Male infertility and urological tumors: Pathogenesis and therapeutical implications.

Most genitourinary tract cancers have a negative impact on male fertility. Although testicular cancers have the worst impact, other tumors such as prostate, bladder, and penis are diagnosed early and treated in relatively younger patients in which couple fertility can be an important concern. The purpose of this review is to highlight both the pathogenetic mechanisms of damage to male fertility in the context of the main urological cancers and the methods of preserving male fertility in an oncological setting, in light of the most recent scientific evidence. A systematic review of available literature was carried out on the main scientific search engines, such as PubMed, Clinicaltrials.Gov, and Google scholar. Three hundred twenty-five relevant articles on this subject were identified, 98 of which were selected being the most relevant to the purpose of this review. There is a strong evidence in literature that all of the genitourinary oncological therapies have a deep negative impact on male fertility: orchiectomy, partial orchiectomy, retroperitoneal lymphadenectomy (RPLND), radical cystectomy, prostatectomy, penectomy, as well as radiotherapy, chemotherapy, and hormonal androgen suppression. Preservation of fertility is possible and includes cryopreservation, hormonal manipulation with GnRH analogs before chemotherapy, androgen replacement. Germ cell auto transplantation is an intriguing strategy with future perspectives. Careful evaluation of male fertility must be a key point before treating genitourinary tumors, taking into account patients' age and couples' perspectives. Informed consent should provide adequate information to the patient about the current state of his fertility and about the balance between risks and benefits in oncological terms. Standard approaches to genitourinary tumors should include a multidisciplinary team with urologists, oncologists, radiotherapists, psycho-sexologists, andrologists, gynecologists, and reproductive endocrinologists.

Increased risk of osteoporosis in postmenopausal women with type 2 diabetes mellitus: a three-year longitudinal study with phalangeal QUS measurements.

Type 2 diabetes mellitus (T2DM) is associated with a higher risk of fractures even in presence of normal or increased bone mineral density. The purpose of this three-year longitudinal study was to evaluate the risk of osteoporotic fractures by assessing the changes of Quantitative Ultrasound (QUS) parameters in a group of postmenopausal women with type 2 diabetes mellitus (T2DM) compared with non-diabetic controls. The measurements were taken on a group of 18 postmenopausal women affected by T2DM and 18 healthy age-matched controls, aged 55-70 years, referring to the Osteolab laboratory at the ISBEM Research Institute (Brindisi, Italy) between 2009 and 2013. Subjects had baseline and 3-year follow-up measurements with phalangeal QUS carried out by a DBM Sonic Bone Profiler 1200 (Igea®); medical history, current drug therapies and risk factors for fractures were recorded for each patient. The analyzed phalangeal QUS parameters were Amplitude-Dependent Speed of Sound (AD-SoS), Bone Transmission Time (BTT), Fast Wave Amplitude (FWA) and Signal Dynamic (SDy). At the baseline visit we found no statistically significant difference between T2DM and non-diabetic patients when looking at phalangeal QUS parameters. At the three-year follow-up visit, a significantly higher decrease of both BTT (P<0.001) and AD-SoS (P<0.001) parameters was found in the T2DM group. On the contrary, the decrease of FWA was significantly higher in non-diabetic controls (P<0.001). Our data confirm the ability of phalangeal QUS to detect differences in the risk of osteoporotic fractures in T2DM postmenopausal women compared to non-diabetic controls. The study suggests that T2DM women present a higher cortical porosity and increased trabecular bone density compared to non-diabetic controls, respectively shown by the higher decrease of both AD-SoS and BTT and the lower decrease of FWA.

Socioeconomic burden of total joint arthroplasty for symptomatic hip and knee osteoarthritis in the Italian population: a 5-year analysis based on hospitalization records.

