Prognostic factors for chronic post-surgical pain after lung and pleural surgery: a systematic review with meta-analysis, meta-regression and trial sequential analysis.

Chronic post-surgical pain is known to be a common complication of thoracic surgery and has been associated with a lower quality of life, increased healthcare utilisation, substantial direct and indirect costs, and increased long-term use of opioids. This systematic review with meta-analysis aimed to identify and summarise the evidence of all prognostic factors for chronic post-surgical pain after lung and pleural surgery. Electronic databases were searched for retrospective and prospective observational studies as well as randomised controlled trials that included patients undergoing lung or pleural surgery and reported on prognostic factors for chronic post-surgical pain. We included 56 studies resulting in 45 identified prognostic factors, of which 16 were pooled with a meta-analysis. Prognostic factors that increased chronic post-surgical pain risk were as follows: higher postoperative pain intensity (day 1, 0-10 score), mean difference (95%CI) 1.29 (0.62-1.95), p < 0.001; pre-operative pain, odds ratio (95%CI) 2.86 (1.94-4.21), p < 0.001; and longer surgery duration (in minutes), mean difference (95%CI) 12.07 (4.99-19.16), p < 0.001. Prognostic factors that decreased chronic post-surgical pain risk were as follows: intercostal nerve block, odds ratio (95%CI) 0.76 (0.61-0.95) p = 0.018 and video-assisted thoracic surgery, 0.54 (0.43-0.66) p < 0.001. Trial sequential analysis was used to adjust for type 1 and type 2 errors of statistical analysis and confirmed adequate power for these prognostic factors. In contrast to other studies, we found that age had no significant effect on chronic post-surgical pain and there was not enough evidence to conclude on sex. Meta-regression did not reveal significant effects of any of the study covariates on the prognostic factors with a significant effect on chronic post-surgical pain. Expressed as grading of recommendations, assessment, development and evaluations criteria, the certainty of evidence was high for pre-operative pain and video-assisted thoracic surgery, moderate for intercostal nerve block and surgery duration and low for postoperative pain intensity. We thus identified actionable factors which can be addressed to attempt to reduce the risk of chronic post-surgical pain after lung surgery.

Determination of volatile organic compounds in exhaled breath of heart failure patients by needle trap micro-extraction coupled with gas chromatography-tandem mass spectrometry.

The analytical performances of needle trap micro-extraction (NTME) coupled with gas chromatography-tandem mass spectrometry were evaluated by analyzing a mixture of twenty-two representative breath volatile organic compounds (VOCs) belonging to different chemical classes (i.e. hydrocarbons, ketones, aldehydes, aromatics and sulfurs). NTME is an emerging technique that guarantees detection limits in the pptv range by pre-concentrating low volumes of sample, and it is particularly suitable for breath analysis. For most VOCs, detection limits between 20 and 500 pptv were obtained by pre-concentrating 25 ml of a humidified standard gas mixture at a flow rate of 15 ml min-1. For all compounds, inter- and intra-day precisions were always below 15%, confirming the reliability of the method. The procedure was successfully applied to the analysis of exhaled breath samples collected from forty heart failure (HF) patients during their stay in the University Hospital of Pisa. The majority of patients (about 80%) showed a significant decrease of breath acetone levels (a factor of 3 or higher) at discharge compared to admission (acute phase) in correspondence to the improved clinical conditions during hospitalization, thus making this compound eligible as a biomarker of HF exacerbation.

Post-operative elimination of sevoflurane anesthetic and hexafluoroisopropanol metabolite in exhaled breath: pharmacokinetic models for assessing liver function.

