Comparative myocardial protection of endoaortic balloon versus external clamp in minimally invasive mitral valve surgery.

AIMS: Minimally invasive mitral valve surgery leads to shorter postoperative recovery time, cosmetic advantages and significant pain reduction compared with the standard sternotomy approach. Both an external aortic clamp and an endoaortic balloon occlusion can be used to manage the ascending aorta and the myocardial protection. In this study, we aimed to compare these two strategies in terms of effectiveness of myocardial protection and associated early postoperative outcomes. METHODS: We investigated the retrospective records of prospectively collected data of patients treated by minimally invasive mitral valve surgery from March 2014 to June 2019. A total of 180 cases (78 in the external aortic clamp group and 102 in the endoaortic balloon clamp group) were collected. A propensity weighting analysis was adopted to adjust for baseline variables. RESULTS: The endoaortic balloon clamp presented higher EuroSCORE II (higher reoperative surgery rate). The intra- and postoperative data were similar between the two groups: the postoperative troponin-I levels, peak of serum lactates and rate of myocardial infarction were also comparable. The endoaortic clamp group recorded longer operative, cardiopulmonary bypass and cross-clamp times. The external clamp group showed a higher rate of postoperative atrial fibrillation and conduction block. CONCLUSIONS: In experienced centers, the use of the endoaortic balloon clamp is safe, reproducible and comparable to the external aortic clamp regarding the effectiveness of myocardial protection: its employment might facilitate minimally invasive mitral valve surgery.

Expression of the Bitter Taste Receptor, T2R38, in Enteroendocrine Cells of the Colonic Mucosa of Overweight/Obese vs. Lean Subjects.

Bitter taste receptors (T2Rs) are expressed in the mammalian gastrointestinal mucosa. In the mouse colon, T2R138 is localized to enteroendocrine cells and is upregulated by long-term high fat diet that induces obesity. The aims of this study were to test whether T2R38 expression is altered in overweight/obese (OW/OB) compared to normal weight (NW) subjects and characterize the cell types expressing T2R38, the human counterpart of mouse T2R138, in human colon. Colonic mucosal biopsies were obtained during colonoscopy from 35 healthy subjects (20 OW/OB and 15 NW) and processed for quantitative RT-PCR and immunohistochemistry using antibodies to T2R38, chromogranin A (CgA), glucagon like peptide-1 (GLP-1), cholecystokinin (CCK), or peptide YY (PYY). T2R38 mRNA levels in the colonic mucosa of OW/OB were increased (> 2 fold) compared to NW subjects but did not reach statistical significance (P = 0.06). However, the number of T2R38 immunoreactive (IR) cells was significantly increased in OW/OB vs. NW subjects (P = 0.01) and was significantly correlated with BMI values (r = 0.7557; P = 0.001). In both OW/OB and NW individuals, all T2R38-IR cells contained CgA-IR supporting they are enteroendocrine. In both groups, T2R38-IR colocalized with CCK-, GLP1- or PYY-IR. The overall CgA-IR cell population was comparable in OW/OB and NW individuals. This study shows that T2R38 is expressed in distinct populations of enteroendocrine cells in the human colonic mucosa and supports T2R38 upregulation in OW/OB subjects. T2R38 might mediate host functional responses to increased energy balance and intraluminal changes occurring in obesity, which could involve peptide release from enteroendocrine cells.

Prucalopride exerts neuroprotection in human enteric neurons.

Serotonin (5-hydroxytryptamine, 5-HT) and its transporters and receptors are involved in a wide array of digestive functions. In particular, 5-HT4 receptors are known to mediate intestinal peristalsis and recent data in experimental animals have shown their role in neuronal maintenance and neurogenesis. This study has been designed to test whether prucalopride, a well-known full 5-HT4 agonist, exerts protective effects on neurons, including enteric neurons, exposed to oxidative stress challenge. Sulforhodamine B assay was used to determine the survival of SH-SY5Y cells, human enteric neurospheres, and ex vivo submucosal neurons following H2O2 exposure in the presence or absence of prucalopride (1 nM). Specificity of 5-HT4-mediated neuroprotection was established by experiments performed in the presence of GR113808, a 5-HT4 antagonist. Prucalopride exhibited a significant neuroprotective effect. SH-SY5Y cells pretreated with prucalopride were protected from the injury elicited by H2O2 as shown by increased survival (73.5 ± 0.1% of neuronal survival vs. 33.3 ± 0.1%, respectively; P < 0.0001) and a significant reduction of proapoptotic caspase-3 and caspase-9 activation in all neurons tested. The protective effect of prucalopride was reversed by the specific 5-HT4 antagonist GR113808. Prucalopride promotes a significant neuroprotection against oxidative-mediated proapoptotic mechanisms. Our data pave the way for novel therapeutic implications of full 5-HT4 agonists in gut dysmotility characterized by neuronal degeneration, which go beyond the well-known enterokinetic effect.

