Smooth muscle adaptation after intestinal transection and resection

Changes in motor function occur in the intestinal remnant after intestinal resection. Smooth muscle adaptation also occurs, particularly after extensive resection. The time course of these changes and their interrelationship are unclear. Our aim was to evaluate changes in canine smooth muscle structure and function during intestinal adaptation after transection and resection. Twenty-five dogs underwent either transection (N=10), 50% distal resection (N=10), or 50% proximal resection (N=5). Thickness and length of the circular (CM) and longitudinal (LM) muscle layers were measured four and 12 weeks after resection.In vitro length-tension properties and response to a cholinergic agonist were studied in mid-jejunum and mid-ileum. Transection alone caused increased CM length in the jejunum proximal to the transection but did not affect LM length or muscle thickness. A 50% resection resulted in increased length of CM throughout the intestine and thickening of CM and LM near the anastomosis. Active tension of jejunal CM increased transiently four weeks after resection. Active tension in jejunal LM was decreased 12 weeks after transection and resection. Sensitivity of CM to carbachol was similar after transection and resection. It is concluded that: (1) Structural adaptation of both circular and longitudinal muscle occurs after intestinal resection. (2) This process is influenced by the site of the intestinal remnant. (3) Only minor and transient changes occur in smooth muscle function after resection. (4) Factors other than muscle adaptation are likely involved in the changes in motor function seen following massive bowel resection.Supported by the VA Merit Review Program.     

Straight ileoanal anastomosis with multiple ileal myotomies as an alternative to pelvic pouch

. An alternative technique of restorative proctocolectomy, by means of straight ileoanal anastomosis with multiple myotomies (SIAM) of the terminal ileum in 15 patients, nine with familial adenomatous polyposis (FAP) and six with ulcerative colitis (UC) is reported. Surgical technique: eight to ten longditudinal myotomies (3 – 4 cm long, on three different circumferential sites) were performed on the terminal ileum for a total length of 12 – 14 cm. Clinical results: at a mean follow up of 44 months (range 3 – 84 months) from the closure of the ileostomy, daytime continence was achieved in all the patients; stool frequency per 24 hours (±SD) was 4.1±1.8 for FAP patients and 5.8±1.7 for UC patients; nocturnal defecation was 1.0±0.5 and 1.2±0.8 for FAP and UC patients respectively; frequent nocturnal soiling was present in 2/5 of UC patients, and in 3/9 of FAP patients. SIAM failed in one UC patient that was converted to an ileoanal reservoir because of poor functional result. Signs of ileal mucosal inflammation were never observed at endoscopic examination. Histopathological assessment showed no evidence of acute terminal ileitis. Manometric findings: a significant postoperative reduction in anal resting pressure was observed after SIAM. Neither the absence of anal inhibitory reflex nor the presence of high pressure waves generated in the terminal ileum during air insufflation were related to the presence of soiling. The closure of the loop ileostomy was followed by an increased capacity and distensibility of the terminal ileum. Values of neorectal compliance were similar in FAP and UC patients although FAP patients were able to reach higher values of maximum tolerated volume and pressure. Conclusions: 1) SIAM can be an alternative to pelvic pouch in patients who have undergone restorative proctocolectomy when the construction of the pouch is not feasible. 2) The functional result observed after SIAM has been shown to be similar to that observed after pouch construction.     

Morphologic characteristics of lesion formation and time course of smooth muscle cell proliferation in a porcine proliferative restenosis model

Objectives. This study was performed to define the evolution of lesion morphology and its relation to thrombus formation and smooth muscle cell proliferation after experimental coronary stent placement.Background. Restenosis after percutaneous revascularization may develop because of thrombus accumulation and smooth muscle cell proliferation. In animal models of restenosis, thrombus may assume a significant role in neointimal formation by providing an absorbable matrix into which smooth muscle cells proliferate.Methods. Twenty-eight oversized stents were placed in the coronary arteries of 23 juvenile domestic pigs. The histologic degree of vessel injury, lesion morphometry and smooth muscle cell proliferation measured by immunolocalization with a monoclonal antibody to proliferating cell nuclear antigen (PCNA) were assessed at 24 h and 7, 14 and 28 days after stent placement.Results. The area of thrombus was minimal at 24 h ([mean ± SE] 0.44 ± 0.12 mm²). Neointimal area at 7 days (0.72 ± 0.20 mm²) was similar to the area of thrombus, followed by a significant increase at 14 days (3.15 ± 0.39 mm²) and 28 days (3.30 ± 0.28 mm²) (p < 0.0036, 24 h and 7 days vs. 14 and 28 days). At 14 and 28 days, neointimal thickness correlated with the histologic degree of vessel injury (p < 0.003). In arteries with severe injury, the increase in neointimal thickness is accounted for by replacement of the damaged media. The smooth muscle cell proliferation index was 18.6 ± 3.5% at 7 days compared with 9.6 ± 1.3% by 14 days (p = 0.0247) and declined to 1.1 ± 0.97% by 28 days (p < 0.008, 7 and 14 days vs. 28 days).Conclusions. Early thrombus formation is minimal, and thrombus accounts for a small portion of subsequent neointimal formation. Smooth muscle cell proliferation and matrix formation are the major factors relating to neointimal formation in this proliferative model of restenosis. The evolution of neointimal formation after coronary stenting shows maximal smooth muscle cell proliferation at 7 days, with a decline to low levels by 28 days. Therefore, these data may be useful for developing effective therapies for restenosis.     

