Early diagnosis of acute intestinal ischaemia: contribution of colour Doppler sonography

The aim of this study was to evaluate the contribution of colour Doppler sonography in the diagnosis of acute intestinal ischaemia. In a two years experience, all patients admitted for acute abdominal pain in our emergency department were evaluated with colour Doppler sonography of the abdomen. The final diagnosis based on clinical evolution, endoscopic or surgical findings and further radiological investigations was compared to the sonographic results. Therapy and final outcome of the patients with acute intestinal ischaemia were also evaluated. In twenty-one patients a final diagnosis of acute intestinal ischaemia (mesenteric ischaemia (n = 13) and ischaemic colitis (n = 8)) was made. Intestinal ischaemia was correctly diagnosed by initial clinical and biological data and further confirmed by sonography in eight cases (mesenteric ischaemia (n = 2) and ischaemic colitis (n = 6)). Eleven other cases were detected by suggestive colour Doppler sonography features (mesenteric ischaemic (n = 10) and ischaemic colitis (n = 1)). Sixteen of the 21 patients had a final favourable outcome (mesenteric ischaemia (10/ 13) and ischaemic colitis (6/8)). We conclude that sonography has a place in the diagnosis of acute intestinal ischaemia and has to be integrated in the diagnostic algorithm of this acute condition. By this way, this diagnosis may be suspected earlier and may allow a prompt and adapted treatment with possible improvement in survival rate.     

Acute coeliac artery occlusion: initial collateral blood flow from the superior mesenteric artery. An experimental study

The collateral blood flow from the superior mesenteric artery after acute occlusion of the coeliac truck was measured in experiments in dogs. Immediately after clamping of the coeliac axis the collateral flow was about 30 % of the original coeliac blood flow. During an observation time of three hours the collateral flow increased, the corresponding value at the end of experiment being about 50 %. At the same time the blood pressure in the coeliac artery rose from a mean value of 20 mmHg to 35 mmHg. The initial collateral blood flow was evidently not sufficient, since after this short occlusion period ischaemic changes, even necrosis, were observed in the liver and stomach in some of the test animals.     

Preconditioning improves myocardial function and reflow, but not vasodilator reactivity, after ischaemia and reperfusion in anaesthetized dogs

1. The present study examines whether three cycles of brief coronary artery occlusion and reperfusion (i.e. ischaemic preconditioning; PC) can prevent vasodilator dysfunction and the impairment of myocardial reflow caused by prolonged ischaemia. Coronary blood flow, left ventricular dP/dt, systemic arterial blood pressure and heart rate were measured in open-chest anaesthetized dogs. 2. Sixty minute occlusion of the left circumflex coronary artery (LCx) and 60 min LCx reperfusion (ISC/REP; group 1) significantly reduced resting coronary blood flow (CBF, initial 29 +/- 3 mL/min; ISC/REP 20 +/- 3 mL/min, P < 0.05 vs initial) and increased coronary vascular resistance (CVR, initial 4.1 +/- 0.6 mmHg/min per mL; ISC/REP 5.8 +/- 1.0 mmHg/min per mL, P < 0.05 vs initial). By contrast CBF and CVR were not affected in dogs subjected to preconditioning before ischaemia (group 2: CBF, initial 24 +/- 4 mL/min; PC+ISC/REP 23 +/- 4 mL/min; CVR, initial 4.7 +/- 0.6 mmHg/min per mL; PC+ ISC/REP 5.3 +/- 1.0 mmHg/min per mL). These data suggest that ischaemic preconditioning prevents the ischaemia-induced impairment of myocardial reflow. 3. Ischaemia and reperfusion impaired coronary dilator responses to the endothelium-dependent dilator acetylcholine (delta CBF, after ISC/REP: 50 +/- 6% of initial) and the endothelium-independent dilator glyceryl trinitrate (delta CBF, ISC/REP: 46 +/- 6% of initial). Despite the improvement in reperfusion in the preconditioned group, there was no significant improvement in responses to acetylcholine (PC+ISC/REP 52 +/- 6% of initial) or glyceryl trinitrate (PC+ISC/REP 59 +/- 6% of initial) after ischaemia and reperfusion. 4. The reduction in left ventricular dP/dt after ischaemia and reperfusion was significantly smaller in the preconditioned group indicating a lower level of impairment of cardiac contractility. In addition, we confirmed that preconditioning caused a significant reduction in infarct size and a reduction in the release of lactate dehydrogenase indicating less cardiac injury. 5. These results suggest that although ischaemic preconditioning was able to improve both myocardial reperfusion and contractility, it was not able to preserve vasodilator function. Such a reduction in vasodilator reserve could prevent adequate myocardial perfusion under conditions of elevated oxygen demand.     

