Fluid Replacement With Hypertonic or Isotonic Solutions Guided by Mixed Venous Oxygen Saturation in Experimental Hypodynamic Sepsis

Background: Splanchnic perfusion is prone to early injury and persists despite normalization of global hemodynamic variables in sepsis. Volume replacement guided by oxygen derived variables has been recommended in the management of septic patients. Our hypothesis was that a hypertonic isoneotic solution Would improve the benefits of crystalloids replacement guided by mixed venous oxygen saturation. Methods: Seventeen anesthetized and mechanically ventilated mongrel dogs received an intravenous infusion of live E. coli in 30 minutes. They were then randomized into three groups: control group (n = 3) bacterial infusion without treatment; normal saline (n = 7), initial fluid replacement with 32 mL/kg of normal saline during 20 minutes; hypertonic solution (n = 7), initial fluid replacement with 4 mL/kg of hypertonic solution during 5 minutes. After 30 and 60 Minutes, additional boluses of normal saline were administered when mixed venous oxygen saturation remained below 70%. Mean arterial pressure, cardiac output; regional blood flows, systemic and regional oxygen-derived variables, and lactate levels were assessed. Animals were observed for 90 minutes and then killed. Hystopathological analysis including apoptosis detection using terminal deoxynucleotidil transferase mediated dUTP-biotin nick end labeling was performed. Results: A hypodynamic septic shock was observed after bacterial infusion. Both the fluid-treated groups presented similar transient benefits in systemic and regional variables. A greater degree of gut epithelial cells apoptosis was observed in normal saline-treated animals. Conclusions: Although normalization of mixed venous oxygen saturation was not associated with restoration of markers of splanchnic or other systemic perfusion variables, the initial fluid savings with hypertonic saline and its latter effect on gut apoptosis may be of interest in sepsis management.

Quantitative myocardial contrast echocardiography during pharmacological stress for diagnosis of coronary artery disease: a systematic review and meta-analysis of diagnostic accuracy studies

Aims We conducted a meta-analysis to evaluate the accuracy of quantitative stress myocardial contrast echocardiography (MCE) in coronary artery disease (CAD). Methods and results Database search was performed through January 2008. We included studies evaluating accuracy of quantitative stress MCE for detection of CAD compared with coronary angiography or single-photon emission computed tomography (SPECT) and measuring reserve parameters of A, beta, and A beta. Data from studies were verified and supplemented by the authors of each study. Using random effects meta-analysis, we estimated weighted mean difference (WMD), likelihood ratios (LRs), diagnostic odds ratios (DORs), and summary area under curve (AUC), all with 95% confidence interval (0). Of 1443 studies, 13 including 627 patients (age range, 38-75 years) and comparing MCE with angiography (n = 10), SPECT (n = 1), or both (n = 2) were eligible. WMD (95% CI) were significantly less in CAD group than no-CAD group: 0.12 (0.06-0.18) (P < 0.001), 1.38 (1.28-1.52) (P < 0.001), and 1.47 (1.18-1.76) (P < 0.001) for A, beta, and A beta reserves, respectively. Pooled LRs for positive test were 1.33 (1.13-1.57), 3.76 (2.43-5.80), and 3.64 (2.87-4.78) and LRs for negative test were 0.68 (0.55-0.83), 0.30 (0.24-0.38), and 0.27 (0.22-0.34) for A, beta, and A beta reserves, respectively. Pooled DORs were 2.09 (1.42-3.07), 15.11 (7.90-28.91), and 14.73 (9.61-22.57) and AUCs were 0.637 (0.594-0.677), 0.851 (0.828-0.872), and 0.859 (0.842-0.750) for A, beta, and A beta reserves, respectively. Conclusion Evidence supports the use of quantitative MCE as a non-invasive test for detection of CAD. Standardizing MCE quantification analysis and adherence to reporting standards for diagnostic tests could enhance the quality of evidence in this field.