Muscle mass,strength, bone mineral density and vascular function in middle-aged people living with HIV vs. age-matched and older controls

IntroductionCombination antiretroviral therapy (cART) substantially extended the life of people living with HIV (PLHIV). However, prolonged HIV infection and cART increase the risk of comorbidities accelerating age-related muscle, bone, and vascular disorders. This cross-sectional study compared muscle mass and strength, bone mineral density (BMD), and vascular function in middle-aged PLHIV treated with cART vs. non-infected age-matched and older controls.MethodsAfter careful screening for secondary diseases and medications, body composition, muscular and vascular function were assessed in 12 PLHIV (43.9±8.7 yrs old; HIV-infection for 16.2±8.6 yrs; on cART for 11.6±9.2 yrs), 12 age-matched (CONT, 43.2±8.5 yrs old), and 12 older (OLDER, 74.4±8.3 yrs old) controls through dual x-ray absorptiometry, isokinetic dynamometry, and venous occlusion plethysmography, respectively.ResultsPLHIV and CONT showed similar relative muscle mass (65.3±8.0 vs. 66.9±7.3%, respectively; P= 0.88) and strength (160.7±53.9 vs. 152.0±52.9 N.m⁻¹, respectively; P= 0.90), which were greater than OLDER (80.6±18.8 N.m^−1; P= 0.001). Total BMD was similar in PLHIV (1.04±0.13 g.cm⁻²) and OLDER (1.00±0.15 g.cm⁻², P= 0.86), and both groups presented lower values than CONT (1.20±0.13 g.cm⁻², P< 0.01). No significant difference across groups was detected for macrovascular reactivity (P= 0.32).ConclusionAge-related osteopenia might be accelerated in middle-aged PLHIV on prolonged cART, as their BMD approached values found in older adults. On the other hand, muscle mass, isokinetic strength, and vasodilation capacity were similar in PLHIV and age-matched uninfected controls.     

Exogenous carbon monoxide attenuates inflammatory responses in the small intestine of septic mice

AIM:To determine whether the carbon monoxide(CO)-releasing molecules(CORM)-liberated CO suppress inflammatory responses in the small intestine of septic mice.METHODS:The C57BL/6 mice(male,n = 36;weight 20 ± 2 g) were assigned to four groups in three respective experiments.Sepsis in mice was induced by cecal ligation and puncture(CLP)(24 h).Tricarbonyldichlororuthenium(Ⅱ) dimer(CORM-2)(8 mg/kg,i.v.) was administrated immediately after induction of CLP.The levels of inflammatory cytokines [interleukin-1(IL-1) and tumor necrosis factor-(TNF-)] in tissue homogenates were measured with enzyme-linked immunosorbent assay.The levels of malondialdehyde(MDA) in the tissues were determined.The levels of nitric oxide(NO) in tissue homogenate were measured and the expression levels of intercellular adhesion molecule 1(ICAM-1) and inducible nitric oxide synthase(iNOS) in the small intestine were also assessed.NO and IL-8 levels in the supernatants were determined after the human adenocarcinoma cell line Caco-2 was stimulated by lipopolysaccharide(LPS)(10 g/mL) for 4 h in vitro.RESULTS:At 24 h after CLP,histological analysis showed that the ileum and jejunum from CLP mice induced severe edema and sloughing of the villous tips,as well as infiltration of inflammatory cells into the mucosa.Semi-quantitative analysis of histological samples of ileum and jejunum showed that granulocyte infiltration in the septic mice was significantly increased compared to that in the sham group.Administration of CORM-2 significantly decreased granulocyte infiltration.At 24 h after CLP,the tissue MDA levels in the midileum and mid-jejunum significantly increased compared to the sham animals(103.68 ± 23.88 nmol/mL vs 39.66 ± 8.23 nmol/mL,89.66 ± 9.98 nmol/mL vs 32.32 ± 7.43 nmol/mL,P 0.01).In vitro administration of CORM-2,tissue MDA levels were significantly decreased(50.65 ± 11.46 nmol/mL,59.32 ± 6.62 nmol/mL,P 0.05).Meanwhile,the tissue IL-1 and TNF-levels in the mid-ileum significantly increased compared to the sham animals(6.66 ± 1.09 pg/mL vs 1.67 ± 0.45 pg/mL,19.34 ± 3.99 pg/mL vs 3.98 ± 0.87 pg/mL,P 0.01).In vitro administration of CORM-2,tissue IL-1 and TNF-levels were significantly decreased(3.87 ± 1.08 pg/mL,10.45 ± 2.48 pg/mL,P 0.05).The levels of NO in mid-ileum and mid-jejunum tissue homogenate were also decreased(14.69 ± 2.45 nmol/mL vs 24.36 ± 2.97 nmol/mL,18.47 ± 2.47 nmol/mL vs 27.33 ± 3.87 nmol/mL,P 0.05).The expression of iNOS and ICAM-1 in the mid-ileum of septic mice at 24 h after CLP induction significantly increased compared to the sham animals.In vitro administration of CORM-2,expression of iNOS and ICAM-1 were significantly decreased.In parallel,the levels of NO and IL-8 in the supernatants of Caco-2 stimulated by LPS was markedly decreased in CORM-2-treated Caco-2 cells(2.22 ± 0.12 nmol/mL vs 6.25 ± 1.69 nmol/mL,24.97 ± 3.01 pg/mL vs 49.45 ± 5.11 pg/mL,P 0.05).CONCLUSION:CORM-released CO attenuates the inflammatory cytokine production(IL-1 and TNF-),and suppress the oxidative stress in the small intestine during sepsis by interfering with protein expression of ICAM-1 and iNOS.     