Sevoflurane (SEV), a commonly used anesthetic agent for invasive surgery, is directly eliminated via exhaled breath and indirectly by metabolic conversion to inorganic fluoride and hexafluoroisopropanol (HFIP), which is also eliminated in the breath. We studied the post-operative elimination of SEV and HFIP of six patients that had undergone a variety of surgeries lasting between 2.5 to 8.5 h using exhaled breath analysis. A classical three compartments pharmacokinetic model developed for the study of environmental contaminants was fitted to the breath data. We found that SEV kinetic behavior following surgery (for up to six days) is consistent across all subjects whereas the production and elimination of HFIP varies to some extent. We developed subject specific parameters for HFIP metabolism and interpreted the differences in the context of timing and dose of anesthesia, type of surgery, and specific host factors. We propose methods for assessing individual patient liver function using SEV as a probe molecule for assessing efficiency of liver metabolism to HFIP. This work is valuable not only for the clinical study of metabolism recovery, but potentially also for the study of the interaction of other manufactured and environmental compounds with human systems biology in controlled exposure and observational studies.

Reoperation rates after breast conserving surgery for breast cancer among women in England: retrospective study of hospital episode statistics.

OBJECTIVES: To examine whether rate of reoperation after breast conserving surgery is associated with patients' characteristics and investigate whether reoperation rates vary among English NHS trusts. DESIGN: Cohort study using patient level data from hospital episode statistics. SETTING: English NHS trusts. PARTICIPANTS: Adult women who had breast conserving surgery between 1 April 2005 and 31 March 2008. MAIN OUTCOME MEASURE: Reoperation rates after primary breast conserving surgery within 3 months, adjusted using logistic regression for tumour type, age, comorbidity, and socioeconomic deprivation. Tumours were grouped by whether a carcinoma in situ component was coded at the time of the primary breast conserving surgery. RESULTS: 55,297 women had primary breast conserving surgery in 156 NHS trusts during the three year period. 11,032 (20.0%, 95% confidence interval 19.6% to 20.3%) women had at least one reoperation. 10,212 (18.5%, 18.2% to 18.8%) had one reoperation only; of these, 5943 (10.7%, 10.5% to 11.0%) had another breast conserving procedure and 4269 (7.7%, 7.5% to 7.9%) had a mastectomy. Of the 45,793 women with isolated invasive disease, 8229 (18.0%) had at least one reoperation. In comparison, 2803 (29.5%) of the 9504 women with carcinoma in situ had at least one reoperation (adjusted odds ratio 1.9, 95% confidence interval 1.8 to 2.0). Substantial differences were found in the adjusted reoperation rates among the NHS trusts (10th and 90th centiles 12.2% and 30.2%). CONCLUSION: One in five women who had breast conserving surgery in England had a reoperation. Reoperation was nearly twice as likely when the tumour had a carcinoma in situ component coded. Women should be informed of this reoperation risk when deciding on the type of surgical treatment of their breast cancer.

Regional variation in use of immediate breast reconstruction after mastectomy for breast cancer in England.

AIMS: English national guidelines recommend that breast reconstruction is made available to women with breast cancer undergoing mastectomy. We examined the use of immediate reconstruction (IR) across English Cancer Networks, who are responsible for the regional organisation of cancer services and ensuring equitable access to treatment. METHODS: We analysed Hospital Episodes Statistics data for all women with breast cancer who underwent mastectomy in the English NHS between April 2006 and February 2009. IR rates were calculated for the 30 Networks. Multivariable logistic regression was used to adjust the rates for patient age, comorbidity, ethnicity and socioeconomic deprivation. RESULTS: Of 44 837 mastectomy patients, 7375 (16.5%) underwent IR. The IR rate was highest in women under 50 years (32.7%) and lowest in women aged 70 years or over (1.5%), and was lower in women with more comorbidities. Unadjusted IR rates varied from 8.4% to 31.9% among the 30 Networks (p<0.001). Adjusting for their patient characteristics did not appreciably reduce Network-level variation, with adjusted IR rates still ranging from 8.0% to 29.4% (p<0.001). The risk-model also suggested that non-white women and those from more deprived areas were less likely to undergo immediate reconstruction. CONCLUSIONS: There is substantial regional variation in immediate reconstruction use in England that is not explained by the characteristics of the local patient population. English Cancer Networks should act to reduce this variation. They should also examine why rates of reconstruction differ between particular patient groups.