OBJECTIVE: To assess the burden of total joint arthroplasties (TJAs) performed for symptomatic hip and knee osteoarthritis (OA) in the Italian population. METHODS: We analyzed national hospitalizations and diagnosis-related group databases to compute incidence, annual percent change (APC), direct costs, and working days lost between 2001 and 2005 following TJA due to OA. RESULTS: In 2005, we recorded a total of 41,816 (APC +5.4; 95% confidence interval [95% CI] 5.1-5.8) and 44,051 (APC +13.4; 95% CI 13.1-13.8) hip and knee arthroplasties, respectively. Women represented the majority of patients undergoing TJA procedures (female:male ratio 1.7:1 for hip arthroplasties and 2.9:1 for knee arthroplasties). When analyzing the data by age groups, most of the patients were in the age groups 65-74 years and ≥75 years, although the highest increases were observed in those ages <65 years. Revisions accounted for 6,387 (APC +4.9; 95% CI 4.0-5.7) and 2,295 (APC +17.4; 95% CI 15.7-19.2) procedures for the hip and knee, respectively. Loss of working days in patients ages <65 years was estimated between 805,000 and 1 million days. Hospital costs increased from 741 million to 1 billion euros over the 5-year period (from 412 to 538 million euros for hip arthroplasties and from 329 to 517 million euros for knee arthroplasties). Rehabilitation costs increased from 228 to 322 million euros. Postoperative complications were estimated between 3.1 and 4.4 million euros. The average costs per patient were 16,835 and 15,358 euros for hip and knee arthroplasties, respectively. CONCLUSION: The socioeconomic burden of TJAs performed for symptomatic OA in Italy is remarkable and calls for the adoption of proper preventive measures.

[Incidence and socioeconomic burden of hip fractures in Italy: extension study 2003-2005]. / Incidenza e costi delle fratture di femore in Italia: studio di estensione 2003-2005.

OBJECTIVES: We aimed to analyze incidence and costs of hip fractures in Italy. METHODS: We analyzed the Italian Ministry of Health national hospitalization and DRGs databases concerning fractures occurred in people > or =65 between 2003 and 2005. We have estimated incidence and direct costs sustained by the National Health Service for hospitalization and treatment of hip fractures on the basis of the value of the Diagnosis Related Groups (DRGs) referring to hip fractures. The expenses of rehabilitation and indirect costs were based on regional estimations. RESULTS: Between 2003 and 2005 we registered almost 90,000 hospital admissions per year (corresponding to 75,000 patients) because of hip fractures in people aged > or =65. Women accounted for the majority of hospital admissions due to hip fractures (78.0%; n=214,519). Among women, 84.3% of fractures (n=180,861) occurred in patients > or =75, which is known to be the age group with the highest prevalence of osteoporosis. Hospitalizations of both men and women showed an increasing trend across all the examined period. Hospital costs increased up to 467 million euros in 2005, while rehabilitation costs rose up to 531 million in the same year. CONCLUSIONS: Hip fractures in the Italian population are increasing and represent a major public health challenge.

Hip fractures in Italy: 2000-2005 extension study.

SUMMARY: A total of 507,671 people > or =65 experienced hip fractures between 2000 and 2005. In 2005, 94,471 people > or =65 were hospitalized due to hip fractures, corresponding to a 28.5% increase over 6 years. Most fractures occurred in patients > or =75 (82.9%; n = 420,890; +16% across 6 years), particularly in women (78.2%; n = 396,967). INTRODUCTION: We aimed to analyze incidence and costs of hip fractures in Italy over the last 6 years. METHODS: We analyzed the national hospitalization and DRG databases concerning fractures occurred in people > or =65 between 2000 and 2005. RESULTS: A total of 507,671 people > or =65 experienced hip fractures across 6 years, resulting in about 120,000 deaths. In year 2005 94,471 people aged > or =65 were hospitalized due to hip fractures, corresponding to a 28.5% increase over 6 years. The majority of hip fractures occurred in patients > or =75 (82.9%; n = 420,890; +16% across 6 years) and particularly in women (78.2%; n = 396,967). Among women, 84.2% of fractures (n = 334,223; +28.0% over 6 years) were experienced by patients > or =75, which is known to be the age group with the highest prevalence of osteoporosis, accounting for 68.6% of the overall observed increase in the total number of fractures. Hip fractures in men > or =75 increased by 33.1% (up to 16,540). Hospitalization costs increased across the six examined years (+36.1%) reaching 467 million euros in 2005, while rehabilitation costs rose up to 531 million in the same year. CONCLUSIONS: Hip fractures of the elderly are increasing and represent a major health problem in industrialized countries such as Italy.