The KIT gene is associated with the english spotting coat color locus and congenital megacolon in Checkered Giant rabbits (Oryctolagus cuniculus).

The English spotting coat color locus in rabbits, also known as Dominant white spotting locus, is determined by an incompletely dominant allele (En). Rabbits homozygous for the recessive wild-type allele (en/en) are self-colored, heterozygous En/en rabbits are normally spotted, and homozygous En/En animals are almost completely white. Compared to vital en/en and En/en rabbits, En/En animals are subvital because of a dilated ("mega") cecum and ascending colon. In this study, we investigated the role of the KIT gene as a candidate for the English spotting locus in Checkered Giant rabbits and characterized the abnormalities affecting enteric neurons and c-kit positive interstitial cells of Cajal (ICC) in the megacolon of En/En rabbits. Twenty-one litters were obtained by crossing three Checkered Giant bucks (En/en) with nine Checkered Giant (En/en) and two en/en does, producing a total of 138 F1 and backcrossed rabbits. Resequencing all coding exons and portions of non-coding regions of the KIT gene in 28 rabbits of different breeds identified 98 polymorphisms. A single nucleotide polymorphism genotyped in all F1 families showed complete cosegregation with the English spotting coat color phenotype (θ=0.00 LOD  =75.56). KIT gene expression in cecum and colon specimens of En/En (pathological) rabbits was 5-10% of that of en/en (control) rabbits. En/En rabbits showed reduced and altered c-kit immunolabelled ICC compared to en/en controls. Morphometric data on whole mounts of the ascending colon showed a significant decrease of HuC/D (P<0.05) and substance P (P<0.01) immunoreactive neurons in En/En vs. en/en. Electron microscopy analysis showed neuronal and ICC abnormalities in En/En tissues. The En/En rabbit model shows neuro-ICC changes reminiscent of the human non-aganglionic megacolon. This rabbit model may provide a better understanding of the molecular abnormalities underlying conditions associated with non-aganglionic megacolon.

Supplemental sodium butyrate stimulates different gastric cells in weaned pigs.

Sodium butyrate (SB) is used as an acidifier in animal feed. We hypothesized that supplemental SB impacts gastric morphology and function, depending on the period of SB provision. The effect of SB on the oxyntic and pyloric mucosa was studied in 4 groups of 8 pigs, each supplemented with SB either during the suckling period (d 4-28 of age), after weaning (d 29 to 39-40 of age) or both, or never. We assessed the number of parietal cells immunostained for H+/K+-ATPase, gastric endocrine cells immunostained for chromogranin A and somatostatin (SST) in the oxyntic mucosa, and gastrin-secreting cells in the pyloric mucosa. Gastric muscularis and mucosa thickness were measured. Expressions of the H+/K+-ATPase and SST type 2 receptor (SSTR2) genes in the oxyntic mucosa and of the gastrin gene in the pyloric mucosa were evaluated by real-time RT-PCR. SB increased the number of parietal cells per gland regardless of the period of administration (P < 0.05). SB addition after, but not before, weaning increased the number of enteroendocrine and SST-positive cells (P < 0.01) and tended to increase gastrin mRNA (P = 0.09). There was an interaction between the 2 periods of SB treatment for the expression of H/K-ATPase and SSTR2 genes (P < 0.05). Butyrate intake after weaning increased gastric mucosa thickness (P < 0.05) but not muscularis. SB used orally at a low dose affected gastric morphology and function, presumably in relationship with its action on mucosal maturation and differentiation.

Effect of fructo-oligosaccharides and different doses of Bifidobacterium animalis in a weaning diet on bacterial translocation and Toll-like receptor gene expression in pigs.

