Late complications of robot-assisted radical cystectomy with totally intracorporeal urinary diversion.

INTRODUCTION AND OBJECTIVES: To evaluate late complications in a large cohort of patients undergoing robot-assisted radical cystectomy (RARC) with totally intracorporeal urinary diversion (ICUD). MATERIALS AND METHODS: We prospectively enrolled patients who underwent RARC and ICUD between August 2012 and June 2019. We excluded patients with Ejection fraction < 36%, retinal vasculopathy, ventriculoperitoneal shunts, and those treated without curative intent. All complications and their onset date have been recorded, defined, and graded according to Clavien classification adapted for radical cystectomy. RESULTS: 210 patients were included, 76% of whom were men, with a mean age of 62 years. Urinary diversions used were Padua Ileal Bladder (PIB) in 80% of cases, and ileal conduit (IC) in 20% of patients (generally older and with more comorbidity). The mean follow-up was 30 ± 22 months. The stenosis rate of uretero-ileal anastomosis was 14%, while a reduction in eGFR (≥ 20%) was observed in about half of the cases. UTIs occurred in 37% of the patients, especially in the first 12 months. Only 2% of patients had bowel occlusion, whereas incisional hernia, lymphocele, and systemic events (metabolic acidosis and major cardiovascular events) occurred respectively in 20%, 10%, and 1% of cases. CONCLUSIONS: Our study evaluates first late complications in a cohort of patients who underwent RARC with ICUD. These data are encouraging and in line with findings from a historical series of open radical cystectomy (ORC). This study is a further step in supporting RARC as a safe and effective surgical option for the treatment of muscle-invasive bladder cancer (MIBC) in tertiary referral centers.

Pelvic floor rehabilitation for defecation disorders.

Pelvic floor rehabilitation is frequently recommended for defecation disorders, in both constipation and fecal incontinence. However, the lack of patient selection, together with the variety of rehabilitation methods and protocols, often jeopardize the results of this approach, causing difficulty in evaluating outcomes and addressing proper management, and above all, in obtaining scientific evidence for the efficacy of these methods for specific indications. The authors represent different gastroenterological and surgical scientific societies in Italy, and their aim was to identify the indications and agree on treatment protocols for pelvic floor rehabilitation of patients with defecation disorders. This was achieved by means of a modified Delphi method, utilizing a working team (10 members) which developed the statements and a consensus group (15 members, different from the previous ones) which voted twice also suggesting modifications of the statements.

Axl receptor tyrosine kinase is a potential therapeutic target in renal cell carcinoma.

BACKGROUND: Axl plays multiple roles in tumourigenesis in several cancers. Here we evaluated the expression and biological function of Axl in renal cell carcinoma (RCC). METHODS: Axl expression was analysed in a tissue microarray of 174 RCC samples by immunostaining and a panel of 11 normal tumour pairs of human RCC tissues by western blot, as well as in RCC cell lines by both western blot and quantitative PCR. The effects of Axl knockdown in RCC cells on cell growth and signalling were investigated. The efficacy of a humanised Axl targeting monoclonal antibody hMAb173 was tested in histoculture and tumour xenograft. RESULTS: We have determined by immunohistochemistry (IHC) that Axl is expressed in 59% of RCC array samples with moderate to high in 20% but not expressed in normal kidney tissue. Western blot analysis of 11 pairs of tumour and adjacent normal tissue show high Axl expression in 73% of the tumours but not normal tissue. Axl is also expressed in RCC cell lines in which Axl knockdown reduces cell viability and PI3K/Akt signalling. The Axl antibody hMAb173 significantly induced RCC cell apoptosis in histoculture and inhibited the growth of RCC tumour in vivo by 78%. The hMAb173-treated tumours also had significantly reduced Axl protein levels, inhibited PI3K signalling, decreased proliferation, and induced apoptosis. CONCLUSIONS: Axl is highly expressed in RCC and critical for RCC cell survival. Targeting Axl is a potential approach for RCC treatment.

Annular erythema in primary Sjogren's syndrome: description of 43 non-Asian cases.

