Exceptional survival of an airplane stowaway, treated successfully with hyperbaric oxygen.

Survival of airplane stowaways is rare. Here we report an exceptional case of successful treatment and full recovery. After a transcontinental flight an unconscious stowaway was discovered in a wheel well of a Boeing 747-400F. Airport paramedics confirmed regular respiration and achieved 100% oxygen saturation (pulse oximetry) by high-flow oxygen. Rectal body temperature was 35.5 °C. On arrival at the emergency department, the patient's vital signs were stable. He did not respond to verbal stimuli. He localized to painful stimuli with both arms, however, there was no reaction to stimuli to both legs. We suspected his neurological deficits were caused by posthypoxic encephalopathy or altitude decompression sickness (DCS), the latter amenable to hyperbaric oxygen therapy (HBOT). HBOT was performed for 5 h (US Navy Treatment Table 6) and afterwards, full neurological recovery was documented. About 24 h after admission a new proximal paresis of the left leg was noted. Assuming recurrence of DCS, daily HBOT was scheduled for three days, after which motor function had again returned to normal. Stowaways travelling in airplane wheel wells experience extreme environmental circumstances. The presented patient survived an eight-hour exposure to calculated barometric pressures as low as 190 mmHg and ambient PO2 of 40 mmHg. Apart from creating awareness of this rare patient category, we want to stress the risk of altitude DCS in unpressurized flights. When DCS is suspected, immediate high-flow oxygen therapy should be initiated, followed by HBOT at the earliest opportunity.

Morphine induces preconditioning via activation of mitochondrial K(Ca) channels.

PURPOSE: Mitochondrial calcium sensitive potassium (mK(Ca)) channels are involved in cardioprotection induced by ischemic preconditioning. In the present study we investigated whether morphine-induced preconditioning also involves activation of mK(Ca) channels. METHODS: Isolated rat hearts (six groups; each n = 8) underwent global ischemia for 30 min followed by a 60-min reperfusion. Control animals were not further treated. Morphine preconditioning (MPC) was initiated by two five-minute cycles of morphine 1 microM infusion with one five-minute washout and one final ten-minute washout period before ischemia. The mK(Ca) blocker, paxilline 1 microM, was administered, with and without morphine administration (MPC + Pax and Pax). As a positive control, we added an ischemic preconditioning group (IPC) alone and combined with paxilline (IPC + Pax). At the end of reperfusion, infarct sizes were determined by triphenyltetrazoliumchloride staining. RESULTS: Infarct size was (mean +/- SD) 45 +/- 9% of the area at risk in the Control group. The infarct size was less in the morphine or ischemic preconditioning groups (MPC: 23 +/- 8%, IPC: 20 +/- 5%; each P < 0.05 vs Control). Infarct size reduction was abolished by paxilline (MPC + Pax: 37 +/- 7%, P < 0.05 vs MPC and IPC + Pax: 36 +/- 6%, P < 0.05 vs IPC), whereas paxilline alone had no effect (Pax: 46 +/- 7%, not significantly different from Control). CONCLUSION: Cardioprotection by morphine-induced preconditioning is mediated by activation of mK(Ca) channels.

Impact of preconditioning protocol on anesthetic-induced cardioprotection in patients having coronary artery bypass surgery.

OBJECTIVE: Anesthetic preconditioning may contribute to the cardioprotective effects of sevoflurane in patients having coronary artery bypass surgery. We investigated whether 2 different sevoflurane administration protocols can induce preconditioning in patients having coronary artery bypass. METHODS: Thirty patients were randomly allocated to 1 of 3 groups. All patients received a total intravenous anesthesia with sufentanil (0.3 microg(-1) x kg x h(-1)) and propofol as target controlled infusion (2.5 microg/mL). The control group had no further intervention; 10 minutes prior to establishing the extracorporeal circulation, patients of the sevoflurane-I group received 1 minimum alveolar concentration of sevoflurane for 5 minutes. Patients of the sevoflurane-II group received (2 times) 5 minutes of sevoflurane, interspersed by 5-minute washout 10 minutes prior to extracorporeal circulation. Troponin I was measured as marker of cardiac cellular damage. RESULTS: Peak levels of troponin I release were observed at 4 hours after cardiopulmonary bypass and were not affected by 1 cycle of sevoflurane administration (controls: 14 +/- 3 ng/mL vs sevoflurane-I group, 14 +/- 3 ng/mL). Two periods of sevoflurane preconditioning significantly reduced cellular damage compared with controls (peak troponin I level sevoflurane-II group, 7 +/- 2 ng/mL). CONCLUSION: These data show that sevoflurane-induced preconditioning is reproducible in patients having coronary artery bypass but depends on the preconditioning protocol used.