Increased smooth muscle contractility of intestine in the genetic null of the endothelin ETB receptor: a rat model for long segment Hirschsprung's disease

BACKGROUND AND AIMS: The endothelin ETB receptor null rat (ETB(-/-)R) has an intestinal segment without ganglia, and this rat is characterised by intestinal obstruction similar to that observed in human Hirschsprung's disease. In the present study, we have examined the myogenic mechanism responsible for obstruction in the ETB(-/-)R. RESULTS: The ETB(-/-)R had an enlarged belly and the average lifespan was 18.1 days. The bowel from the rectum to the lower part of the small ileum was constricted whereas the upper region was dilated with faecal stasis and thus presented as megaileum. The constricted muscle segments without ganglia had a greater increase in absolute force when stimulated by carbachol, high K+, and endothelin-1 compared with that of normal siblings. In contrast, in the dilated part with ganglia, the absolute contractile force due to these stimulants in the ETB(-/-)R was not different from that in the ETB(+/+)R. Such a functional hypertrophy of the musculature was observed in parts of the colon, caecum, and distal ileum without ganglia but not in the part of the proximal ileum and jejunum with ganglia. Morphological study demonstrated that the thickness of the circular and longitudinal muscle layers was greater in the constricted part of the intestine in the ETB(-/-)R, and these changes were associated with an increase in the number of smooth muscle cells. CONCLUSIONS: Our findings suggest that both increased contractility of smooth muscle and increased thickness of the intestinal muscular wall may contribute to the intestinal obstruction in the ETB(-/-)R.     

The ultrastructural bases for coordination of intestinal motility

The electrical control activity (slow waves) of dog small intestine is characterized by phase locking of potential changes in a frequency plateau in the upper intestine. In the distal intestine, phase locking does not occur, though frequencies of each segment are pulled up (increased) by adjacent, more proximal segments. This suggests poorer coupling in the distal compared to the proximal intestine. Electron microscopic studies of the intestine revealed no differences in appearance or number of nexuses (found only in circular muscle) or of intermediate contacts (found in both muscle layers) in duodenum and upper jejunum as compared with ileum. Thus, differences in cell to cell contacts could not explain poorer coupling in the ileum. No difference in innervation of these two regions was observed. However, evidence was obtained that circular muscle cells of the ileum, unlike those of the duodenum, are not oriented perpendicularly to the longitudinal muscle layer. This could provide a structural basis for poorer coupling and for the observed phase lag of potentials around the circumference of the ileum.     

Association of beta-blocker use with increased aortic wave reflection

Studies have found less cardiovascular risk reduction in patients treated with beta-blockers (BBs) compared with other agents. We compared the severity of aortic atherosclerosis, arterial stiffness, and wave reflection in patients treated and not treated with BBs. Seventy-two patients, 37 treated with BBs and 35 not treated, referred for transesophageal echocardiography were studied. Augmentation index (AI), heart-rate-corrected AI (AI-75), aortic systolic (SBP) and diastolic blood pressure, pulse wave velocity (PWV), and aortic intima-media thickness (MAIMT) were measured. There were no differences in MAIMT (2.8 ± 1.6 mm vs. 2.4 ± 1.2 mm, P = .20) and PWV (8.9 ± 2.0 m/s vs. 8.5 ± 2.6 m/s, P = .46) between the BB and non-BB groups. The BB group had higher AI (28.7 ±11.9% vs. 22.3 ± 14.1%, P = .04), AI-75 (27.7 ± 10.7% vs. 20.1± 11.0%, P = .005), aortic SBP (140 ± 21 mm Hg vs. 125 ± 21 mm Hg, P = .01), and aortic pulse pressure (62 ± 20 mm Hg vs. 47 ± 19 mm Hg, P = .01) than the non-BB group despite similar brachial blood pressure. BB use was associated with increased aortic wave reflection despite similar degree of aortic atherosclerosis.     

