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.

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.

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.

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.

Mechanisms of impaired exercise capacity in short duration experimental hyperthyroidism.

To investigate the mechanism of reduced exercise tolerance in hyperthyroidism, we characterized cardiovascular function and determinants of skeletal muscle metabolism in 18 healthy subjects aged 26 +/- 1 yr (mean +/- SE) before and after 2 wk of daily ingestion of 100 micrograms of triiodothyronine (T3). Resting oxygen uptake, heart rate, and cardiac output increased and heart rate and cardiac output at the same submaximal exercise intensity were higher in the hyperthyroid state (P less than 0.05). However, maximal oxygen uptake decreased after T3 administration (3.08 +/- 0.17 vs. 2.94 +/- 0.19 l/min; P less than 0.001) despite increased heart rate and cardiac output at maximal exercise (P less than 0.05). Plasma lactic acid concentration at an equivalent submaximal exercise intensity was elevated 25% (P less than 0.01) and the arteriovenous oxygen difference at maximal effort was reduced (P less than 0.05) in the hyperthyroid state. These effects were associated with a 21-37% decline in activities of oxidative (P less than 0.001) and glycolytic (P less than 0.05) enzymes in skeletal muscle and a 15% decrease in type IIA muscle fiber cross-sectional area (P less than 0.05). Lean body mass was reduced (P less than 0.001) and the rates of whole body leucine oxidation and protein breakdown were enhanced (P less than 0.05). Thus, exercise tolerance is impaired in short duration hyperthyroidism because of decreased skeletal muscle mass and oxidative capacity related to accelerated protein catabolism but cardiac pump function is not reduced.

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.

Effect of hyperthyroidism of short duration on cardiac sensitivity to beta-adrenergic stimulation.

The effect of hyperthyroidism on cardiac sensitivity to beta-adrenergic stimulation in humans is controversial. To determine whether heart rate and left ventricular contractile sensitivity to beta-adrenergic stimulation are altered by hyperthyroidism in human subjects, the frequency, velocity and extent of left ventricular shortening at rest and during a 4-stage graded dose isoproterenol infusion were characterized in eight young healthy subjects before and after 2 weeks of daily administration of 100 micrograms of triiodothyronine (T3). The rate and extent of left ventricular shortening were determined by Doppler and two-dimensionally guided M-mode echocardiography. In the hyperthyroid state, heart rate at rest was faster (57 +/- 3 vs. 68 +/- 4 beats/min; p less than 0.001) and the slope of the relation of heart rate to the rate of isoproterenol infusion was 36% steeper (1,538 +/- 126 vs. 1,131 +/- 95; p less than 0.05). The left ventricular ejection time was shorter and the mean velocity of left ventricular circumferential fiber shortening (mVcf) was greater during all stages of isoproterenol infusion in the hyperthyroid versus the euthyroid state (p less than 0.01). After adjustment for the faster heart rate after T3 administration, left ventricular ejection time and mVcf were similar in the euthyroid and hyperthyroid states at baseline and during maximal beta-adrenergic stimulation but shortened and enhanced, respectively, during stages 1 and 2 of isoproterenol infusion (p less than 0.05). There was no effect of T3 administration on left ventricular mass, dimensions, end-systolic wall stress or stroke volume at rest or during any stage of isoproterenol infusion. These results indicate that in human subjects hyperthyroidism of short duration increases the sensitivity of heart rate and left ventricular shortening velocity to beta-adrenergic stimulation in the absence of changes in left ventricular mass, loading conditions or extent of shortening.

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.

Effect of exercise training on left ventricular performance in older women free of cardiopulmonary disease.