Xenon induces late cardiac preconditioning in vivo: a role for cyclooxygenase 2?

BACKGROUND: Xenon induces early myocardial preconditioning of the rat heart in vivo, but whether xenon induces late cardioprotection is not known. Cyclooxygenase-2 (COX-2) has been shown to be an important mediator in the signal transduction of myocardial ischemic late preconditioning (i-LPC). We investigated whether xenon induces late preconditioning (Xe-LPC) and whether COX-2 activity and/or expression are involved in mediating this effect. METHODS: Anesthetized male Wistar rats were instrumented with a coronary artery occluder. After 7 d of recovery, animals were randomized to 1 of 5 groups each containing 8 animals. The i-LPC group underwent 5 min of coronary occlusion to induce i-LPC. Xe-LPC was achieved by administration of xenon (70 volume%) for 15 min. Additional rats were pretreated with the COX-2 inhibitor NS-398 (5 mg kg(-1) body weight i.p.) with and without Xe-LPC. A group of sham operated animals not undergoing i-LPC or Xe-LPC served as controls (Con). After 24 h, all animals were anesthetized and underwent 25 min of myocardial ischemia induced by tightening of the coronary artery occluder followed by 2 h of reperfusion. Myocardial infarct size was assessed by triphenyltetrazolium chloride staining. In additional experiments, hearts were excised at different time points after preconditioning to investigate COX-2 mRNA and protein expression by polymerase chain reaction and infrared Western blot, respectively. RESULTS: Both i-LPC and Xe-LPC reduced myocardial infarct size (% of the area at risk) compared with Con (i-LPC: 29 +/- 7%; Xe-LPC 31 +/- 8%, both P < 0.05 vs Con 64 +/- 6%). NS-398 abolished the cardioprotective effect of Xe-LPC (61 +/- 6%, P < 0.05 vs Xe-LPC). COX-2 mRNA and protein expression was only increased in the i-LPC group, but not in the Xe-LPC group. CONCLUSION: Xenon induces late myocardial preconditioning that is abolished by functional blockade of COX-2 activity. In contrast to i-LPC, Xe-LPC did not lead to an increased expression of COX-2 mRNA and protein. These data suggest differences in COX-2 regulation in i-LPC and Xe-LPC.

Physiological levels of glutamine prevent morphine-induced preconditioning in the isolated rat heart.

Morphine induces cardioprotection against ischaemia-reperfusion injury. While aiming to investigate the underlying signal transduction cascade of morphine preconditioning in isolated Langendorff-perfused rat hearts, the expected cardioprotection was not detectable. Thus, we investigated the influence of different preconditioning protocols and substrate conditions on cardioprotection in this experimental model. Isolated rat hearts underwent 35 min global ischaemia followed by 60 min reperfusion. Morphine PC was initiated by 3 cycles of 5 min 1 muM morphine with either 5 min washout [3PC5 (5)] or 15 min washout [3PC5 (15)] before ischaemia; by 15 min morphine with 15 min washout before ischaemia [PC15 (15)]; or by 15 min 10 muM morphine with 15 min washout [PC15 (15)-10 microM]. Ischaemic preconditioning was initiated by 3 cycles of 3 min ischaemia; in another group, hearts received 1 muM morphine continuously for 10 min before ischaemia until the end of reperfusion [continued morphine]. To investigate the effects of glutamine, two groups received a glutamine-free perfusate: a control group, and a morphine preconditioning group [3PC5 (15)]. Ischaemic preconditioning reduced infarct size by 75%, and continued morphine by 46% compared to control group. With the glutamine containing perfusate, none of the morphine PC pretreatments had an effect on infarct size. In glutamine-free perfusate, 3 cycles of 5 min 1 microM morphine with 15 min washout reduced infarct size from 45%+/-8% (control) to 20%+/-5% (3PC5 (15). Cardioprotection by morphine-induced preconditioning is model dependent: in the isolated rat heart, morphine preconditioning is prevented by a glutamine containing perfusate.

The regulation of mitochondrial respiration by opening of mKCa channels is age-dependent.