Physiological and pharmacological properties of a modified Brooke ileostomy: justification for retaining the most distal ileum

Purpose

The traditional Brooke ileostomy removed the last 8–15 cm of the ileum due to concern of occurrence of terminal ileal Crohn’s disease, vide infra the ileocolic sphincter was removed. Retaining all the terminal ileum has the potential of retaining the ileocolic sphincter. Our aim was to investigate whether a high-pressure zone existed within the last few centimetres of the ileum and its response to pharmacological stimuli.

Methods

A balloon manometry catheter was introduced into the stoma of 16 patients who had formation of an end ileostomy (ileocolic sphincter retained, ICS). Recordings were made at 1 cm intervals from the meatus in order to identify the maximum intra-luminal resting and intra-abdominal pressure. At the point of maximum resting pressure, the response to phenylephrine (10 % gel) and glyceryl trinitrate (GTN) (0.2 % paste) was recorded. Results were recorded using an Ohmeda Oestiva 5 manometry system (in millimeter of mercury) and data were analysed using ANOVA. Results were compared with 13 historical controls (ileocolic sphincter removed).

Results

There was no significant difference in resting intra-abdominal pressure between the two groups (historical controls 8.5?±?3.0 mmHg; ICS 9.0?±?3.2 mmHg), p?=?NS. The maximum resting intra-luminal pressure in ICS patients exceeded historical controls 16?±?2.9 vs 10.0?±?2.5 mmHg, p?<?0.001. In ICS patients, phenylephrine increased the resting pressure to 26.0?±?3.5 mmHg, p?<?0.001. In historical controls, the pressure remained unchanged, 12?±?4.7 mmHg, p?=?NS. Subsequent addition of GTN to both groups lowered maximum intra-luminal pressure to pre-study values, 10?±?4.2 mmHg (ICS) and 7?±?3.5 mmHg (controls), p?=?NS.

Conclusion

Retention of the ileocolic sphincter in a modified Brooke ileostomy preserves a physiological high-pressure zone, the properties of which can be modified by pharmacological agents.     

Cellular basis of diabetic nephropathy: V. Endoglin expression levels and diabetic nephropathy risk in patients with Type 1 diabetes

Endoglin is an accessory receptor molecule that, in association with transforming growth factor β (TGF-β) family receptors Types I and II, binds TGF-β1, TGF-β3, activin A, bone morphogenetic protein (BMP)-2 and BMP-7, regulating TGF-β dependent cellular responses. Relevant to diabetic nephropathy, endoglin, expressed in vascular endothelial and smooth muscle cells, fibroblasts, and mesangial cells, negatively regulates extracellular matrix (ECM). The aim of this study was to evaluate endoglin expression in cultured skin fibroblasts from patients with Type 1 diabetes with and without diabetic nephropathy. Kidney and skin biopsies were performed in 125 Type 1 diabetic patients. The 20 with the fastest rate of mesangial expansion (estimated by electron microscopy) and proteinuria (“fast-track”) and the 20 with the slowest rate and normoalbuminuria (“slow-track”), along with 20 controls were studied. Endoglin mRNA expression was assessed by microarray and quantitative real-time polymerase chain reaction (QRT-PCR) and protein expression by Western blot. Age and sex distribution were similar among groups. Diabetes duration was similar (20±8 vs. 24±7 years), hemoglobin A1c lower (8.4±1.2% vs. 9.4±1.5%), and glomerular filtration rate higher (115±13 vs. 72±20 ml/min per 1.73 m²) in slow-track vs. fast-track patients. Microarray endoglin mRNA expression levels were higher in slow-track (1516.0±349.9) than fast-track (1211.0±274.9; P=.008) patients or controls (1223.1±422.9; P=.018). This was confirmed by QRT-PCR. Endoglin protein expression levels correlated with microarray (r=0.59; P=.044) and QRT-PCR (r=0.61; P=.034) endoglin mRNA expression. These studies are compatible with the hypothesis that slow-track Type 1 diabetic patients, strongly protected from diabetic nephropathy, have distinct cellular behaviors that may be associated with reduced ECM production.     

