Health-related quality of life trajectories in melanoma patients after electrochemotherapy: real-world insights from the InspECT register.

BACKGROUND: Electrochemotherapy (ECT) effectively controls skin metastases from cutaneous melanoma. OBJECTIVES: This study aimed to evaluate health-related quality of life (HRQoL) in melanoma patients pre-/post-ECT and its effect on treatment outcome. METHODS: The analysis included prospective data from the International Network for Sharing Practices of ECT register. Following the Standard Operating Procedures, patients received intravenous or intratumoural bleomycin (15,000 IU/m2 ; 1000 IU mL/cm3 ) followed by 100-microsecond, 1000-V/cm electric pulses. Endpoints included response (RECIST v3.0), local progression-free survival (LPFS), toxicity (CTCAE v5.0), and patient-reported HRQoL at baseline, one, two, four and ten months (EuroQol [EQ-5D-3L], including 5-item utility score [EQ-5D] and visual analogue scale for self-reported health state [EQ-VAS]). Comparisons within/between subgroups were made for statistical and minimal important differences (MID). HRQoL scores and clinical covariates were analysed to identify predictors of response in multivariate analysis. RESULTS: Median tumour size was 2 cm. Complete response rate, G3 toxicity and one-year LPFS in 378 patients (76% of the melanoma cohort) were 47%, 5%, and 78%. At baseline, age-paired HRQoL did not differ from the general European population. Following ECT, both EQ-5D and EQ-VAS scores remained within MID boundaries, particularly among complete responders. A subanalysis of the EQ-5D items revealed a statistically significant deterioration in pain/discomfort and mobility (restored within four months), and self-care and usual activities (throughout the follow-up) domains. Concomitant checkpoint inhibition correlated with better EQ-5D and EQ-VAS trajectories. Baseline EQ-5D was the exclusive independent predictor for complete response (RR 14.76, p=0.001). CONCLUSIONS: HRQoL of ECT melanoma patients parallels the general population and is preserved in complete responders. Transient deterioration in pain/discomfort and mobility and persistent decline in self-care and usual activities may warrant targeted support interventions. Combination with checkpoint inhibitors is associated with better QoL outcomes. Baseline HRQoL provides predictive information which can help identify patients most likely to respond.

Baseline metabolic disturbances and the twenty-five years risk of incident cancer in a Mediterranean population.

BACKGROUND AND AIMS: Obesity is predictive of metabolic syndrome (metS), type 2 diabetes, cardiovascular (CV) disease and cancer. The aim of the study is to assess the risk of incident cancer connected to obesity and metS in a Mediterranean population characterized by a high prevalence of obesity. METHODS AND RESULTS: As many as 1133 subjects were enrolled in two phases and followed for 25 years (859 subjects) or 11 years (274 subjects) and incident cancer was registered in the follow-up period. Anthropometric measures and biochemical parameters were filed at baseline and evaluated as predictors of incident cancer by measuring hazards ratios (HR) using multivariate Cox parametric hazards models. Best predictive threshold for metabolic parameters and metS criteria were recalculated by ROC analysis. Fasting Blood Glucose >5.19 mmol/L [HR = 1.58 (1.0-2.4)] and the TG/HDL ratio (log10) (Males > 0.225, Females > 0.272) [HR = 2.44 (1.3-4.4)] resulted independent predictors of survival free of cancer with a clear additive effect together with age classes [45-65 years, HR = 2.47 (1.3-4.4), 65-75 years HR = 3.80 (2.0-7.1)] and male gender [HR = 2.07 (2.3-3.1)]. CONCLUSIONS: Metabolic disturbances are predictive of cancer in a 25 years follow-up of a Mediterranean population following a traditional Mediterranean diet. The high prevalence of obesity and metS and the observed underlying condition of insulin resistance expose this population to an increased risk of cardiovascular disease and cancer despite the healthy nutritional habits.

The in vivo trypanocidal effect of the diterpene 5-epi-icetexone obtained from Salvia gilliesii.