ST segment changes in the ECG. Anesthesia induction with propofol, etomidate or midazolam in patients with coronary heart disease

Induction of anaesthesia with propofol and fentanyl can lead to marked reductions in mean arterial pressure (MAP) and heart rate (HR). Thus, the application of propofol in patients with severely reduced coronary artery perfusion is controversial. METHODS. The study group consisted of 60 patients undergoing coronary artery bypass grafting (CABG). Anaesthesia was induced over 30 s with propofol (P 1.5 mg/kg), etomidate (E 0.3 mg/kg), or midazolam (M 0.15 mg/kg) following a bolus dose of fentanyl (5 micrograms/kg). Vecuronium was used as a muscle relaxant. During induction we continuously measured MAP and HR and recorded the occurrence of myocardial ischaemia using an automatic ST-segment analyser (Marquette 7010). ST-segment deviations of more than 1 mm in leads II and V5 were interpreted as significant signs of myocardial ischaemia. RESULTS. All groups showed reductions in MAP and HR on induction that were marked in the P group. Intubation caused elevation of MAP and HR to pre-induction levels (HR: all groups) or slightly above (MAP: E, M). Four patients in the P group and 3 in each other group showed significant ST-segment deviation prior to induction. In the P group these deviations disappeared in 2 patients after injection while they remained unchanged in the M group. In the E group injection had no effect on the ischaemic ECG changes but produced another case of significant ST-segment deviation. Laryngoscopy and intubation produced no further significant ST-segment deviation in either group. DISCUSSION. Induction is a critical phase of anaesthesia, especially in patients with limited coronary reserve. Induction agents should alleviate the stress response while causing minimal haemodynamic changes. Despite marked reductions in MAP in the P group, the number of patients with ischaemic ECG changes was cut by half. Their number was unchanged or even raised in the other groups. After application of P, with an alleged reduction of coronary perfusion, a compensational reduction in myocardial oxygen consumption may occur.     

A study of the contribution of changes in the cerebral blood volume to the haemodynamic response to anoxia in rat brain

A susceptibility contrast agent which does not pass into the extra-cellular space was used to study the effect of changes in the relative cerebral blood volume (CBV) on the haemodynamic response to anoxia, for both normal and ischaemic brain tissue, in a rat model of acute focal ischaemia. In non-ischaemic tissue a strong CBV component was observed in the haemodynamic response, both during and after anoxia. During anoxia the change in the CBV of the non-ischaemic tissue was estimated to be 40% in the caudate putamen and 70% in the frontal-parietal cortex. For severely ischaemic tissue (ischaemic caudate putamen) there was no change in the CBV during anoxia while in areas of moderate ischaemia (ischaemic frontal parietal cortex) a change of 20% was observed. The effect of the contrast agent on spin-echo images was consistent with a small reduction in the microvascular blood volume of the ischaemic tissue.     

The relationship between glutamate release and cerebral blood flow after focal cerebral ischaemia in the cat: effect of pretreatment with enadoline (a kappa receptor agonist)

The effect of the kappa-opioid agonist enadoline (CI-977) upon the relationship between cerebral blood flow and glutamate release was simultaneously assessed (using microdialysis and hydrogen clearance techniques respectively) at the same anatomical locus in the cerebral cortex (suprasylvian gyrus) after permanent middle cerebral artery (MCA) occlusion in halothane-anaesthetised cats. During controlled graded ischaemia, pretreatment with enadoline (0.3 mg/kg i.v. followed by continuous infusion at 0.15 mg/kg/h), initiated 30 min prior to MCA occlusion, significantly attenuated the marked increases in extracellular glutamate, aspartate and GABA observed in the focal ischaemic penumbra. The present data are consistent with the hypothesis that the neuroprotective efficacy of enadoline in focal cerebral ischaemia is due to inhibition of glutamate release in the ischaemic penumbra.     