The protective potency of ischemic preconditioning decreases with increasing age. A key step in ischemic preconditioning is the opening of mitochondrial Ca(2+) sensitive K(+) (mK(Ca)) channels, which causes mild uncoupling of mitochondrial respiration. We hypothesized that aging reduces the effects of mK(Ca) channel opening on mitochondrial respiration. We measured the effects of mK(Ca) channel opener NS1619 (30 microM) on mitochondrial respiration in isolated heart mitochondria from young (2-3 months) and old (22-26 months) Wistar rats. Oxygen consumption was monitored online after addition of 250 microM ADP (state 3 respiration), and after complete phosphorylation of ADP to ATP (state 4 respiration) in the presence or absence of the mK(Ca) channel blocker paxilline (5 microM). The respiratory control index (RCI) was calculated as state 3/state 4. In mitochondria from young rats, NS1619 increased state 4 respiration by 11.9+/-4.1% (mean+/-S.E.M.), decreased state 3 respiration by 7.6+/-2.5%, and reduced the RCI from 2.6+/-0.03 (control) to 2.1+/-0.06 (all P<0.05, n=12 for all groups). Paxilline blocked the effect of NS1619 on state 4 respiration (0.7+/-2.8%), but did not affect the decrease in state 3 respiration; paxilline blunted the decrease of RCI. In mitochondria from old rats, NS1619 had neither effect on state 4 (0.4+/-1.6%), and state 3 respiration (-7.4+/-1.5%), nor on RCI (3.0+/-0.13 vs. 3.2+/-0.11, n=12). Increasing age reduced the effects of mK(Ca) opening on mitochondrial respiration. This might be one underlying reason of the decreased protective potency of ischemic preconditioning in the aged myocardium.

Influence of groin incision, duration of ischemia, and prostaglandin E1 on ischemia-reperfusion injury of the lower limb.

OBJECTIVE: The influences of groin incision, duration of ischemia, and the effects of prostaglandin E1 (PGE1) on ischemia-reperfusion (I/R) injury of the hind limb in rabbits were evaluated. DESIGN: A prospective study. SETTING: Laboratory. PARTICIPANTS: In 64 rabbits, bilateral hind limb ischemia was induced by occlusion of the abdominal aorta. Volume changes, neuromuscular function of the hind limb, and creatine kinase (CK) release were measured as variables of tissue injury. INTERVENTIONS: Eight rabbits served as untreated controls (CON). In 2 groups (each n = 14), 3 hours of ischemia were followed by 3 hours of reperfusion (I/R). In 2 different groups (each n = 14), 45 minutes of ischemia were followed by 2 hours of reperfusion. To determine effects of PGE1, 1 I/R group of each ischemia duration was treated intravenously with 80 ng/kg/min of PGE1 starting 30 minutes after the onset of ischemia (I/R-PGE1). To determine effects of groin incision on edema formation, volume changes were determined in the "operated" right (CON-R, 3h-R, 3h-PGE1-R and 45 min-R, 45 min-PGE1-R) or in the "nonoperated" left hind limb (CON-L, 3h-L, 3h-PGE1-L and 45 min-L, 45 min-PGE1-L), representing a subgroup analysis. MEASUREMENTS AND MAIN RESULTS: Volume changes after I/R occurred only in operated legs after ischemia (3h-R: 2.3 +/- 0.3 mL, p < 0.0001 v CON-R and 3h-L; 45 min-R: 0.8 +/- 0.2 mL, p < 0.01 v 45 min-L). PGE1 reduced edema formation in the operated legs (3h-PGE1-R: 1.0 +/- 0.4 mL, p < 0.0001 v 3h-R; 45 min-PGE1-R: 0.5 +/- 0.3 mL, p = 1.0 v 45 min-R). Groin incision without I/R had no effect on edema formation (CON-R: -0.13 +/- 0.17 mL of baseline). The increase of CK release from 616 +/- 584 U/L in controls to 5,921 +/- 2,156 U/L after 3 hours of ischemia (p < 0.001) was attenuated by treatment with PGE1 (3,732 +/- 2,653, p < 0.05 v I/R). Forty-five minutes of ischemia did not lead to cellular damage as measured by CK release (I/R: 606 +/- 364 U/L). Recovery of neuromuscular function was not affected by PGE1. CONCLUSION: Development of edema during I/R depends on groin incision of the hind limb and on the duration of ischemia. The I/R injury is attenuated by PGE1 treatment, in terms of reduced edema formation and CK release, but not in terms of neuromuscular function.