Experimental study of a new vascular anastomotic technique in a swine model: short and mid-term results.

This study reports the development of a new open external vascular stent: the lock stent device (LSD). It enables a novel end-to-end sleeve anastomotic technique, named locked anastomosis (LA). The LA technique consists of inserting a graft sleeve within an artery, secured in place by an internal stent and an external LSD. The internal stent, graft, vessel wall, and LSD are fastened together with single sutures. The LSD placement does not require a complete transection of the vessel wall as it can be enlarged and then relaxed to clasp the vessel neck. The tensile strength of the LA technique was accurately measured ex vivo and its stability successfully tested in vivo by acute pressure peak tests and mid-term survival studies. Ex vivo, the ratio between the tensile strength of the LA technique with two, three, and six stitches and that of hand-sewn anastomoses was 0.41 +/- 0.02, 0.59 +/- 0.17, and 1.03 +/- 0.04. In vivo, LA anastomoses tolerated marked increases in blood pressure (peak systolic pressure 195-230 mm Hg) for periods of 15-25 min without leakage. Five pigs survived 10 weeks with abdominal aorto-aortic bypass performed according to the LA technique with three stitches. Aortograms showed no narrowing or thromboses, and histological findings confirm uniform flattening of the aortic wall at the anastomosis, with proliferating neointima and uniformly hypotrophic media. Minimal changes were observed in the adventitia.

Risk factors for cataract subtypes waterclefts and retrodots: two case-control studies.

UNLABELLED: Waterclefts and retrodots are independently associated with visual impairment, yet a review identified no data on risk factors. PURPOSE: To investigate risk factors for these two human lens cataract subtypes. METHOD: Two nested case-control studies: The host study comprised 1078 subjects (55 years) attending the Somerset and Avon Eye Study (SAES). In total, 197 watercleft cases (Oxford grade 0.2 in either eye) and 199 retrodot cases (Oxford grade 1.0 in either eye) were individually age/gender matched to controls. Detailed ophthalmic and potential risk factor data were collected, including body mass index (BMI), smoking, alcohol, diabetes, hypertension, analgesics, vitamin supplementation, nutrition, sunlight exposure, dehydration, hormonal (women), blood lipids, glucose, urea, creatinine, uric acid, and vitamin levels. RESULTS: For waterclefts, univariable analysis identified BMI, alcohol intake, vitamin status, sunlight, urea, creatinine, and uric acid as possible risk factors. Multivariable analysis identified two independent associations. Total number of 'any' analgesics in the previous year: adjusted P<0.01 (U-shaped risk profile, unadjusted high vs medium use (=reference) OR 2.39, 95% CI 1.35-4.26 with medium use vs none (=reference) OR 0.43, 95% CI 0.26-0.72); total sunlight: adjusted P=0.03 (unadjusted highest exposure vs lowest (=reference) OR 3.25, 95% CI 1.11-9.50). For retrodots, univariable analysis identified alcohol, HRT, and lipids. Multivariable analysis identified two independent associations. Mean number of alcohol units consumed per month, adjusted P=0.02 and HDL cholesterol levels, adjusted P=0.02 (unadjusted ORs NS both). CONCLUSION: This is the first available published information on risk factors for the human cataractous lens features waterclefts and retrodots.

Cardiopulmonary bypass in ewe's fetus: advances and setbacks in our learning curve.