Role of sodium in antigen-induced contraction of tracheal smooth muscle in dogs

We examined the role of Na⁺ influx in the airway response to antigen (ragweed pollen extract) in sensitized dogs, using amiloride analogs to block Na⁺-dependent processes. In in vivo studies, respiratory resistance was measured in amiloride treated and untreated groups. The resistance increased by 9.3 cmH₂O·L⁻¹·sec in response to ragweed aerosol in the untreated group, but increased only by 5.2 cmH₂O·L⁻¹·sec in the treated group. In in vitro studies, isometric tension was measured in ragweed pollen sensitized tracheal strips. Tissues were treated with amiloride or its derivatives (50 μM) for specifically blocking Na⁺ channels (phenamil), Na⁺-H⁺ exchanger [5-(N-methylN-guanidinocarbonyl methyl)-amiloride] r Na⁺-Ca²⁺ exchanger [5(4-chlorobenzyl)-2′,4′-dimethylbenzamil]. In untreated strips, tension increased in response to ragweed by 1.9 ± 0.5 mN/mg. The increase was reduced by phenamil (95.2 ± 2.5%; P<0.01 and amiloride (41.7 ± 13.1%; P<0.01), but not by the other two agents. Furthermore, phenamil also inhibited histamine-induced tension response and histamine-induced ²²Na⁺ uptake of the muscle. We conclude that antigen-induced airway response is attenuated blocking Na⁺ influx in smooth muscle.     

“Supranormal” Cardiac Function in Athletes Related to Better Arterial and Endothelial Function

Objective: Athlete's heart is associated with left ventricular (LV) hypertrophy (LVH), and “supranormal” cardiac function, suggesting that this is a physiological process. Hypertrophy alone cannot explain increase in cardiac function, therefore, other mechanisms, such as better ventriculo‐arterial coupling might be involved. Methods: We studied 60 male (21 ± 3 years) subjects: 27 endurance athletes, and a control group of 33 age‐matched sedentary subjects. We assessed global systolic and diastolic LV function, short‐ and long‐axis myocardial velocities, arterial structure and function and ventriculo‐arterial coupling, endothelial function by flow‐mediated dilatation, and amino‐terminal pro‐brain natriuretic peptide (NT‐proBNP) and biological markers of myocardial fibrosis and of oxidative stress. Results: Athletes had “supranormal” LV longitudinal function (12.4 ± 1.0 vs 10.1 ± 1.4 cm/s for longitudinal systolic velocity, and 17.4 ± 2.6 vs 15.1 ± 2.4 cm/s for longitudinal early diastolic velocity, both P < 0.01), whereas ejection fraction and short‐axis function were similar to controls. Meanwhile, they had better endothelial function (16.7 ± 7.0 vs 13.3 ± 5.3%, P < 0.05) and lower arterial stiffness (pulse wave velocity 7.1 ± 0.6 vs 8.8 ± 1.1 m/s, P = 0.0001), related to lower oxidative stress (0.259 ± 0.71 vs 0.428 ± 0.88 nmol/mL, P = 0.0001), with improved ventriculo‐arterial coupling (37.1 ± 21.5 vs 15.5 ± 13.4 mmHg.m/s³× 10³, P = 0.0001). NT‐proBNP and markers of myocardial fibrosis were not different from controls. LV longitudinal function was directly related to ventriculo‐arterial coupling, and inversely related to arterial stiffness and to oxidative stress. Conclusions: “Supranormal” cardiac function in athletes is due to better endothelial and arterial function, related to lower oxidative stress, with optimized ventriculo‐arterial coupling; athlete's heart is purely a physiological phenomenon, associated with “supranormal” cardiac function, and there are no markers of myocardial fibrosis. (Echocardiography 2010;27:659‐667)     

Intestinal absorption of lithocholate and its sulfate and glucuronide in rats

The absorption of lithocholate and its sulfate and glucuronide in rat jejunum and terminal ileum was studied. Tracer amounts of radiolabelled bile acids were administered to the ligated intestinal segments, and their absorption was monitored by biliary excretion through a bile duct catheter. Absorption of lithocholate was faster in the terminal ileum than in the jejunum. Although the sulfation reduced lithocholate absorption in the jejunum, it did not affect lithocholate absorption in the terminal ileum. This was due to the Na⁺-dependency of ileal absorption of lithocholate-sulfate assessed by perfusion studies. In contrast, the glucuronidation markedly reduced lithocholate absorption both in the jejunum and the terminal ileum. These findings indicate that the glucuronidation is more effective than sulfation in detoxifying lithocholate as far as the prevention of its intestinal absorption is concerned.     

