Hypothermic retrograde venous perfusion with adenosine cools the spinal cord and reduces the risk of paraplegia after thoracic aortic clamping

OBJECTIVE: We evaluated the utility of retrograde venous perfusion to cool the spinal cord and protect neurologic function during aortic clamping. We hypothesized that hypothermic adenosine would preserve the spinal cord during ischemia. METHODS: Six swine (group I) underwent thoracic aortic occlusion for 30 minutes at normothermia. Group II animals underwent spinal cooling by retrograde perfusion of the paravertebral veins with hypothermic (4 degrees C) saline solution during aortic occlusion. The spinal cords of group III animals were cooled with a hypothermic adenosine solution in a similar fashion. Intrathecal temperature was monitored and somatosensory evoked potentials assessed the functional status of spinal pathways. RESULTS: Spinal cooling without systemic hypothermia significantly improved neurologic Tarlov scores in group III (4.8 +/- 0.2) and group II (3.8 +/- 0.4) when compared with group I scores (1.3 +/- 0.6) (P <.001). Furthermore, 5 of the 6 animals in group III displayed completely normal neurologic function, whereas only one animal in group II and no animals in group I did (P =.005). Somatosensory evoked potentials were lost 10.6 +/- 1.4 minutes after ischemia in group I. In contrast, spinal cooling caused rapid cessation of neural transmission with loss of somatosensory evoked potentials at 6.9 +/- 1.2 minutes in group II and 7.0 +/- 0.8 minutes in group III (P =.06). Somatosensory evoked potential amplitudes returned to 85% of baseline in group III and 90% of baseline in group II compared with only 10% of baseline in group I (P =.01). CONCLUSIONS: We conclude that retrograde cooling of the spinal cord is possible and protects against ischemic injury and that adenosine enhances this effect. The efficacy of this method may be at least partly attributed to a more rapid reduction in metabolic and electrical activity of the spinal cord during ischemia.     

Mild hypothermia protects obese rats from fulminant hepatic necrosis induced by ischemia-reperfusion

BACKGROUND: Obese Zucker rats demonstrate increased susceptibility to hepatic ischemia-reperfusion injury. This study evaluates the effect of mild systemic hypothermia on ischemia-induced acute fulminant necrosis during warm ischemia and reperfusion, and investigates blood metabolic profiles under normothermic and mildly hypothermic conditions. METHODS: The left and median hepatic lobes of male, obese, Zucker rats were exposed to 75 minutes of ischemia under either normothermic (36.9 +/- 0.3 degrees C) or mildly hypothermic (33.3 +/- 0.1 degrees C) conditions followed by 8 hours of reperfusion. Animals were killed and tissue and blood were harvested for analysis of histology, liver enzymes, and metabolic 1H-NMR spectroscopy. RESULTS: Liver enzyme activities were significantly higher in the normothermic group when compared with mildly hypothermic animals. Histologic analysis showed greater than 75% necrosis in the normothermic group, whereas in the mildly hypothermic group necrosis was less than 25%. Blood from normothermic animals contained greater concentrations of lactate (190%, P = .001) and lower concentrations of glucose (60%, P = .01) than hypothermic animals; hepatic osmolyte betaine was also increased in blood from the normothermic group (220%, P = .0002). In addition, normothermic rats had increased concentrations of circulating fatty acids, triglycerides, glutamate, succinate, and acetate when compared with the hypothermic. CONCLUSION: Mild hypothermia decreased hepatic necrosis in obese rats. NMR blood profiles indicate that hypothermia protects hepatic metabolism.     

Objective assessment of CNS function within 6 hours of spinal cord ischemia in rabbits

Purpose To develop a neurologic scoring (NS) system to objectively assess CNS function shortly after spinal cord ischemia. Methods Spinal cord ischemia was induced by temporarily clamping the infrarenal aorta in 27 rabbits anesthetized with isoflurane/N₂O/O₂ without muscle relaxants. Animals were divided ito group I, normothermic ischemia [I-a, 11 min (n=8); I-b, 12 min (n=8)], and group II, 60 min hypothermic ischemia targeted to II-a, 29.5°C (n=5), and II-i, 30.0°C (n=6). Postischemic neurologic function was scored from 0 to 6. Results Seventy-five percent of each group I subgroup ended with paraplegia. Function in the I-b group tended to be worse than in I-a (NS=1.7vs 1.9P>0.05). Hypothermia of 29.9±0.1°C protected partially (NS=2.8), whereas 29.4±0.1°C resulted in significantly higher NS, starting at 150 min (P<0.05vs IIi) with total recovery 5.5 hours (P<0.0001) post re-perfusion. Conclusions Protection of the spinal cord from ischemia can be objectively quantitated by our system. Protection strategies can be compared within 6 h of the ischemia-insult.     