Fetal cardiac surgery represents a surgical challenge and several centers are attempting to establish a suitable methodology in animals. We present our experience with extra-corporeal bypass procedures in preterm and term sheep fetuses. Twenty-two fetuses (103-139 days gestation, mean 115 days gestation) underwent a 1-hour period of right heart-to-pulmonary artery extracorporeal circulation followed by 1 hour of observation. Animals were divided into group 1 and group 2, according to gestational age (above and below 0.85). Three pumps were used: centrifugal without (group 1) reservoir, centrifugal with (group 2) reservoir, and roller with reservoir (group 2). Experiments were completed in 75% of fetuses in group 1 and in 37% of fetuses in group 2. Bleeding was the main cause of failure, especially for group 2. A slow deterioration of blood gas status was noted in group 1, while this trend could be partially reversed in group 2 with corrective measures. Complete heart bypass could not be achieved in either group, and residual fluctuations in arterial pressure were observed. During bypass, body temperature decreased more in group 2 than in group 1. We conclude that cardiac bypass is feasible over a short period in near-term fetuses. A successful outcome may also be obtained in younger fetuses, but better measures need to be implemented for the prevention of surgical bleeding.

Vascular patterns in reactive lymphoid tissue and in non-Hodgkin's lymphoma.

The few studies published on angiogenesis in lymphoma have raised the question of whether or not microvessel density (MVD) is associated with more aggressive disease and have reported the observation that in follicular lymphomas, vessels are mature rather than immature. We investigated MVD and the vascular phenotype within follicular or diffuse large B-cell lymphomas, reactive nodes and tonsils. Vascular phenotype was defined by the expression or loss of reactivity to the antibody LH39 (detecting the LH39 laminin epitope of the basement membrane in mature vessels) and by detection of alpha V beta 3 (expressed on immature vessels). In reactive nodes and in follicular lymphomas, MVD was higher in the paracortex than in germinal centres or in neoplastic follicles. However, in neoplastic follicles an increase in alpha V beta 3-positive endothelium suggested the activation of an angiogenic pathway different from that present in the reactive follicles. In large B-cell lymphomas, MVD was higher than in reactive and neoplastic follicles but lower than in the reactive paracortex. The number of immature vessels (LH39 negative) and of alpha V beta 3-positive vessels was higher than in reactive lymph nodes and follicular lymphoma suggesting that a switch to a different angiogenic pathway has occurred. Finally, we have demonstrated that within reactive and neoplastic follicles vascular regression is occurring, perhaps constraining the growth of reactive follicles alongside other phenomena such as apoptosis. Vascular regression was previously believed to occur in adults only in ovarian and endometrial tissue. We conclude that different types of angiogenesis are present in follicular lymphomas and large B-cell lymphomas. This has implications for possible future therapies.

What motivates interest in attending a familial cancer genetics clinic?

The motivation of people who seek advice about a family history of cancer was explored in a cross sectional study of new cancer referrals to five regional cancer genetics centres in England: the PACT (patient and clinical team) psychosocial study. One hundred sixty-two people took part. Measures were source of referral, estimated and perceived cancer risk, level of cancer worry, and personal and family-centred reasons for wanting to be seen in clinic. General practitioners referred more people than hospital doctors, and referred a larger proportion of people at low genetic risk of developing cancer. More than half of the participants had been the first to raise the issue of their family history of cancer. Personal motivation for referral is clearly different for those who have had a diagnosis of cancer and for those with children, compared to unaffected and childless people, and is characterised by altruistic concern for other family members rather than a perception of increased personal risk. Men and people from ethnic minorities are very significantly under-represented. Understanding people's motivation may be useful in targeting genetic counselling for people with a family history of cancer.

Vascular phenotype in angiogenic and non-angiogenic lung non-small cell carcinomas.

