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The cardioprotective effects of glucocorticoids in the acute setting of ischemia/reperfusion have been experimentally demonstrated in animals1–7 and humans.8 Although the mechanisms underlying glucocorticoid cardioprotection are not known with certainty, glucocorticoids are reported to preserve cellular function in ischemia thereby prolonging the period of myocardial viability. In previous studies, glucocorticoids were reported to improve lactate imbalance and prevent the leakage of intracellular enzymes caused by myocardial ischemia.6,7 At the same time, deleterious effects of glucocorticoids on ischemia-induced neuronal damage have been shown in various animal models, despite the ability of glucocorticoids to alleviate cerebral edema caused by traumatic brain injury and hemorrhage.9–13 Further, steroids are not indicated for traumatic brain injury in humans, as they do not improve clinical outcomes.14 Because adenosine 5′-triphosphate (ATP) provides energy to maintain membrane functional integrity in both the heart and brain, and ATP depletion precedes loss of cellular viability, the different effects of the agents in ATP utilization in the heart and brain during ischemia could well explain differences in ischemia-induced organ injury. In the present study, therefore, we investigated the effect of dexamethasone, a glucocorticoid without mineralocorticoid activity, on ischemia-induced reduction of ATP in the mouse heart and brain. In addition, we examined the effect of metyrapone, a potent inhibitor of the synthesis of glucocorticoids, to assess the role of endogenous glucocorticoids. We hypothesized that ATP levels would be diminished in neuronal tissue subjected to dexamethasone and improved in cardiac tissue subjected to dexamethasone. In contrast, ATP levels would be improved in neuronal tissue subjected to metyrapone and diminished in cardiac tissue subjected to metyrapone.

Seishu Hanaoka (1760–1835) left behind no books that he himself had written. This is why many aspects of Hanaoka-style general anesthesia using a mixture of herbal extracts, which he called mafutsu-san, remain unknown. We are able to learn about this technique today because there are several descriptions of it in books written by his students, such as Mafutsuto-Ron (“Treatise on Mafutsuto”) by Gendai Kamata (1794–1854) and Yohka-Hiroku (“Secret Records of Surgery”) by Gencho Homma (1804–1872). On the other hand, Geka-Kihai-Zufu (“Illustrations of Surgical Cases”), a surgical textbook, by Gendai Kamata, containing one of the oldest illustrations of general anesthesia published in 1840, was recently rediscovered (2011). For the first time, this book revealed, in the form of a picture image, the actual circumstances of Hanaoka-style general anesthesia. We therefore compared the descriptions of general anesthesia featured in these three documents, and thereby investigated the actual anesthetic management and the procedures used. We found that the circumstances under which Hanaoka-style general anesthesia, using fabrics and futon mattresses, as well as blindfolding and constraining the patient’s body during surgery, were exactly as described in Mafutsuto-Ron and Yohka-Hiroku. In addition, besides a surgeon conducting an operation, there was a physician who observed the patient’s general condition. Gendai Kamata, the author of Geka-Kihai-Zufu, is believed to have recognized the importance of anesthetic care of surgical patients.

Seishū Hanaoka and Gendai Kamada are two Japanese pioneers in anesthesiology. Seishū Hanaoka was the world's first surgeon on record to successfully perform surgery under general anesthesia in 1804. Seishū discovered that six medicinal herbs containing Datura , stramonium, and Aconitum had anesthetic properties. From these, he developed Mafutsusan. His fame spread across Japan, and he was inundated with requests from patients and prospective students. He founded a private medical school (Shunrinken) and trained more than 1000 students. Gendai Kamada was an outstanding pupil of Seishū Hanaoka. From the perspective of the history of anesthesiology, three of Gendai's achievements had a global impact. (1) In 1839, he wrote the first textbook of clinical anesthesiology, Mafutsuto-ron ; (2) in 1840, he authored Gekakihai-zufu , which included some of the oldest illustrations of surgery under general anesthesia; and (3) he trained Gensei Matsuoka, the world's second anesthesiologist.

On October 13, 1804, Seishu Hanaoka performed a mastectomy on Kan Aiya in Hirayama, Kii Province Japan, in what is considered to be the first operation under general anesthesia. She was anesthetized with a mixture of herbs known as Mafutsuto. Although Seishu did not record his anesthetic practices, his student, Gendai Kamada, documented the use of Mafutsuto in Mafutsuto-Ron. Written in 1839, Mafutsuto-Ron is 10 pages and covers six topics, including preoperative management, dosing and administering Mafutsuto, induction of general anesthesia, common errors, and postoperative precautions. Mafutsuto-Ron, therefore, meets the requirements to be considered the first extant anesthesia textbook. We present a complete English translation of Mafutsuto-Ron.