OBJECTIVE: Our aim was to study the possible synergic action of one prebiotic with increasing dietary doses of a probiotic strain of Bifidobacterium animalis on the translocation of bifidobacteria and on Toll-like receptor (TLR) gene expression in different organs of weaned piglets. METHODS: Sixty-four pigs, reared from 21 to 35 d of age, were fed eight different diets according to a 2 x 4 factorial design: a control diet or the control diet supplemented with three different levels of B. animalis (10(7), 10(9), 10(11) colony-forming units/d), crossed with 0% or 2% sugar beet fructo-oligosaccharides. Pigs were then sacrificed, and the jejunum mucosa, ileocecal lymph nodes, and liver were sampled to determine the presence of Bifidobacterium spp. DNA and to quantify the expression of TLR2-, TLR4-, and tumor necrosis factor-alpha-encoding genes. RESULTS: We found Bifidobacterium spp. genus-specific DNA in lymph nodes of subjects from all dietary treatments, including the control diet, but it increased with the bifidobacteria oral dose (P = 0.065). The linear effect of the dose of B. animalis on the expression of the TLR2-encoding gene in the lymph nodes was observed when fructo-oligosaccharides were added to the diet (P < 0.05). Tumor necrosis factor-alpha-encoding gene expression was positively correlated with TLR4- and TLR2-encoding gene expressions (P < 0.001 and P < 0.01, respectively) and negatively correlated with bifidobacteria DNA (P < 0.05). Moreover, the expression of the TLR4-encoding gene showed a positive correlation with TLR2-encoding gene expression (P < 0.001). In contrast, there was no correlation between expressions of the TLR2- and TLR4-encoding genes with the bifidobacteria DNA. CONCLUSION: Soon after weaning, the translocation of the commensal bacteria in the ileocecal lymph nodes is a physiologic process. Moreover, diet affects the expression of the TLR2-encoding gene.

Metabolism of hibernating myocardium assessed by microdialysis during surgical revascularization: report of a case.

We present an 80-year-old woman with hibernating myocardium in the left anterior descending coronary artery (LAD) territory who underwent surgical revascularization and metabolic evaluation of the dysfunctioning segments by microdialysis (microD) technique. Myocardial lactate, pyruvate, and glucose did not show obvious changes throughout the procedure. Conversely, myocardial glycerol and glutamate concentrations markedly increased early after cardioplegic arrest and subsided after weaning from cardiopulmonary bypass (CPB) and recovery of myocardial function. Intraoperative myocardial microD may add relevant pathophysiologic information on hibernating myocardium undergoing coronary flow restoration and, eventually, improve patient care.

Long-term outcome of survivors of prolonged intensive care treatment after cardiac surgery.

BACKGROUND: The relative impact of perioperative risk profile and postoperative complications on long-term outcome in cardiac surgical patients is currently unclear. The aim of this work was to assess the relative predictive value of the European System for Cardiac Operative Risk Evaluation (EuroSCORE) and Sequential Organ Failure Assessment (SOFA) on long-term event-free survival in this patient population. METHODS: Preoperative and postoperative variables, EuroSCORE and SOFA, 30-day mortality, and long-term mortality or hospital admission for cardiovascular events were assessed in 115 consecutive cardiac surgical patients in whom multiorgan dysfunction syndrome developed postoperatively. RESULTS: Mean age was 70 +/- 8 years, 41% were women, EuroSCORE averaged 7.87 +/- 3.99, and postoperative stay in the intensive care unit was 10.3 +/- 8.2 days. In-hospital 30-day mortality was 10.4% (n = 12). During 1998 person-months follow-up, 12 (11.6%) of 103 patients discharged alive died, and 46 (44.7%) met the combined end point of all-cause death or cardiovascular admission. By Cox multivariate analysis, maximum SOFA (hazard ratio [HR], 2.17; 95% confidence interval [CI], 1.34 to 3.51) and maximum cardiovascular score (HR, 2.35; 95% CI, 1.22 to 4.51) independently predicted all-cause mortality. EuroSCORE (HR, 1.33; 95% CI, 1.01 to 1.76), maximum cardiovascular score (HR 2.09; 95% CI 1.41 to 3.10), and maximum liver score (HR 2.67; 95% CI, 1.46 to 4.86) were independently associated with the combined end point. CONCLUSIONS: High-risk cardiac surgical patients with postoperative multiorgan dysfunction syndrome show excess mortality and cardiovascular morbidity after hospital discharge. Combined preoperative and postoperative risk stratification identifies patients with the highest likelihood of death or early readmission.