The search for new compounds with trypanocidal activity is crucial for the treatment of Chagas' disease. Previous in vitro studies have shown that the diterpene 5-epi-icetexone (ICTX) is active against Trypanosoma cruzi. The aim of this work was to evaluate the effect of ICTX on the parasites in infected mice, in an experimental model that mimics the acute phase of the disease. Swiss albino mice were infected with T. cruzi and treated daily with 10mg/kg/day ICTX (i.p.). Infected mice and mice injected with either saline or the vehicle DMSO were used as controls. Animals' survival and parasitemia were monitored once a week and histological studies were made at necropsy by the 5th week after infection. It was observed that the administration of ICTX increased the survival of mice infected, and induced a significant decrease in the parasitemia, as compared to controls. A similar protective effect was observed when animals were treated orally with benznidazole (BZN, used as a control of antiparasitic effect). By the 5th week post-infection, the presence of amastigote nests was observed within the fibers of the cardiac and skeletal muscle in controls, but not in animals treated with either ICTX or BZN. In addition, inflammatory infiltrates were observed in the tissues of controls, but not in animals treated with the drugs. We conclude that ICTX has an antiparasitic effect against T. cruzi, thus constituting an interesting option for the treatment of Chagas' disease, alone or combined with other drugs.

An abietane diterpene from Salvia cuspidata and some new derivatives are active against Trypanosoma cruzi.

The Plant Kingdom is an excellent source for obtaining natural compounds with antiprotozoal activity. In the present work, we studied the effect of the diterpene 12-hydroxy-11,14-diketo-6,8,12-abietatrien-19,20-olide (HABTO) obtained from the aerial parts of Salvia cuspidata on Trypanosoma cruzi epimastigotes. This compound was found to inhibit parasite growth even at low concentrations (IC50 5 µg/mL) and with low toxicity on mammalian cells. In addition, this diterpene induced an intense vacuolization within the parasites. In order to obtain analogs with greater lipophilicity, chemical modifications on the enol moiety were carried out to obtain the acetyl (AABTO), the sylil (SABTO) and the allyl (ALLABTO) derivatives. We observed that the SABTO was the most effective one on the parasites, and the effect could be attributed to a greater lipophilicity of this compound. Taking into account these data we conclude that the increase of lipophilicity by chemical modifications is an adequate strategy for improving the trypanocidal activity of this kind abietane diterpenes.

Left atrial appendage occlusion with the Watchman device in a patient with paroxysmal atrial fibrillation and intolerance of all forms of anticoagulation due to hereditary haemorrhagic telangiectasia.

An elderly woman presented to our attention because of paroxysmal atrial fibrillation and cerebrovascular events requiring systemic anticoagulation and a concomitant, serious bleeding diathesis (the Osler-Weber-Rendu syndrome, or hereditary haemorrhagic telangiectasia). Her risk of suffering a major stroke was significant given a CHA(2)DS(2)VASc score of 6. However, she was unable to tolerate any form of anticoagulation because of torrential epistaxis and previous gastrointestinal haemorrhage on antiplatelet therapy. We proceeded with percutaneous occlusion of the left atrial appendage with a Watchman device. Ten months post-procedure she is well, without recurrence of neurological symptoms, and off all forms of anticoagulation. The current internationally accepted practice post-deployment of the Watchman device mandates warfarin transition for 6 months to allow for endothelialisation of the device. However, there is no evidence in the literature to support left atrial appendage occlusion without any peri-procedural antiplatelet and anticoagulation therapy and therefore our case represents novel and important anecdotal evidence that secondary stroke prevention with left atrial appendage occlusion may be effective and safe even in patients who cannot tolerate any form of anticoagulation at all.

Chemically modified poly(2-hydroxyethyl methacrylate) cryogel for the adsorption of heparin.