We have previously described a group of non-small cell lung carcinomas without morphological evidence of neo-angiogenesis. In these tumours neoplastic cells fill up the alveoli and the only vessels present appear to belong to the trapped alveolar septa. In the present study we have characterised the phenotype of the vessels present in these non-angiogenic tumours, in normal lung and in angiogenic non-small cell lung carcinomas. The vessels, identified by the expression of CD31, were scored as mature when expressing the epitope LH39 in the basal membrane and as newly formed when expressing alphaVbeta3 on the endothelial cells and/or lacking LH39 expression. In the nine putative non-angiogenic cases examined, the vascular phenotype of all the vessels was the same as that of alveolar vessels in normal lung: LH39 positive and alphaVbeta3 variable or negative. Instead in 104 angiogenic tumours examined, only a minority of vessels (mean 13.1%; range 0--60%) expressed LH39, while alphaVbeta3 (in 45 cases) was strongly expressed on many vessels (mean 55.5%; range 5--90%). We conclude that in putative non-angiogenic tumours the vascular phenotype is that of normal vessels and there is no neo-angiogenesis. This type of cancer may be resistant to some anti-angiogenic therapy and different strategies need to be developed.

A new technique for total hepatectomy in the pig for testing liver support devices.

BACKGROUND: A large animal model of total hepatectomy is suitable to test the efficacy of any system designed to support patients in hepatic coma. The models previously described in the pig entail a significant degree of surgical trauma, which might alter the evolution of the ensuring hepatic failure and compromise the reproducibility of the model. METHODS: Twenty-eight pigs underwent a total hepatectomy according to a new technique. A model was considered satisfactory when it required no blood transfusions and when hematologic and hemodynamic parameters determined before, during, and until 4 hours after hepatectomy showed no significant variations. Moreover, to revive the pattern of hepatic coma produced in the anhepatic model, 7 pigs were monitored until brain death occurred. RESULTS: Twenty-five pigs (89%) underwent a smooth total hepatectomy with minimal variations of the selected parameters. They constituted a highly homogeneous group. Survival of the 7 pigs, followed up until brain death occurred, ranged from 625 to 1595 minutes (mean 1013.57 minutes). The animals remained stable until a few hours before brain death, an event heralded by a final sharp increase of the serum ammonia level and by a well-evident decline of both arterial pressure and liver-dependent clotting factors. CONCLUSIONS: This technique of total hepatectomy allows the construction of a reproducible model of anhepaty suitable to test the efficacy of any system conceived to temporarily replace hepatic functions.

Preoperative p53, bcl-2, CD44 and E-cadherin immunohistochemistry as predictors of biochemical relapse after radical prostatectomy.

PURPOSE: Since radical prostatectomy is performed to cure prostate cancer, identification of markers enabling preoperative prediction of relapse after radical prostatectomy is essential to counsel and select patients for adjuvant therapy. Aberrant p53, bcl-2, CD44 and E-cadherin immunohistochemistry has been associated with aggressiveness in prostate cancer. We assessed these biomarkers in biopsy and radical prostatectomy specimens as predictors of biochemical relapse. MATERIALS AND METHODS: A total of 76 patients with untreated clinically localized prostatic adenocarcinoma underwent radical prostatectomy. Preoperative (prostate specific antigen, biopsy Gleason score) and postoperative (pathological stage and margin status) variables, biopsy and radical prostatectomy biomarker immunohistochemistry were correlated with relapse. Univariate and multivariate statistical analyses identified significant predictors. RESULTS: Of the 76 patients 23 (30%) had relapse (mean followup 38 months). Aberrant p53, bcl-2, CD44 and E-cadherin expression was observed in 64, 12, 85 and 12% of biopsies and 57, 20, 64 and 49% of radical prostatectomy specimens, respectively. Biopsy Gleason 7 to 10 and biopsy p53, respectively, gave the highest positive and negative predictive values for relapse. Relapse occurred in 13% of patients with normal biopsy p53 and in half with aberrant p53. Multivariate analysis revealed Gleason score and p53 to be independent preoperative predictors (p = 0.01 and 0.02, respectively). Estimated risk of relapse was 3.5 times higher in patients with Gleason scores 7 to 10 and 24% higher in those with aberrant p53. Significant postoperative predictors were bcl-2, p53, Gleason score and margin status (p = 0.01, 0.01, 0.04 and 0.01, respectively). CONCLUSIONS: Aberrant biopsy p53 is associated with a significantly worse outcome after radical prostatectomy than normal p53, highlighting a potential clinical role for p53. Postoperative p53 and bcl-2 were significant predictors of outcome after radical prostatectomy.