Changes in local cerebral blood flow, local EEG, and flow in the distal stump of the middle cerebral artery in cats with occlusion of the middle cerebral artery

The local EEG, the local cerebral blood flow (lCBF), and the flow in the distal stump of the occluded middle cerebral artery was simultaneously recorded in 28 acute experiments in cats. Nembutal anaesthesia was used eleven times, and Halothane anaesthesia 17 times. The recordings were made via platinum electrodes: 12 in the ischaemic hemisphere, and 2-3 in the opposite non-ischaemic hemisphere. The flow in the occluded middle cerebral artery was recorded via a platinum electrode introduced into this artery via the transorbital approach. The changes in lEEG, lCBF, and middle cerebral artery flow were studied during normotension, hypertension, and hypotension. A beneficial effect of hypertension was noted in the acute phase of brain ischaemia. Hypertension counteracted also the "diaschisis" in the non-ischaemic part of the ischaemic hemisphere and in the opposite non-ischaemic hemisphere. A correlation between lEEG changes and lCBF changes was noted. In addition, an interesting discrepancy was observed between the rapid H2 clearance in the middle cerebral artery stump and the much slower H2 clearance in the ischaemic brain area. Significant differences between experiments under Halothane and experiments under Nembutal anaesthesia were noted. In the acute phase those changes are probably the result of the different levels of blood pressure in those two groups.     

Beneficial effects of prostaglandin E1 on ischemic colitis following surgery on the abdominal aorta

To determine the effects of prostaglandin E1 (PGE1) on the intestinal circulation, an experimental dog model of ischemic colitis following abdominal aortic reconstruction was made by ligating the inferior mesenteric artery (IMA) and the internal iliac artery, with the creation of a 50% stenosis in the superior mesenteric artery (SMA). The parameters of enteric ischemia included the blood flow of the SMA, the tissue blood flow in the small intestine and left colon, the mean stump pressure of the IMA (IMAP), and the IMAP/mean systemic blood pressure ratio. With the continuous infusion of 10 ng/kg per minute of PGE1 into the descending thoracic aorta, these values increased significantly on the seventh postoperative day compared with those on the day of operation. These results thus suggest that the continuous intraarterial infusion of PGE1 may reduce ischemic changes in the colon following abdominal aortic reconstruction.     

Significance of selective arteriographic patterns in the celiac axis and superior mesenteric artery in portal hypertension

Selective celiac and superior mesenteric arteriographies were performed in patients with portal hypertension. An arterioarterial (A-A) shunt between the superior mesenteric artery and the celiac axis via pancreatic arcades was found in fifteen of forty-three patients with associated massive splenomegaly. A mild A-A shunt disappeared after portacaval anastomosis alone, whereas a prominent A-A shunt was reduced but persisted. The persisting A-A shunt disappeared after splenectomy. These findings led us to suggest that the paucity of the blood flow in the common hepatic artery concomitant with increased splenic arterial flow to the massively enlarged spleen may result in a compensatory supply to the liver from the superior mesenteric artery via the shunt.     

Algorithms in the diagnosis and management of exotic diseases. XVI. Tuberculosis

With few exceptions, the incidence of left colon ischemia following abdominal aortic reconstruction has been reported to be one to 2 percent. All reports of such ischemic events are retrospective analyses of clinically manifest or autopsy. Fifty patients were studied prospectively to determine more accurately the incidence of this complication. Aortic reconstruction was performed in 23 patients for occlusive disease (OD) and in 27 for aneurysm disease (AD). No emergency operations were performed. All patients underwent colonoscopy within 4 days of operation. Three instances of colon ischemia were noted, an incidence of 6 percent (OD 4.3 percent, AD 7.4 percent). Each patient recovered uneventfully. Two patients had diarrhea, but only after colon ischemia was recognized. Arteriographic opacification of the inferior mesenteric artery by the superior mesenteric artery collateral (meandering mesenteric artery) was documented in 35 percent of patients with OD and in 27 percent of patients with AD. Colon ischemia did not develop when this collateral was identified. The inferior mesenteric artery was patent at the aorta in all who developed colon ischema. Although clinically significant colitis following aortic reconstruction is rare, colonoscopy after operation may prove to be valuable for early recognition of ischemic changes before clinical manifestations preclude effective management.     