Objective: Ischemic preconditioning (IP) has been shown to attenuate intracellular Na þ accumulation and Ca 2þ overload during ischemia and reperfusion, both of which are closely related to the outcome of myocardial damage. We compared the effects of single- and four-cycle IP in Na þ ,K þ -activated adenosine 5 0 -triphosphatase (Na þ ,K þ -ATPase) and Ca 2þ -activated adenosine 5 0 -triphosphatase (Ca 2þ -ATPase) activities in in vivo rabbit hearts, correlating these differences to the quality of protection against subsequent ischemia. Methods: The morphological outcome was evaluated in in vivo rabbit hearts subjected to 30 min of coronary occlusion and reperfusion for 180 min by assessing the ratio of infarct volume to risk zone volume. The effects of single- and four-cycle preconditioning ischemia were then examined. Another set of in vivo rabbit hearts was subjected to the measurement of ATPase activities at the conclusion of final preconditioning ischemia and at 60 min after reperfusion following 30 min of ischemia. Results: The infarct volume was reduced by single-cycle IP to 38% of that in the control group. The four-cycle IP further reduced the infarct volume, which was 11% of that in the control group. Na þ ,K þ -ATPase activity at 60 min after reperfusion in the four-cycle group was increased to 172% of that in the control group (10.8 mmol ADP/h/mg protein), whereas no difference was found in the single-cycle group. On the other hand, Ca 2þ -ATPase activity at the conclusion of IP was increased by single-cycle IP, the value being 255% of that in the control group (4.9 mmol ADP/h/mg protein). The four-cycle IP further increased the activity, and the value was 158% of that in the single-cycle group. Conclusions: Since increases in Na þ ,K þ -ATPase and Ca 2þ -ATPase activities contribute to the decrease in intracellular Ca 2þ concentration, the enhancement of these activities by four-cycle IP may be involved in the additional protection. q 2004 Elsevier B.V. All rights reserved.

A 54-year-old woman with a 21-year history of systemic lupus erythematosus (SLE) was admitted to the Matsuyama Red Cross Hospital due to subcutaneous and gingival hemorrhaging. She was diagnosed with acquired factor VIII inhibitors based on a prolonged activated partial-thromboplastin time (APTT) and factor VIII inhibitors. Steroid pulse and factor VIII plasma concentrate were administered to her, not long after which she was transferred to Ehime University Hospital due to gallbladder hematoma. Although her APTT and factor VIII activity were improved after treatment with human factor VIII, she died of multiple organ failure. The autopsy demonstrated a ruptured gallbladder.

Purpose. We conducted a survey to clarify the actual circumstances in which the lungs could not be ventilated and the trachea could not be intubated (CVCI). Methods. A questionnaire was mailed to all the university hospitals in Japan, asking about CVCI they had experienced during induction of anesthesia in 1998, and before 1997. Results. Answers were obtained from 60 of 83 institutes. CVCI occurred in 26 of 151 900 cases of general anesthesia (0.017%) in 1998. Eighteen cases occurred after induction of anesthesia by several induction methods. Five cases occurred after repeated attempts at tracheal intubation by laryngoscopy and fiberscopy in patients under awake or anesthetized conditions. In the remaining 3 cases, the situation of occurrence was not documented. Patients with CVCI had anatomical abnormalities around the upper airways, mostly from acquired diseases. CVCIs after induction of anesthesia were successfully treated by restoration of spontaneous respiration, blind intubation, laryngeal mask airway, and transtracheal approaches, and CVCIs after repeated attempts at intubation were treated mostly by transtracheal approaches. No serious consequences occurred in any patients in 1998. Twenty cases were reported before 1997, and 2 were specific, in which CVCI followed malplacement of a tracheal tube, and serious consequences, death and brain damage, respectively, followed. In other patients, no serious consequences occurred, although cardiac arrest occurred in 1 patient. Conclusion. This survey demonstrates that CVCI can occur in any situation in which the airway is not established. Furthermore, effective treatments may be different depending on the situation, and delayed recognition of tracheal tube misplacement may lead to a serious outcome.