[Multivariate analysis of prognostic factors and survival in patients with "glioblastoma multiforme"]. / Multivariate analysis of prognostic factors and survival inpatients with "glioblastoma multiforme".

PURPOSE: The aim of this study was to evaluate the survival of patients with "glioblastoma multiforme", to analyse the prognostic factors influencing the survival rate and to review recent results in the literature. MATERIALS AND METHODS: Seventy five patients underwent radiation treatment between May 1998 and April 2003. Among the factors under investigation we ascertained that sex, chemotherapy, conformal treatment, surgery, and the choice of the irradiation area (whole brain or only the involved field) did not influence the survival in a statistically significant manner. RESULTS: Whereas age and total dose were the 95% statistically significant variables. Hazard ratio of patients older than 58 years compared to younger patients was 1.69. The death risk was 69% in older than younger patients. A greater irradiation dose improved the survival with an increase of the median survival days. The total dose lower than 6000 cGy caused an increase of 81.8% in the death risk. The median survival from the diagnosis to the death was 14.7 months (446 days) and 1-, 2- and 3- year survival rate was 69.3%, 38.4%, and 14.7% respectively. CONCLUSIONS: The current medical literature and our experience attests that the use of temozolomide improves the survival of these patients.

Incidence and costs of hip fractures compared to acute myocardial infarction in the Italian population: a 4-year survey.

INTRODUCTION: Few data are available about the incidence and costs of hip fractures in Italy. We aimed to determine the impact of hip fractures vs. acute myocardial infarction (AMI). METHODS: We studied the national hospitalization database to calculate their incidence and costs in adults aged >or=45 between 1999 and 2002. RESULTS: In 2002, there were 86,719 hip fractures with a 10.0% increase over 4 years. We observed a predominance of women (77.1%) and a strong age effect: 92.7% of patients were >or=65 years old and 80% of fractures occurred in women aged >or=75, showing a clear relationship with the incidence of osteoporosis. Hospitalizations due to AMI after 45 years of age in 1999 were only 9% higher than those for hip fracture, although this difference increased over the 4 examined years up to 24%. Considering the DRGs costs, hip fractures resulted in being more expensive than AMI overall and concerning elderly people. CONCLUSIONS: This study shows that in the Italian population aged >or=45, hospitalizations following hip fracture and AMI between 1999 and 2002 were comparable, while hip fractures' direct costs were higher and grew faster than costs for AMI. Hip fractures in Italy are a serious medical problem and a leading health-cost driver.

Chronobiology of rupture and dissection of aortic aneurysms.

A growing body of evidence suggests that the occurrence of cardiovascular events is not evenly distributed over time, but shows peculiar temporal patterns that vary with time of day, day of the week, and month (season) of the year. These patterns coincide with the temporal variation in the pathophysiologic mechanisms that trigger cardiovascular events and the physiologic changes in body rhythms. These two factors in combination contribute to the periodicity in susceptibility to acute cardiovascular events. The classic assumption of epidemiologic studies that there is a constancy in risk for disease during the various time domains has now been challenged by the emerging new concept of chronorisk. In the last two decades temporal patterns (circadian, weekly, seasonal) have been identified for several acute cardiovascular diseases, such as acute myocardial infarction, sudden death, pulmonary embolism, and stroke, with peak incidence for most in the morning and during winter. One of the most life-threatening cardiovascular emergencies, aortic aneurysm rupture or dissection, also demonstrates periodicity, characterized by a similar temporal distribution, which suggests a common pathophysiologic mechanism or triggers similar to other cardiovascular acute emergencies. We review the data on chronobiology of acute aortic rupture or dissection, and discuss various pathophysiologic mechanisms that account for this variability. It is likely that identification of consistent recurring patterns in the underlying risk mechanisms could provide potential new insights for more precise diagnosis and efficacious therapeutic intervention.

Awareness of breast cancer genetics and interest in predictive genetic testing: a survey of a southern Italian population.