Various clinical procedures, such as cardiovascular surgery or extracorporeal blood purification, involve systemic anticoagulation using heparin. High concentrations of circulating heparin require neutralization due to possible serious bleeding complications. The intravenous administration of the heparin antagonist protamine sulfate is routinely clinically performed, but is frequently associated with adverse reactions. Therefore, there is a need for a valid and safe alternative to achieve extracorporeal heparin removal from blood or plasma, such as a filter, a matrix, or an adsorbent. Here, we describe the development of a macroporous poly(2-hydroxyethyl methacrylate)-based monolithic cryogel functionalized with l-lysine (pHEMA-lys) and the characterization of its selective heparin adsorption. The maximum binding capacity was quantified in vitro using aqueous and serum solutions under static and dynamic conditions, and fresh human plasma under static conditions. The pHEMA-lys bound 40,500 IU and 32,500 IU heparin/g cryogel at the equilibrium in aqueous solution and 50% serum, respectively. In human plasma spiked with 100 IU/mL of heparin, the binding was still highly efficient (4330 IU/g cryogel after 30 min, i.e., 87% of the initial concentration). The cryogels showed good blood compatibility, as indicated by negligible adsorption of albumin, antithrombin III, and total protein, and may thus be suitable for extracorporeal heparin removal.

Outcomes of chemoradiation for patients with locally advanced non-small-cell lung cancer.

BACKGROUND: Historically, long-term survival rates in locally advanced non-small-cell lung cancer (NSCLC) have been disappointingly low, and treatment toxicities have been significant. AIMS: To assess survival outcomes, treatment toxicities, patterns of disease recurrence and prognostic variables for patients with locally advanced NSCLC treated with concurrent chemoradiation. METHODS: Patients who completed treatment with chemotherapy and simultaneous chest irradiation for locally advanced NSCLC at the Royal Prince Alfred Hospital (Sydney, Australia) in the period January 1994 to July 2009 were identified. We retrospectively reviewed the patients' medical records to obtain patient demographic data, clinical data, information on tumour characteristics and treatment administered, and outcome data such as survival, treatment toxicities and tumour recurrence patterns. RESULTS: Our patient cohort consisted largely of urban-dwelling male smokers with good baseline performance status. As of December 2012, 93/105 patients had died. Median overall and progression-free survival was 20 months and 11 months respectively. The 5-year survival rate was 17%. Eight patients had survived longer than 8 years, and 13 patients enjoyed progression-free survival longer than 3 years. Locoregional tumour recurrence occurred most frequently, followed by brain and bone metastases. Adverse effects from chemoradiation included varying degrees of gastrointestinal, pulmonary and haematological toxicity. Three deaths occurred from radiation-induced pneumonitis. Weight loss at presentation was statistically significantly associated with worse overall survival in univariate analyses (P = 0.01). CONCLUSIONS: Our survival results are consistent with the recent international literature and indicate that a proportion of patients with locally advanced NSCLC can enjoy prolonged survival following treatment with concurrent chemoradiation.

Diagnosing oral lichenoid contact reaction: clinical judgment versus skin-patch test.

AIM: Objective of this study was to compare the skin-patch test with the clinical diagnosis of oral lichenoid contact reaction (OLCR) as indicators for amalgam replacement. METHODS: Of 53 patients (38 female and 15 male; mean age 48.7) with oral lichen planus (OLP), 26 were identified as having OLCR, and clinically graded according to the proximity of their lesions with amalgam fillings: class I (weak association), class II (moderate association), and class III (strong association). All OLCR patients were skin-patch tested for both standard (Brazilian) and specific allergens (TROLAB, Germany). Patients were considered skin-patch positive only if they developed positive skin reactions for thimerosal and/or amalgam components. Amalgam replacement was indicated in all class II and III patients. For class-I patients, amalgam replacement was indicated only if they were skin-patch test positive. Readings for the skin-patch test were made at 48h and 96h. RESULTS: Of the 26 patients with OLCR, two missed the follow-up and were excluded, leaving 24 cases. Of these, four were class-I, and all were negative for the skin-patch test. Twelve were class-II, of whom seven were skin-patch positive. Eight were class-III, of whom six were skin-patch positive. Following amalgam replacement in the 12 class-II patients, six showed improvement and six had complete resolution, while in the eight class-III patients, two showed improvement and six a complete resolution. CONCLUSION: Clinical diagnosis of OLCR lesions is a more reliable indicator for the question of amalgam replacement than is the skin-patch test.

Effects of hemoperfusion with an immobilized polymyxin-B fiber column on cytokine plasma levels in patients with abdominal sepsis.