Recipient bed vascularity and the survival of ischaemic flaps

The purpose of this study was to identify the length of the ischaemic period required to induce the 'no-reflow' phenomenon in a rat epigastric flap on an avascular recipient site. The vascularity of the recipient bed may affect flap survival in the early postischaemic stage after flap transfer. Initially, we designed epigastric flaps in 300-350 g Sprague-Dawley rats and separated the rats into four groups of 5 rats each (total 20 rats). In groups 1, 2, 3, the flaps were made ischaemic for 1 hour, 6 hours and 10 hours, respectively, by temporarily clipping the epigastric artery and vein. In group 4, the epigastric artery and vein were divided to create permanent ischaemia. In groups 1, 2 and 3, ischaemia was ended by removing the clips. After the ischaemic flaps were reperfused, their viability was studied by measuring the flap survival rate at postoperative day 7. Flap survival was studied by direct observations, laser Doppler flowmeter measurement of flap blood flow, histopathology, and carbon particle perfusion of the flap vasculature. Ischaemic flaps of groups 1 and 2 recovered almost completely after reperfusion due to the short period of ischaema. In a second series of experiments, in order to evaluate the contribution to flap survival of the recipient vascularised bed, another four groups of epigastric flaps (of 5 animals each, using the same time periods as above) were raised and a piece of Biobrane was interposed between the flap and the recipient bed before the flap wound was closed, to eliminate all nutrient supply from the recipient bed. THe results showed that the combined effect of the reperfused flap vasculature plus the metabolic contribution of the recipient bed significantly (P < 0.01) increased the extent of flap survival of the 6- and 10-hour ischaemic flaps as well as the divided pedicle flaps, which were never reperfused. An absolute 'no-reflow' rat model flap for further flap salvage studies was also developed.     

Essential hypertension: could the basic defect be in blood supply of vasomotor centre?

Various factors have been implicated in the pathogenesis of essential hypertension, although the exact cause of essential hypertension is still unknown. In this paper it is suggested that the basic pathology in essential hypertension may be an inherited defect in the blood supply of that part of reticular formation of rostral ventrolateral medulla which contains the pressor area. The posited defect is one in which the arterial branch supplying blood to the above-mentioned pressor area of vasomotor center arises from an artery which is stenosed. The other branches of this stenosed artery supply adjacent areas of medullary reticular formation concerned with other neurological functions. Due to this stenosis there is ischaemia of the pressor area resulting in increased systemic arterial pressure. During stress, the blood requirement of adjacent areas of the reticular formation (whose function is still not clearly defined) may increase, thus further decreasing blood flow to vasopressor area and increasing the cerebral ischaemic response. After a prolonged time, this increased blood pressure can cause hyaline arteriolar nephrosclerosis in kidney, which may participate in the maintenance of elevated systemic arterial pressure.     

Embolization for ruptured superior mesenteric artery aneurysms

Superior mesenteric artery (SMA) aneurysms are very uncommon. They are difficult to detect until they rupture and cause hypovolaemic shock. We performed embolization in four cases of aneurysm of branches of the superior mesenteric artery, succeeding in three cases without the need for surgical treatment. In the first case, the aneurysm was excised because of migration of a microcoil into the left hepatic artery. It was not retrieved because sufficient blood flow to the liver was shown on angiography after migration and no ischaemic change of liver was detected on laparotomy. In the second case, the aneurysm arose from the anterior pancreaticoduodenal artery. In the third case, the patient had two SMA aneurysms; one had been resected at surgery, another was revealed on follow-up angiography and embolized with microcoils. The fourth patient had a jejunal artery aneurysm with extravasation; haemostasis was achieved by packing it. In all four cases, no major complications were observed in the clinical course after embolization. Microcoils were considered to be the desirable embolic material, in order to prevent post-therapeutic ischaemic change. Embolization should be the treatment of choice for SMA aneurysms, because it is less invasive and takes less time than surgical treatment.     

Social anxiety, hypomania and the bipolar spectrum: data, theory and clinical issues