Myocardial washout of sonicated iopamidol does not reflect the transmural distribution of coronary blood flow.

It has been shown in previous studies that myocardial contrast echocardiography provides quantitative information on coronary blood flow. However, the ability of contrast echo to assess the transmural (endo/epicardial) distribution of blood flow is still debated. To test this hypothesis, the left circumflex coronary arteries of six anaesthetized open-chested dogs were cannulated and perfused with blood from the femoral artery. At different rates of coronary blood flow, during adenosine-induced coronary vasodilation, sonicated iopamidol and radionuclide labelled microspheres were injected into the coronary cannula, immediately proximal to a mixing chamber. Two-D echo images were digitized and myocardial time-intensity curves were obtained for the endocardial, mid- and epicardial layers. A good correlation existed between contrast washout of the entire ventricular wall and coronary flow (r = 0.85). However, the washout rate from the endo-, mid- and epicardial layers showed weak correlations with corresponding regional blood flows measured by microspheres (r = 0.56, 0.71 and 0.58, respectively). No significant relationship was found between the endo/epicardial washout ratio and the corresponding flow ratio by microspheres. Thus, measurement of the transmural distribution of coronary blood flow by myocardial contrast echocardiography remains an elusive goal.

The choice of surgical procedure for peritonitis due to colonic perforation.

OBJECTIVE: Because the choice of surgical procedure for colonic perforation is still matter of debate, we retrospectively studied peritonitis caused by spontaneous colonic perforation to assess predictors of mortality and the safety of primary resection and anastomosis. DESIGN: Case series. PATIENTS: We investigated one hundred thirty-six consecutive patients with peritonitis due to colonic perforation who were surgically treated in an emergency surgery department. Eighty-one patients underwent primary resection and anastomosis, thirty-three underwent the Hartmann procedure, and twenty-two had simple colostomy. The seriousness of peritonitis was assessed in terms of Hinchey stage, the Mannheim Peritonitis Index (MPI), and the acute physiology and chronic health evaluation (APACHE) II score. RESULTS: The overall mortality rate was 20%. The APACHE II scores and MPIs were lower for survivors than for nonsurvivors. The mortality rate was 6% for primary resection and anastomosis, 30% for the Hartmann procedure, and 59% for simple colostomy, but the severity scores were significantly lower in patients who underwent primary resection than those of patients who had the Hartmann procedure and colostomy, respectively. CONCLUSIONS: Since primary resection and anastomosis has been shown to be safe, we suggest that is is proper, even in the presence of peritonitis. In spite of this, we conclude that the surgical procedure does not influence outcome but that the mortality rate is related to the severity of peritonitis, accurately measured by APACHE II score and MPI.

Effects of coronary blood flow on myocardial grey level amplitude in two dimensional echocardiography: an experimental study.