OBJECTIVE: The objective of this paper is to evaluate the prevalence and characterize the main epidemiological, clinical and immunological features of annular erythema (AE) in non-Asian patients with primary Sjögren's syndrome (SS). METHODS: We carried out a retrospective study searching for AE in 377 Spanish patients with primary SS fulfilling the 2002 American-European criteria. In addition, we searched PubMed (1994-2012) using the MeSH terms "annular erythema" and "primary Sjögren's syndrome" for additional cases. All cases with AE reported in patients with SS associated with systemic lupus erythematosus were excluded. RESULTS: In our Spanish cohort, we found 35 (9%) patients diagnosed with AE. All were white females, with a mean age of 47 years at diagnosis of AE. AE preceded diagnosis of SS in 27 (77%) patients. Cutaneous AE lesions involved principally the face and upper extremities. All patients reported photosensitivity, with cutaneous flares being reported during the warmest months in 93% of patients. Immunological markers consisted of anti-Ro/La antibodies in 31 (89%) patients. In the literature search, we identified eight additional non-Asian patients with primary SS diagnosed with AE. In comparison with 52 Asian patients, the 43 non-Asian patients with AE related to primary SS were more frequently women (100% vs 78%, p=0.008), and cutaneous lesions were less frequently reported in the face (55% vs 81%, p=0.045) and more frequently in the neck (40% vs 14%, p=0.041). Immunologically, non-Asian patients had a lower frequency of anti-Ro antibodies and a higher frequency of negative Ro/La antibodies, although the differences were not statistically significant. CONCLUSION: AE is not an exclusive cutaneous feature of Asian patients with primary SS. In addition to the characteristic cutaneous expression, AE has a very specific clinical and immunological profile: often presenting before the fulfillment of SS criteria, overwhelmingly associated with anti-Ro antibodies but weakly associated with other immunological markers and the main systemic SS-related features.

Bronchiectasis in primary Sjögren's syndrome: prevalence and clinical significance.

OBJECTIVES: To analyse the prevalence and clinical significance of bronchiectasis in a large series of patients with primary Sjögren's syndrome (SS) and evaluate its impact on disease expression and outcomes. METHODS: The study cohort included 507 patients with primary SS. Bronchiectasis were diagnosed according to pulmonary computed tomography (CT). As a control group, we included 37 consecutive SS patients evaluated by pulmonary CT during the same study period without pulmonary involvement. RESULTS: Fifty primary SS patients had bronchiectasis according to the pulmonary CT. Nine patients were excluded due to non-autoimmune processes and 41 were classified as bronchiectasis associated with primary SS (40 women, mean age of 64 years). All cases of bronchiectasis were of the cylindrical type and were located in the inferior lobes in 29 cases (71%). Patients with bronchiectasis were older at diagnosis of SS (60.39 vs. 52.54 years, p=0.022) and had a higher frequency of hiatus hernia (41% vs. 16%, p=0.024) in comparison with controls. Immunologically, patients with bronchiectasis had a lower frequency of anti-Ro/SS-A antibodies (27% vs. 54%, p=0.022) but a higher frequency of anti-smooth muscle--SMAantibodies (82% vs. 60%, p=0.043). During follow-up, patients with bronchiectasis had a higher frequency of respiratory infections (56% vs. 3%, p<0.001) and pneumonia (29% vs. 3%, p=0.002) in comparison with those without. CONCLUSIONS: Patients with primary SS and bronchiectasis are characterised by an older age, a high frequency of hiatus hernia, a specific immunologic pattern (low frequency of anti-Ro/SS-A and high frequency of anti-SMA) and during follow-up a much higher frequency of respiratory infections and pneumonia.

Optimal treatment duration of glyceryl trinitrate for chronic anal fissure: results of a prospective randomized multicenter trial.