Protection against ischemic spinal cord injury: One-shot perfusion cooling and percutaneous topical cooling

Purpose: We investigated the protective effect of two methods of hypothermia against ischemic spinal cord injury: one-shot perfusion cooling and percutaneous topical cooling.Methods: Twenty-five rabbits were divided into five equal groups. The abdominal aorta was isolated proximally by a vascular clamp and distally by an inflated balloon catheter for 60 minutes. Group I served as control. In groups II (2.5 ml/min) and III (5.0 ml/min), hypothermic lactated Ringer's solution was infused for 3 minutes from the distal end of the catheter. Ice blocks were placed behind the backs of rabbits 30 minutes before ischemia in group IV. Group V underwent the procedures combined with those in groups II and IV (infusion of hypothermic solution plus placement of ice blocks). Another 15 rabbits underwent laminectomy at the L₂ or L₃ level. A temperature probe was inserted into the spinal cord to monitor cord temperature continuously during the procedures in all five groups (three rabbits per group).Results: Neurologic status on the second postoperative day in groups IV and V was significantly superior to that in group I (p < 0.01), but the neurologic status of groups II and III did not differ significantly from the neurologic status of group I. The spinal cord temperature in groups II and III dropped rapidly with the infusion, but it rose again quickly. In contrast, the spinal cord was kept sufficiently hypothermic during ischemia in groups IV and V.Conclusions: We concluded that the percutaneous cooling method can keep the spinal cord sufficiently hypothermic during ischemia to lead to a significantly superior neurologic outcome. (J VASC SURG 1994;19:882-7.)     

Effect of delayed induction of postischemic hypothermia on spinal cord damage induced by transient ischemic insult in rabbits

Objective: This study was performed to determine the effect of delayed induction of mild hypothermia after transient spinal cord ischemia in rabbits. Methods: Abdominal aortic occlusion was performed for 15 minutes to induce spinal cord ischemia at a rectal temperature of 37.3±0.3°C. Four groups of rabbits were investigated: Group 1 (n=8) was subjected to ischemia and reperfused at the same temperature for 7 hours; Group 2 (n=8) was subjected to ischemia and reperfused at the same temperature for 1 hour, followed by 6 hours of systemic hypothermia (32.5±0.5°C); Group 3 (n=8) was subjected to ischemia, reperfusion at the same temperature for 3 hours and then 6 hours of systemic hypothermia (32.5±0.5°C); and Group 4 (n=8) comprised non-ischemic controls. Neurological status of all rabbits in Groups 1– 3 was recorded and animals were sacrificed 1 week after ischemic injury. Spinal cord sections were examined microscopically to determine the extent of ischemic neuronal damage. Results: Mean modified Tarlov’s score at 1 week after ischemic insult was 0.5±0.8 in Group 1, compared to 4.3±1.5 in Group 2 and 2.9±1.8 in Group 3. Mean total number of surviving neurons within examined sections of spinal cord was significantly greater for Groups 2 and 3 compared with Group 1 (Group 1, 81±66.1; Group 2, 293.4±110.9; Group 3,227.1± 105.5; p<0.001). Conclusions: Delayed postischemic hypothermia induced within 3 hours after reperfusion significantly reduces ischemia-induced spinal cord neuronal damage in rabbits.     

The Effect of Graded Postischemic Spinal Cord Hypothermia on Neurological Outcome and Histopathology after Transient Spinal Ischemia in Rat

Background: Previous data have shown that postischemic brain hypothermia is protective. The authors evaluated the effect of postischemic spinal hypothermia on neurologic function and spinal histopathologic indices after aortic occlusion in the rat.