持続血液濾過透析(CHDF)中にメシル酸ナファモスタット(NM)による高カリウム血症を生じた慢性腎不全症例を経験した.症例は68歳の男性.肺水腫のため緊急入院し処置中に心停止を起こした.すぐに蘇生し人工呼吸下にNM30mg・hr-1を用いたCHDFを行った.入院時の血清K+は4.7mEq・l-1であったが,CHDF開始20時間後から急速に上昇し最高6.5mEq・l-1に達した.この高カリウム血症はNMをヘパリンに変更することで改善した.NMによる高カリウム血症の発生機序は尿へのカリウム排泄の抑制とされる.本症例は無尿の慢性腎不全のためこの機序による高カリウム血症ではない.NMが腎以外に作用して高カリウム血症を生じたと考えられた.

Rationale Coffin-Lowry syndrome (CLS) is a rare inherited disease with specific clinical features, such as mental retardation, facial dysmorphism, and cardiac abnormality. In particular, the characteristic facial features of CLS, including retrognathia and large tongue, are associated with difficult ventilation and/or intubation, which is a serious problem of anesthesia management. However, case reports on anesthesia management of CLS are very limited as there are only two published English reports till date. In this case report, we discuss anesthetic and postoperative considerations in patients with CLS, focusing on difficult airway management, and summarize past reports including some Japanese articles. Patient concerns A 25-year-old man with CLS was planning to undergo laminectomy because of progressive quadriplegia caused by calcification of the yellow ligament. We suspected difficulty in airway management because of several factors in his facial features, short thyromental and sternomental distances in computed tomography, severe obesity, and sleep apnea syndrome. Diagnoses Difficult airway was suspected. However, because of mental retardation, awake intubation was considered difficult. Interventions We selected bronchofiberscope-guided nasotracheal intubation, maintaining spontaneous breathing under moderate sedation with a propofol target-controlled infusion. Outcomes Airway management was safely performed during anesthesia induction. Lessons In many patients with CLS, difficult intubation was reported, and sedation or slow induction maintaining spontaneous breathing was mainly selected for anesthesia induction. Spontaneous breathing should be maintained during anesthesia induction in case of CLS patients.

先天性右横隔膜ヘルニアの術後に肺葉肺気腫を生じた生後106日の女児に,右肺中・下葉切除術が予定された.生下時より高頻度人工換気による呼吸管理を受けていたが,肺葉肺気腫は次第に増悪し,PaO2/FIO2は80mm Hg以下,PaCO2は100mm Hg以上を示すようになった.人工呼吸単独では術中,術後のガス交換が不十分になると判断し,ヘパリン結合膜型人工肺を用いた体外式肺補助(ECLA)を併用して呼吸管理を行なった.術中に肺葉切断面から多量の血液が健側肺へ流れ込み,ガス交換のほとんどをECLAに依存する状況となった.本症例では,術中,術後の生命維持にECLAは不可欠であったと考えられた.

Endotoxemia has been reported as a mechanism for the fatal sequela after heatstroke. Subsequent disseminated fungal infection in a heatstroke patient has been also described. Beta-D-glucan, a constituent of the fungal cell wall, is an early diagnostic measure for fungal infection. In a heatstroke case, we examined for the first time levels of serum beta-d-glucan and endotoxin. A 34-year-old man with a body temperature of 43.5 degrees C was admitted in a state of shock. Prior to the development of disseminated intravascular coagulopathy (DIC), a remarkable elevation of serum beta-D-glucan level to 116 pg/mL (normal level6.0 pg/mL) was revealed on the first day of admission. However, serum endotoxin was not detected when using a method that excluded beta-D-glucan contamination from endotoxin measurement (normal level1.0 pg/mL). This change of beta-D-glucan level was accompanied by a depressed neutrophil function, especially in phagocytosis of 34% (normal range 70-90%) but not in bacterocidal function (81% versus a normal range of 70-100%). After intensive care including continuous hemodiafiltration, the patient regained consciousness but remained ataxic due to cerebellar infarction, which might have resulted from DIC, and subsequent bilateral fungal oculitis were revealed 45 days after admission. This case report demonstrates the elevation of serum beta-D-glucan but normal endotoxin levels after heatstroke, which may prompt further study to re-examine the serum levels of endotoxin in such catastrophic insults.

