Laparoscopic Hartmann's procedure for fecal peritonitis resulting from perforation of the left-sided colon in elderly and severely ill patients.

BACKGROUND: Traditional treatment for fecal peritonitis resulting from perforation of the left-sided colon has been performed using Hartmann's procedure to reduce the high mortality caused by anastomotic leakage. However, the morbidity rates associated with abdominal incision (due in great part to wound infection, and dehiscence of abdominal fascia) are high. Therefore, we propose using laparoscopic Hartmann's procedure with abdominal incisions only for the port site to reduce the high morbidity associated with the laparoscopic procedure as compared to open surgery. METHODS: Between April 2008 and July 2011, we treated 16 consecutive patients (median age, 83 years) with fecal peritonitis resulting from perforations in the left-sided colon due to various causes. The American Society of Anesthesiologists score of each patient was either IV or V. Patients underwent a four-port laparoscopic Hartmann's procedure. Specimens were extracted through the stoma site. Irrigation of the abdominal cavity with more than 10 L of saline was performed in every case, as was insertion of three 10-mm silicon drains via the port site into the left- and right subphrenic spaces or the pouch of Douglas. RESULTS: The median total surgical time was 166 min (range, 123-250 min). There were no intraoperative complications, and there was no need to convert to open surgery. Fourteen patients survived. There was no wound infection or dehiscence of abdominal fascia. Successful laparoscopic reversals of the laparoscopic Hartmann's procedure were performed in all 14 survivors. CONCLUSIONS: This laparoscopic Hartmann's procedure is a promising surgical strategy for treating fecal peritonitis arising from perforation of the left-sided colon.

Fluorometric measurement of intracellular pH in vivo in feline cerebral cortex during ischemia and reperfusion.

Intracellular acidosis has been considered to play an pivotal role in the progression of neuronal damage after cerebral ischemia. However, continuous measurement of the intracellular potential of hydrogen (pH) has not been done during and after ischemia. We measured temporal changes in intracellular pH in the feline cerebral cortex in vivo during and after ischemia using a novel fluorescent pH probe, 2',7'-biscarboxyethyl carboxyfluorescein (BCECF). A closed cranial window was installed in the left temporal skull. BCECF acetoxymethyl ester was superfused over the cortex, hydrolyzed and trapped in cortical cells. Intracellular pH was measured utilizing excitation light at 507 nm and fluorescent light at 550.5 nm. Focal cerebral ischemia for 60 minutes was induced by means of middle cerebral artery occlusion. Intracellular pH in the severely ischemic group became significantly acidic (p < 0.01) during ischemia and the acidosis persisted for at least 30 minutes after recirculation. The pH change was not significant in the mildly ischemic group. The severity of ischemia was determined based on the mean transit time, which was calculated from the hemodilution curve obtained by bolus injection of saline. The extent of ischemia was further confirmed pathologically (p < 0.01). The above results suggest that intracellular acidosis resulting from severe ischemia persists even after recirculation.

Neuroprotective effect of YM90K, a novel AMPA/kainate receptor antagonist, in focal cerebral ischemia in cats.

We studied the effect of a novel alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate antagonist, YM90K [6-(1H-imidazol-1-yl)-7-nitro-2, 3(1H, 4H)-quinoxalinedione monohydrochloride], in a focal cerebral ischemia model using anesthetized cats. Cats were subjected to permanent occlusion of the middle cerebral artery (MCA) for 6 h, then killed and examined histologically. The amount of ischemic damage was assessed in 12 stereotaxic coronal sections. Treatment with YM90K (i.v. infusion of 0.5 mg/5 ml/kg/h) starting 10 min after MCA occlusion markedly reduced the volume of ischemic damage (from 2823 +/- 164 mm3 of the cerebral hemisphere in saline-treated cats to 1737 +/- 305 mm3 in YM90K-treated cats). No essential differences were observed between YM90K-and saline-treated cats concerning physiological variables or brain temperature. These results further support the notion that the AMPA/kainate receptor plays an important role in the pathogenesis of focal cerebral ischemia. This evidence for the neuroprotective efficacy of YM90K in a gyrencephalic species suggests its therapeutic potential in the treatment of human stroke.

Guillain-Barré syndrome with bilateral tonic pupils.