Z1046, (S)-6[[6-[[2-(2-methoxyphenoxy)ethyl]amino]propyl]amino]-5,6,7,8-tetra-h ydro-1,2-naphtalenediol dihydrochloride, is an agonist at both dopamine D1 and D2 receptors. Since stimulation of dopamine D2 receptors inhibits noradrenaline release, and because cardiac noradrenaline release has been implicated in the genesis of early ischaemia-induced, life-threatening ventricular arrhythmias, the effect of Z1046 has been examined for its effects on coronary artery occlusion in chloralose urethane anaesthetised mongrel dogs. Z1046 (10 microg kg(-1) intravenously or 1 microg kg(-1) by local intracoronary injection) decreased heart rate and reduced arterial blood pressure and coronary blood flow, effects prevented by the prior administration of domperidone (40 microg kg(-1) i.v.). The ischaemic changes induced by a 25-min occlusion of the left anterior descending coronary artery (including ST-segment elevation and ventricular ectopic activity) were much less marked in those dogs administered Z1046 and survival from the combined ischaemia reperfusion insult was increased from 7% to 36% (P < 0.05). These effects of Z1046 were partly attenuated by domperidone. We conclude that the anti-ischaemic effects of Z1046 are due to inhibition of cardiac sympathetic responses. Studies using rat isolated perfused mesenteric vascular bed preparations subjected to sympathetic nerve stimulation confirmed that Z1046 inhibits synaptic transmission without modifying vascular responses to noradrenaline.     

Experimental occlusion of the central artery of the retina. IV: Retinal tolerance time to acute ischaemia

Ophthalmoscopic, fluorescein angiographic, electrophysiological, and morphological studies on 63 eyes of rhesus monkeys with acute transient experimental occlusion of the central artery of the retina (OCAR) showed that the retina suffered irreparable damage after ischaemia of 105 minutes but recovered well after ischaemia of 97-98 minutes. The tolerance time of the brain to acute transient ischaemia is many times shorter than that of the retina. The metabolism of ischaemic neurones (in the retina and brain) is discussed with a view to explaining this difference, and also the various factors possibly responsible for the retina's longer tolerance to ischaemia, as compared to the brain.     

Ergonovine-echo test to assess the significance of chest pain at rest without ECG changes

The aim of this study was to assess the feasibility and diagnostic role of ergonovine maleate infusion under continuous two-dimensional echocardiographic monitoring for the identification of vasospastic myocardial ischaemia in patients with chest pain at rest not associated with diagnostic ECG changes. One hundred and twenty-eight consecutive patients, selected on the basis of absence of ischaemic ECG changes during angina at rest before or during hospitalization, were enrolled in the study. Ergonovine maleate was i.v. administered in scaled doses (from 0.025 to 0.2 mg at 10 min intervals) under echocardiographic, electrocardiographic and systemic blood pressure monitoring. Wall motion asynergies were observed in 33 patients, accompanied by typical chest pain in 24 patients and by ECG changes in 25 (ST elevation in 13 patients, ST depression in seven, T wave changes in five). All patients were able to complete the test. Non life-threatening ventricular arrhythmias were observed in four patients exclusively in association with ischaemia. In seven patients with a positive test, coronary artery spasm was documented at angiography. In 16 patients with a positive test, the vasospastic event was reproduced by a hyperventilation-echo test or a second ergonovine maleate-echo test performed within 3 days of the first examination. In none of the patients with a negative test was documentation of myocardial ischaemia due to a primary reduction in coronary blood flow. Thus, in patients who do not show ECG changes during chest pain at rest, the ergonovine maleate-echo test is feasible and safe; it permits the recognition of ischaemic episodes on the basis of wall motion abnormalities when conventional 12-lead ECG-recorded chest pain is non-diagnostic.     

Pelvic radiation therapy as a risk factor for ischemic colitis complicating abdominal aortic reconstruction

Ischemic colitis is an infrequent but potentially devastating complication of abdominal aortic reconstruction. Identification of patients with predisposing risk factors for the development of ischemic colitis can guide intraoperative measures to preserve or restore colonic blood flow during aortic surgery. Previous radiation therapy for pelvic malignancy may be one such predisposing risk factor. Two cases are presented in which ischemic colitis complicated abdominal aortic reconstruction in the setting of previous pelvic irradiation. In the months after radiation therapy for prostate cancer, one patient underwent infrarenal abdominal aortic aneurysm repair. Ischemic infarction of the sigmoid colon developed acutely after surgery and required emergent sigmoid colectomy. The second patient underwent reconstruction of an infrarenal abdominal aortic aneurysm after having had radiation therapy for a bladder tumor. Despite an initial satisfactory result, the patient's abdominal pain and diarrhea progressively worsened and he eventually required sigmoid colectomy for severe ischemic colitis. In both of these patients, the inferior mesenteric arteries were patent and had not been reimplanted. The association of pelvic radiation therapy with ischemic colitis after aortic reconstruction should focus attention to the operative details for maintaining the colonic circulation in these patients. Reimplantation of the inferior mesenteric artery in particular may prevent both the acute and the insidious variants of this complication in patients who undergo aortic surgery and decrease the incidence of this complication in patients with a history of radiation therapy to the pelvis.     

