infusion starting at 0.5 microg x kg(-1) x min(-1) increased to 2 microg x kg(-1) x min(-1) maintaining a stable heart rate; Group II received a placebo infusion titrated in the same volumes following induction of anesthesia. Measured and derived hemodynamic data, tissue oxygen delivery and extraction and gut permeability were recorded at set time points throughout the procedure. RESULTS: Dopexamine infusion (0.5 -2 microg x kg x min(-1)) was associated with enhanced hemodynamic function (MAP 65 +/- 5.5 vs 92 +/- 5.7 mm Hg, P = <0.05) only during the period of aortic cross clamping. However, during the most part of infrarenal abdominal aortic surgery, dopexamine did not reduce systemic vascular resistance index, mean arterial pressure nor oxygen extraction compared with the control group. The lactulose/ rhamnose permeation ratio was elevated above normal in both groups (0.22 and 0.29 in groups I and II respectively). CONCLUSIONS: Dopexamine infusion (0.5 -2 microg x kg(-1) x min(-1)) did not enhance hemodynamic function and tissue oxygenation values during elective infrarenal abdominal aortic aneurysm repair.     

Myocardial protection by ischemic preconditioning and delta-opioid receptor activation in the isolated working rat heart.

OBJECTIVE: delta-Opioid receptors are involved in the cardioprotective effect of ischemic preconditioning. This study was designed (1) to assess the protective capacities of ischemic preconditioning and the synthetic delta-opioid receptor agonist D-Ala(2)-D-Leu(5) enkephalin (DADLE) in a functionally oriented experimental model of ischemia and reperfusion and (2) to assess whether the effects of both protective measures are similarly blocked by naloxone, a nonspecific delta-opioid receptor antagonist. METHODS: Sixty-four isolated working rat hearts were subjected to 45 minutes of hypothermic ischemia at 30 degrees C followed by 25 minutes of normothermic reperfusion. Rats were pretreated with DADLE (1 mg/kg body weight intravenously), naloxone (3 mg/kg body weight intravenously), or a combination thereof within 60 minutes before onset of isolated heart perfusion. During the preischemic perfusion period, 8 hearts per group were preconditioned by one cycle of 5 minutes of normothermic global ischemia and subsequent reperfusion whereas another 8 served as nonpreconditioned controls. The postischemic functional recovery of hearts and their creatine kinase leakage were determined. RESULTS: Pretreatment with DADLE and ischemic preconditioning improved the postischemic recovery of aortic flow when compared with nonpreconditioning (57.7% +/- 4.0% and 60.8% +/- 4.3% vs 40.0% +/- 4.2% of preischemic baseline value, P <.001). Combined pretreatment with DADLE before ischemic preconditioning afforded additional aortic flow recovery compared with pretreatment with DADLE alone (68.6% +/- 3.3% vs 57.7% +/- 4.0% of preischemic baseline value; P =.038). With combined pretreatment, early postischemic creatine kinase release was lower than control in hearts without pretreatment (0.48 +/- 0.11 vs 0.80 +/- 0.12 IU/5 minutes per heart; P =.001). Naloxone abolished the beneficial functional effects of pretreatment with DADLE and ischemic preconditioning. CONCLUSIONS: Pharmacologic activation of delta-opioid receptors affords improvement of functional protection in isolated working rat hearts similar to that conferred by classic ischemic preconditioning. The combination of both pretreatments reduces ischemic cellular damage and further adds to postischemic functional recovery. These changes are reversed by naloxone, an observation providing evidence that ischemic preconditioning involves signaling through opioid receptors.     

Neuroprotective effect of regional carnitine on spinal cord ischemia--reperfusion injury.

OBJECTIVE: The purpose of this study was to investigate the effect of regional infusion of carnitine on spinal cord ischemia--reperfusion (I--R) in rabbits. METHODS: The 36 rabbits were divided into four equal groups, group I (sham operated, no I--R injury), group II (control, only I--R), group III (I--R+intraaortic lactated Ringer's, LR, during aortic occlusion), group IV (I--R+LR plus 100mg/kg carnitine). Spinal cord ischemia was induced by clamping the aorta both below the left renal artery and above the aortic bifurcation. The spinal cord function of all animals was assessed clinically 24h after aortic declamping. Spinal cord samples were taken to measure the levels of tissue malondialdehyde (MDA) and to evaluate the histopathological changes. RESULTS: We found significant increases in the levels of MDA in groups II and III compared with group I (P<0.01), and elevation of MDA in group IV was insignificant. In group II, all animals (100%) were paraplegic with Tarlov's score of 0 and in group III, eight animals (88%) were paraplegic with Tarlov's score of 0 or 1. None of the animals (0%) from group IV was paraplegic. Histologic examination of spinal cords from group IV animals revealed that the appearance of the spinal cord was relatively preserved, whereas spinal cords from groups II and III had evidence of acute neuronal injury. CONCLUSION: The results suggest that regional infusion of carnitine during aortic clamping reduces spinal cord injury and prevents neurologic damage in rabbit spinal cord I--R model.     