Cavopulmonary anastomosis improves left ventricular assist device support in acute biventricular failure

Objective: Right ventricular failure during left ventricular assist device (WAD) support can result in severe hemodynamic compromise with high mortality. This study investigated the acute effects of cavopulmonary anastomosis on right ventricular loading and WAD performance in a model of severe biventricular failure. Methods: LVAD support was performed by means of centrifugal pump implantation in 14 anesthetized dogs (20-30 kg) with severe biventricular failure obtained by ventricular fibrillation induction. Animals were randomized to be submitted to classical cavopulmonary anastomosis (Glenn shunt) or to control group and were maintained under WAD support for 2 h. Left and right atrial, right ventricular and systemic pressures were monitored, white total pulmonary flow was simultaneously recorded by transonic flowmeters located on the superior vena cava and pulmonary trunk. Blood gas and venous lactate determinations were also obtained. Results: Ventricular fibrillation maintenance resulted in acute WAD performance impairment after 90 min in the control group, while animals with Glenn circuit maintained normal WAD pump flow (55 +/- 13 ml kg(-1) min(-1) vs 21 +/- 4 ml kg(-1) min(-1), p < 0.001) and better peripheral perfusion (blood lactate of 29 +/- 10 pg/ml vs 46 +/- 9 pg/ml, p < 0.001). Left and right atrial pressures did not change significantly, while right ventricular pressure was tower in animals with Glenn circuit (13 +/- 3 mmHg vs 22 +/- 8 mmHg, p = 0.005). Right ventricular unloading with Glenn shunt also resulted in superior total pulmonary flow (59 +/- 13 ml kg(-1) min(-1) vs 17 +/- 3 ml kg(-1) min(-1), p < 0.001). Conclusion: The concomitant use of cavopulmonary anastomosis during LVAD support in a model of severe biventricular failure limited right ventricular overloading and resulted in better hemodynamic performance. (C) 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Initial hepatosplanchnic blood flow distribution and oxygen metabolism in experimental model of hypotensive brain death

Background: Organs from the so-called marginal donors have been used with a significant higher risk of primary non function than organs retrieved from the optimal donors. We investigated the early metabolic changes and blood flow redistribution in splanchnic territory in an experimental model that mimics marginal brain-dead (BD) donor. Material/Methods: Ten dogs (21.3 +/- 0.9 kg), were subjected to a brain death protocol induced by subdural balloon inflation and observed for 30 min thereafter without ally additional interventions. Mean arterial and intracranial pressures, heart rate, cardiac output (CO), portal vein and hepatic artery blood flows (PVBF and HABF, ultrasonic flowprobe), and O(2)-derived variables were evaluated. Results: An increase in arterial pressure, CO, PVBF and HABF was observed after BD induction. At the end, an intense hypotension with normalization in CO (3.0 +/- 0.2 VS. 2.8 +/- 2.8 L/min) and PVBF (687 +/- 114 vs. 623 +/- 130 ml/min) was observed, whereas HABF (277 33 vs. 134 28 ml/min, p<0.005) remained lower than baseline values. Conclusions: Despite severe hypotension induced by sudden increase of intracranial pressure, the systemic and splanchnic blood flows were partially preserved without signs of severe hypoperfusion (i.e. hyperlactatemia). Additionally, the HABF was mostly negatively affected in this model of marginal BD donor. Our data suggest that not only the cardiac output, but the intrinsic hepatic microcirculatory mechanism plays a role in the hepatic blood flow control after BD.

Evaluation of rhBMP-2 and Natural Latex as Potential Osteogenic Proteins in Critical Size Defects by Histomorphometric Methods