OBJECTIVE: The aims were: (1) to evaluate whether differences in absolute and cyclic echocardiographic image amplitude exist in different layers (subendocardium and subepicardium) and regions (septal, anterior, lateral, inferior wall) of the canine left ventricle; (2) to assess the dependence of these variables upon local variations of coronary blood flow. METHODS: In six anaesthetised open chest dogs the circumflex coronary artery was cannulated and perfused by a roller pump with blood from their own femoral artery. Maximum coronary vasodilatation was obtained by continuous adenosine infusion. The absolute values and the transmural distribution of coronary blood flow were measured by radionuclide labelled microspheres. Echo images were obtained in short axis view by a commercially available electronic sector scanner with a 5.0 MHz transducer directly placed on the epicardial surface of the right ventricle, and digitised off-line into a matrix of 256 x 256 pixels with 25% grey level per pixel. The average grey level was calculated for each region of interest. RESULTS: In 32 different conditions, circumflex flow ranged from 0.80 to 12.89 ml.min-1.g-1 and the endocardial/epicardial ratio of flow from 0.53 to 1.73. In the circumflex region (subjected to flow changes) segmental amplitude varied from 76(SD 20) (end diastole) to 56(18) (end systole), p < 0.001. In all regions, a consistent cyclic variation was found, ranging from 9(14) to 28(16)%. For all levels of flow, subendocardial and subepicardial regions showed similar values of both absolute amplitude and cyclic variation. No significant relationship was found between transmural distribution of blood flow and either segmental amplitude (r = 0.26) or cyclic variation (r = 0.04). CONCLUSIONS: (1) a consistent cyclic grey level variation is present in all regions of the canine left ventricle, but subendocardial and subepicardial layers show similar values of both absolute amplitude and cyclic variation; (2) in the absence of severe underperfusion and echocardiographically detectable dyssynergy, absolute amplitude and cyclic variation are totally unrelated to changes in coronary blood flow.

Myocardial washout of sonicated iopamidol reflects coronary blood flow in the absence of autoregulation.

OBJECTIVES: The aim of the study was to evaluate the relation between measurements derived from myocardial contrast echocardiography and coronary blood flow. BACKGROUND: Contrast echocardiography has the potential for measuring blood flow. METHODS: In six open chest anesthetized dogs, the left circumflex coronary artery was cannulated and perfused with blood drawn from the left femoral artery. While adenosine was infused into the circuit, circumflex flow was generated by a calibrated roller pump to the point of abolishing coronary autoregulation. At each of 25 levels of coronary blood flow, paired bolus injections of sonicated iopamidol were performed proximal to a mixing chamber. The perfused area of the left circumflex coronary artery was labeled by radioactive microspheres injected into the perfusion line. Two-dimensional echocardiographic images of the left ventricular short axis were digitized off-line, and myocardial videodensity was measured in the area perfused by the left circumflex coronary artery to generate time-intensity curves. RESULTS: The washout slope of curves showed a good correlation with coronary blood flow, ranging from 0.5 to 12.5 ml/min per g of tissue. This correlation was good both in individual dogs (correlation coefficient [r] ranging from 0.78 to 0.96) and in the group of animals as a whole (r = 0.85). Washout slope also showed a good correlation with coronary diastolic pressure (r = 0.80), which ranged from 23 to 114 mm Hg, suggesting a possible primary effect of pressure on contrast washout. However, coronary blood flow appeared to be a stronger predictor of washout slope (partial F = 26.5, p < 0.001) than did perfusion pressure (partial F = 5.9, p < 0.05 by multiple regression). The injection to injection variability in myocardial washout slope appeared to be high (24%). The gamma variate fitting of curves did not improve the correlation with coronary flow (r = 0.78). CONCLUSIONS: Myocardial washout of sonicated iopamidol reflects coronary blood flow in a model in which coronary autoregulation is abolished.

[A mathematical model of the vascular architecture and of the distribution of resistances in the coronary tree]. / Modello matematico dell'architettura vascolare e della distribuzione delle resistenze nell'albero coronarico.

The architecture and resistance distribution of the coronary arteriolar tree downstream 100 mu diameter vessels are still largely unknown, due to technical difficulties in direct visualization. In this study we propose a mathematical model of the architecture and the single vessel resistance distribution of terminal arteriolar vasculature in the beating dog heart, based on the analysis of embolization-induced changes of total coronary resistance. Coronary embolization was performed by injecting several boluses of 15 mu (6 cases) and 25 mu (6 cases) plastic microspheres into the maximally vasodilated (adenosine infusion) left circumflex artery of the open chest dog. The relation between the number of plastic beads progressively injected to embolize 15 mu and 25 mu vessels and the resulting increase in total coronary resistance (occlusion function) was obtained in each experiment. If we consider a binary symmetric vascular tree with i) equal resistance for vessels of the same branching order and ii) optimal ratio between resistance of parent and daughter vessels at all branching sites, the simulation of embolization in such a system shows that the occlusion function of the terminal vessels N in the linear portion between 0 and N/2 occluded vessels has a slope S' which is 5.6 times lower than the slope S" between N/2 and 3/4 N occluded vessels and 3.6 times lower than the S' of the occlusion function of the preterminal vessels. The occlusion function in our experiments has a ratio S"/S' close to that predicted by the model and a ratio between the S' of the 25 mu and that of 15 mu experiments equal to 4.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary effects of adenosine in conscious man.