We realized the looks of Gendai Kamada. At first, we found in a figure, in "Seishu Hanaoka and His Surgery" by Syuzo Kure, that the portrait described as that of Gendai is his father's. And we discovered the illustrations that illustrate the looks of Gendai in "Gekakihaizufu", which was a textbook of clinical anesthesia and surgery, printed in 1840. Using these illustrations, we realized the looks of Gendai Kamada.

The relationships between the speed of deterioration in severe asthma attack and clinical characteristics as measured by arterial blood gas values, duration of mechanical ventilation needed, and course of peak inspiratory pressure (PIP) during mechanical ventilation were studied. Twenty-six patients with severe bronchial asthma who underwent mechanical ventilation were classified into 3 groups according to the time interval from the first symptoms of asthma attack to endotracheal intubation: rapid onset group-(ROG: n=9

"Seishu Hanaoka and his surgery" by Shuzo Kure is one of the most important books for the study of Seishu Hanaoka. However, several incorrect descriptions have been pointed out in the book. Therefore, we checked the content about Seicho Kamata, a distinguished disciple of Seishu Hanaoka (p.154-163) in the book, and found three incorrect descriptions. The figure being described as that of Seicho Kamata is his father's. His graveyard being described as "Nyohoji" is truly "Daizenji". Seicho Kamata is also described as the second distinguished disciple of Seishu Hanaoka ; however, authors think that he was the first distinguished disciple from his career. Further investigation into the content of the book is necessary.

Seigo Miyoshi,1 Ryoji Ito,1 Hitoshi Katayama,1 Kentaro Dote,2 Mayuki Aibiki,3 Hironobu Hamada,1,4 Takafumi Okura,1 Jitsuo Higaki1 1Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine, 2Intensive Care Division, Ehime University Hospital, 3Department of Emergency and Critical Care Medicine, School of Medicine, Ehime University, Shitsukawa, Toon, Ehime, 4Department of Physical Analysis and Therapeutic Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi, Minami-ku, Hiroshima, Japan Background: Neutrophil elastase, alveolar thrombin generation, and fibrin deposition play crucial roles in the development of acute respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC). However, the usefulness of combination therapy with a selective neutrophil elastase inhibitor, sivelestat, and recombinant human soluble thrombomodulin (rhTM) for patients with ARDS and DIC remains unknown. Methods: We conducted a retrospective data analysis of 142 ARDS patients with DIC to assess the effects of sivelestat combined with rhTM. Patients were divided into four groups: control (no sivelestat or rhTM treatment), sivelestat treatment alone, rhTM treatment alone, and combined treatment with sivelestat and rhTM. A Cox proportional hazard model was used to assess subject mortality rates. The efficacy of these drugs was evaluated based on survival rate, number of ventilator-free days, and change in PaO2/FIO2 (P/F) ratios and DIC scores before and at 7 days after a diagnosis of ARDS with DIC. Results: Multivariate analysis showed that patient age, combination therapy, gas exchange, organ failure, cause, associated disease score, and serum C-reactive protein levels were predictors of mortality for patients with ARDS and DIC. As compared with untreated controls, combination therapy significantly improved the 60-day survival rate of patients with ARDS and DIC. There were significantly more ventilator-free days for those who received combination therapy than for untreated controls. P/F ratios and DIC scores were significantly improved with sivelestat alone, rhTM alone, or their combination as compared with untreated controls. Conclusion: Our results suggest that combined treatment with sivelestat and rhTM has beneficial effects on survival and the respiratory and DIC status of patients with ARDS and DIC. Keywords: sivelestat, recombinant human soluble thrombomodulin, disseminated intravascular coagulation, acute respiratory distress syndrome&nbsp

Object. The clinical features, possible causes, and contributing factors associated with novel spontaneous pain following unilateral cordotomy were investigated to clarify the mechanism and clinical importance of this pain. Methods. Forty-five patients who underwent cordotomy for severe unilateral cancer pain were included in this study. New pain occurred in 33 (73.3%) of 45 patients. Pathological conditions of tissue demonstrated on imaging corresponded to new pain in eight patients, referred pain in five, and neither of these in 15 patients. New pain was centered opposite the site of the original pain in a mirror-image location in 28 patients and rostral to the original pain in five patients. It was temporary in seven patients, weaker than the original pain in 25, and as severe as the original pain in one patient. The incidence of moderate or severe pain was significantly higher in patients with confirmed tissue disease (six of eight patients) than in those without (six of 20 patients). An important contributing factor to the occurrence of new pain was the achievement of analgesia by performing the cordotomy. Conclusions. The present results indicate that new pain occurs frequently after unilateral cordotomy. Nonetheless, cordotomy may still be indicated for unilateral uncontrollable pain because new pain, when present, was weaker and more easily controlled than the original pain in nearly all cases. The authors speculate that new pain may represent a type of referred pain from the original painful area or may arise from sensitization of contralateral spinal nociceptive circuits due to metastasis or tumor infiltration, and that new pain is potentiated by the interruption of descending inhibitory pathways.