Endurance exercise training increases aerobic exercise capacity (maximal oxygen consumption rate [VO2max]) and attenuates the age-related decline in left ventricular (LV) function during exercise in older men. To determine whether similar adaptations occur in older women, 10 subjects (aged 63 +/- 4 years mean +/- SE) were studied before and after 9 to 12 months of endurance exercise training. They exercised 3.85 +/- 0.06 days/week at 81 +/- 0.3% of maximal heart rate. LV function at rest and during supine exercise was assessed by radionuclide ventriculography. VO2max was increased by 21% (from 1.40 +/- 0.1 to 1.7 +/- 0.1 liter/min; p < 0.001) in response to training. Maximal heart rate and systolic blood pressure during treadmill exercise were unchanged (161 +/- 5 beats/min before vs 164 +/- 3 beats/min after; p = NS, and 208 +/- 7 mm Hg before vs 214 +/- 8 mm Hg after; p = NS, respectively) after training. LV ejection fraction at rest (70.4 +/- 2% before vs 70 +/- 1% after) and during peak exercise (78.6 +/- 2% before vs 79.3 +/- 2% after) did not change in response to training. Furthermore, the increases in ejection fraction from rest to exercise were similar before and after training (change: 8.8 +/- 1 vs 9.1 +/- 1%). Stroke volume and cardiac output at peak exercise also did not change in response to training.(ABSTRACT TRUNCATED AT 250 WORDS)

Prescribing exercise intensity for older women.

OBJECTIVE: For the purpose of prescribing exercise intensity, the American College of Sports Medicine (ACSM) provides guidelines for relating the perceived level of exertion and the heart rate (HR) response during exercise, expressed either as a percentage of maximal HR or of HR reserve, to a percentage of maximal aerobic power (VO2max). However, because maximal HR and VO2max decline with age, it is possible that these guidelines are not appropriate for an older population. The purpose of this study was to evaluate in 60- to 72-year-old women the relationships among the common methods of prescribing exercise intensity. DESIGN: Participants were 112 healthy but sedentary women, aged 66 +/- 4 years, who performed treadmill walking at four speeds. SETTING: Subjects were recruited from the community, and exercise tests were performed at a university laboratory facility. MEASUREMENTS: VO2max and maximal HR were determined during treadmill walking. The HR and VO2 responses to walking 6 minutes at each of four speeds ranging from 67 to 107 m/min, along with ratings of perceived exertion (RPE) and plasma lactate levels, were determined on a separate day. RESULTS: The exercise bouts required an average of 55 +/- 10%, 64 +/- 12%, 77 +/- 12%, and 91 +/- 9% of VO2max. Corresponding HR values were 64 +/- 8%, 70 +/- 9%, 81 +/- 10%, and 92 +/- 7% of maximal HR, and they were within the expected ranges based on ACSM guidelines. HR values as a percentage of HR reserve were much lower than expected based on the guidelines. RPE values were lower than expected at a given %VO2max, and plasma lactate levels were also relatively low, suggesting that older women are able to exercise at a higher percentage of VO2max than levels currently recommended. CONCLUSIONS: The results indicate that HR expressed as a percentage of maximal HR is an appropriate method of prescribing exercise intensity in healthy, sedentary 60- to 72-year-old women. The HR reserve method is not recommended in this population because it will likely result in the exercise being performed at a higher than expected percentage of VO2max.

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.

Effects of age and gender on cardiovascular responses to phenylephrine.