BACKGROUND: Chronic anal fissure (CAF) is a painful condition that is unlikely to resolve with conventional conservative management. Previous studies have reported that topical treatment of CAF with glyceryl trinitrate (GTN) reduces pain and promotes healing, but optimal treatment duration is unknown. METHODS: To assess the effect of different treatment durations on CAF, we designed a prospective randomized trial comparing 40 versus 80 days with twice daily topical 0.4% GTN treatment (Rectogesic, Prostrakan Group). Chronicity was defined by the presence of both morphological (fibrosis, skin tag, exposed sphincter, hypertrophied anal papilla) and time criteria (symptoms present for more than 2 months or pain of less duration but similar episodes in the past). A gravity score (1 = no visible sphincter; 2 = visible sphincter; 3 = visible sphincter and fibrosis) was used at baseline. Fissure healing, the primary endpoint of the study, maximum pain at defecation measured with VAS and maximum anal resting pressure were assessed at baseline and at 14, 28, 40 and 80 days. Data was gathered at the end of the assigned treatment. RESULTS: Of 188 patients with chronic fissure, 96 were randomized to the 40-day group and 92 to the 80-day group. Patients were well matched for sex, age, VAS and fissure score. There were 34 (19%) patients who did not complete treatment, 18 (10%) because of side effects. Of 154 patients who completed treatment, 90 (58%) had their fissures healed and 105 (68%) were pain free. There was no difference in healing or symptoms between the 40- and the 80-day group. There was no predictor of fissure healing. A low fissure gravity score correlated with increased resolution of pain (P < 0.05) and improvement of VAS score (P < 0.05) on both univariate and multivariate analysis. A lower baseline resting pressure was associated with better pain resolution on univariate analysis (P < 0.01). VAS at defecation and fissure healing significantly improved until 40 days (P < 0.001), while the difference between 40 and 80 days was not significant. CONCLUSION: We found no benefits in treating CAF with topical GTN for 80 days compared to 40 days. Fissure healing and VAS improvement continue until 6 weeks of treatment but are unlikely thereafter.

[Comparison of conventional technique, Ligasure Precise and Harmonic Focus in total thyroidectomy]. / Studio comparativo tra tecnica tradizionale, Ligasure Precise ed Harmonic Focus nella tiroidectomia totale.

The aim of this study was to compare the results obtained using an electrothermal bipolar vessel sealing system (Ligasure Precise), a harmonic curved shears (Harmonic Focus) and traditional technique in total thyroidectomy. We have enrolled 93 patients and assigned randomly to three groups of 31 pt: groups L (Ligasure Precise), F (Harmonic Focus) and C (traditional thecnique). Recorded data were demographics, preoperative serum calcium levels, operation time, length of hospital stay, weight of exported gland and pathology, postoperative calcemia at one and two days and recurrent laryngeal nerve paralysis. The three groups did not present statistically significant differences in term of age, gender and pathology classification. No postoperative haemorrhages were observed. The overall incidence of hypocalcemia was 38.9% (36 pt) and the mean days of hospitalization were 2.3 days without statistically significant differences between the three groups. Only one patient (group F) presented temporary recurrent laryngeal nerve paralysis. Mean operation time (minutes) was significantly reduced by approximately 15% in group F (62.7+/-14.1) compared with group C (72.7+/-13.6; Kruskal-Wallis test: p<0.05). Both devices resulted safe and efficient. The only advantage observed was a significant reduction operation time when using Harmonic Foscus curved shears compared to the other techniques.

Vitamin D Deficiency as a Predictive Factor of Transient Hypocalcemia after Total Thyroidectomy.

BACKGROUND: Total thyroidectomy (TT) is recommended in the treatment of malignant and benignant thyroid diseases, and, to date, transient hypocalcemia is the most frequent complication after the procedure. We prospectively evaluated the role of vitamin D deficiency as a predictor of postoperative hypocalcemia. METHODS: This is a prospective cohort study which was conducted between January 2016 and April 2019. A total of 177 consecutive patients (141 (79.7%) women and 36 (20.3%) men) who underwent TT were included in the current study. Hypocalcemia occurred when serum calcium levels were below 8.0 mg/dL or 1.10 mmol/L. Patients were divided into two groups (Group 1, normocalcemic; Group 2, hypocalcemic) and were assessed taking into consideration preoperative serum 25-hydroxy vitamin D (25-OHD) levels, preoperative serum calcium levels, thyroid hormone levels, sex, body mass index (BMI), and smoking habits. Vitamin D deficiency was defined as 25-OHD levels <25 ng/mL. RESULTS: The incidence of postoperative asymptomatic and symptomatic hypocalcemia in the two groups was 19.8% and 15.8%, respectively. Preoperative 25-OHD level was significantly different between Group 1 and Group 2 (31.5 ± 15.0 ng/mL vs 18.7 ± 9.8 ng/mL,p=0.017). Logistic regression analysis revealed that preoperative vitamin D deficiency was a significant predictive factor of postoperative hypocalcemia (p=0.012), and, specifically, the risk of hypocalcemia increased 15-fold in patients with a preoperative vitamin D level <25 ng/mL (odds ratio [OR], 14.8). CONCLUSIONS: Postoperative hypocalcemia is significantly associated with low preoperative levels of serum 25-OHD. Our studies demonstrate that vitamin D deficiency (<25 ng/mL) is an independent predictive factor of postoperative hypocalcemia.