Is It Safe to Initiate Selective Cerebral Perfusion with Normothermia?

OBJECTIVE: Preceding selective cerebral perfusion (P-SCP) is a method whereby SCP and systemic perfusion start simultaneously, and the arch vessels are clamped. Cerebral circulation is isolated from systemic circulation to avoid cerebral embolization due to detachment of atherosclerotic material from the aorta, caused by the "sandblasting" effect of high-velocity jets of blood exiting the aortic cannula. However, neither the safety of SCP at normothermia nor the influence of extended SCP time has been sufficiently clarified. To clarify the safety of P-SCP, the comparison study of P-SCP and conventional SCP (C-SCP) was performed retrospectively. METHODS: Fifty-seven patients (C-SCP group: 29 patients; P-SCP: 28 patients) underwent surgery between 1992 and 2002. RESULTS: Nine (15.8%) in-hospital death occurred; 4 in the C-SCP group (13.8%) and 5 in the P-SCP group (17.9%) (NS). The SCP time was 136.6 +/- 68.5 minutes in the C-SCP group and 195.8 +/- 30.7 minutes in the P-SCP group (p < 0.05). One patient in each group exhibited postoperative neurological dysfunction. CONCLUSION: It may be little dangerous to initiate the SCP with normothermia. P-SCP may be useful in cases in which there is pedunculated atherosclerotic material, or mural thrombus in the ascending and arch aorta.     

Age-related changes in the ability of hypothermia and cardioplegia to protect ischemic rabbit myocardium

Hypothermia combined with pharmacologic cardioplegia protects the globally ischemic adult heart, but this benefit may not extend to children; poor postischemic recovery of function and increased mortality may result when this method of myocardial protection is used in children. The relative susceptibilities to ischemia-induced injury modified by hypothermia alone and by hypothermia plus cardioplegia were assessed in isolated perfused immature (7- to 10-day-old) and mature (6- to 24-month-old) rabbit hearts. Hearts were perfused aerobically with Krebs-Henseleit buffer in the working mode for 30 minutes, and aortic flow was recorded. This was followed by 3 minutes of hypothermic (14 degrees C) coronary perfusion with either Krebs or St. Thomas' Hospital cardioplegic solution No. 2, followed by hypothermic (14 degrees C) global ischemia (mature hearts 2 and 4 hours; immature hearts 2, 4, and 6 hours). Hearts were reperfused for 15 minutes in the Langendorff mode and 30 minutes in the working mode, and recovery of postischemic function was measured. Hypothermia alone provided excellent protection of the ischemic immature rabbit heart, with recovery of aortic flow after 2 and 4 hours of ischemia at 97% +/- 3% and 93% +/- 4% (mean +/- standard deviation) of the preischemic value. Mature hearts protected with hypothermia alone recovered only minimally, with 22% +/- 16% recovery of preischemic aortic flow after 2 hours; none were able to generate flow at 4 hours. St. Thomas' Hospital solution No. 2 improved postischemic recovery of aortic flow after 2 hours of ischemia in mature hearts from 22% +/- 16% to 65% +/- 6% (p less than 0.05), but actually decreased postischemic aortic flow in immature hearts from 97% +/- 3% to 86% +/- 10% (p less than 0.05). To investigate any dose-dependency of this effect, we subjected hearts from both age groups to reperfusion with either Krebs solution or St. Thomas' Hospital solution No. 2 for 3 minutes every 30 minutes throughout a 2-hour period of ischemia. Reexposure to Krebs solution during ischemia did not affect postischemic function in either age group. Reexposure of immature hearts to St. Thomas' Hospital solution No. 2 caused a decremental loss of postischemic function in contrast to incremental protection with multidose cardioplegia in the mature heart. We conclude that immature rabbit hearts are significantly more tolerant of ischemic injury than mature rabbit hearts and that, unexpectedly, St. Thomas' Hospital solution No. 2 damages immature rabbit hearts.