A 53-year-old patient with Guillain-Barré syndrome preceded by herpes simplex virus infection developed bilateral tonic pupils with light-near dissociation. Pharmacological tests for pupils suggested postganglionic involvement of the parasympathetic and sympathetic nerves. A demyelinating process of peripheral autonomic nerves was suspected to be the cause of the tonic pupils and autonomic dysfunction.

The effect of hyperglycemia on intracellular calcium in stroke.

The effect of hyperglycemia on cytosolic free calcium ([Ca2+]i) during temporary focal cerebral ischemia was investigated in cats using a fluorometric technique. The middle cerebral artery (MCA) was occluded for a period of 1 h, after which the clip was removed. In seven animals, plasma glucose was raised to 500-700 mg/dl by infusion of a 50% glucose solution starting 30 min after MCA occlusion, while eight animals were kept normoglycemic during and following occlusion. MCA occlusion induced a significant, but identical, elevation of the [Ca2+]i signal ratio (400/506 nm) in both the normoglycemic group (from 1.40 to 1.97 +/- 0.34, p less than 0.01) and in the hyperglycemic group (from 1.40 to 2.00 +/- 0.53, p less than 0.01) at the end of the occlusion. Between 10 and 30 min after reopening, the [Ca2+]i signal ratio decreased to control levels in the normoglycemic group (1.40 +/- 0.11 and 1.36 +/- 0.08 at 10 and 30 min after reopening, respectively), but remained elevated in the hyperglycemic group (1.69 +/- 0.18 and 1.65 +/- 0.21 at 10 and 30 min after reopening, respectively). There was a statistically significant difference between the two groups (p less than 0.01). These data suggest that hyperglycemia may be harmful to calcium recovery during the early recirculation period following focal cerebral ischemia.

Effect of superoxide dismutase on intracellular calcium in stroke.

To clarify the relationship between calcium metabolism and free radical damage during the reperfusion period following ischemia, we investigated the effect of superoxide dismutase (SOD) on changes in cytosolic free calcium, cortical blood flow, and histologic changes following focal cerebral ischemia and reperfusion in 12 cats. Using indo-1, a fluorescent intracellular Ca2+ indicator, we simultaneously measured changes in the Ca2+ signal ratio (400:500 nm), NADH signal (464 nm), and reflectance (340 nm) during ultraviolet excitation (340 nm) directly from the cortex in vivo. The middle cerebral artery (MCA) was occluded for 1 h; only cats in which the EEG amplitude was depressed to less than 10% of control during the occlusion were entered into the study. Starting 2 min prior to release of the occlusion and continuing for 4 min, SOD (10,000 U/kg) was slowly infused in six cats, while in six cats, the vehicle only was infused. During MCA occlusion, the Ca2+ signal ratio increased significantly in both groups with no significant difference between the groups. During reperfusion, the Ca2+ signal ratio remained at a high level in the vehicle-treated group, while in the SOD-treated group, the Ca2+ signal ratio decreased. There was a statistically significant difference between the two groups at 10, 20, and 30 min after reperfusion (p less than 0.01). The histologically damaged area in the SOD-treated group was significantly smaller than that in the vehicle-treated group (p less than 0.01). These data suggest that the histoprotective action of SOD may be due to its ability to attenuate increases in intracellular calcium during the recirculation period following focal cerebral ischemia.

Mechanism underlying protective effect of MK-801 against NMDA-induced neuronal injury in vivo.

The effects of the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 and the dihydropyridine calcium antagonist nimodipine on NMDA-induced phenomena were investigated using an in vivo fluorometric technique with indo-1. Indo-1, a fluorescent cytosolic free calcium ([Ca2+]i) indicator, was loaded into the cat cortex approximately 500 microns in depth by superfusion with the membrane-permeant indo-1 acetoxy-methyl ester (indo-1-AM). Changes in [Ca2+]i signals (400 and 506 nm) and reduced nicotinamide adenine dinucleotide (NADH) fluorescence (464 nm) were simultaneously measured directly from the cortex during ultraviolet excitation (340 nm). Superfusion of 100 microM NMDA over the exposed cortex induced an elevation of the [Ca2+]i signal ratio (400/506 nm), biphasic changes in NAD/NADH redox state (initial oxidation followed by progressive reduction), and characteristic changes in the EEG (abrupt depression in amplitude followed by an excitatory pattern of 18-22 Hz polyspikes or sharp waves). These changes were completely blocked by treatment with MK-801 and reduced by nimodipine. The mechanism underlying the protective effects of systemically administered MK-801 on the NMDA-induced neuronal injury was verified in vivo.