Self-monitoring of Blood Pressure in Patients With Hypertension-Related Multi-morbidity: Systematic Review and Individual Patient Data Meta-analysis.

BACKGROUND: Studies have shown that self-monitoring of blood pressure (BP) is effective when combined with co-interventions, but its efficacy varies in the presence of some co-morbidities. This study examined whether self-monitoring can reduce clinic BP in patients with hypertension-related co-morbidity. METHODS: A systematic review was conducted of articles published in Medline, Embase, and the Cochrane Library up to January 2018. Randomized controlled trials of self-monitoring of BP were selected and individual patient data (IPD) were requested. Contributing studies were prospectively categorized by whether they examined a low/high-intensity co-intervention. Change in BP and likelihood of uncontrolled BP at 12 months were examined according to number and type of hypertension-related co-morbidity in a one-stage IPD meta-analysis. RESULTS: A total of 22 trials were eligible, 16 of which were able to provide IPD for the primary outcome, including 6,522 (89%) participants with follow-up data. Self-monitoring was associated with reduced clinic systolic BP compared to usual care at 12-month follow-up, regardless of the number of hypertension-related co-morbidities (-3.12 mm Hg, [95% confidence intervals -4.78, -1.46 mm Hg]; P value for interaction with number of morbidities = 0.260). Intense interventions were more effective than low-intensity interventions in patients with obesity (P < 0.001 for all outcomes), and possibly stroke (P < 0.004 for BP control outcome only), but this effect was not observed in patients with coronary heart disease, diabetes, or chronic kidney disease. CONCLUSIONS: Self-monitoring lowers BP regardless of the number of hypertension-related co-morbidities, but may only be effective in conditions such obesity or stroke when combined with high-intensity co-interventions.

Mannose-binding lectin-low genotypes are associated with milder systemic and immunological disease expression in primary Sjögren's syndrome.

OBJECTIVE: To investigate the association of mannose-binding lectin (MBL)-low genotypes with the clinical and immunological expression of primary SS. METHODS: Eighty-one patients with primary SS who fulfilled the 2002 classification criteria were included in the study. MBL2 polymorphisms were investigated by sequence-based DNA typing of the promoter and exon 1. Genotypes 0/0, 0/XA or XA/XA were considered as MBL-low and XA/A, A/0 and A/A as MBL-sufficient. Control groups included 46 patients who exclusively fulfilled the 1993 SS criteria, 114 SLE patients and 104 healthy individuals. RESULTS: Twelve (15%) SS patients had MBL-low genotypes, of whom six (7%) had genotype 0/XA, five (6%) had genotype 0/0 and one (1%) had genotype XA/XA. A higher prevalence of the XA/A genotype (32 vs 17%, P = 0.01) was found in primary SS patients in comparison with SLE patients. No patient with primary SS carrying MBL-low genotypes had purpura, glomerulonephritis or neurological involvement (0 vs 29%, P = 0.025). Immunologically, patients carrying MBL-low genotypes had a lower frequency of anti-Ro/SS-A antibodies (17 vs 55%, P = 0.014), anti-La/SS-B antibodies (8 vs 48%, P = 0.009) and low C4/C3 levels (0 vs 32%, P = 0.016). No patient with primary SS carrying the homozygous MBL-deficient genotype 0/0 had anti-Ro/SS-A or anti-La/SS-B antibodies, low C3/C4 levels or circulating cryoglobulins. CONCLUSION: SS patients with MBL-low genotypes have a less pronounced systemic and immunological disease expression in comparison with those carrying MBL-sufficient genotypes. In primary SS, MBL deficiency may represent a protective factor against the development of more aggressive autoimmune damage.

Why is there recurrence after transcystic laparoscopic bile duct clearance? Risk factor analysis.