Methods: Spinal ischemia was induced by aortic occlusion lasting 10 min. After ischemia, spinal hypothermia was induced using a subcutaneous heat exchanger. Three studies were conducted. In the first study, the intrathecal temperature was decreased to 34, 30, or 27 [degree sign]C for 2 h beginning with initial reperfusion. In the second study, hypothermia (target intrathecal temperature 27 [degree sign]C) was initiated with reflow and maintained for 15 or 120 min. In the third study, the intrathecal temperature was decreased to 27 [degree sign]C for 2 h starting 5, 60, or 120 min after normothermic reperfusion. Animals survived for 2 or 3 days, at which time they were examined and perfusion fixed with 4% paraformaldehyde.

Results: Normothermic ischemia followed by normothermic reflow resulted in spastic paraplegia and spinal neuronal degeneration. Immediate postischemic hypothermia (27 [degree sign]C for 2 h) resulted in decreasing motor dysfunction. Incomplete protection was noted at 34 [degree sign]C. Fifteen minutes of immediate cooling (27 [degree sign]C) also provided significant protection. Delay of onset of post-reflow hypothermia (27 [degree sign]C) by 5 min or more failed to provide protection. Histopathologic analysis revealed temperature-dependent suppression of spinal neurodegeneration, with no effect of delayed cooling.     

Postconditioning, a series of brief interruptions of early reperfusion, prevents neurologic injury after spinal cord ischemia

OBJECTIVE: We sought to test whether postconditioning, a series of brief mechanical interruptions of reperfusion applied during the onset of reperfusion, can prevent neurologic injury of the spinal cord after transient ischemia. SUMMARY BACKGROUND DATA: Ischemia-reperfusion injury of the spinal cord is the principal mechanism leading to the paraplegia after surgery for descending and thoracoabdominal aortic aneurysms. Postconditioning has recently been demonstrated to confer cardioprotection by attenuating reperfusion injury. METHODS: Spinal cord ischemia was induced in rabbits by infrarenal aorta occlusion for 25 minutes. Control animals underwent no additional intervention. Two groups of animals underwent postconditioning consisting of 4 or 6 cycles of 1-minute occlusion/1-minute reperfusion, respectively, which were applied 1 minute after the start of reperfusion. In 2 additional groups, 6 cycles of postconditioning started 5 or 10 minutes after the onset of reperfusion, respectively. Hind-limb motor function was assessed during a 10-day recovery period using the modified Tarlov criteria. Histologic examination of the spinal cord was performed, and the number of intact motor neurons was counted. RESULTS: Compared with controls, 4 cycles of postconditioning significantly increased the Tarlov score and the number of intact motor neurons. Six cycles of postconditioning did not further improve the neuroprotection. Postconditioning starting 5 minutes after reperfusion still resulted in powerful neuroprotection, but the neuroprotection disappeared completely when postconditioning was delayed for 10 minutes. CONCLUSIONS: Postconditioning prevents neurologic injury of the spinal cord after ischemia, and the first few minutes of reperfusion are crucial to neuroprotection by postconditioning.     

Mild hypothermia provides significant protection against ischemia/reperfusion injury in livers of obese and lean rats

OBJECTIVE: To evaluate the effect of anesthesia induced mild systemic hypothermia on hepatic injury in lean and obese rats during warm ischemia. SUMMARY BACKGROUND DATA: Hepatic warm ischemia during surgery remains a significant problem, particularly in organs with presumed baseline dysfunction. METHODS: The left and median lobes of male lean and obese Zucker rats were exposed to 75 minutes of ischemia under either mild hypothermic or normothermic conditions. After 75 minutes of ischemia, the organs were reperfused and animals were observed for 24 hours. Surviving animals were killed and blood and tissue was harvested to determine liver enzymes and examine the histology. RESULTS: Mild hypothermia significantly decreased hepatocellular injury in both lean and obese rats. Biochemical markers of hepatic injury were significantly reduced in hypothermic groups (P < 0.01). Survival in normo- and hypothermic lean groups were not different at 24 hours of reperfusion. However, hypothermia profoundly increased survival in obese rats when compared with normothermic obese rats (100% versus 20%, P < 0.01). Necrosis was more pronounced in both normothermic lean and obese animals who experienced more than >75% necrosis when compared with hypothermic animals. In contrast, mild hypothermia reduced necrosis in lean rats to less than 25% and in obese rats to less than 50%. CONCLUSIONS: We demonstrated in a clinically relevant model that mild hypothermia significantly reduces hepatic injury in a warm ischemia model in lean and obese rats and significantly improved 24-hour survival in obese rats.     