Intracellular calcium and pathophysiological changes in cerebral ischemia.

The role of calcium as a mediator in neuronal death during ischemia is now quite strong. Evidence supporting this link included studies in cell cultures, measurements of calcium accumulation in the mitochondria during ischemia as well as direct measurements of shifts in extracellular calcium using microelectrodes. Since high concentrations of intracellular free calcium have been hypothesized to lead to neuronal damage, direct in vivo measurements of this parameter in ischemia are important. The studies outlined demonstrate that changes in intracellular free calcium occur in focal ischemia and describe the time course of these changes. They indicate that cellular damage can be attenuated by the use of agents that block calcium channels (both voltage-sensitive and receptor-operated) and support the concept that these agents owe their beneficial effects to their ability to reduce the accumulation of intracellular calcium.

Combined therapy with MK-801 and nimodipine for protection of ischemic brain damage.

Calcium ion can enter ischemic neurons through both receptor-operated and voltage-sensitive Ca2+ channels. To attenuate this Ca2+ entry and Ca2(+)-induced neuronal injury, we tried a combined treatment with the noncompetitive N-methyl-D-aspartate (NMDA) antagonist, MK-801, and the dihydropyridine calcium antagonist, nimodipine, in a cat middle cerebral artery occlusion (1 hour) and reperfusion (3 hours) model. We measured changes in cytosolic free calcium, nicotinamide adenine dinucleotide/reduced nicotinamide adenine dinucleotide redox state, and blood flow in the cat cortex using a newly developed fluorometric technique with indo-1, a fluorescent intracellular Ca2+ indicator. The combined treatment, starting 5 minutes into ischemia, was effective in reducing both Ca2+ entry and histologic damage and in enhancing recovery of the electroencephalogram following reperfusion. MK-801 alone was also effective, but to a lesser extent. These data suggest that the dual blockade of Ca2+ entry using MK-801 and nimodipine may be a useful tool for protection against ischemic brain damage.

Cytosolic free calcium during focal cerebral ischemia and the effects of nimodipine on calcium and histologic damage.

The role of calcium as a mediator in neuronal death during ischemia is now quite strong. Evidence supporting this link includes studies in cell cultures and measurements of calcium accumulation in the mitochondria during ischemia, as well as direct measurements of shifts in extracellular calcium using microelectrodes. Since it is dangerously high concentrations of the intracellular free calcium that have been hypothesized to lead to neuronal damage, direct in vivo measurements of this parameter in ischemia are important. A technique for the measurement of intracellular free calcium is described, along with data from studies that dramatically demonstrate the time course of changes in intracellular free calcium induced by focal ischemia. Additional data are also presented that indicate that cellular damage can be attenuated by the use of agents that block calcium channels (nimodipine, which blocks voltage-sensitive calcium channels, and MK-801, which blocks receptor-operated channels) and support the concept that these agents owe their beneficial effects to their ability to reduce the accumulation of intracellular calcium.

Alterations in cytosolic free calcium in the cat cortex during bicuculline-induced epilepsy.

Influx of calcium ion (Ca++) into the neurons has recently been implicated in the generation of seizure activity. Utilizing indo-1, a fluorescent Ca++ indicator, changes in cytosolic free calcium ([Ca++]i), NAD/NADH redox state and hemodynamics were simultaneously measured in vivo from the cat cortex during bicuculline-induced seizure activity. A ratio of indo-1-Ca++ fluorescence at 400 and 506 nm during ultraviolet excitation (340 nm) was utilized as a measure of changes in [Ca++]i. Alterations in the NAD/NADH redox state and local cortical blood volume (1CBV) were assessed at 464 nm and 340 nm, respectively. Local cortical blood flow (1CBF) was calculated from 1CBV and mean transit time determined from cortical hemodilution curves. Electroencephalogram (EEG) was monitored from the same cortical region as the optical measurements. The [Ca++]i signal ratio started to increase 19 +/- 2 sec prior to the onset of seizure activity on the EEG and remained elevated until the activity was suppressed by an intravenous administration of diazepam (2 mg/kg). The early increase in [Ca++]i is presumably due to a synaptic Ca++ entry associated with facilitated excitatory neurotransmission. The NAD/NADH redox state became oxidized during the seizure activity and started to recover as the EEG activity was suppressed. The 1CBV and 1CBF increased by 17 +/- 8% and 68 +/- 16%, respectively, 10 min into the seizure activity. This study provides direct in vivo evidence suggesting a possible role of calcium entry into the neurons in the epileptogenesis.