This in vivo study evaluated the osteogenic potential of two proteins, recombinant human bone morphogenetic protein-2 (rhBMP-2) and a protein extracted from natural latex (Hevea brasiliensis, P-1), and compared their effects on bone defects when combined with a carrier or a collagen gelatin. Eighty-four (84) Wistar rats were divided into two groups, with and without the use of collagen gelatin, and each of these were divided into six treatment groups of seven animals each. The treatment groups were: (1) 5 mu g of pure rhBMP-2; (2) 5 mu g of rhBMP-2/monoolein gel; (3) pure monoolein gel; (4) 5 mu g of pure P-1; (5) 5 mu g of P-1/monoolein gel; (6) critical bone defect control. The animals were anesthetized and a 6 mm diameter critical bone defect was made in the left posterior region of the parietal bone. Animals were submitted to intracardiac perfusion after 4 weeks and the calvaria tissue was removed for histomorphometric analysis. In this experimental study, it was concluded that rhBMP-2 allowed greater new bone formation than P-1 protein and this process was more effective when the bone defect was covered with collagen gelatin (P < 0.05). Anat Rec, 293:794-801, 2010. (C) 2010 Wiley-Liss, Inc.

Morphologic and morphometric evaluation of experimental acute crush injuries of the sciatic nerve of rats

In order to qualify and quantify nerve fiber lesion following an acute crush injury, a morphologic and morphometric study was carried out in 25 Wistar rats divided into live groups of five animals each according to the crushing load applied, i.e., 500,1000, 5000, 10 000, and 15 000 g. The injury was produced under general anesthesia on a 5 mm-long intermediate segment of the right sciatic nerve for 10 min using a dead-weight machine. The animals were killed with an excessive dose of anesthetics 72 h later and submitted to perfusion with a fixing solution through the abdominal aorta immediately after death. Both the right and left sciatic nerves were removed and prepared for histologic and morphometric examinations: 5 mu m-thick sections stained with 1% Toluidine blue were examined under a light microscope equipped with a video camera linked to a computer loaded with a graphic program (KS 400). The morphometric studies included measuring total number of fibers, fiber density, fiber diameter, myelin fiber area, axon diameter, axon area and G ratio. The results showed that damage to the nerve fibers began to appear as early as with the 500g load and was similar in all groups despite the load applied, increasing with the 10000 and 15000g loads, although the external supporting tissues and small diameter fibers were preserved. The predominant type of lesion produced was axonotmesis. (c) 2008 Elsevier B.V. All rights reserved.

Utility of Ictal Single Photon Emission Computed Tomography in Mesial Temporal Lobe Epilepsy With Hippocampal Atrophy: A Randomized Trial

BACKGROUND: The development of newer diagnostic technologies has reduced the need for invasive electroencephalographic (EEG) studies in identifying the epileptogenic zone, especially in adult patients with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS). OBJECTIVE: To evaluate ictal single photon emission computed tomography (SPECT) in the evaluation and treatment of patients with MTLE-HS. METHODS: MTLE patients were randomly assigned to those with (SPECT, n = 124) and without ictal SPECT (non-SPECT, n = 116) in an intent-to-treat protocol. Primary end points were the proportion of patients with invasive EEG studies, and those offered surgery. Secondary end points were the length of hospital stay and the proportion of patients with secondarily generalized seizures (SGS) during video-EEG, postsurgical seizure outcome, and hospital cost. RESULTS: The proportion of patients offered surgery was similar in the SPECT (85%) and non-SPECT groups (81%), as well as the proportion that had invasive EEG studies (27% vs 23%). The mean duration of hospital stay was 1 day longer for the SPECT group (P < 0.001). SGS occurred in 51% of the SPECT and 26% of the non-SPECT group (P < 0.001). The cost of the presurgical evaluation was 35% higher for the SPECT compared with the non-SPECT group (P < 0.001). The proportion of patients seizure-free after surgery was similar in the SPECT (59%) compared with non-SPECT group (54%). CONCLUSION: Ictal-SPECT did not add localizing value beyond what was provided by EEG-video telemetry and structural MRI that altered the surgical decision and outcome for MTLE-HS patients. Ictal-SPECT increased hospital stay was associated with increased costs and a higher chance of SGS during video-EEG monitoring. These findings support the notion that a protocol including ictal SPECT is equivalent to one without SPECT in the presurgical evaluation of adult patients with MTLE-HS.