BACKGROUND: Before starting a molecular screening program for breast cancer risk and in order to develop ad hoc educational strategies, a population survey in Apulia, Italy, was performed to gather information on women's awareness of breast cancer genetics and their attitude toward genetic testing for breast cancer risk. PATIENTS AND METHODS: A consecutive series of 677 healthy women with or without a family history of breast cancer, who attended the outpatient clinics of Lega Italiana per la Lotta contro i Tumori in Bari, Italy, for preventive visits, were asked to complete a 20-item questionnaire on socio-demographics, risk perception, psychological characteristics and interest in genetic testing for breast cancer predisposing genes. RESULTS: Most women (77%) reported knowing something about the genetics of breast cancer; only 7% of the women were not interested at all in genetic testing. These figures were not significantly different for women with or without a family history of breast cancer. The two most frequently cited reasons for being interested in genetic testing, accounting for more than 50% of collected responses, were 'to learn about your children's risk' and 'to help advance research'. On multiple logistic regression analysis, only older age [odds ratio (OR) 1.9; 95% confidence interval (CI) 1.3-2.9] was associated with women's knowledge of genetic testing. Moreover, marital status (OR 4.0; 95% CI 1.1-14.6) and thinking of cancer (OR 2.2; 95% CI 1.0-4.7) independently predicted the interest in having genetic testing. CONCLUSIONS: Southern Italian women seem highly interested in genetic testing for breast cancer risk. However, their expectations mainly regard their concerns about their children or their altruistic need to help research rather than the idea of a direct clinical benefit. The great interest of the women in genetic testing probably reflects their inappropriate knowledge of the information that genetic testing can provide for breast cancer risk analysis.

The role of oral contrast administration immediately prior to the computed tomographic evaluation of the blunt trauma victim.

BACKGROUND: It is unclear whether the administration of oral contrast followed by immediate computerised tomographic (CT) scanning presents a significant risk of aspiration and whether it is useful in the diagnosis of hollow viscus injury. OBJECTIVE: Determine the number of intestinal perforations diagnosed by oral contrast enhanced CT scans for blunt trauma and identify those who developed aspiration pneumonitis causally related to oral contrast administration. METHODS: We analysed a database of consecutive blunt trauma admissions over a 2-year period. The majority received oral contrast immediately prior to CT scanning. We determined the number of intestinal perforations identified by abdominal CT confirmed at laparatomy and the number of cases of aspiration pneumonia. RESULTS: Nine (1%) of the 1173 CT scans identified enteric perforations. Oral contrast enhanced CT scans demonstrated pneumoperitoneum (3), extraluminal contrast extravasation (2), and the presence of free fluid with small bowel wall thickening (8). In this same cohort, eight (0.7%) cases of aspiration pneumonia were diagnosed within 48 h of admission in patients with a mean GCS of 4.25; only one (0.1%) was temporally related to oral contrast administration. In a prospective study, none of the 65 consecutive patients who received oral contrast had witnessed aspiration. CONCLUSIONS: Oral contrast administration given immediately prior to CT scanning does not increase the risk of clinically significant aspiration and assists in the detection of enteric perforation.

Serial evaluation of perfusion defects in patients with a first acute myocardial infarction referred for primary PTCA using intravenous myocardial contrast echocardiography.