Effects of nitrous oxide on the rat heart in vivo: another inhalational anesthetic that preconditions the heart?

BACKGROUND: For nitrous oxide, a preconditioning effect on the heart has yet not been investigated. This is important because nitrous oxide is commonly used in combination with volatile anesthetics, which are known to precondition the heart. The authors aimed to clarify (1) whether nitrous oxide preconditions the heart, (2) how it affects protein kinase C (PKC) and tyrosine kinases (such as Src) as central mediators of preconditioning, and (3) whether isoflurane-induced preconditioning is influenced by nitrous oxide. METHODS: For infarct size measurements, anesthetized rats were subjected to 25 min of coronary artery occlusion followed by 120 min of reperfusion. Rats received nitrous oxide (60%), isoflurane (1.4%) or isoflurane-nitrous oxide (1.4%/60%) during three 5-min periods before index ischemia (each group, n = 7). Control animals remained untreated for 45 min. Additional hearts (control, 60% nitrous oxide alone%, and isoflurane-nitrous oxide [0.6%/60%, in equianesthetic doses]) were excised for Western blot of PKC-epsilon and Src kinase (each group, n = 4). RESULTS: Nitrous oxide had no effect on infarct size (59.1 +/- 15.2% of the area at risk vs. 51.1 +/- 10.9% in controls). Isoflurane (1.4%) and isoflurane-nitrous oxide (1.4%/60%) reduced infarct size to 30.9 +/- 10.6 and 28.7 +/- 11.8% (both P < 0.01). Nitrous oxide (60%) had no effect on phosphorylation (2.3 +/- 1.8 vs. 2.5 +/- 1.7 in controls, average light intensity, arbitrary units) and translocation (7.0 +/- 4.3 vs. 7.4 +/- 5.2 in controls) of PKC-epsilon. Src kinase phosphorylation was not influenced by nitrous oxide (4.6 +/- 3.9 vs. 5.0 +/- 3.8; 3.2 +/- 2.2 vs. 3.5 +/- 3.0). Isoflurane-nitrous oxide (0.6%/60%, in equianesthetic doses) induced PKC-epsilon phosphorylation (5.4 +/- 1.9 vs. 2.8 +/- 1.5; P < 0.001) and translocation to membrane regions (13.8 +/- 13.0 vs. 6.7 +/- 2.0 in controls; P < 0.05). CONCLUSIONS: Nitrous oxide is the first inhalational anesthetic without preconditioning effect on the heart. However, isoflurane-induced preconditioning and PKC-epsilon activation are not influenced by nitrous oxide.

Morphine induces late cardioprotection in rat hearts in vivo: the involvement of opioid receptors and nuclear transcription factor kappaB.

UNLABELLED: Delta1-opioid receptor agonists can induce cardioprotection by early and late preconditioning (LPC). Morphine (MO) is commonly used for pain treatment during acute coronary syndromes. We investigated whether MO can induce myocardial protection by LPC and whether a nuclear transcription factor kappaB (NF-kappaB)-dependent intracellular signaling pathway is involved. Rats were subjected to 25 min of regional ischemia and 2 h of reperfusion 24 h after treatment with saline (NaCl; 0.9% 5 mL), lipopolysaccharide of Escherichia coli (LPS; 1 mg/kg), or MO (3 mg/kg). LPS is a trigger of LPC and served as positive control. Naloxone (NAL) was used to investigate the role of opioid receptors in LPC and was given before NaCl, LPS, or MO application (trigger phase) or before ischemia-reperfusion (mediator phase). Infarct size (percentage area at risk) was 59% +/- 9%, 51% +/- 6%, or 53% +/- 10% in the NaCl, NAL-NaCl, and NaCl-NAL groups, respectively. Pretreatment with MO reduced infarct size to 20% +/- 6% after 24 h (MO-24h), and this effect was abolished by NAL in the trigger (NAL-MO, 53% +/- 14%) and in the mediator (MO-NAL, 60% +/- 8%) phases. Pretreatment with LPS reduced infarct size to 23% +/- 8%. NAL administration in the trigger phase had no effect on infarct size (NAL-LPS 30% +/- 16%), whereas NAL during the mediator phase of LPC abolished the LPS-induced cardioprotection (LPS-NAL 54% +/- 8%). The role of NF-kappaB in morphine-induced LPC was investigated by Western blot and electrophoretic mobility shift assay. Morphine and LPS treatment increased phosphorylation of the inhibitory protein kappaB, leading to an increased activity of NF-kappaB. Thus, MO induces LPC similarly to LPS and it is likely that this cardioprotection is mediated at least in part by activation of NF-kappaB. Opioid receptors are involved as mediators in both MO- and LPS-induced LPC but as triggers only in MO-induced LPC. IMPLICATIONS: Like lipopolysaccharide, morphine induces late preconditioning and activation of nuclear transcription factor-kappaB. Opioid receptors are involved as mediators in both morphine- and lipopolysaccharide-induced late preconditioning but as triggers only in morphine-induced late preconditioning.