Passive elastic wall properties in isolated guinea pig small intestine

The aim was to study and compare the passive biomechanical wall properties in the isolated duodenum and distal ileum of the guinea pigin vitro. The organ bath contained a Krebs-Ringer solution with 10^?2 M MgCl₂ to abolish smooth muscle contractile activity. Stepwise inflation of an intraluminal balloon, in which the cross-sectional area (CSA) was measured, provided the distension stimulus. The circumferential wall tension-strain distributions and wall stiffness-strain relations were computed from steady-state values of these measurements in order to evaluate the passive elastic properties. The CSA always reached equilibrium within the 2-min distension period. The CSAs obtained in the distal ileum were higher than those in the duodenum (P<0.001). The basal CSA was 17.31±1.14 mm² and 12.96±0.42 mm² for the distal ileum and the duodenum, respectively (P<0.01). At a maximum pressure of 6 kPa, the CSA of the ileum was 56.63±1.81 mm² and 36.86±1.76 mm² for the duodenum (P<0.01). The circumferential wall tension-strain distributions showed an exponential behavior that accorded well with the equationY=exp(a+bX) with determination coefficients of 0.96±0.01 and 0.99±0.00 in the duodenal segments in the distal ileal segments, respectively. The values ofa (intercept with they-axis) were 0.54±0.11 and ?0.35±0.19 for the duodenal and ileal segments, respectively (P<0.001). The slope of the curves (b values) were 4.34±0.35 in the duodenal and 5.23±0.37 in the ileal segments (0.1>P>0.05). In conclusion, differences in elastic properties were found between the proximal and distal small intestine.     

Myocardial systolic velocities and deformation assessed by speckle tracking for early detection of left ventricular dysfunction in asymptomatic patients with severe primary mitral regurgitation

Aims: In asymptomatic patients with severe primary mitral regurgitation (PMR), early detection of left ventricular (LV) dysfunction indicates the optimal timing of mitral valve surgery; however, normal ejection fraction (EF) and end‐systolic diameter (ESD) can mask significant LV impairment. Methods: We studied 28 asymptomatic patients (59 ± 13 years, 18 male) with severe PMR, EF > 60%, and ESD < 45 mm, and 10 age‐matched healthy subjects. All underwent echocardiography with tissue velocity imaging to assess LV geometry, EF, and longitudinal systolic function; and two‐dimensional speckle tracking to assess longitudinal strain (LS) and longitudinal strain rate (LSR), and radial strain (RS) and radial strain rate (RSR). Patients were reevaluated 14 days after successful mitral valve repair and divided in: IA, with a postoperative EF reduction >10% (13 patients) and IB, with an EF reduction <10% (15 patients). Results: Patients with PMR had longitudinal dysfunction and decreased radial systolic deformation, by comparison with controls, although EF and ESD were similar. Subgroup IA had significantly lower S_TVI, LS, and RS than IB (7.3 ± 0.9 vs 10.8 ± 1.5 m/s; ?16.0 ± 4.2% vs ?21.7 ± 2.1%; and 37.4 ± 2.5% vs 41.6 ± 2.4%; all p < 0.001) although preoperative LV mass index, LV diameters, and EF were similar. Multiple stepwise regression analysis showed that S_TVI and the combination of S_TVI and LS represent the main independent predictors for a postoperative EF reduction >10% (r²= 0.52, p < 0.001; and r²= 0.70, p < 0.001, respectively). Conclusion: Myocardial systolic velocities as well as radial and longitudinal LV deformation assessed by speckle tracking can detect subclinical LV dysfunction and predict impaired postoperative LV function in asymptomatic patients with severe PMR. (Echocardiography 2012;29:326‐333)     

Phasic and Tonic Stress–Strain Data Obtained in Intact Intestinal Segment In Vitro

The function of the small intestine is to a large degree mechanical, and it has the capability of deforming its shape by generating phasic (short-lasting) and tonic (sustained) contraction of the smooth muscle layers. The aim of this study was to obtain phasic and tonic stress-strain (normalized force-length) curves during distension of isolated rat jejunum and ileum (somewhat similar to the isometric length-tension diagram known from in vitro studies of muscle strips). We hypothesized that the circumferential stress-strain data depend on longitudinal stretch of the intestine. Intestinal segments were isolated from ten Wistar rats and put into an organ bath containing 37 degrees C aerated Krebs solution. Ramp distension was done on active and passive intestinal segments at longitudinal stretch ratios of 0, 10, and 20%. Ramp pressures from 0 to 7.5 cmH(2)O were applied to the intestinal lumen at each longitudinal stretch ratio. Passive conditions were obtained by adding the calcium antagonist papaverine to the solution. Total and passive circumferential stress and strain were computed from the length, diameter and pressure data and from the zero-stress state geometry. The active stress was defined as the total stress minus the passive stress. The total and passive circumferential stresses increased exponentially as a function of the strain. The amplitude of both the total and passive stress was biggest in the jejunum. The total circumferential stress decreased whereas the passive circumferential stress increased when the intestine was stretched longitudinally. Consequently, longitudinal stretching caused the active circumferential stress to decrease. The passive circumferential stress during longitudinal stretching increased more in the jejunum than in the ileum. Therefore, the active circumferential stress decreased most in the jejunum. In conclusion, the circumferential active-passive stress and strain depend on the longitudinal stretch and differs between the jejunum and ileum.     