Nimodipine attenuates both increase in cytosolic free calcium and histologic damage following focal cerebral ischemia and reperfusion in cats.

To clarify the mechanism of its effect on ischemic stroke, we investigated the effect of nimodipine, a dihydropyridine calcium antagonist, on changes in cytosolic free calcium, cortical blood flow, and histologic changes following focal cerebral ischemia and reperfusion in 14 cats. Using indo-1, a fluorescent intracellular Ca2+ indicator, we simultaneously measured changes in the Ca2+ signal ratio (400:506 nm), reduced nicotinamide adenine dinucleotide fluorescence (464 nm), and reflectance (340 nm) during an ultraviolet excitation (340 nm) directly from the cat cortex in vivo. In six cats treated with vehicle only, the calcium signal ratio increased from 5 minutes after middle cerebral artery occlusion to 30 minutes into reperfusion. The elevation of cytosolic free calcium was significantly attenuated by nimodipine, which was administered by intravenous infusion in eight cats starting 5 minutes after occlusion. Nimodipine had no effect on cortical blood flow during ischemia but induced a hyperperfused state following reperfusion. Nimodipine did not modify changes in the mitochondrial oxidation-reduction state. Nimodipine proved to have beneficial effects on recovery of the electroencephalogram following reperfusion as well as on the extent of focal histologic damage. Our results suggest that nimodipine, when administered during the early stage of focal ischemia, can favorably modify the outcome of stroke by reducing the Ca2+ entry during both the ischemic and reperfusion periods.

Direct evidence for calcium-induced ischemic and reperfusion injury.

Changes in cytosolic free calcium [( Ca2+]i) in the cat cortex were measured in vivo by indo-1 fluorometry during cerebral ischemia and reperfusion and were correlated to the histopathological ischemic changes. These changes were most pronounced in stroke cases with an increase in [Ca2+]i throughout the ischemic and reperfusion periods. Cases without a [Ca2+]i increase showed no histopathological change in the cortical gyrus in which [Ca2+]i was measured. The data support the hypothesis that an increase in [Ca2+]i during cerebral ischemia and reperfusion leads to neuronal damage.

Effects of a selective inhibitor of cyclic AMP phosphodiesterase on the pial microcirculation in feline cerebral ischemia.

We evaluated the effects of cilostazol, a selective inhibitor of cyclic adenosine monophosphate phosphodiesterase, on the pial vessels of adult cats subjected to endothelial damage followed by middle cerebral artery occlusion. Six cats were treated with cilostazol and four with 30% N,N-dimethylformamide in 70% saline (solvent). The brain surface was irradiated with ultraviolet rays through a cranial window for 3 minutes to selectively damage the endothelium of the pial vessels in both groups. Beginning 32 minutes after termination of the irradiation, the middle cerebral artery was occluded for 30 minutes. Thirty minutes before occlusion, intravenous infusion of 30 micrograms/kg/min cilostazol or 0.1 ml/kg/min solvent was begun and continued until the end of the study. Before occlusion, the infusion of cilostazol induced a significant (p less than 0.05) dilatation while the infusion of solvent produced no significant changes in the diameter of the pial arteries. The pial veins of solvent-treated cats showed significant (p less than 0.05) constriction during occlusion, whereas cilostazol-treated cats exhibited only mild constriction of the pial veins. The formation of platelet thrombi after occlusion was significantly (p less than 0.05) inhibited in the pial veins of cilostazol-treated compared with solvent-treated cats. Similarly, the microcirculation of the pial veins was effectively restored after reopening of the middle cerebral artery in cilostazol-treated compared with solvent-treated cats. Our data suggest that cilostazol is an effective antithrombotic agent as well as a potent vasodilator acting on vascular smooth muscle.