AIMS: To investigate whether myocardial contrast echocardiography using Sonazoid could be used for the serial evaluation of the presence and extent of myocardial perfusion defects in patients with a first acute myocardial infarction treated with primary PTCA, and specifically, (1) to evaluate safety and efficacy of myocardial contrast echocardiography to detect TIMI flow grade 0--2, (2) to evaluate the success of reperfusion and (3) to predict left ventricular recovery after 4 weeks follow-up. METHODS AND RESULTS: Fifty-nine patients underwent serial myocardial contrast echocardiography, immediately before primary PTCA (MCE1), 1 h (MCE2) and 12--24 h after PTCA (MCE3). A perfusion defect was observed in 21 of 24 patients (88%) with anterior acute myocardial infarction. All but one had TIMI flow grade 0--2 prior to PTCA. Nine of 31 patients (29%) with inferior acute myocardial infarction showed a perfusion defect and all had TIMI flow grade 0-2 prior to PTCA. Restoration of TIMI flow grade 3 was achieved in 73% of the patients by primary PTCA. A reduction in size of the initial perfusion defect of at least one segment (16 segment model) or no defect vs persistent defect in patients with anterior acute myocardial infarction was associated with improved global left ventricular function at 4 weeks; mean global wall motion score index 1.29+/-0.21 vs 1.66+/-0.31 (P=0.009). Multiple regression analysis in patients with an anterior acute myocardial infarction revealed that the extent of the perfusion defect at MCE3 was a significant (P=0.0005) independent predictor for left ventricular recovery at 4 weeks follow-up. The only other independent predictor was TIMI flow grade 3 post PTCA (P=0.007). CONCLUSION: Intravenous myocardial contrast echocardiography immediately prior to primary PTCA seems safe and is capable of detecting the presence of a perfusion defect and its subsequent dynamic changes, particularly in patients with a first anterior acute myocardial infarction. A significant reduction in size of the initial perfusion defect using serial myocardial contrast echocardiography predicts functional recovery after 4 weeks and these findings underscore the potential diagnostic value of intravenous myocardial contrast echocardiography.

Right ventricular infarction: the role of echocardiography.

Echocardiographic evaluation of patients with right ventricular (RV) ischemia and infarction has a clear clinical relevance, because the presence of RV infarction is associated with a highly increased early in-hospital mortality, which can be dramatically reduced by successful early reperfusion. However, infarcted RV did recover its function regardless of the infarcted artery patency. This observation suggests that RV myocardium almost always remains viable. This article illustrates the clinical value of echocardiography, including the transthoracic and transesophageal approaches, Doppler, and three-dimensional ultrasound, for the assessment of RV dimensions, shape, and global and regional function, and the estimation of right atrial involvement that in cases of ischemia may further modulate RV performance. In addition, the use of stress echocardiography to detect RV ischemia and evaluate the viability of infarcted RV myocardium is discussed.

Age dependency of myocardial structure: a quantitative two-dimensional echocardiographic study in a normal population.

Histological changes of the myocardium occur with aging due to an increase in collagen content, hypertrophy of fibers, and patchy fibrosis. Quantitative analysis of conventional echocardiographic images provides an in vivo assessment of myocardial structure by the evaluation of the gray level distribution; with this technique, a relation between myocardial fibrosis and pathological ultrasonic response has been documented. The aim of this study was to evaluate the relation between ultrasonically assessed myocardial structure and age in a normal population. Seventy-eight subjects (47 men; mean age, 51 years; age range, 23-87 years) without apparent cardiovascular and systemic disease underwent conventional two-dimensional echocardiographic examinations. Still frames at end-diastole from apical four-chamber view were digitized and converted in matrices of 256 x 256 pixels. First-order statistical analysis was performed to describe a region of interest in the interventricular septum. The following parameters were studied: mean (gray level amplitude), standard deviation (overall contrast), uniformity (tonal organization), and entropy (tendency of gray levels to be spread). Myocardial structure was assessed in 75 of 78 subjects, divided into three groups: I, age 23-40 years; II, age 41-65 years; and III, > 65 years. Significant differences for all the parameters were found between the age groups. Age correlated directly with mean and entropy (r = 0.77 and 0.69, respectively) and inversely with uniformity (r = 0.70). Our results suggest that quantitative echocardiography can reveal age-related changes in myocardial structure that are characterized by a greater echogenicity and loss in tonal organization, possibly due to increased collagen content within the fibers.

Oleic acid inhibits endothelial activation : A direct vascular antiatherogenic mechanism of a nutritional component in the mediterranean diet.