Objective: The mechanism by which ischemic preconditioning protects the heart is presumed to be related to the reduction of energy consumption during a subsequent myocardial infarction. Since the sympathetic nervous system enhances cardiac function and energy consumption, we investigated the relation between ischemic preconditioning and the turnover rate of noradrenaline (NA) in the rat heart. Methods: The effect of 3 cycles of 5-min occlusions of the rat left coronary artery on changes in arterial blood pressure and heart rate provoked by a subsequent 30 min of ischemia were examined until 60 min after reperfusion. The effect of 3 cycles of occlusions on the infarct size was also evaluated 60 min after reperfusion by comparing the infarcted area with the area at risk in these animals (6 per preconditioned and sham-operated group). The tissue concentration of NA during sustained ischemia was determined in the left ventricle, the intraventricular septum, and the right ventricle in the preconditioned and sham-operated groups. Changes in the turnover rate of NA after 3 cycles of occlusions were also evaluated by assessing the alpha-methyl- p -tyrosine-induced depletion of NA ( n =7 per group). Results: A series of transient occlusions reduced the infarct size 60 min after a sustained ischemia for 30 min. Arterial pressure and heart rate were not affected. The concentration of NA was decreased in the left ventricle 60 min after the onset of sustained ischemia in both the preconditioned and sham-operated groups. The treatment with alpha-methyl- p -tyrosine decreased the NA concentration in all regions of the heart in the sham-operated group after 60 min. However, the treatment with alpha-methyl- p -tyrosine did not deplete the NA concentration in both the occluded and nonoccluded regions in the preconditioned group. Conclusions: Transient ischemia ameliorated the heart injury induced by a subsequent sustained ischemia, as assessed histologically. The activity of the sympathetic nervous system in all regions of the heart was reduced by transient ischemia in the left coronary vascular bed. These findings suggest that the inhibition of the sympathetic nervous system by the treatment of ischemic preconditioning takes part in the cardiac protection.

Fever is frequently observed in critically ill patients. An independent association of fever with increased mortality has been observed in non-neurological critically ill patients with mixed febrile etiology. The association of fever and antipyretics with mortality, however, may be different between infective and non-infective illness. We designed a prospective observational study to investigate the independent association of fever and the use of antipyretic treatments with mortality in critically ill patients with and without sepsis. We included 1,425 consecutive adult critically ill patients (without neurological injury) requiring > 48 hours intensive care admitted in 25 ICUs. We recorded four-hourly body temperature and all antipyretic treatments until ICU discharge or 28 days after ICU admission, whichever occurred first. For septic and non-septic patients, we separately assessed the association of maximum body temperature during ICU stay (MAXICU) and the use of antipyretic treatments with 28-day mortality. We recorded body temperature 63,441 times. Antipyretic treatment was given 4,863 times to 737 patients (51.7%). We found that treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen independently increased 28-day mortality for septic patients (adjusted odds ratio: NSAIDs: 2.61, P = 0.028, acetaminophen: 2.05, P = 0.01), but not for non-septic patients (adjusted odds ratio: NSAIDs: 0.22, P = 0.15, acetaminophen: 0.58, P = 0.63). Application of physical cooling did not associate with mortality in either group. Relative to the reference range (MAXICU 36.5°C to 37.4°C), MAXICU ≥ 39.5°C increased risk of 28-day mortality in septic patients (adjusted odds ratio 8.14, P = 0.01), but not in non-septic patients (adjusted odds ratio 0.47, P = 0.11). In non-septic patients, high fever (≥ 39.5°C) independently associated with mortality, without association of administration of NSAIDs or acetaminophen with mortality. In contrast, in septic patients, administration of NSAIDs or acetaminophen independently associated with 28-day mortality, without association of fever with mortality. These findings suggest that fever and antipyretics may have different biological or clinical or both implications for patients with and without sepsis. ClinicalTrials.gov: NCT00940654