Transcranial myogenic motor-evoked potentials after transient spinal cord ischemia predicts neurologic outcome in rabbits

OBJECTIVE: Myogenic transcranial motor-evoked potentials (tc-MEPs) were applied to monitor spinal cord ischemia in the repairs of thoracoabdominal aortic aneurysms. We investigated whether tc-MEPs after spinal cord ischemia/reperfusion could be used to predict neurologic outcome in leporine model. METHODS: Tc-MEPs were measured at 30-second intervals before, during, and after spinal cord ischemia (SCI) induced by balloon occlusion of the infrarenal aorta. Twenty rabbits were divided into five groups. Four groups (n = 4 animals in each group) had transient ischemia induced for 10, 15, 20, or 30 minutes. In fifth group, the terminal aorta at the aortic bifurcation was occluded for 30 minutes. All animals were evaluated neurologically 48 hours later, and their spinal cords were removed for histologic examination. RESULTS: The tc-MEPs in each SCI group rapidly disappeared after SCI. After reperfusion, the recovery of tc-MEPs amplitude was inversely correlated to duration of SCI. Tc-MEPs amplitude at one hour after reperfusion was correlated with both neurologic score and number of neuron cells in the spinal cord 48 hours later. Logistic regression analysis demonstrated that the neurologic deficits differed significantly between animals with tc-MEPs amplitude of less than 75% of the baseline and those with an amplitude of more than 75%. CONCLUSIONS: The amplitude of tc-MEPs after ischemia /reperfusion of the spinal cord showed a high correlation with durations of SCI, with neurologic deficits, and with pathologic findings of the spinal cord. Tc-MEPs, therefore, could be used to predict neurologic outcome. In particular, tc-MEPs whose amplitude recovered by less than 75% indicated a risk of paraplegia.     

The effect of graded postischemic spinal cord hypothermia on neurological outcome and histopathology after transient spinal ischemia in rat

BACKGROUND: Previous data have shown that postischemic brain hypothermia is protective. The authors evaluated the effect of postischemic spinal hypothermia on neurologic function and spinal histopathologic indices after aortic occlusion in the rat. METHODS: Spinal ischemia was induced by aortic occlusion lasting 10 min. After ischemia, spinal hypothermia was induced using a subcutaneous heat exchanger. Three studies were conducted. In the first study, the intrathecal temperature was decreased to 34, 30, or 27 degrees C for 2 h beginning with initial reperfusion. In the second study, hypothermia (target intrathecal temperature 27 degrees C) was initiated with reflow and maintained for 15 or 120 min. In the third study, the intrathecal temperature was decreased to 27 degrees C for 2 h starting 5, 60, or 120 min after normothermic reperfusion. Animals survived for 2 or 3 days, at which time they were examined and perfusion fixed with 4% paraformaldehyde. RESULTS: Normothermic ischemia followed by normothermic reflow resulted in spastic paraplegia and spinal neuronal degeneration. Immediate postischemic hypothermia (27 degrees C for 2 h) resulted in decreasing motor dysfunction. Incomplete protection was noted at 34 degrees C. Fifteen minutes of immediate cooling (27 degrees C) also provided significant protection. Delay of onset of post-reflow hypothermia (27 degrees C) by 5 min or more failed to provide protection. Histopathologic analysis revealed temperature-dependent suppression of spinal neurodegeneration, with no effect of delayed cooling. CONCLUSIONS: These findings indicate that the immediate period of reperfusion (0-15 min) represents a critical period that ultimately defines the degree of spinal neuronal degeneration. Hypothermia, when initiated during this period, showed significant protection, with the highest efficacy observed at 27 degrees C.     

Peri-ischemic aminoguanidine fails to ameliorate neurologic and histopathologic outcome after transient spinal cord ischemia.