AIM: Incidence of common bile duct stones (CBDS) is approximately 10% in patients with symptomatic gallstones undergoing laparoscopic cholecystectomy. Transcystic laparoscopic common bile duct exploration (TC-CBDE) is safe and efficient in achieving bile duct clearance from stones, with a success rate of between 85% and 95%. The aim of this retrospective study is the evaluation of risk factors and recurrence in patients treated with TC-CBDS. METHODS: From October 2003 until September 2007, 110 consecutive patients with common bile duct stones and gallbladder were included in the study. Average age was 64 years (range 21-82 years). The procedure was completed laparoscopically in 106 patients (96.4%): with TC-CBDE in 90 patients (85%), who are the object of this study; and with TC-CBDE + perioperative guide wire papillotomy ("rendezvous") in 16 cases (15%). In the 90 patients treated with TC-CBDE which we examined, the risk factors were: preoperative liver function tests, diameter of the common bile duct (normal 8 mm or less), number of stones (3 with biliary sludge predicted a recurrence (p < 0.05) while the other factors did not show important clinical variables. CONCLUSION: TC-CBDE is safe and effective in the majority of cases of CBDS. The incidence of recurrence is low but there are some risk factors, such as number of stones >3 with biliary sludge, which do not favor the successful outcome of the procedure. In such cases, it is essential that the TC-CBDE is integrated with other procedures which, although more complex, assure the clearance of the bile duct.

Different perception of chronic constipation between patients and gastroenterologists.

BACKGROUND: There is a certain number of subjects that consider themselves to be constipated (self diagnosed constipation; SDC). The Rome Criteria separate FC from IBS-C, but some SDC patients do not meet the Rome criteria (no Rome Constipation; NRC). Our aims were to evaluate the percentage of SDC subjects with a diagnosis of FC and IBS-C and to compare demographic and clinical features, symptoms, and quality of life in the different SDC groups (FC, IBS-C, NRC). METHODS: During a 2-month period, 934 patients and 980 accompanying persons (AP) were asked to complete a survey. The presence of FC or IBS-C was assessed. SDC subjects were invited to record the stool consistency (Bristol scale) and to fill in the Constipation Severity Index (CSI), obstructed defecation syndrome (ODS) and patient assessment of constipation-quality of life (PAC-QoL). The use of laxatives and enemas was evaluated. KEY RESULTS: The probability of the ROME III criteria being present was higher in SDC compared with no-SDC (OR 20.5). NRC was present in 13.5% of the SDC. In the patients' group the agreement between a diagnosis of Rome III and SDC was good (K 0.62), whereas in the AP it was moderate (K 0.56). NRC showed lower mean values of ODS, CSI and PAC-QoL, higher Bristol scale and a lower use of laxatives and enemas compared to IBS-C and FC. No differences were found between IBS-C and FC. CONCLUSIONS AND INFERENCES: The Rome III criteria identify subjects with a greater clinical impact, but separation of FC and IBS-C does not seem justified.

[Preliminary results in the use of a new composite prosthesis in incisional hernia repair]. / Risultati preliminari sull'utilizzo di una nuova protesi intraperitoneale nel trattamento del laparocele.

The repair of incisional hernias with the use of prosthetic biomaterials is the standard of care today. There are different prosthetic biomaterials that can be used to repair incisional hernias. These materials can be divided into products that are single component or a combination. Incisional hernia repair using the intraperitoneal implantation of a prosthesis requires mesh with impervious properties. This is preliminary study with a new composite non resorbable mesh in polyethylene terephthalate-polyurethane (HI-TEX PARP MP) used for incisional hernia repair in intraperitoneal implantation. This mesh has one permeable side in polyethylene terephthalate (PET) for rapid tissue fixation and another side in polyurethane (PEU), hydrophobic in order to avoid cell penetration. This is a preliminary study of medical records of 24 patients (17 women and 7 men) in whom intraperitoneal placement of composite prosthetics in polyethylene terephthalate-polyurethane (HI-TEX PARP MP) was used between September 2004 and September 2006. The incisional hernias were recurrent in 8 patients. The underside of the mesh was placed in direct contact with the visceral peritoneum, whereas the upper side made contact with the subcutaneous tissue. No intraoperative complications occurred. Postoperatively, 1 had seromas, 1 had phlegmon of the wound without removing prosthetics. There was 1 death but not dependent of the surgical performance. The follow-up, was 12 months (range 1 month-2 years); none had discomfort; only one patient had recurrence. Intraperitoneal placement of HI-TEX PARP MP has several advantages over other techniques including minimal adhesions, a decreased risk of infection and recurrences. In addition this mesh is more economics than the other prosthetics in use.