The following parameters were monitored simultaneously in 15 dogs, in order to evaluate the efficacy of conventional CPR (C-CPR), new CPR (N-CPR), and open-chest CPR (O-CPR) on cerebral perfusion: arterial blood pressure (BP), central venous pressure (CVP), intrathoracic airway pressure, blood flow in carotid artery, intracranial pressure (ICP), sagittal sinus blood flow (sinus BF) and pressure (sinus P), and blood flow in cerebral cortex (cortical BF). The sinus blood flow was measured by the direct-method and with a cannulating electromagnetic flowmeter. The cortical blood flow was measured with a termocouple tissue flowmeter. Intracranial pressure was obtained by measuring subarachmoid cerebrospinal fluid pressure. Ventricular fibrillation was induced electrically. Chest compression and ventilation were always done manually in all cardiopulmonary resuscitation. The mean blood pressures during C-CPR, N-CPR and O-CPR were 52, 68 and 95 mmHg, respectively, and mean carotid blood flows per stroke were 36, 71 and 131% of the control values, respectively. The intracranial pressures were 30, 42 and 36 mmHg, respectively, giving the calculated cerebral perfusion pressures (BP-ICP) of 22, 27 and 60 mmHg, respectively. This should have been reflected in cerebral blood flow. Sinus blood flows/min were 18, 18 and 42%, and sinus blood flows per stroke were 55, 45 and 127% of control values, respectively; the differences between C-CPR and N-CPR were not significant. This was also true for cortical blood flow. From this we conclude that, firstly, N-CPR is not significantly better than C-CPR in cerebral perfusion because of its accompanying high intracranial pressure, secondly, O-CPR is far superior to the other two methods in respect of cerebral perfusion.

We have developed a new method producing total cerebral ischemia (TCI) in dogs; clamping ascending aorta with aorto-atrial bypass formation. Clamping ascending aorta provides TCI, the duration of which can be controlled up to the periods of 10 min. Beyond this interval, it is difficult to maintain TCI because of heart failure from high afterload. Blood outflow from left ventricle is completely obstructed except for coronary circulation which is small relative to the blood volume expelled from left ventricle, even if venous return to the heart is reduced. Aorto-atrial bypass formation during aortic clamping provides two distinctive advantages. First, adjusting aortic pressure in an appropriate level low enough not to overload myocardium but still high enough to maintain sufficient coronary blood flow is possible by regulating the blood flow through the bypass tubing, and secondly drug administration and blood volume control is possible through the tubing. These result in better preservation of myocardium, enabling longer TCI and longer survivals after TCI. We were successful in having up to 18 min of TCI with this method. Seventy-five percent of dogs of 12 min TCI and 40% of 15 min TCI survived 7 days, limit of experiment, after TCI, but no dogs of 18 min TCI survived for more than 3 days.

Objectives: Both hypothermia and ischemic preconditioning are known to provide tolerance to myocardial ischemia and reperfusion. The aim of this study was to determine whether hypothermia during the ischemic preconditioning period attenuates the protective effect of ischemic preconditioning. Methods: Experiments were performed in buffer-perfused isolated rabbit hearts. All hearts underwent 45 minutes of regional ischemia, followed by 2 hours of reperfusion. Ischemic preconditioning was elicited by either one or four periods of 5 minutes of regional ischemia. Hypothermia (25° C) was induced beginning either 20 or 50 minutes before the 45-minute period of regional ischemia; normothermia (38° C) was restored 10 minutes before the 45-minute period of regional ischemia. Except for the hypothermic periods noted, hearts were maintained at 38° C. Results: Normothermic ischemic preconditioning with either one or four cycles of 5 minutes of coronary occlusion resulted in a profound reduction of infarct size (58% reduction with one cycle, p < 0.05; 95% reduction with four cycles, p < 0.01). Hypothermic ischemic preconditioning with one cycle of 5-minute coronary occlusion resulted in no reduction of infarct size but hypothermic ischemic preconditioning with four cycles of 5-minute coronary occlusions resulted in a 94% reduction of infarct size (p < 0.01). Myocardial glycogen and lactate levels were maintained near control levels during hypothermic ischemia. Conclusions: From these data we conclude that hypothermia during the preconditioning period increases the threshold for eliciting the infarct limitation of ischemic preconditioning. (J Thorac Cardiovasc Surg 1998;116:319-26)