Inhibition of neurotoxic events that lead to delayed cellular damage may prevent motor function loss after transient spinal cord ischemia. An important effect of the neuroprotective substance aminoguanidine (AG) is the inhibition of inducible nitric oxide synthase (iNOS), a perpetrator of focal ischemic damage. The authors studied the protective effects of AG on hind limb motor function and histopathologic outcome in an experimental model for spinal cord ischemia, and related these findings to the protein content of iNOS in the spinal cord. Temporary spinal cord ischemia was induced by 28 minutes of infrarenal balloon occlusion of the aorta in 40 anesthetized New Zealand White rabbits. Animals were assigned randomly to two treatments: saline (n = 20) or AG (n = 20; 100 mg/kg intravenously before occlusion). Postoperatively, treatment was continued with subcutaneous injections twice daily (saline or 100 mg/kg AG). Normothermia (38 degrees C) was maintained during ischemia, and rectal temperature was assessed before and after subcutaneous injections. Animals were observed for 96 hours for neurologic evaluation (Tarlov score), and the lumbosacral spinal cord was examined for ischemic damage after perfusion and fixation. Lastly, iNOS protein content was determined using Western blot analysis 48 hours after ischemia in five animals from each group. Neurologic outcome at 96 hours after reperfusion was the same in both groups. The incidence of paraplegia was 67% in the saline-treated group versus 53% in the AG-treated group. No differences in infarction volume, total number of viable motoneurons, or total number of eosinophilic neurons were present between the groups. At 48 hours after reperfusion, iNOS protein content in the spinal cord was increased in one animal in the AG-treated group and in three animals in the control group. The data indicate that peri-ischemic treatment with high-dose AG in rabbits offers no protection against a period of normothermic spinal cord ischemia. There was no conclusive evidence of spinal cord iNOS inhibition after treatment with AG.     

Intrathecal Magnesium Sulfate Administration at the Time of Experimental Ischemia Improves Neurological Functioning by Reducing Acute and Delayed Loss of Motor Neurons in the Spinal Cord

Background: In this study, the authors determined the effect of magnesium sulfate on intrathecal glutamate concentrations, hindlimb motor function, and histopathology after a transient episode of spinal cord ischemia.

Methods: Fifty-two New Zealand White rabbits underwent spinal cord ischemia for 30 min. Fifteen minutes before ischemia, animals received intrathecal magnesium sulfate (MgSO4) (3 mg/kg) or placebo (artificial cerebrospinal fluid). Intrathecal microdialysis samples were measured for glutamate using high-performance liquid chromatography. Neurologic function and spinal cord histopathology were assessed throughout the recovery period.

Results: Intrathecal glutamate levels in placebo-treated animals were higher after spinal cord ischemia compared with sham- and MgSO4-treated animals. MgSO4-treated animals had increased lower extremity motor function compared with the placebo group (64.7% vs 14.3%, P < 0.01). Histologic examination of placebo-treated animals revealed significant motor neuron cell loss at thoracolumbar levels by Day 7 (P < 0.05), whereas lower lumbar regions displayed significant neuron loss on Day 1. Spinal cords from MgSO4-treated animals exhibited less neuronal loss in lumbar regions. Similar effects were present in the thoracolumbar segments on Day 7. A significant correlation existed between diminished neuronal loss and hind leg movement (Tarlov score) and demonstrates that the neurologic outcome after MgSO4 treatment was related to lower lumbar ventral horn cell survival (r2 = 0.812, P < 0.001).     

Collaborative therapy with nebivalol and L-NAME for spinal cord ischemia/reperfusion injury