Determinants of coronary compliance in patients with coronary artery disease: An intravascular ultrasound study

Objectives. The aim of this study was to elucidate determinants of coronary compliance in patients with coronary artery disease.Background. Intravascular ultrasound potentially enables in vivo evaluation of coronary artery compliance.Methods. Twenty-seven patients (mean age [±SD] 57 ± 11 years, three women) undergoing coronary angioplasty were studied with intravascular ultrasound imaging. A mechanical intravascular ultrasound system (4.8F, 20 MHz) was used. A total of 58 dilferent coronary segments (proximal to the target angiographic lesion) were studied. Of these, 35 were located in the left anterior descending, 9 in the left main, 8 in the left circumflex and 6 in the right coronary arteries. During intravascular ultrasound imaging, 22 segments (38%) appeared normal, but 36 (62%) had plaque (24 fibrotic, 3 lipidic and 9 calcified). Systolic-diastolic changes in area (ΔA) and pressure (ΔP) with respect to vessel area (A) were used to study normalized compliance (Normalized compliance = [ΔA/AJ/ΔP [mm Hg⁻¹×x 10³]).Results. Lumen area and plaque area were 12.6 ± 5.7 and 3 ± 3 mm², respectively. Plaque was concentric (more than two quadrants) at 10 sites, but the remaining 26 plaques were eccentric. Compliance was inversely related to age (r = −0.34, p < 0.05) but was not related to other clinical variables. Compliance was greater in the left main coronary artery (3.9 ± 2.1 vs. 1.8 ± 1.2 mm Hg⁻¹, p < 0.05) and in coronary segments with normal findings on ultrasound imaging (2.9 ± 1.9 vs. 1.6 ± 1.1 mm Hg⁻¹, p < 0.01). Moreover, at diseased coronary segments compliance was lower in calcified plaques than in other types of plaques (1.2 ± 9.7 vs. 2.3 ± 1.6 mm Hg⁻¹, p < 0.01) but was similar in concentric and eccentric plaques (1.6 ± 1.5 vs. 1.6 ± 0.9 mm Hg⁻¹). Plaque area (r = − 0.38, p < 0.01) was inversely correlated with compliance. On multivariate analysis, only age and plaque area were independently related to compliance.Conclusions. Intravascular ultrasound may be used to evaluate compliance in patients with coronary artery disease. Compliance is reduced with increasing age and is mainly determined by the arterial site and by the presence, size and characteristics of plaque on intravascular ultrasound imaging.     

Epicardial adipose tissue is tightly associated with exercise intolerance in patients with type 2 diabetes mellitus with asymptomatic left ventricular structural and functional abnormalities

AimsThis study aimed to elucidate whether the volume of epicardial adipose tissue (EAT) is associated with left ventricular (LV) structural and functional abnormalities and exercise capacity in patients with type 2 diabetes mellitus (T2DM).MethodsEAT thickness and LV structural and functional abnormality components (e.g., global longitudinal strain, E/e', LV mass index, relative wall thickness) were measured using echocardiography in 176 patients with asymptomatic stage A and B heart failure (SAHF and SBHF, respectively) and 62 healthy controls (HC). Peak oxygen uptake (peakVO2) was measured by using cardiopulmonary exercise testing.ResultsEven when matching study participants for age, sex, and body mass index, the EAT was thicker (HCs 5.5 ± 1.2 versus SAHF 6.4 ± 1.0 and SBHF 9.3 ± 1.7 mm) and peakVO2 was lower (HC 24.1 ± 3.3 versus SAHF 19.1 ± 2.0 and SBHF 16.9 ± 3.1 ml/kg/min) in the heart failure (HF) group than in the HC group (p < 0.001). EAT thickness (β = −0.189, p < 0.001) and peakVO2 were significantly associated, even after adjusting for multivariates (R² = 0.457).ConclusionsIn T2DM patients with asymptomatic HF, EAT may be associated with LV structural and functional abnormalities and exercise intolerance.     