AIM: The beneficial role of hemofiltration with immobilized polymyxin-B fiber (PMX) columns in sepsis, especially sepsis due to gram-negative bacteria, has previously been emphasized. Although the efficacy of PMX-B fiber-mediated hemofiltration in reducing plasma levels of cytokines has been reported, other studies did not confirm this observation. Here we report the effects of PMX-B fiber-mediated hemofiltration on outcome and cytokine plasma levels in patients with abdominal sepsis. METHODS: Twelve consecutive patients admitted to the Intensive Care Unit (October 2006-December 2007) for severe sepsis/septic shock from abdominal infection were treated with standard therapy and 2 cycles of hemofiltration with PMX cartridges. Clinical data and plasma levels of IL-6, IL-10 and TNF-a were measured 24 hours before and after PMX treatment. RESULTS: Plasma concentrations (pg/mL) of IL-6, IL-10 and TNF-a were significantly lower after hemofiltration with a PMX fiber column (279.9+/-69.2 vs. 130.9+/-18.4, 166.4+/-36.7 vs. 45.5+/-12.2, 83.1+/-13.5 vs. 23.9+/-5.1 pg/mL, respectively; P<0.05). After treatment, patients required lower doses of norepinephrine (0.3+/-0.1 vs. 0.8+/-0.1 mg/kg/min) and reduced lactate levels, recovery of respiratory function and improved Simplified Organ Failure Assessment (SOFA) scores. After 28 days, 6 patients (50%) had survived. Subgroup analysis demonstrated that survivors had higher IL-6 and lower IL-10 and TNF-a pre-treatment plasma levels (pg/mL) compared with deceased patients (324.4+/-41.1 vs.235.3+/-38.4; 98.5+/-16.1 vs. 234.3+/-48.6, 44.5+/-9.0 vs.121.6+/-52.3 pg/mL, respectively; P<0.05). No adverse events imputable to the treatment were recorded. CONCLUSION: Hemofiltration with a PMX fiber column was able to reduce plasma levels of IL-6, IL-10 and TNF-a, especially in patients surviving at 28 days. Use of the technique was associated with lower norepinephrine support and an increased PaO2/FiO2 ratio.

Comparison between single-step and balloon dilatational tracheostomy in intensive care unit: a single-centre, randomized controlled study.

BACKGROUND: Balloon dilatational tracheostomy using the Ciaglia Blue Dolphin device has recently been introduced as a modification of the Ciaglia technique. The aim of this study was to compare the new Dolphin system with the single-step dilatational tracheostomy (Ciaglia Blue Rhino) in intensive care unit (ICU) patients. METHODS: Consecutive patients admitted to the ICU of the Emergency Department (Careggi Teaching Hospital, Florence, Italy) from January 2009 to October 2009, aged >18 years and with an indication for percutaneous dilatational tracheostomy (PDT), were enrolled. Exclusion criteria were infection/injury/malignancy of the neck, thyroid gland hypertrophy, severe head injury with uncontrolled intracranial hypertension, and coagulopathy. Patients were randomly assigned to undergo PDT using either the Ciaglia Blue Rhino (n=35) or the Ciaglia Blue Dolphin technique (n=35). Groups were compared according to tracheal puncture, tracheal tube placement time, procedure-related complications, and bleeding. RESULTS: Baseline clinical data were comparable between the two groups. Median procedure time was significantly shorter in the Rhino group compared with the Dolphin group (1.5 vs 4 min, P = 0.035). The presence of limited intra-tracheal bleeding at bronchoscopy examination after 6 h from PDT was more frequent in the Dolphin group than in the Rhino group patients (68.6% vs 34.3%, respectively, P = 0.008). No major bleeding occurred in either group. CONCLUSIONS: PDT using the Ciaglia Blue Dolphin technique is a feasible and viable option in ICU patients, but the Rhino technique had a shorter execution time and seemed to be associated with fewer tracheal injuries.

The value of lung ultrasound monitoring in H1N1 acute respiratory distress syndrome.

We present the case of a healthy young male who developed acute respiratory failure as a result of infection with influenza A/H1N1 of swine-origin and in whom ventilatory support was optimised and recovery of lung function was monitored by the use of sequential chest ultrasound examinations. The potential pivotal role of bedside lung ultrasonography in H1N1-induced respiratory failure is discussed.