BACKGROUND: The age-associated impairment in left ventricular (LV) systolic function appears to be mostly detectable during exercise or sympathetic stimulation. We hypothesized that the decline in cardiac function could be unmasked by an acute increase in afterload induced by phenylephrine. We further sought to examine whether the deterioration in cardiac function is influenced by gender. METHODS: We studied 17 young (20-31 years old) and 21 older healthy subjects (60-75 years old) who were given infusions of incremental doses of phenylephrine following cardiac muscarinic receptor blockade with atropine. Left ventricular systolic function was assessed with 2-D echocardiography. RESULTS: The young subjects exhibited a paradoxical increase in heart rate in response to alpha-adrenergic stimulation, but the older subjects did not (p < .01). The increase in systolic blood pressure in response to phenylephrine was influenced by age and gender (i.e., greater in the younger men and older women), whereas the increase in diastolic blood pressure was greater in the younger than the older subjects of both sexes. The changes in LV end-diastolic diameter with phenylephrine were unaffected by age or gender. The slope of the systolic shortening-end systolic wall stress relationship was significantly steeper in the older subjects, suggesting a decline in the contractile response to an acute increase in afterload with aging. CONCLUSIONS: This study's findings suggest that age can significantly influence the cardiovascular responses to alpha-adrenergic stimulation and that phenylephrine, by acutely increasing afterload, is effective in unmasking the age-associated deterioration in left ventricular systolic function. Further, it appears that the increase in systolic blood pressure in response to an alpha-adrenergic challenge is significantly influenced not only by age but also by gender.

Gender-related differences in left ventricular filling dynamics in older subjects after endurance exercise training.

The present study was designed to determine if gender affects the adaptive response to endurance exercise training of left ventricular filling dynamics in older individuals. Recently, it was shown that gender influences the cardiovascular responses to endurance exercise training in older subjects. Older men improve left ventricular systolic performance and increase maximal cardiac output in response to endurance exercise training, whereas older women do not. Twelve men (65 +/- 1 years old; mean +/- SE) and 10 women (64 +/- 1) were studied before and after 9 months of endurance exercise training. Maximal O2 uptake was determined during treadmill exercise. Left ventricular filling dynamics and ejection fraction (EF) at rest and during supine exercise were assessed by Tc-99m radionuclide ventriculography. When expressed relative to body weight, maximal O2 uptake (VO2 max) was increased by 24% (27.3 +/- 1.5 to 34.0 +/- 1.5 ml/kg/min; p < .01) in men and 27% (21.9 +/- 1.0 to 27.8 +/- 1.0 ml/kg/min; p < .01) in women in response to endurance exercise training. In men, the time-to-peak filling rate (TPFR) decreased (-19.8 +/- 6.7 ms; p < .05) during exercise at a comparable heart rate in response to training. In contrast, the change in TPFR in women (+2.7 +/- 6.0 ms) was small and insignificant. Peak filling rate (PFR) at rest and during exercise was similar before and after training in men and women. The change in left ventricular systolic reserve at a comparable heart rate from pre-to posttraining improved in men (delta EF 4 +/- 3%; p < .05), but not in women (-2 +/- 3%). The results indicate that the adaptive response of left ventricular filling dynamics to endurance exercise training is influenced by gender in older subjects. Older men show improvement in left ventricular filling dynamics, whereas older women do not.

Effects of age and gender on the cardiovascular responses to isoproterenol.

We studied the effects of age and gender on cardiovascular responses to beta-adrenergic stimulation with the use of two-dimensional echocardiography in 16 young (aged 20-31) and 20 older (aged 60-75) healthy individuals. Following administration of atropine, each subject was given an infusion of isoproterenol at incremental doses from 0.010 to 0.030 microgram kg-1 min-1. The slopes of the fractional shortening-end-systolic wall stress (FS-sigma es) relationships were steeper in the young men (-0.87 +/- 0.28, n = 8) compared to the older men (-0.41 +/- 0.13, n = 10), and in the young women (-0.55 +/- 0.14, n = 8) compared to the older women (-0.38 +/- 0.13, n = 10). Furthermore, the magnitude of the age-associated differences in these slopes was larger in the men (old vs young) than in the women (old vs young) which, in the absence of changes in preload, suggests a greater decline in the contractile response to isoproterenol with advancing age in men compared to women. Furthermore, the men exhibited a greater attenuation of chronotropic response to isoproterenol than did the women. These observations suggest that gender plays a significant role in the age-associated decline in inotropic and chronotropic responses to beta-adrenergic stimulation, with men exhibiting a greater decline with aging than women.