Postoperative neurologic deficit is the most devastating complication after thoracoabdominal aortic aneurysm repair. Our aim was to investigate whether nebivolol has protective effects during ischemia or reperfusion and the most effective mechanism of protection via inhibiting nitric oxide (NO) release with an NO synthase inhibitor in an experimental model of spinal cord ischemia/reperfusion injury. Spinal cord ischemia was induced by occlusion of the infrarenal aorta for 30 min. Thirty-one rabbits were divided into five groups according to the administration period of nebivolol and/or N(G)-nitro-L-arginine methyl ester (L-NAME): control group; group NI, nebivolol during ischemic period; group NR, nebivolol during reperfusion period; group NILR, nebivolol during ischemic period and L-NAME during reperfusion period; and group LINR, L-NAME during ischemic period and nebivolol during reperfusion period. Blood samples were taken at both ischemia and reperfusion periods to obtain nitrite/nitrate levels. After neurologic evaluation at 24 hr of reperfusion, malondialdehyde (MDA) levels were measured. Neurologic impairment was significantly lower in group LINR (Tarlov score 3.4 +/- 0.6, p < 0.05). MDA levels were lower in nebivolol-treated animals, but the lowest value was achieved in the NR group, 35.6 +/- 2.7 nmol/g (p < 0.001). Nitrite levels were decreased significantly in all nebivolol-treated animals in the reperfusion period, but the lowest value was measured in the LINR group (455 +/- 137 vs. 1,760 +/- 522 nmol/mL, p < 0.001). Prophylactic use of nebivolol reduced neurologic injury, and combining with L-NAME provided the best clinical improvement by attenuating the inflammatory mileu in this experimental model. Combination of nebivolol and L-NAME appears to be an effective option for spinal cord protection against ischemia/reperfusion injury.     

Protecting the ischemic spinal cord during aortic clamping: The influence of selective hypothermia and spinal cord perfusion pressure

Purpose: We verified the hypothesis that selective deep hypothermia of the spinal cord during double thoracic aortic clamping can prevent postoperative paraplegia in dogs.Methods: Normal saline solution was circulated from the cisterna magna through an extracorporeal perfusion system consisting of a reservoir, a pump, and a heat exchanger, back into the subarachnoid space at the level of the medullary cone at a rate of 25 ml/min, starting 30 minutes before clamping, and ending after removal of the clamps. The thoracic aorta was cross-clamped below the left subclavian artery and above the diaphragm for a period of 45 minutes. Cerebrospinal fluid, intracranial, and central venous pressure and aortic pressure proximal, between, and distal to the clamps were continuously recorded. In five dogs, temperature of the circulating normal saline solution at the inflow level was maintained at 2° ±1.5° C (group 1), in five controls at 37° ±0.8° C (group 2). Five dogs underwent continuous cerebrospinal fluid drainage starting before clamping until sacrifice (group 3). Dogs were observed for up to 4 days, and neurologic function was graded by an independent observer with the Tarlov scale. Animals were then killed, and their spinal cords were prepared for microscopic examination.Results: Hemodynamic parameters were not significantly different between groups. All dogs in groups 2 and 3 were paraplegic with histologic evidence of spinal cord infarction. All animals in group 1 were neurologically normal without microscopic evidence of infarction ( p < 0.005).Conclusions: Selective deep hypothermia of the spinal cord prevents paraplegia after 45 minutes of double aortic clamping in dogs. Cerebrospinal fluid drainage was not effective in preventing paraplegia in this model. (J VASC SURG 1994;19:788-96.)     

Ischemia-reperfusion injury of the spinal cord: Protective effect of the hydroxyl radical scavenger dimethylthiourea

Purpose: This study was undertaken to evaluate whether neurologic outcome after aortic cross-clamping in rabbits could be improved with perioperative infusion of the hydroxyl radical scavenger dimethylthiourea and, if so, to determine whether it is effective during the period of ischemia, reperfusion, or both. Methods: In 41 New Zealand White rabbits, a snare occlusion device was placed at operation around the infrarenal aorta and tunneled into a subcutaneous position. Animals were then allowed to recover and, 48 hours later, randomized into four groups. In each group, the infrarenal aorta was occluded by tightening the snare in the awake animal. In groups 1, 2, and 3, cross-clamp time was 21 minutes. Group 1 (control) animals received saline solution, whereas group 2 (preclamp 21) received dimethylthiourea 750 mg/kg intravenously just before aortic clamping. In group 3 (prerep 21), dimethylthiourea was given just before reperfusion. Group 4 received dimethylthiourea before clamping, with cross-clamp time extended to 31 minutes. A second dose of saline solution or dimethylthiourea was given 12 hours after clamping in controls and the three treatment groups, respectively. Animals were observed for 5 days, and final neurologic recovery was graded by an independent observer. Animals were then killed, and their spinal cords were removed for histologic examination. Results: Complete paraplegia and marked histologic spinal cord injury at 5 days were seen in 91% (10/11) of group 1 (control) animals, whereas all animals in group 2 (preclamp 21) showed neurologic recovery (p < 0.0001). In group 3 (prerep 21), the final paraplegia rate was 50% (5 of 10), in group 4 (preclamp 31), 100% (10 of 10). Conclusions: Our results suggest that hydroxyl radicals play an important role in ischemia-reperfusion injury of the spinal cord and that treatment with dimethylthiourea can prevent paraplegia after 21 minutes of aortic cross-clamping in rabbits. (J VASC SURG 1994;20:444-50.)     