Sevoflurane confers additional cardioprotection after ischemic late preconditioning in rabbits.

BACKGROUND: Sevoflurane exerts cardioprotective effects that mimic the early ischemic preconditioning phenomenon (EPC) by activating adenosine triphosphate-sensitive potassium (KATP) channels. Ischemic late preconditioning (LPC) is an important cardioprotective mechanism in patients with coronary artery disease. The authors investigated whether the combination of LPC and sevoflurane-induced preconditioning results in enhanced cardioprotection and whether opening of KATP channels plays a role in this new setting. METHODS: Seventy-three rabbits were instrumented with a coronary artery occluder. After recovery for 10 days, they were subjected to 30 min of coronary artery occlusion and 120 min of reperfusion (I/R). Controls (n = 14) were not preconditioned. LPC was induced in conscious animals by a 5-min period of coronary artery occlusion 24 h before I/R (LPC, n = 15). Additional EPC was induced by a 5-min period of myocardial ischemia 10 min before I/R (LPC+EPC, n = 9). Animals of the sevoflurane (SEVO) groups inhaled 1 minimum alveolar concentration of sevoflurane for 5 min at 10 min before I/R with (LPC+SEVO, n = 10) or without (SEVO, n = 15) additional LPC. The KATP channel blocker 5-hydroxydecanoate (5-HD, 5 mg/kg) was given intravenously 10 min before sevoflurane administration (LPC+SEVO+5-HD, n = 10). RESULTS: Infarct size of the area at risk (triphenyltetrazolium staining) was reduced from 45 +/- 16% (mean+/-SD, control) to 27 +/- 11% by LPC (P < 0.001) and to 27 +/- 17% by sevoflurane (P = 0.001). Additional sevoflurane administration after LPC led to a further infarct size reduction to 14 +/- 8% (LPC+SEVO, P = 0.003 vs. LPC; P = 0.032 vs. SEVO), similar to the combination of LPC and EPC (12 +/- 8%; P = 0.55 vs. LPC+SEVO). Cardioprotection induced by LPC+SEVO was abolished by 5-HD (LPC+SEVO+5-HD, 41 +/- 19%, P = 0.001 vs. LPC+SEVO). CONCLUSIONS: Sevoflurane administration confers additional cardioprotection after LPC by opening of KATP channels.

Effect of acute hyperglycaemia and diabetes mellitus with and without short-term insulin treatment on myocardial ischaemic late preconditioning in the rabbit heart in vivo.

Diabetes mellitus (DM) and the resulting hyperglycaemia may interfere with the cardioprotective effect of ischaemic late preconditioning (LPC). Therefore, we investigated the effect of acute hyperglycaemia (part 1) and the effect of alloxan-induced DM with or without short-term insulin treatment (part 2) on LPC. Rabbits, chronically instrumented with a coronary artery occluder, were subjected to 30 min coronary artery occlusion and 2 h reperfusion (I/R) and infarct size (IS) was assessed. In part 1, four groups were studied. Controls were not treated further. LPC induced by a 5-min period of myocardial ischaemia 24 h before I/R reduced IS from 42+/-14 (controls) to 22+/-8% of the area at risk. Hyperglycaemia (600 mg dl(-1) by dextrose infusion, H(600)) before and during the 30 min ischaemia tended to increase IS (57+/-16%, P=0.14 vs. controls) and blocked cardioprotection by LPC (H(600)+LPC, 59+/-19%, P=1.0 vs. H(600), P=0.0003 vs. LPC). In part 2, LPC reduced infarct size from 43+/-13% (control) to 23+/-10% ( P=0.003). In diabetic animals, IS was 39+/-11%, and cardioprotection by LPC could not be elicited (DM+LPC, 41+/-16%, P=0.02 vs. LPC). Short-term insulin treatment (I, 90 min before I/R, blood glucose <150 mg dl(-1)) did not restore the cardioprotective effects of LPC (DM+I, 42+/-15%; DM+LPC+I, 40+/-10%, P=0.03 vs. LPC). It is concluded that acute hyperglycaemia and DM block the cardioprotection induced by LPC in rabbits and that the cardioprotection is not restored by short-term insulin treatment.