Hyperbaric oxygen on the healing of ischemic colonic anastomosis - an experimental study in rats

The aim of the present study was to evaluate the effect of hyperbaric oxygen therapy (HBO(2)) on the healing process of ischemic colonic anastomoses in rats Forty Wistar rats were divided into four groups control (Group I), control and HBO(2) (Group 11), ischemia (Group III), ischemia and HBO(2) (Group IV) Ischemia was achieved by clamping four centimeters of the colonic arcade On the eighth therapy day, the anastomotic region was removed for quantification of hydroxyproline and immunohistochemical determination of metalloproteinases 1 and 9 (MMP1,MMP9) The immunohistochemical studies showed significantly larger metalloproteinase-labeled areas in Group IV compared with Group III for both MMP1 and MMP9 (p<001) This finding points to a higher remodeling activity of the anastomoses in this experimental group Additionally, animals subjected to hyperbaric oxygen therapy showed both a reduction in interstitial edema and an increase in hydroxyproline concentrations [at the anastomotic site] Therefore, we conclude that HBO(2) is indeed beneficial in anastomotic ischemia

Ictal technetium-99 m ethyl cysteinate dimer single-photon emission tomographic findings in epileptic patients with polymicrogyria syndromes: A Subtraction of ictal-interictal SPECT coregistered to MRI study

Purpose To describe the ictal technetium-99 m-ECD SPECT findings in polymicrogyria syndromes (PMG) during epileptic seizures. Methods We investigated 17 patients with PMG syndromes during presurgical workup, which included long-term video-electroencephalographic (EEG) monitoring, neurological and psychiatry assessments, invasive EEG, and the subtraction of ictal-interictal SPECT coregistered to magnetic resonance imaging (MRI) (SISCOM). Results The analysis of the PMG cortex, using SISCOM, revealed intense hyperperfusion in the polymicrogyric lesion during epileptic seizures in all patients. Interestingly, other localizing investigations showed heterogeneous findings. Twelve patients underwent epilepsy surgery, three achieved seizure-freedom, five have worthwhile improvement, and four patients remained unchanged. Conclusions Our study strongly suggests the involvement of PMG in seizure generation or early propagation. Both conventional ictal single-photon emission computed tomography (SPECT) and SISCOM appeared as the single contributive exam to suggest the localization of the epileptogenic zone. Despite the limited number of resective epilepsy surgery in our study (n=9), we found a strong prognostic role of SISCOM in predicting surgical outcome. This result may be of great value on surgical decision-making of whether or not the whole or part of the PMG lesion should be surgically resected.

Bronchial responsiveness during esophageal acid infusion

Among the possible mechanisms explaining the worsening of asthma due to gastroesophageal reflux disease (GERD) is the increase in bronchial hyperresponsiveness. The effects of GERD on bronchial hyperresponsiveness in patients with bronchial asthma have yet to be studied in significant detail. The aim of this study was to determine the effects of esophageal acid perfusion on bronchial responsiveness to bradykinin in patients with both asthma and GERD. In 20 patients with asthma and GERD disease, esophageal pH was monitored with a pH meter and bronchial responsiveness was evaluated by aerosol inhalation of bradykinin during esophageal acid perfusion and, 24 h earlier or later the patients were submitted to another bronchial provocation test without acid infusion. No significant changes were observed in FEV1, FEF25-75%, FVC, or PEF during acid perfusion. The response to the bronchial provocation test did not differ between the control day and the day of acid infusion (p = 0.61). The concentration provoking a 20% fall in FEV1 (geometric mean +/- geometric SD) was 1.09 +/- 5.84 on the day of acid infusion and 0.98 +/- 5.52 on the control day. There is no evidence that acid infusion changes bronchial responsiveness to bradykinin. These findings strongly question the significance of acid infusion as a model to study the pathogenesis of GERD-induced asthma.