Subclinical Myocardial Impairment Occurred in Septal and Anterior LV Wall Segments After Anthracycline-Embedded Chemotherapy and did not Worsen During Adjuvant Trastuzumab Treatment in Breast Cancer Patients

In a previous study of breast cancer patients, we found changes in cardiac function and size during the early stages of adjuvant trastuzumab (Herceptin^®) therapy. Here we present a subgroup analysis of this patient cohort. This subgroup received a anthracycline-embedded chemotherapy followed by at least 3 months up to 6 months of adjuvant Herceptin^® therapy. Twenty-seven female breast cancer patients with Her-2/-neu overexpression were studied using conventional echocardiography and 2D speckle tracking. These methods were done before anthracycline-embedded chemotherapy, before adjuvant trastuzumab therapy, and both 3 and 6 months after the start of the therapy (T3, T6). The LV–EF (Simpson biplane) decreased significantly from before the chemotherapy to after the chemotherapy and further decreased after 3 months of trastuzumab therapy (66.2 ± 1.5 vs. 58.7 ± 1.2 vs. 55.6 ± 1.3 vs. 55.9 ± 1.5 %; p < 0.05). The stroke volume index remained constant after chemotherapy (22.0 ± 0.8 vs. 22.6 ± 1.3 ml/m²; p = 0.9), but increased significantly during trastuzumab therapy (26.7 ± 1.1 and 27.3 ± 1.0 ml/m²; p < 0.01). Global longitudinal strain exclusively decreased during chemotherapy (?21.0 ± 0.5 vs. ?18.9 ± 0.5 %, p < 0.001). Regional longitudinal strain decreased significantly after chemotherapy in septal, anteroseptal, anterolateral, and apex segments. Mitral valve regurgitation increased during the whole treatment, but especially during trastuzumab. Right ventricular function decreased exclusively during chemotherapy. Anthracycline-embedded chemotherapy in patients with breast cancer led to a decrease in LV function, especially of the septal and anterior segments, and did not worsen during adjuvant trastuzumab treatment.     

Brain function rescue effect of lactate following hypoglycaemia is not an adaptation process in both normal and Type I diabetic subjects

Aims/hypothesis. We have previously shown that lactate protects brain function during insulin-induced hypoglycaemia. An adaptation process could, however, not be excluded because the blood lactate increase preceded hypoglycaemia.¶Methods. We studied seven healthy volunteers and seven patients with Type I (insulin-dependent) diabetes mellitus with a hyperinsulinaemic (1.5 mU · kg^–1· min^–1) stepwise hypoglycaemic clamp (4.8 to 3.6, 3.0 and 2.8 mmo/l) with and without Na-lactate infusion (30 μmol · kg^–1· min^–1) given after initiation of hypoglycaemic symptoms.¶Results. The glucose threshold for epinephrine response was similar (control subjects 3.2 ± 0.1 vs 3.2 ± 0.1, diabetic patients = 3.5 ± 0.1 vs 3.5 ± 0.1 mmol/l) in both studies. The magnitude of the response was, however, blunted by lactate infusion (AUC; control subjects 65 ± 28 vs 314 ± 55 nmol/l/180 min, zenith = 2.6 ± 0.5 vs 4.8 ± 0.7 nmol/l, p < 0.05; diabetic patients = 102 ± 14 vs 205 ± 40 nmol/l/180 min, zenith = 1.4 ± 0.4 vs 3.2 ± 0.3 nmol/l, p < 0.01). The glucose threshold for symptoms was also similar (C = autonomic 3.0 ± 0.1 vs 3.0 ± 0.1, neuroglycopenic = 2.8 ± 0.1 vs 2.9 ± 0.1 mmol/l, D = autonomic 3.2 ± 0.1 vs 3.2 ± 0.1, neuroglycopenic 3.1 ± 0.1 vs 3.2 ± 0.1 mmol/l) but peak responses were significantly attenuated by lactate (score at 160 min C = 2.6 ± 1 vs 8.8 ± 1, and 0.4 ± 0.4 vs 4.8 ± 1, respectively; p = 0.02–0.01, D = 1.3 ± 0.5 vs 6.3 ± 1.7, and 2.3 ± 0.6 vs 5.7 ± 1.1 p = 0.07–0.02). Cognitive function deteriorated in both studies at similar glucose thresholds (C = 3.1 ± 0.1 vs 3.0 ± 0.1, D = 3.2 ± 0.1 vs 3.3 ± 0.2 mmol/l). Although in normal subjects a much smaller impairment was observed with lactate infusion (Δ four-choice reaction time at 160 min = 22 ± 12 vs 77 ± 31 ms; p = 0.02), in Type I diabetic patients lactate infusion was associated with an improvement in cognitive dysfunction (0.2 ± 0.4 vs –38 ± 0.2 Δ ms, p = 0.0001).¶Conclusion/interpretation. A blood lactate increase after the development of hypoglycaemic symptoms reduces counterregulatory and symptomatic responses to insulin-induced hypoglycaemia and favours brain function rescue both in normal and diabetic subjects. These findings confirm that lactate is an alternative substrate to glucose for cerebral metabolism under hypoglycaemic conditions. [Diabetologia (2000) 43: 733–741]