Cytosolic free calcium, NAD/NADH redox state and hemodynamic changes in the cat cortex during severe hypoglycemia.

Using indo-1, a fluorescent Ca2+ indicator, in vivo fluorometric measurements were made of changes in cytosolic free Ca2+, NAD/NADH redox state, and hemodynamics directly from the cat cortex during and after severe insulin-induced hypoglycemia. Cytosolic free Ca2+ started to increase when the EEG became isoelectric, remained at a significantly high level (p less than 0.05) during the period of isoelectric EEG (IEEG), and recovered to the control level 6 min following an intravenous infusion of glucose. The NAD/NADH redox state oxidized significantly during IEEG and then recovered rapidly to the control level after the glucose infusion. Local cortical blood volume (LCBV) increased gradually during the progression of hypoglycemia, reaching the maximal level (146 +/- 7%) at the end of IEEG, and then started to recover. The mean transit time (MTT) through the cortical microcirculation was shortened during the IEEG (control: 3.84 +/- 0.41 s versus IEEG: 2.73 +/- 0.17 s, p less than 0.05), whereas it was prolonged during the 30-min recovery period (5.68 +/- 0.58 s, p less than 0.05). Local cortical blood flow calculated from the LCBV and MTT showed a twofold increase 5 min into IEEG (201 +/- 27% of control, p less than 0.05), recovered 15 min into the recovery period, and then decreased to 77% of control (p less than 0.05) by 30 min. The data support the hypothesis that hypoglycemic brain damage might be mediated by an elevation of cytosolic free calcium.

Cytosolic free calcium and NAD/NADH redox state in the cat cortex during in vivo activation of NMDA receptors.

Activation of the N-methyl-D-aspartate (NMDA) receptors and the concomitant Ca2+ entry have been implicated in neuronal injury in a variety of pathological states. The effects of extracellular Mg2+ concentrations and D,L-2-amino-5-phosphonovaleric acid (APV), a competitive NMDA receptor antagonist on the NMDA-induced responses were investigated in vivo. In vivo fluorometric measurements were made of changes in cytosolic free Ca2+ ([Ca2+]i) and NADH fluorescence directly from the cat cortex using indo-1, a fluorescent Ca2+ indicator. Changes in [Ca2+]i were assessed utilizing the ratio of indo-1 emission at two wavelengths (400 and 506 nm) during excitation with ultraviolet light (340 nm). Application of 100 microM NMDA to the cortex produced a significant increase in the [Ca2+]i signal ratio at physiological concentrations of Mg2+ (1.2 mM). This increase was enhanced in the absence of Mg2+ and was completely blocked either at 5 mM Mg2+ or in the presence of 50 microM APV. The NAD/NADH redox state was initially oxidized, which was also blocked by either high Mg2+ or APV. The application of NMDA elicited characteristic electroencephalogram (EEG) changes consisting of a marked reduction in amplitude and regular spikes (17-20 Hz). These EEG changes did not appear in the presence of APV. In addition to NMDA receptor antagonists, the level of extracellular Mg2+ is a potent physiological modulator of the NMDA response.

Stable prostacyclin analogue preventing microcirculatory derangement in experimental cerebral ischemia in cats.

We evaluated the effect of a stable synthetic prostacyclin analogue, TRK-100, on the microcirculatory derangement occurring in feline pial vessels with endothelial damage after middle cerebral artery occlusion. Fifteen adult cats were divided into an untreated group (Group 1, n = 8) and a treated group (Group 2, n = 7). Thirty minutes after 10 minutes of ultraviolet irradiation, which selectively damaged endothelium in the pial vessels, the middle cerebral artery was occluded in both groups and maintained for 30 minutes. In Group 2, 50 ng/kg/min TRK-100 was continuously infused intravenously following ultraviolet irradiation. In both the pial arteries and veins, platelet aggregate adhesion to the endothelium with subsequent thrombus formation was significantly (p less than 0.01 and p less than 0.05, respectively) inhibited during middle cerebral artery occlusion in Group 2 compared with Group 1. Similarly, blood flow stasis in the pial veins was effectively prevented in Group 2 during occlusion. Furthermore, the pial artery diameter returned to the control level during the late period of occlusion, whereas in Group 1 the pial artery remained constricted. Our data suggest that TRK-100 can prevent microcirculatory derangement in the acute stage of ischemic stroke.