Moderate Hypothermie in der Aortenbogenchirurgie: eine Gefahr für das Rückenmark?

Surgery of the transverse arch still is one of the most challenging procedures in cardiovascular surgery associated with significant (neurologic) morbidity and mortality. In the past, selective cerebral perfusion (SCP) in combination with deep hypothermia gained widespread acceptance as the standard approach in aortic arch surgery. In recent years, SCP in combination with moderate hypothermia of up to 28°C, more recently even up to 32°C was introduced to avoid deep hypothermia-associated complications. However, this new perfusion strategy may lead to prolonged distal ischemia during mild hypothermia (or even normothermia), and therefore, bares an underestimated risk for the viscerals and the spinal cord. This article illustrates the development of various neuroprotective perfusion strategies utilized in modern aortic surgery focussing in particular on the core temperature managment during the currently most widely adopted technique ?C antegrade SCP ?C and discusses the pros and cons of the current trend towards normothermic core temperature management by critically reviewing the contemporary experimental and clinical literature.     

Establishment of a local cooling model against spinal cord ischemia representing prolonged induction of heat shock protein

OBJECTIVES: Paraplegia is one of the serious complications of thoracoabdominal aortic operations. Regional hypothermia protects against spinal cord ischemia although the protective mechanism remains unknown. We attempted to create a simple model of local cooling under transient spinal cord ischemia and evaluated the effect using functional and histologic findings. METHODS: Male domesticated rabbits were divided into 3 groups: control, normothermic group (group N), and local hypothermic group (group H). A balloon catheter was used for spinal cord ischemia by abdominal aortic clamping. A cold pack attached to the lumbar region could lower the regional cord temperature initially. Neurologic function was evaluated by the Johnson score. Cell damage was analyzed by observing motor neurons with the use of hematoxylin and eosin staining, terminal deoxynucleotidyl transferase-mediated deoxy-uracil triphosphate biotin in situ nick end labeling (TUNEL), and immunoreactivity of heat shock protein. RESULTS: Physiologic estimation showed that local hypothermia improved the functional deficits (group N, 1.3 +/- 0.9; group H, 4.9 +/- 0.3; P =.0020). Seven days after reperfusion, there was a significant difference in the motor neuron numbers between groups N and H (group N, 7.2 +/- 1.9; group H, 20.4 +/- 3.2; P =.0090). The number of TUNEL-positive motor neurons was reduced significantly (group N, 7.2 +/- 2.4; group H, 1.0 +/- 0.7; P =.0082). Heat shock protein immunoreactivity was prolonged up to 2 days after reperfusion in the hypothermic group. CONCLUSIONS: These results suggest that local hypothermia extended the production of heat shock protein in spinal cord motor neurons after reperfusion and inhibited their apoptotic change.     