Interictal hyperemia correlates with epileptogenicity in polymicrogyric cortex

Objective: To investigate pathophysiological factors underlying the presence of interictal hyper-perfusion within the limits of the polymicrogyric (PMG) cortex in epileptic patients. Methods: Retrospective observational study on interictal perfusion by Single Photon Emission Computed Tomography (SPECT) in 16 patients with PMG and its correlations with a number of clinical and neurophysiological variables. Patients underwent video-EEG monitoring, neurological and psychiatric assessments, invasive EEG, and the interictal SPECT coregistered to Magnetic Resonance Imaging (MRI). Results: Patients with interictal hyperperfusion within the PMG cortex had a significantly higher spike rate on interictal EEG than patients with normal perfusion. Interictal hyperperfusion was not correlated to sex, age at epilepsy onset, age at evaluation, number of seizures per month, presence of initial precipitating insult (IPI), abnormal neurological examination, EEG findings, ictal serniology, and seizure outcome. The high interictal spike rate did not correlate to a high frequency of seizures per month. Conclusions: Our work provides further evidences for an intrinsic epileptogenesis of the PMG cortex during the interictal state, which accounts for the major rote of PMG tissue in seizure generation. These results might help to increase our understanding about epileptogenesis related to the PMG cortex, providing new toots for more tailored epilepsy surgery in PMG patients. (c) 2008 Elsevier B.V. All rights reserved.

Ethanol consumption increases blood pressure and alters the responsiveness of the mesenteric vasculature in rats

Chronic ethanol Consumption and hypertension are related. In the current study we investigated whether changes in reactivity of the mesenteric arterial bed could account for the increased blood pressure associated with chronic ethanol intake. Changes in reactivity to phenylephrine and acetylcholine were investigated in the perfused mesenteric bed from rats treated with ethanol for 2 or 6 weeks and their age-matched controls. Mild hypertension was observed in chronically ethanol-treated rats. Treatment of rats for 6 weeks induced an increase in the contractile response of endothelium-intact mesenteric bed to phenylephrine, but not denuded rat mesenteric bed. The phenylephrine-induced increase in perfusion pressure was not altered after 2 weeks` treatment with ethanol. Moreover, acetylcholine-induced endothelium-dependent relaxation was reduced by ethanol treatment for 6 weeks, but not 2 weeks. Pre-treatment with indometacin, a cyclooxygenase inhibitor, reduced the maximum effect induced by phenylephrine (E-max) in endothelium-intact mesenteric bed from both control and ethanol-treated rats. No differences in the E-max values for phenylephrine were observed between groups in the presence of indometacin. L-NNA, a nitric oxide (NO) synthase (NOS) inhibitor, increased the E-max for phenylephrine in endothelium-intact mesenteric bed from control rats but not from ethanol-treated rats. Levels of endothelial NOS (eNOS) mRNA were not altered by chronic ethanol consumption. However, chronic ethanol intake strongly reduced eNOS protein levels in the mesenteric bed. This study shows that chronic ethanol consumption increases blood pressure and alters the reactivity of the mesenteric bed. Moreover, the increased vascular response to phenylephrine observed in the mesenteric bed is maintained by two mechanisms: an increased release of endothelial-derived vasoconstrictor prostanoids and a reduced modulatory action of endothelial NO, which seems to be associated with reduced post-transcriptional expression of eNOS.

Sustained Ventricular Tachycardia Is Associated with Regional Myocardial Sympathetic Denervation Assessed with (123)I-Metaiodobenzylguanidine in Chronic Chagas Cardiomyopathy