[Urethral recurrence of invasive carcinoma following BCG treatment for bladder Ca in situ]. / Recidiva uretrale di Ca infiltrante dopo trattamento con BCG per Ca in situ vescicale.

CIS is a flat, high-grade, non-invasive microscopic urothelial carcinoma. It is considered a precursor of invasive bladder cancer. CIS is classified as primary, secondary or concurrent, when occurred as isolated CIS without cuncurrent papillary tumors, or detected during the follow-up of patients with a previous papillary tumor, or finally in the presence of bladder neoplasm. BCG is widely established as the treatment of choice for CIS with a success rate of approximately 70%. BCG reduces the risk of progression of CIS into invasive carcinoma in 30 to 50% of cases. Direct and prolonged contact between the urothelium and BCG is a prerequisite for successful therapy. Discovery of CIS in the prostatic or membranous urethra represents an ominous sign. CIS may be present only in the epithelial lining of the prostatic urethra or in the ducts, or in the worst case it may be found in the prostatic tissue stroma. Urethral involvement by CIS is at high risk of tumor progression and development of metastases due to reduced thickness of lamina propria and absence of muscolaris mucosa. 83 patients, enrolled from 1/1996 to 12/2005 at our urological department with CIS: primary (focal and multifocal) in 25, secondary in 7 and cuncurrent in 51 (associated with T1bG3 cancer in 37 cases), and urethral CIS in 5 and conservatively treated by TUR and intravescical instillations of BCG, 4 developed afterwords only invasive cancer of the urethra in the absence of bladder involvement. In 2 cases cancer arised from the prostatic fossa after TURP, in 1 from membranous urethra and in the last from prostatic ducts. Among the 4 patients, 3 were treated by cystoprostatourethrectomy and Platinum-based chemotherapy, 1 refused surgical treatment. Two patients died for disseminated disease. 1 patient is alive at 60-month's follow-up. In the last patient cancer relapsed at 36-month's follow-up. We conclude that prostatic/urethral involvement during follow-up after successful intravesical treatment with BCG in CIS represents a high risk of developing invasive and incontrolled cancer. A careful watch is recommended in these patients.

Simvastatin reduces reperfusion injury by modulating nitric oxide synthase expression: an ex vivo study in isolated working rat hearts.

OBJECTIVE: We tested the hypothesis of beneficial effects of the 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA)-reductase inhibitor simvastatin in a model of ischemia-reperfusion, and investigated potential mechanisms. METHODS: Isolated working rat hearts were subjected to 15 min global ischemia and 22-180 min reperfusion in the presence or absence of simvastatin (10-100 microM). We evaluated creatinephosphokinase and nitrite levels in coronary effluent, heart weight changes, microvascular permeability (extravasation of fluoresceine-labeled albumin), ultrastructural alterations, and the expression of endothelial (e) and inducible (i) nitric oxide synthase (NOS) (by reverse-transcribed polymerase chain reaction and Western blotting) in the presence or absence of the transcriptional inhibitor actinomycin-D. RESULTS: Simvastatin (25 microM) significantly reduced myocardial damage and vascular hyperpermeability, concomitant with a reduction in endothelial and cardiomyocyte lesions. Protection became less evident at 50 microM and reverted to increased damage at 100 microM. At 25 microM, simvastatin significantly increased eNOS mRNA and protein compared with untreated hearts, probably due to a post-transcriptional regulation since unaltered by animal pretreatment with actinomycin D. Simvastatin also significantly decreased iNOS mRNA and protein, as well as nitrite production after ischemia-reperfusion. The addition of the NOS inhibitor N(pi)-nitro-L-arginine methylester (L-NAME, 30 microM) to 25 microM simvastatin-treated hearts significantly reduced cardioprotection against ischemia-reperfusion. CONCLUSIONS: In this model, in the absence of perfusing granulocytes, the acute administration of a pharmacologically relevant simvastatin concentration reduces ischemia-reperfusion injury and prevents coronary endothelial cell and cardiomyocyte damage by cholesterol-independent, NO-dependent mechanisms.