Self-perceived normality in defecation habits.

BACKGROUND: Available information on normal bowel habits was mainly gathered by means of telephone interviews or mailed questionnaires. AIMS: We undertook a prospective study to evaluate the defecatory habits in subjects perceiving themselves as normal concerning this function. SUBJECTS AND METHODS: A questionnaire (4-week diary with "yes-no" daily answers to six questions concerning bowel habits) was distributed to 204 subjects perceiving their defecation behaviour as normal. RESULTS: The completed questionnaire was returned by 140 subjects. No significant differences were found between sexes or age groups for any variable, even though straining at stool and feeling of incomplete and/or difficult evacuation showed a trend to increase with age. No subject had less than three bowel movements per week or more than three per day. The percentage of symptoms linked to an abnormal defecatory behaviour was well below 10%. Fifty-five percent of subjects reported at least one parameter of abnormal functioning; the most frequent was straining at stool and the rarer was the manual manoeuvres to help defecation. CONCLUSIONS: In normal subjects the prevalence of symptoms considered in Rome II criteria as part of an abnormal defecatory behaviour (in more than 25% of defecations) is well below 10%, manual manoeuvres are almost never used to help defecation, and the frequency of defecations is at least three per week.

Exercise-induced increases in atrial natriuretic factor are attenuated by endurance training.

Short-term exercise has been associated with increased plasma levels of atrial natriuretic factor, a potent dilating and natriuretic hormone. In this study, the effect of exercise training on atrial natriuretic factor release during short-term exercise was investigated in men without a history of cardiovascular or other major disease. A well trained group of 10 men who exercised an average of 6,618 kcal/week was compared with a minimally trained group of 9 men who exercised 1,479 kcal/week. Maximal oxygen uptake was 55.2 ml/kg per min in the well trained group and 42.5 ml/kg per min in the minimally trained group (p less than 0.05). Plasma for atrial natriuretic factor, norepinephrine and epinephrine was obtained at rest, at 4 min of exercise and at maximal exercise. Atrial natriuretic factor was lower at rest in the minimally trained than in the well trained men (23 vs. 35.9 pg/ml, p less than 0.05). At maximal exercise, atrial natriuretic factor increased 2.6 times the value at rest in minimally trained men (59.8 pg/ml, p less than 0.05 vs. rest), but did not change in well trained men (34 pg/ml). In minimally trained men at rest, at 4 min of exercise and at maximal exercise, plasma levels of atrial natriuretic factor correlated with heart rate, cardiac output, mean arterial pressure and plasma levels of norepinephrine and epinephrine; these correlations were not found in the well trained group. Thus, short-term exercise results in a significant increase in atrial natriuretic factor in minimally trained but not in well trained men.(ABSTRACT TRUNCATED AT 250 WORDS)

Technological advances and the next 50 years of cardiology.

The fiftieth anniversary of the ACC and the end of the twentieth century are arbitrary points in time, yet they seem to coincide with a true watershed. The last 50 years have brought a rush of new techniques and understandings that have, for the first time, given cardiovascular specialists real tools to prevent and fight cardiovascular disease. Only now, for the first time, has science begun to understand exactly what happens when plaque forms in an artery, when heart muscle fibers cross-link and weaken, when an atrial chamber fibrillates, and when heart muscle cells die en masse after a heart attack. We are beginning to track down the actual chemical, mechanical, and electrical pathways by which the heart is damaged or dies. When we can interfere with those pathways and stop the chain of events, we will have defeated heart disease. Imagination is rapid, but progress is often both uncertain and slow because of the many constraints of cost, regulation, and time needed to test and evaluate new developments. Yet we can now foresee a future in which medical science might actually defeat cardiovascular disease the way it has defeated polio, smallpox, and other serious scourges of the past.

Indomethacin attenuates the constriction of canine epicardial coronary arteries to acetylcholine in the absence of endothelium: contribution of platelets to vasoconstriction in vivo.