Riluzole prevents ischemic spinal cord injury caused by aortic crossclamping

BACKGROUND: Recent studies support the involvement of glutamate neurotoxicity in the pathophysiology of spinal cord injury induced by aortic crossclamping. We investigated the effects of riluzole, a neuroprotective drug that blocks glutamatergic neurotransmission, in a rabbit model of spinal cord ischemia. METHODS: The infrarenal aortas of New Zealand White albino rabbits (n = 40) were occluded for 40 minutes. Experimental groups were as follows: sham operation group (n = 5), control group undergoing occlusion but receiving no pharmacologic intervention (n = 10), experimental group A (n = 10) receiving 8 mg/kg riluzole intravenously 30 minutes before ischemia, experimental group B (n = 10) receiving 4 mg/kg riluzole intravenously 30 minutes before ischemia and at the onset of reperfusion, and experimental group C (n = 10) receiving 8 mg/kg riluzole intravenously at the onset of reperfusion. Neurologic status was assessed at 6, 24, and 48 hours after the operation and then daily until the fifth day. All animals were killed at 24, 48, or 120 hours after the operation. Spinal cords were harvested for histopathologic studies, immunohistochemical studies for microtubule-associated protein 2, and search for morphologic features of apoptosis by the terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate-biotin nick-end labeling staining method. RESULTS: All animals in the control group became paraplegic. Except for 1 rabbit in group C, all riluzole-treated animals had better neurologic function. Luxol fast blue and terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate-biotin nick-end labeling staining methods demonstrated typical morphologic changes characteristic of necrosis and apoptosis in control animals. Riluzole prevented or attenuated ischemia-induced necrosis, apoptosis, and cytoskeletal proteolysis, depending on the dose and the timing of administration. CONCLUSION: Riluzole may have therapeutic utility during high-risk operations on the thoracoabdominal aorta.     

Moderate hypothermia reduces postischemic edema development and leukotriene production

Using the bilateral carotid artery occlusion model of cerebral ischemia in the gerbil, we studied the effect of moderate hypothermia (30 to 31 degrees C) on the postischemic production of prostanoids (cyclooxygenase pathway) and leukotrienes (lipoxygenase pathway) and accompanying changes in cerebral edema formation. Hypothermia capable of slowing central evoked potential conduction time was studied over the course of 40 minutes of cerebral ischemia and for up to 2 hours of reperfusion. The successful induction of cerebral ischemia was confirmed by somatosensory evoked potential amplitude changes. Measurements of 6-ketoprostaglandin F1 alpha (PGF1 alpha) and leukotriene B4 (LTB4) (radioimmunoassay) and cerebral edema (specific gravity) were made at early (10 minutes) and late (2 hours) reperfusion times. Although both white and gray matter showed no early significant difference in edema accumulation between normothermic and hypothermic gerbils at 10 minutes of reperfusion, hypothermic animals demonstrated significantly less white matter edema (specific gravity, 1.0397 +/- 0.0010 vs. 1.0341 +/- 0.0012, P less than 0.01) and gray matter edema (specific gravity, 1.0408 +/- 0.0009 vs. 1.0365 +/- 0.0008, P less than 0.01) by 2 hours of reperfusion. Production of PGF1 alpha was not significantly different between normothermic and hypothermic animals during the reperfusion period; however, hypothermic gerbils demonstrated significantly lower production of LTB4 at 10 minutes reperfusion time compared to normothermic animals (1.49 +/- 0.79 vs. 5.28 +/- 1.49 pg/mg of protein, P less than 0.05). This difference between the two groups in LTB4 levels was no longer detectable at 2 hours of reperfusion time.(ABSTRACT TRUNCATED AT 250 WORDS)     

羟乙基淀粉行急性等容血液稀释对兔脊髓缺血-再灌注损伤的保护作用

目的 探讨用羟乙基淀粉(HES130/0.4)急性等容血液稀释(ANH)对兔脊髓缺血-再灌注损伤的保护作用.方法 24只新西兰雄性大白兔,随机均分成三组:HES组,生理盐水组(NS组),对照组(C组).HES组和NS组分别用HES130/0.4和生理盐水行ANH,使红细胞压积(Hct)达30%.ANH的方法为:15 min内经股动脉恒速放出计算的血量,同时利用微量输液泵经静脉输注与放血量等量的液体(HES组)或输注3倍于放血量的液体(NS组),放血和输液速度相等,维持术中大白兔的血压和心率恒定.稳定15 min后,行肾下腹主动脉(IRA)阻闭建立脊髓缺血-再灌注损伤模型.分别于稀释前、稀释后和腹主动脉开放后采集动脉血进行血气分析.评估再灌注后4、8、12、24及48 h后肢运动功能,并于48 h处死动物取脊髓(L5)制标本行病理组织学观察.结果 再灌注后48 h.HES组和NS组动物的后肢运动功能比C组明显改善(P＜0.05或P＜0.01);HES组和NS组动物脊髓前角正常运动神经元计数比C组显著增加(P＜0.05或P＜0.01),但两组间差异无统计学意义.结论 HES130/0.4行适度ANH对脊髓缺血-再灌注损伤具有显著地保护作用.