Cardiac sympathetic denervation and ventricular arrhythmia are frequently observed in chronic Chagas cardiomyopathy (CCC). This study quantitatively evaluated the association between cardiac sympathetic denervation and sustained ventricular tachycardia (SVT) in patients with CCC. Methods: We prospectively investigated patients with CCC and left ventricular ejection fraction (LVEF) greater than 35% with SVT (SVT group: n = 5 15; mean age +/- SD, 61 +/- 8 y; LVEF, 51% +/- 8%) and patients without SVT (non-SVT group: n = 11; mean age +/- SD, 55 +/- 10 y; LVEF, 57% +/- 10%). Patients underwent myocardial scintigraphy with (123)I-metaiodobenzylguanidine ((123)I-MIBG) for the evaluation of sympathetic innervation and resting perfusion with (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) for the evaluation of myocardial viability. A visual semiquantitative score was attributed for regional uptake of each radiotracer using a 17-segment left ventricular segmentation model (0, normal; 4, absence of uptake). A mismatch defect was defined as occurring in segments with a 99mTc-MIBI uptake score of 0 or 1 and a (123)I-MIBG score of 2 or more. Results: Compared with the non-SVT group, the SVT group had a similar (99m)Tc-MIBI summed score (6.9 +/- 7.5 vs. 4.4 +/- 5.2, respectively, P = 0.69) but a higher (123)I-MIBG summed score (10.9 +/- 7.8 vs. 22.4 +/- 9.5, respectively, P = 0.007) and a higher number of mismatch defects per patient (2.0 +/- 2.2 vs. 7.1 +/- 2.0, respectively, P < 0.0001). The presence of more than 3 mismatch defects was strongly associated with the presence of SVT (93% sensitivity, 82% specificity; P = 0.0002). Conclusion: In CCC, the amount of sympathetically denervated viable myocardium is associated with the occurrence of SVT. Myocardial sympathetic denervation may participate in triggering malignant ventricular arrhythmia in CCC patients with relatively well-preserved ventricular function.

Esophageal Contractions in Patients with Chronic Progressive External Ophthalmoplegia

Background Chronic progressive external ophthalmoplegia is a mitochondrial myopathy that causes muscular or multisystem symptoms and has dysphagia as one manifestation. Aim To evaluate esophageal contractions in patients with chronic progressive external ophthalmoplegia. Methods We studied 14 patients with chronic progressive external ophthalmoplegia and 16 asymptomatic volunteers. The diagnosis of the disease was established by the clinical picture and by mitochondrial DNA analysis in skeletal muscle. We used the manometric method with a perfusion catheter that recorded the esophageal contractions at 2, 7, 12, 17, and 22 cm from the lower esophageal sphincter (LES). All subjects performed in the supine position 20 swallows of a 5-ml bolus of water at room temperature, ten every 30 s and ten every 10 s. Results The amplitude, duration, and area under the curve of contractions at 17 and 22 cm from the LES were lower in patients than in volunteers for swallows performed at 10-s and 30-s intervals (P < 0.01). There was no difference in contractions at 7 and 2 cm, except for the contractions at 2 cm after swallows performed at 30-s intervals. The interval between the onset of contractions between 7 and 2 cm and between 22 and 2 cm was lower in patients than in volunteers, with swallows performed every 10 s and every 30 s. Conclusions There is impairment of esophageal contractions in patients with chronic progressive external ophthalmoplegia, mainly in the proximal esophageal body.

USE OF A LARGE GAUGE NEEDLE FOR PERCUTANEOUS SECTIONING OF THE ACHILLES TENDON IN CONGENITAL CLUBFOOT

Objective: To evaluate the percutaneous Achilles tendon sectioning technique using a large gauge needle for the correction of residual equinus of congenital clubfoot treated with the Ponseti method. Methods: Fifty-seven Achilles tendon sections were prospectively evaluated in thirty-nine patients with clubfoot, treated with the Ponseti method between July 2005 and December 2008. The tenotomy was performed percutaneously with a large gauge needle. Ultrasound scan was performed immediately after the section, to ascertain whether the tenotomy was complete, as well as stump separation. Results: There was complete tendon section in all cases, but the need to perform the section maneuver more than once was common, due to the persistence of the residual strands between tendon stumps. The Thompson test and dynamic ultrasound evaluation were able to detect incomplete tenotomies. The mean ultrasound measurement of the tendon gap was 5.70 +/- 2.23 mm. Two patients had abnormal bleeding, which was controlled by digital pressure and did not compromise foot perfusion. Conclusion: Percutaneous Achilles tendon sectioning with a needle proved to be efficient and safe to correct residual equinus of clubfoot treated with the Ponseti technique.