This study was designed to evaluate the in vivo effect of acetylcholine on endothelial-damaged canine epicardial coronary arteries and the potential contribution of platelets to those acetylcholine-induced responses. Changes in left anterior descending artery cross-sectional area were determined by quantitative angiography in the closed chest anesthetized dog. Baseline cross-sectional area of the left anterior descending artery was not changed by removal of the endothelium by balloon-tipped catheter. Increased constrictor tone produced by prostaglandin F2 alpha was comparable in endothelium-intact and endothelium-removed vessels, supporting an endothelium-independent mechanism for prostaglandin F2 alpha in vivo. Acetylcholine produced anterior descending artery vasodilation with the endothelium intact; a comparable maximal dilator response was also obtained in the presence of increased constrictor tone (prostaglandin F2 alpha). In contrast, acetylcholine produced vasoconstriction of the anterior descending artery when the endothelium was removed. To evaluate the mechanism of acetylcholine-induced vasoconstriction in endothelium-removed vessels, the same protocol was completed in the presence of the platelet inhibitor indomethacin. Indomethacin did not alter baseline cross-sectional area or the dilator response to acetylcholine in endothelium-intact vessels. In contrast, the constrictor response in endothelium-removed vessels was antagonized, and a dilator response comparable with that in endothelium-intact vessels was produced by acetylcholine. The results of this study provide an experimental basis for the observations in human studies in which apparently atherosclerotic vessels constrict in response to acetylcholine. Removal of the endothelium in vivo abolishes the dilator response to acetylcholine and converts the acetylcholine response to vasoconstriction or vasospasm.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiographic demonstration of spontaneous diffuse three vessel coronary artery spasm.

The spontaneous occurrence of diffuse three vessel coronary artery spasm was documented during routine coronary angiography in three patients with a history of variant angina. Quantitative angiographic analysis of 18 arterial segments demonstrated that the mean luminal diameter of 1.47 mm during spasm increased to 2.47 mm after the administration of nitroglycerin (p less than 0.0001). The underlying coronary arteries were normal or near normal. Although multivessel spasm has previously been considered to be uncommon and its spontaneous occurrence during angiography only rarely documented, these cases suggest that it may be more common than previously recognized. In addition to important diagnostic considerations, this phenomenon may have important implications regarding the pathophysiologic role of endothelium in coronary artery spasm.

Action and localization of vasoactive intestinal peptide in the coronary circulation: evidence for nonadrenergic, noncholinergic coronary regulation.

Vasoactive intestinal polypeptide, a neurotransmitter peptide detected in animal and human hearts, has been found in nerves of coronary arteries. To determine the amount and distribution of vasoactive intestinal polypeptide in the large coronary vessels and its possible participation in coronary vasoregulation, two groups of animals were studied. In the first group, 11 anesthetized dogs were sacrificed to collect three (1 cm) segments along the circumflex and left anterior descending coronary arteries. These segments represented proximal (I), middle (II) and distal (III) portions of the two arteries. Concentrations (ng/g) of vasoactive intestinal polypeptide-like immunoreactive substance were determined by radioimmunoassay. Vasoactive intestinal polypeptide-like immunoreactivity was present in the left anterior descending (I = 7.28 +/- 1.65, II = 3.74 +/- 0.57, III = 2.29 +/- 0.53) and circumflex (I = 4.16 +/- 1.52, II = 4.58 +/- 1.13, III = 4.00 +/- 0.81) coronary arteries. The difference in vasoactive intestinal polypeptide-like immunoreactivity among epicardial segments of the anterior descending artery was significant, but there was no significant difference among segments of the circumflex coronary artery. In the second group (eight closed chest anesthetized dogs), the effects of vasoactive intestinal polypeptide intracoronary infusion on epicardial coronary constriction were examined at rest and with the artery constricted by serotonin. Left anterior descending (segments I, II and III) artery responses (% area change) to vasoactive intestinal polypeptide and vasoactive intestinal polypeptide plus serotonin were examined using quantitative coronary angiography. Vasoactive intestinal polypeptide infusion resulted in significant vasodilation in all the segments (I, II and III) of the left anterior descending artery.(ABSTRACT TRUNCATED AT 250 WORDS)