MK-954 (losartan potassium) exerts endothelial protective effects against reperfusion injury: evidence of an e-NOS mRNA overexpression after global ischemia.

BACKGROUND: the cardiac Renin-Angiotensin system (RAS) plays an important role in the regulation of coronary flow and cardiac function and structure in normal and pathological conditions such as ischemia-reperfusion (I/R) injury. The aim of this study was to investigate the effects of the Angiotensin II type 1 (AT-1) receptor antagonist MK-954 (losartan potassium) on postischemic endothelial dysfunction and NOS mRNA expression (inducible nitric oxide synthase, iNOS; endothelial nitric oxide synthase, eNOS) in isolated working rat hearts. METHODS: isolated working rat hearts were subjected to 15 min global ischemia and 180 min reperfusion. MK-954 was added to perfusion buffer (a modified Krebs-Henseleit solution) at 1 microM concentration. We assessed functional parameters, creatin kinase (CK) release, heart weight changes, microvascular postischemic hyperpermeability (FITC-albumin extravasation) and morphological ultrastructural alterations. eNOS and iNOS mRNA levels were also detected by the means of multiplex RT-PCR technique using glyceraldehyde-3-phosphate dehydrogenase (G3PDH) gene as internal control; results were expressed as densitometric ratio. RESULTS: in Losartan-treated hearts we observed a significant reduction of postischemic contractile dysfunction, CK release and myocardial ultrastructural damage; postischemic FITC-albumin extravasation was significantly reduced respect to controls. Moreover, 1 microM Losartan produced a significant reduction of eNOS/G3PDH respect to untreated hearts submitted to I/R. Regarding iNOS/G3PDH ratio, no significant changes were detected in Losartan-treated hearts compared with controls. CONCLUSIONS: our study revealed that Losartan treatment before ischemia, and during reperfusion, is able to reduce the reperfusion injury of the rat heart by reducing mechanical and microcirculatory dysfunction and necrotic cell death, ameliorating cardiac ultrastructure and endothelial protection, probably inducing eNOS over-expression and reducing post-ischemic hyperpermeability of coronary microcirculation.

Adaptations in beta-adrenergic cardiovascular responses to training in older women.

To determine whether endurance exercise training can alter the beta-adrenergic-stimulated inotropic response in older women, we studied 10 postmenopausal healthy women (65.4 +/- 0.9 yr old) who exercised for 11 mo. Left ventricular (LV) function was evaluated with two-dimensional echocardiography during infusion of isoproterenol after atropine. Maximal O(2) consumption increased 23% in response to training (from 1.35 +/- 0.06 to 1.66 +/- 0.07 l/min; P = 0.004). Training had no effect on baseline LV function, end-diastolic diameter, LV wall thickness, or LV mass. The increase in LV systolic function in response to isoproterenol was unaffected by training. Furthermore, neither the systolic shortening-to-end-systolic wall stress relationship nor the end-systolic wall stress-to-end-systolic diameter relationship during isoproterenol infusion changed with training. We conclude that older postmenopausal women can increase their maximal O(2) consumption with exercise training without eccentric LV hypertrophy or enhancement of beta-adrenergic-mediated LV contractile function. These observations provide an explanation for the finding that maximal cardiac output and stroke volume are not increased in older women in response to training.

Estrogen increases hyperemic microvascular blood flow velocity in postmenopausal women.

BACKGROUND: Epidemiologic studies suggest that estrogen replacement therapy (ERT) is protective against vascular disease. ERT confers this benefit by lowering lipid levels and improving arterial function. However, its effect on the microvasculature in vivo is unknown. Thus the purposes of this study were to evaluate effect of estrogen status on the hyperemic response of the microvasculature in vivo in postmenopausal women and to compare the hyperemic response of the microvasculature in postmenopausal women taking ERT with that of premenopausal women. METHODS: We measured forearm microvasculature flow velocity by using a laser Doppler in a cross section of 64 healthy premenopausal and postmenopausal women 23 to 72 years old. Microvasculature blood flow velocity was measured at baseline. throughout 2 minutes of ischemia, and immediately after the ischemic period was terminated (i.e., during the peak hyperemic response). RESULTS: The peak of the hyperemic flow velocity (PHFV) in the postmenopausal women who were taking long-term ERT at usual doses was greater than that of postmenopausal women who were not currently taking ERT (p < .0001). Moreover, the PHFV of postmenopausal women taking ERT was similar to that of premenopausal women. Multivariate regression analysis showed estrogen status and baseline flow velocity to be independent predictors of PHFV. CONCLUSIONS: Current, long-term ERT at usual replacement doses is associated with improved microvascular responses in postmenopausal women, which may explain some of its beneficial vascular effects.