Isoflurane preconditions myocardium against infarction via release of free radicals.

BACKGROUND: Isoflurane exerts cardioprotective effects that mimic the ischemic preconditioning phenomenon. Generation of free radicals is implicated in ischemic preconditioning. The authors investigated whether isoflurane-induced preconditioning may involve release of free radicals. METHODS: Sixty-one alpha-chloralose-anesthetized rabbits were instrumented for measurement of left ventricular (LV) pressure (tip-manometer), cardiac output (ultrasonic flowprobe), and myocardial infarct size (triphenyltetrazolium staining). All rabbits were subjected to 30 min of occlusion of a major coronary artery and 2 h of subsequent reperfusion. Rabbits of all six groups underwent a treatment period consisting of either no intervention for 35 min (control group, n = 11) or 15 min of isoflurane inhalation (1 minimum alveolar concentration end-tidal concentration) followed by a 10-min washout period (isoflurane group, n = 12). Four additional groups received the radical scavenger N-(2-mercaptoproprionyl)glycine (MPG; 1 mg. kg-1.min-1) or Mn(III)tetrakis(4-benzoic acid)porphyrine chloride (MnTBAP; 100 microg.kg-1.min-1) during the treatment period with (isoflurane + MPG; n = 11; isoflurane + MnTBAP, n = 9) or without isoflurane inhalation (MPG, n = 11; MnTBAP, n = 7). RESULTS: Hemodynamic baseline values were not significantly different between groups (LV pressure, 97 +/- 17 mmHg [mean +/- SD]; cardiac output, 228 +/- 61 ml/min). During coronary artery occlusion, LV pressure was reduced to 91 +/- 17% of baseline and cardiac output to 94 +/- 21%. After 2 h of reperfusion, recovery of LV pressure and cardiac output was not significantly different between groups (LV pressure, 83 +/- 20%; cardiac output, 86 +/- 23% of baseline). Infarct size was reduced from 49 +/- 17% of the area at risk in controls to 29 +/- 19% in the isoflurane group (P = 0.04). MPG and MnTBAP themselves had no effect on infarct size (MPG, 50 +/- 14%; MnTBAP, 56 +/- 15%), but both abolished the preconditioning effect of isoflurane (isoflurane + MPG, 50 +/- 24%, P = 0.02; isoflurane + MnTBAP, 55 +/- 10%, P = 0.001). CONCLUSION: Isoflurane-induced preconditioning depends on the release of free radicals.

The direct myocardial effects of xenon in the dog heart in vivo.

UNLABELLED: Xenon has minimal hemodynamic side effects, but no data are available on its direct myocardial effects in vivo. We examined myocardial function during the global and regional administration of xenon in the dog heart. Anesthetized (midazolam/piritramide) dogs (n = 8) were instrumented for measurement of left ventricular pressure, cardiac output, and blood flow in the left anterior descending coronary artery (LAD) and circumflex coronary artery. Regional myocardial function was assessed by sonomicrometry in the antero-apical and the postero-basal wall. Hemodynamics were recorded during baseline conditions and during inhalation of 50% or 70% xenon, respectively. Subsequently, a bypass containing a membrane oxygenator was installed from the carotid artery to the LAD, allowing xenon administration only to the LAD-dependent myocardium. No changes in myocardial function were observed during inhalation of xenon. The regional administration of 50% xenon had no significant effect on regional myocardial function (systolic wall thickening and mean velocity of systolic wall thickening). Seventy percent xenon reduced systolic wall thickening by 7.2% +/- 4.0% and mean velocity of systolic wall thickening by 8.2% +/- 4.0% in the LAD-perfused area (P < 0.05). There were no changes of global hemodynamics, coronary blood flow, and regional myocardial function in the circumflex coronary artery-dependent myocardium. Xenon produces a small but consistent direct negative inotropic effect in vivo. IMPLICATIONS: Regional administration of xenon direct to the left anterior descending-perfused myocardium resulted in a small but consistent negative inotropic effect of the noble gas in the dog heart in vivo.