Because oleic acid is implicated in the antiatherogenic effects attributed to the Mediterranean diet, we investigated whether this fatty acid can modulate endothelial activation, ie, the concerted expression of gene products involved in leukocyte recruitment and early atherogenesis. We incubated sodium oleate with human umbilical vein endothelial cells for 0 to 72 hours, followed by coincubation of oleate with human recombinant tumor necrosis factor, interleukin (IL)-1alpha, IL-1beta, IL-4, Escherichia coli lipopolysaccharide (LPS), or phorbol 12-myristate 13-acetate for a further 6 to 24 hours. The endothelial expression of vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and intercellular adhesion molecule-1 was monitored by cell surface enzyme immunoassays or flow cytometry, and steady-state levels of VCAM-1 mRNA were assessed by Northern blot analysis. At 10 to 100 micromol/L for >24 hours, oleate inhibited the expression of all adhesion molecules tested. After a 72-hour incubation with oleate and a further 16-hour incubation with oleate plus 1 microg/mL LPS, VCAM-1 expression was reduced by >40% compared with control. Adhesion of monocytoid U937 cells to LPS-treated endothelial cells was reduced concomitantly. Oleate also produced a quantitatively similar reduction of VCAM-1 mRNA levels on Northern blot analysis and inhibited nuclear factor-kappaB activation on electrophoretic mobility shift assays. Incubation of endothelial cells with oleate for 72 hours decreased the relative proportions of saturated (palmitic and stearic) acids in total cell lipids and increased the proportions of oleate in total cell lipids without significantly changing the relative proportions of polyunsaturated fatty acids. Although less potent than polyunsaturated fatty acids in inhibiting endothelial activation, oleic acid may contribute to the prevention of atherogenesis through selective displacement of saturated fatty acids in cell membrane phospholipids and a consequent modulation of gene expression for molecules involved in monocyte recruitment.

Alpha-adrenergic blockade improves recovery of myocardial perfusion and function after coronary stenting in patients with acute myocardial infarction.

BACKGROUND: AMI reperfusion by thrombolysis does not improve TIMI flow and LV function. The role of infarct-related artery (IRA) stenosis and superimposed changes in coronary vasomotor tone in maintaining LV dysfunction must be elucidated. METHODS AND RESULTS: Forty patients underwent diagnostic angiography 24 hours after thrombolysis. Seventy-two hours after thrombolysis, the culprit lesion was dilated with coronary stenting. During angioplasty, LV function was monitored by transesophageal echocardiography. Percent regional systolic thickening was quantitatively assessed before PTCA, soon after stenting, 15 minutes after stenting, and after phentolamine 12 microg/kg IC (n=10), the alpha1-blocker urapidil 600 microg/kg IV (n=10), or saline (n=10). Ten patients pretreated with beta-blockers received urapidil 10 mg IC. Coronary stenting significantly improved thickening in IRA-dependent and in non-IRA-dependent myocardium (from 27+/-15% to 38+/-16% and from 40+/-15% to 45+/-15%, respectively). Simultaneously, TIMI frame count decreased from 39+/-11 and 40+/-11 in the IRA and non-IRA, respectively, to 23+/-10 and 25+/-7 (P<0.05). Fifteen minutes after stenting, thickening worsened in both IRA- and non-IRA-dependent myocardium (to 19+/-14% and 28+/-14%, P<0.05), and TIMI frame count returned, in both the IRA and non-IRA, to the values obtained before stenting. Phentolamine and urapidil increased thickening to 36+/-17% and 41+/-14% in IRA and to 48+/-11% and 49+/-17% in non-IRA myocardium respectively, and TIMI frame count decreased to 16+/-6 and to 17+/-5, respectively. Changes were attenuated with beta-blocker pretreatment. CONCLUSIONS: Our finding that alpha-adrenergic blockade attenuates vasoconstriction and postischemic LV dysfunction supports the hypothesis of an important role of neural mechanisms in this phenomenon.

Contrast echocardiography in the diagnosis of myocardial stunning.

The identification of viable myocardium within dysfunctional myocardium has important clinical implications. By using a microvascular tracer, myocardial contrast echocardiography may have the potential for prediction of myocardial viability in the acute and subacute phases of myocardial infarction. In the case presented, the normal myocardial perfusion observed after intravenous injection of the contrast agent, combined with severe wall motion abnormality following prolonged chest pain, suggested myocardial stunning. This was confirmed by normal coronary angiography and by restoration of normal left ventricular function at 1-month follow-up echocardiography.