A continuous dietary supply of free calcium formate negatively affects the parietal cell population and gastric RNA expression for H+/K+-ATPase in weaning pigs.

Baby formula acidification can be used to reduce diarrhea. Calcium formate is a dietary acidifier frequently used in animal weaning diets; it is also a source of available calcium. Gastric acidification reduces gastrin release and hydrochloric acid (HCl) secretion. To study the medium-term effects on fundic gastric mucosa, we fed weaning pigs control diets or diets supplemented with free or fat-protected calcium formate. We evaluated the following: 1) the number of HCl-secreting parietal cells, by immunohistochemistry using an antibody against H(+)/K(+)-ATPase; 2) the number of enteroendocrine cells immunohistochemically stained with chromogranin A (CGA), somatostatin, and histamine (HIS); and 3) the expression of the H(+)/K(+)-ATPase gene, by real-time RT-PCR in the oxyntic mucosa. Cells co-staining for CGA and HIS were defined as enterochromaffin-like (ECL) cells. Pigs fed calcium formate had fewer parietal cells and a lower expression of the H(+)/K(+)-ATPase gene than the controls (P < 0.05). This reduction did not occur in pigs fed fat-protected calcium formate. Somatostatin immune-reactive cells were also more numerous in pigs fed free calcium formate than in controls (P < 0.05). The number of ECL cells was not affected. Using covariance analysis, the number of parietal cells explained part of the differences in the expression of H(+)/K(+)-ATPase gene (positive correlation, r = 0.385, P < 0.01), and excluded the statistical significance of the diet. In the future, the effects on the oxyntic mucosa should be checked when the diet supplemented with calcium formate is discontinued. Furthermore, a reduction in the number of parietal cells could impair the absorption of vitamin B-12 due to a reduced secretion of the intrinsic factor by these cells.

Myocardial lactate metabolism in relation to preoperative regional wall motion and to early functional recovery after coronary revascularization.

OBJECTIVE: To evaluate myocardial lactate metabolism as a marker of functional status after surgical coronary revascularization. DESIGN: Single-center, prospective, cohort study. SETTING: Tertiary care teaching hospital. PARTICIPANTS: Fifty patients with stable angina, ejection fraction >0.40, undergoing coronary artery bypass surgery for multiple-vessel disease. MEASUREMENTS AND MAIN RESULTS: Before (T1) and 30 minutes (T2) after coronary artery bypass grafting, the authors simultaneously sampled blood from artery and coronary sinus to determine myocardial lactate dynamics and performed transesophageal echocardiography (TEE) to assess segmental wall motion. Wall motion score index (WMSI) was calculated with an online/offline comparison. At T2, WMSI improved from 1.40 +/- 0.31 to 1.17 +/- 0.23 (p = 0.0001). Preoperatively, 2 patterns of lactate balance were found: 39 patients were lactate extractors (17% +/- 10%) and 11 were lactate producers (-11% +/- 11%). At T2, lactate metabolism was shifted towards a pattern opposite to the baseline: delta lactate extraction was -8% +/- 16% in extractors at T1 versus 7% +/- 9% in producers at T1 (p = 0.003). Changes in WMSI were not correlated with changes in lactate utilization. No single preoperative variable predicted postoperative WMSI or its changes from baseline. Cardiopulmonary bypass (CPB) time was the only significant predictor of postoperative lactate extraction by multivariate regression (r = -0.46, p = 0.001): at T2, patients in the highest CPB time quartile showed frank lactate production (-6% +/- 13%) when compared with those in the lowest quartile (15% +/- 11%, p = 0.005). However, postoperative WMSI was similar in different CPB time groups. CONCLUSIONS: Myocardial lactate metabolism pattern is not associated with functional status before and early after successful coronary revascularization. CPB time was the only significant predictor of postoperative lactate extraction. Measurement of lactate does not appear to be a valuable tool to assess the coupling of myocardial regional function and metabolism in the setting of coronary artery surgery and mild-to-moderate functional impairment.