Effect of endurance exercise training on left ventricular size and remodeling in older adults with hypertension.

BACKGROUND: It is not known whether exercise training can induce a reduction of blood pressure (BP) and a regression of left ventricular hypertrophy (LVH) in older hypertensive subjects. This study was designed to determine whether endurance exercise training, by lowering BP, can induce regression of LVH and left ventricular (LV) concentric remodeling in older hypertensive adults. METHODS: We studied 11 older adults with mild to moderate hypertension (BP 152.0 +/- 2.5/91.3 +/- 1.5 mm Hg, mean +/- SE), 65.5 +/- 1.2 years old, who exercised for 6.8 +/- 3.8 months. Seven sedentary hypertensive (BP 153 +/- 3/89 +/- 2 mm Hg) subjects, 68.5 +/- 1 years old, served as controls. LV size and geometry and function were assessed with the use of two-dimensional echocardiography. RESULTS: Exercise training increased aerobic power by 16% (p < .001), and it decreased systolic (p < .05) and diastolic (p < .05) BP, LV wall thickness (from 12.8 +/- 0.4 mm to 11.3 +/- 0.3 mm; p < .05), and the wall thickness-to-radius (h/r) ratio (from 0.48 +/- 0.02 to 0.41 +/- 0.01; p < .05). There were no significant changes in the controls. The changes in LV mass index (deltaLVMI) were different between the two groups. LV mass index decreased in the exercise group (deltaLVMI - 14.3 +/- 3.3 g) but not in the controls (deltaLVMI 1.4 +/- 4.1 g; p = .009). A multiple stepwise regression analysis showed that among clinical and physiological variables including changes in resting systolic BP, aerobic power, body mass index, and systolic BP during submaximal and maximal exercise, only the reduction in resting systolic BP correlated significantly with a regression of concentric remodeling (delta h/r ratio r = .80; p = .003). The other variables did not add to the ability of the model to predict changes in the h/r ratio. CONCLUSIONS: The data suggest that exercise training can reduce BP and induce partial regression of LVH and LV concentric remodeling in older adults with mild or moderate hypertension.

Enhanced inotropic response to dobutamine in strength-trained subjects with left ventricular hypertrophy.

To determine whether strength-trained individuals with physiological concentric left ventricular (LV) hypertrophy exhibit enhanced inotropic responses to catecholamines, we studied 11 bodybuilders, aged 33.0 +/- 2 (SE) yr old, and 10 sedentary healthy subjects, aged 31.3 +/- 2.4 yr old, at baseline and during infusion of incremental doses of dobutamine after atropine. The bodybuilders had larger LV mass, posterior wall and septal wall thicknesses, and wall thickness-to-radius ratio, assessed with two-dimensional echocardiography, than did the sedentary subjects. There was a significant correlation between LV mass and lean body mass irrespective of training status. Baseline LV fractional shortening was similar in the two groups. There was a greater inotropic response to dobutamine in the strength-trained individuals, as evidenced by a steeper slope of the fractional shortening-end-systolic wall stress relationship with a higher y-axis intercept and by a shallower end-systolic wall stress-end systolic diameter relationship without changes in end-diastolic diameter. The heart rate response to dobutamine was attenuated in the strength-trained athletes. There was a significant correlation (r = 0.604, P < 0.05) between the inotropic sensitivity to dobutamine and LV mass normalized for lean body mass in the bodybuilders. The data suggest that concentric LV physiological hypertrophy in the resistance-trained individuals is associated with enhanced inotropic but not chronotropic responses to catecholamines.