Coronary collateral circulation behaviour and myocardial viability in chronic total occlusion treated with coronary angioplasty.

AIMS: We explored the role of microcirculation integrity following the chronic occlusion of an infarct-related artery to assess the behaviour of collateral circulation during and after reperfusion by coronary angioplasty METHODS AND RESULTS: Eighteen patients with a proximally occluded left anterior descending artery and firm evidence of intercoronary collateral circulation were studied with selective coronary angiography and selective intracoronary myocardial contrast echocardiography, before coronary angioplasty, and at 5 and 15 min and 12 h later. Myocardial enhancement during myocardial contrast echocardiography was evaluated with a semiquantitative score (0-3), which was correlated to basal and 6 months' regional left ventricular wall motion results. 16/18 procedures were successfully performed; four patients with an inadequate acoustic window were excluded. Restenosis was evident at the 6 months' follow-up in two patients. Basal myocardial contrast echocardiography indicated that 81/192 segments from the left anterior descending coronary artery and 90/192 from the right coronary artery were perfused; no perfusion was observed in 21 segments either before or after coronary angioplasty. After coronary angioplasty, the angiographic intercoronary collateral circulation immediately disappeared, and myocardial contrast echocardiography revealed that there was a progressive reduction of segments perfused by the right coronary artery and an increase in segments perfused by the left anterior descending coronary artery. Regional left ventricular wall motion analysis demonstrated that there was abnormal motion in 51/192 segments. There was no improvement in segments with score 0 and abnormal motion after 6 months (100% sensitivity), but 16/17 segments with score 3 did show an improvement (98% specificity). The predictive value of intermediate scores (1-2) in detecting long-term improvement, was only 43%. CONCLUSION: These data show that the adaptive mechanism observed in the behaviour of epicardial and microvascular circulation after reperfusion of a chronic occluded infarct-related artery can vary. In addition, this study clearly shows that microvascular integrity detected by myocardial contrast echocardiography can provide myocardial viability.

Postischemic left ventricular dysfunction is abolished by alpha-adrenergic blocking agents.

OBJECTIVES: We sought to evaluate the efficacy of alpha-adrenergic blocking agents in counteracting left ventricular (LV) dysfunction occurring after transient ischemia in humans. BACKGROUND: The mechanisms underlying postischemic LV dysfunction are largely unknown. METHODS: Percutaneous transluminal coronary angioplasty (PTCA) provides a clinical model of ischemia and reperfusion. In 50 patients undergoing coronary stenting for 77+/-5% stenosis, LV function was monitored by transesophageal echocardiography during and 30-min after PTCA. Fifteen minutes after stenting, 15 patients received 12 microg/kg body weight of the alpha-blocker phentolamine intracoronarily, 15 patients received 600 microg/kg of the alpha1-blocker urapidil intravenously, 10 patients received the combination of phentolamine and 1.2 mg of propranolol intracoronarily, and 10 patients received saline. RESULTS: Fifteen minutes after successful coronary dilation, significant contractile dysfunction occurred in previously ischemic and nonischemic myocardium. LV dysfunction was accompanied by an increase in coronary resistance and diffuse vasoconstriction. Alpha-blockers counteracted LV dysfunction and coronary resistance and the increase in vasoconstriction. Phentolamine and urapidil increased global LV shortening from 34+/-9% to 45+/-8% and to 49+/-8%, respectively (p < 0.05). After the administration of propranolol combined with phentolamine, LV dysfunction remained unchanged (34+/-6%), as in control subjects. CONCLUSIONS: LV dysfunction occurs after PTCA, as described in animal models after ischemia. Alpha-blockers abolished LV, macrocirculatory and microcirculatory dysfunction, whereas the alpha-blocker effect was prevented by combining alpha- and beta-blockers. The evidence of diffuse rather than regional dysfunction, together with the opposite effects of alpha- and beta-blockade, supports the hypothesis of neural mechanisms eliciting postischemic LV dysfunction.

Detection of perfusion defects during coronary occlusion and myocardial reperfusion after thrombolysis by intravenous administration of the echo-enhancing agent BR1.