delta -function bosons in a one-dimensional potential well

The neuroprotective efficacy of the hydroperoxide scavenger ebselen was assessed in a model of transient focal ischaemia that utilises the potent vasoconstrictor peptide endothelin-1 to induce temporary occlusion of the middle cerebral artery (MCA). Pretreatment with ebselen (10 or 30 mg/kg p.o., 40 min pre-MCA occlusion) dose dependently reduced the volume of ischaemic damage assessed 4 h post-endothelin-1 application in the anesthetised rat. The lower dose of ebselen (10 mg/kg) resulted in a non-significant 35% reduction in the total volume of ischaemic damage compared with the vehicle control. In contrast the higher dose of ebselen (30 mg/kg) significantly reduced the volume of ischaemic damage in the cerebral hemisphere and cerebral cortex by 48% and 53%, respectively. The marked reduction in brain damage achieved with ebselen cannot be attributed to drug-induced alterations in blood pressure, body temperature or arterial blood gases since these physiological variables were closely monitored and were not significantly altered by ebselen treatment. Thus ebselen is an effective neuroprotective agent against acute focal ischaemic-reperfusion injury.     

Value of calcium channel blockers in the prevention of ventricular fibrillation of ischemic etiology: experimental arguments

The prevention of ventricular fibrillation raises a special problem when related to myocardial ischaemia, since class I antiarrhythmic drugs are then ineffective and may even behave as profibrillatory agents: the usual antifibrillatory properties of these drugs which are inhibitors of sodium channel, activated at high potentials, disappear with the disappearance of the role of sodium channel caused by ischaemic depolarization. Calcium channel then replacing sodium channel, calcium channel inhibitors should tend to prevent ischaemic ventricular fibrillation. Therefore, vulnerability to ventricular fibrillation was assessed in open-chest pigs by the threshold for fibrillation electrically induced with impulses of 100 ms duration at the rate of 180 beats/min. Ischaemia was produced by total occlusion of the left anterior descending coronary artery near its origin. Electrical fibrillation threshold was measured at the end of ischaemic period of increasing duration (30, 60, 120, 180, 240, 360 s) under control conditions and after i.v. administration of verapamil (50 micrograms/kg loading dose and 2 micrograms/kg/min infusion). Unaffected by verapamil when coronary circulation was normal, fibrillation threshold was raised by the drug when lowered by ischaemia, increasingly with the prolongation of ischaemia responsible for depolarization of the fibres, up to 500%. The rise of fibrillation threshold resulted in a delay in the triggering of fibrillation which occurs when the fibrillation threshold (6-8 mA) falls down to the pacing threshold (0.3-0.4 mA). These experiments tend to confirm the positive results recently obtained in man with verapamil in the prevention of postinfarction sudden death, provided that myocardial contractility is not too much adversely affected. But, in these experiments, left ventricular dP/dt max was not reduced by more than 15%, even just after the loading dose and returned to its control values within a few minutes.     

Inhibition of ischaemic tolerance in the gerbil hippocampus by quercetin and anti-heat shock protein-70 antibody

To clarify the role of heat shock protein-70 (HSP70) in ischaemic tolerance following pretreatment with sublethal cerebral ischaemia, we examined whether the induction of tolerance in the gerbil hippocampus is inhibited by quercetin, an inhibitor of HSP70 expression, or anti-HSP70 antibody. A 3 min period of forebrain ischaemia was induced following pretreatment with 2 min of ischaemia and 3 days of reperfusion. Quercetin or anti-HSP70 antibody was continuously infused into the left lateral ventricle using an implanted osmotic minipump started 3 h after or 2 h before the first ischaemia. The animals were killed 4 days after the second ischaemia for histological observations. Both agents produced no neuronal damage in the brain following a single 2 min period of ischaemia. The neuronal density of the CA1 hippocampus in animals subjected to treatment with quercetin and anti-HSP70 antibody was significantly lower than vehicle-treated animals but were significantly higher than animals with a single 3 min period of ischaemia. Thus, the present study showed that quercetin and anti-HSP70 antibody prevent the induction of ischaemic tolerance. The result suggests that HSP70 expression, at least in part, plays a role in the induction of ischaemic tolerance.