Adenosine has been reported to play an important role in several cardiac functions, including the regulation of total and regional myocardial perfusion. This hypothesis is based on extensive investigations in animal models, but very limited information is available on the cardiovascular actions of adenosine in conscious man and the effects of the intracoronary administration of adenosine are unknown. The purpose of this study was to measure total and regional coronary blood flow after bolus injections of 0.1, 0.5, 1.0, and 2.5 mg of adenosine into the left anterior descending coronary branch. A three-thermistor thermodilution catheter was advanced into the coronary sinus to measure simultaneously the great cardiac vein flow and the coronary sinus flow. Six patients with normal coronary angiograms and normal ventricular function completed the study. Intracoronary injections of adenosine were free from significant adverse effect and caused a dose-related increase of great cardiac vein flow. A linear relation was found between flow increment and the log of adenosine dose (y = 18.929x + 74.84, r2 = 0.951). The highest flow, measured after the maximal dose, was almost three times greater than control flow (155 +/- 2 vs 58 +/- 3 ml min-1, P less than 0.001). We also observed a flow response in the territory not directly exposed to adenosine, as indicated by a marked increase of coronary sinus blood flow that was linearly related to the adenosine dose (y = 29.113x = 112.635, r2 = 0.98). These preliminary observations suggest: (1) Intracoronary injections of adenosine in conscious man can be performed without significant adverse effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Persistence of subendocardial perfusion after subtotal coronary embolisation.

The effects of acute subtotal embolisation of small coronary arteries on regional coronary flow and vasodilator reserve were investigated in seven open chest dogs. Unlabelled plastic microspheres (26(2) micron in diameter) were injected as boluses of 200,000-400,000 microspheres into the circumflex artery. Embolisation was repeated until reactive hyperaemia was totally abolished, which occurred after the injection of 62,000(4000) microspheres per gram. Intracoronary adenosine was then infused for 20 min at 1.2 mg.min-1. Regional myocardial blood flow was measured by radioactive microspheres under control conditions, after coronary embolisation, and during adenosine infusion. Coronary blood flow (0.98(0.07) ml.min-1.g-1) was reduced to 0.66(0.08) ml.min-1.g-1 after embolisation (p less than 0.005) when reactive hyperaemia was practically abolished. Embolisation reduced epicardial flow from 0.93(0.08) to 0.40(0.09) ml.min-1.g-1 (p less than 0.001), whereas endocardial flow was unchanged (1.03(0.11) vs 0.92(0.14) ml.min-1.g-1; NS); as a consequence, the endocardial to epicardial flow ratio increased from the control value of 1.11(0.06) to 2.31(0.35) (p less than 0.005). Adenosine infusion increased coronary blood flow from 0.66(0.08) to 1.66(0.41) ml.min-1.g-1 (p less than 0.05). Endocardial blood flow increased more than epicardial blood flow, leading to a further increase in the endocardial to epicardial flow ratio (3.79(0.13); p less than 0.05). Thus it is concluded that (a) embolisation of small arteries abolishes the reactive hyperaemic response to transient coronary occlusion; (b) microembolisation predominantly reduces subepicardial perfusion; and (c) adenosine administration may increase total and regional flow after subtotal occlusion of coronary small arteries.