The purpose of this study was to detect myocardial perfusion defects as a result of coronary occlusion and myocardial reperfusion after thrombolysis with intravenous (i.v.) administration of the echo contrast agent BR1 (Bracco Research, Switzerland), which consists of microbubbles (median diameter 2.5 microm) containing sulfur exafluoride in a phospholipidic shell. To generate a coronary thrombosis, a copper coil was advanced into the left circumflex coronary artery in eight anesthetized dogs with opened chest cavities. Coronary occlusion occurred 18 +/- 10 minutes after the insertion of the coil and was documented both by an electromagnetic flow meter (as zero blood flow) and by radiolabeled microspheres (as myocardial perfusion defect). After 2 hours of occlusion, streptokinase was infused i.v.; reperfusion was documented by both the flow-meter and microspheres. Left ventricular cavity enhancement was apparent after all contrast injections. Peak cavity intensity did not increase with dose and was not affected by signal processing (suggesting signal saturation), whereas the duration of contrast effect significantly increased with the dose (from 26 +/- 16 to 147 +/- 74 seconds). Myocardial contrast intensity also increased after contrast (from 15 +/- 12 to 21 +/- 18 gray level/pixel, p < 0.001). Contrast echo detected myocardial perfusion defects (corresponding to 17% +/- 11% of LV cross-sectional area) in all the injections performed during coronary occlusion and detected myocardial reperfusion with a sensitivity of 50% versus microspheres. The extent of perfusion defects by contrast echo showed a good correlation with microspheres (r = 0.73). Myocardial reperfusion was not detected by changes in heart rate, aortic pressure, pulmonary arterial pressure, cardiac output, left ventricular fractional area change, or wall-motion score index. Hemodynamic parameters were not affected by contrast injections. Thus, the i.v. administration of BR1 allows us to accurately detect myocardial perfusion defects during coronary occlusion and, to a lesser extent, myocardial reperfusion after thrombolysis.

Impact of chronic patency of infarct-related coronary artery on prevalence of myocardial ischemia during the pharmacologic and exercise stress test.

BACKGROUND: Even late restoration of anterograde coronary flow may have beneficial effects on left ventricular function, electrophysiology, and survival in postinfarction patients. HYPOTHESIS: The patency or occlusion of an infarct-related coronary artery in the chronic phase may also be associated with myocardial ischemia provoked by pharmacologic and physiologic stress tests. METHODS: High-dose dipyridamole echocardiography test (DET) (up to 0.84 mg/kg over 10 min), exercise electrocardiography (EET), and coronary angiographic data in a group of 127 in-hospital patients who had survived an acute myocardial infarction were analyzed. Patients who had only angiographic evidence of infarct-related single artery disease (> or = 50% luminal diameter reduction) and no previous revascularization were enrolled in the study. DET and EET were performed (DET in all, EET in 118 patients) within 5 days before coronary angiography. Fifty-seven patients had total occluded infarct arteries (Group 1) with various degrees of collateral circulation (2.6 +/- 1.1 collateral score, by a 3 grading system), whereas the other 70 patients had patent infarct arteries (Group 2) with significant residual stenoses (82 +/- 13% diameter reduction). RESULTS: The prevalence of rest angina or effort angina and topography of the infarct-related coronary artery did not differ between the two groups (all p = NS). There were more patients with Q wave in Group 1 than in Group 2 (72 vs. 57%, p = 0.08) compared with non-Q wave infarction (Group 1 = 28 vs. Group 2 = 43%, p = 0.08). Ischemia in the infarct-related artery territory detected by DET (defined as new wall motion dyssynergy or marked worsening of resting hypokinesia) was 61% in Group 1 and 41% in Group 2 (p = 0.025). EET was positive in 26 of 54 (48%) Group 1 and in 21 of 64 (33%) Group 2 patients (p = 0.09). CONCLUSIONS: Patients with occluded infarct-related arteries have a higher prevalence of ischemia during DET and EET regardless of the presence of collateral flow. These results suggest that the presence of partial anterograde flow in the prolonged period could have a favorable influence on prevalence of residual ischemia in these patients.