Analysis and prevention of falls among community-dwelling older adults in southern Thailand.

AIM: To analyse fall prevalence, risk factors and perceptions among Thai older adults to design a prevention model. DESIGN: Quantitative and qualitative data were collected using a convergent parallel mixed-methods design. METHODS: A cross-sectional analysis was conducted using secondary data from health screenings of older adults in 20 subdistrict hospitals in southern Thailand from January 2018 to September 2019 (n = 12,130). In-depth interviews (IDIs) and focus group discussions (FGDs) were conducted with purposively sampled participants who were representatives of older adults and stakeholders (n = 50). RESULTS: The quantitative analysis showed that the prevalence of falls was 12.1%. The independent risk factors were female gender, employment status, cognitive impairment, semi-dependent functional ability, balance problems, vision impairment, hearing difficulties, use of medications, reliance on assistive devices and access to outdoor toilets. The qualitative analysis revealed misconceptions on falls and fall prevention measures among older adults and community stakeholders. In Thailand, healthcare providers and community nurses play a crucial role in providing primary advice and conducting interventions, yet they encounter obstacles due to lack of personnel, time constraints, limited resources, inadequate support and unclear policies. Stakeholders stress the urgency of improving practice guidelines, developing evidence-based strategies and aligning with government policies. CONCLUSIONS: Fall risk factors and prevention challenges among older adults were identified. Effective fall prevention programmes are needed. IMPACT: The identified fall events may guide public health agencies and local administrations in planning fall prevention programmes. For implementation in Thai communities, teamwork among leaders and stakeholders is key. PATIENT OR PUBLIC CONTRIBUTION: IDIs and FGDs were conducted with older adults, village health volunteers, nurses, healthcare providers, local organization administrators and village headmen.

Ranolazine Attenuates the Electrophysiological Effects of Myocardial Stretch in Langendorff-Perfused Rabbit Hearts.

PURPOSE: Mechanical stretch is an arrhythmogenic factor found in situations of cardiac overload or dyssynchronic contraction. Ranolazine is an antianginal agent that inhibits the late Na (+) current and has been shown to exert a protective effect against arrhythmias. The present study aims to determine whether ranolazine modifies the electrophysiological responses induced by acute mechanical stretch. METHODS: The ventricular fibrillation modifications induced by acute stretch were studied in Langendorff-perfused rabbit hearts using epicardial multiple electrodes under control conditions (n = 9) or during perfusion of the late Na(+) current blocker ranolazine 5 µM (n = 9). Spectral and mapping techniques were used to establish the ventricular fibrillation dominant frequency, the spectral concentration and the complexity of myocardial activation in three situations: baseline, stretch and post-stretch. RESULTS: Ranolazine attenuated the increase in ventricular fibrillation dominant frequency produced by stretch (23.0 vs 40.4 %) (control: baseline =13.6 ± 2.6 Hz, stretch = 19.1 ± 3.1 Hz, p < 0.0001; ranolazine: baseline = 1.4 ± 1.8 Hz, stretch =14.0 ± 2.4 Hz, p < 0.05 vs baseline, p < 0.001 vs control). During stretch, ventricular fibrillation was less complex in the ranolazine than in the control series, as evaluated by the lesser percentage of complex maps and the greater spectral concentration of ventricular fibrillation. These changes were associated to an increase in the fifth percentile of VV intervals during ventricular fibrillation (50 ± 8 vs 38 ± 5 ms, p < .01) and in the wavelength of the activation (2.4 ± 0.3 vs 1.9 ± 0.2 cm, p < 0.001) under ranolazine. CONCLUSIONS: The late inward Na(+) current inhibitor ranolazine attenuates the electrophysiological effects responsible for the acceleration and increase in complexity of ventricular fibrillation produced by myocardial stretch.

Dynamics of serum-induced endothelial cell apoptosis in patients with myocardial infarction.

BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI) reperfused with primary coronary intervention (PCI), the dynamics of endothelial cell (EC) viability, apoptosis and necrosis and its relationship with the structural consequences on the left ventricle have not been addressed so far. DESIGN: In 20 STEMI patients, we incubated human umbilical vein endothelial cells (HUVECs) with serum drawn before reperfusion and subsequently afterwards (24, 96 h, 30 days). Viability, apoptosis and necrosis percentages were evaluated by flow cytometry. Values were compared with 12 age- and sex-matched control subjects with normal coronary arteries. Cardiac magnetic resonance (CMR) was performed during the first week after infarction. RESULTS: Serum from STEMI patients induced a progressive loss of EC viability, with a nadir of 67.7 ± 10.2% at 96 h (baseline: 75 ± 6% and controls: 80.2 ± 3.9%, P < 0.001 in both cases). This is due to an increase in apoptosis that peaked at 96 h after reperfusion (15.2 ± 7.1% vs. 11 ± 6 at baseline and 5.8 ± 1.6% in controls, P < 0.001 in both cases). However, no significant dynamic changes in EC necrosis were detected. Extensive myocardial oedema (> 30%, median of left ventricular mass) was the only CMR variable significantly associated with a higher percentage of EC apoptosis at 96 h (extensive vs. nonextensive oedema: 18.3 ± 6.8% vs. 12.1 ± 6.3%, P < 0.05). CONCLUSIONS: Dynamic changes in EC viability occur in the setting of STEMI patients reperfused with PCI, these changes peak late after reperfusion, they are mainly the result of an increase of apoptosis and are associated with the presence of extensive myocardial oedema.

Interleukin 6 and cognitive dysfunction.

The interleukin-6 (IL-6) is a pleiotropic cytokine that plays a key role in interaction between immune and nervous system. Although IL-6 has neurotrophic properties and beneficial effects in the CNS, its overexpression is generally detrimental, adding to the pathophysiology associated with CNS disorders. The source of the increase in peripheral IL-6 remains to be established and varies among different pathologies, but has been found to be associated with cognitive dysfunction in several pathologies. This comprehensive review provides an update summary of the studies performed in humans concerning the role of central and peripheral IL-6 in cognitive dysfunction in dementias and in other systemic diseases accompained by cognitive dysfuction such as cardiovascular, liver disease, Behçet's disease and systemic lupus erythematosus. Further research is needed to correlate specific deficits in IL-6 and its receptors in pathologies characterized by cognitive dysfunction and to understand how systemic IL-6 affects high cerebral function in order to open new directions in pharmacological treatments that modulate IL-6 signalling.

Ventricular fibrillation conduction through an isthmus of preserved myocardium between radiofrequency lesions.

BACKGROUND: Selective local acceleration of myocardial activation during ventricular fibrillation (VF) contributes information on the interactions between neighboring zones during the arrhythmia. This study analyzes these interactions, centering the observations on an isthmus of myocardium between two radiofrequency (RF) lesions. METHODS: In nine isolated rabbit hearts, a gap of preserved myocardium was established between two RF lesions in the anterolateral left ventricle (LV) wall. Before, during, and after increasing the spatial heterogeneity of VF by local myocardial stretching, VF epicardial recordings were obtained. RESULTS: Local stretch in the anterior LV wall decreased the excitable window (17 ± 7 ms vs 26 ± 7 ms; P < 0.05) and increased the dominant frequency (DFr; 18.9 ± 5.0 Hz vs 15.2 ± 3.6 Hz; P < 0.05) in this zone, without changes in the non-stretched posterolateral zone (25 ± 4 ms vs 27 ± 6 ms, ns and 14.1 ± 2.7 Hz vs 14.3 ± 3.0 Hz, ns). The DFr ratio at both sides of the gap was inversely correlated to the excitable window ratio (R = -0.57; P = 0.002). Before (31% vs 26%), during (29% vs 22%), and after stretch suppression (35% vs 25%), the wavefronts passing through the gap from the posterolateral to the anterior LV wall were seen to predominate. The number of wavefronts that passed from the anterior to the posterolateral LV wall was related to the excitable window in this zone (R = 0.41; P = 0.03). CONCLUSIONS: The VF acceleration induced in the stretched zone does not increase the flow of wavefronts toward the non-stretched zone in the adjacent gap of preserved myocardium. The absence of significant changes in the electrophysiological parameters of the non-stretched myocardium limits the arrival of wavefronts in this zone.

Interleukin Inhibitors in Cytokine Release Syndrome and Neurotoxicity Secondary to CAR-T Therapy.

INTRODUCTION: Chimeric antigen receptor T-cell (CAR-T) therapy is an innovative therapeutic option for addressing certain recurrent or refractory hematological malignancies. However, CAR-T cells also cause the release of pro-inflammatory cytokines that lead to life-threatening cytokine release syndrome and neurotoxicity. OBJECTIVE: To study the efficacy of interleukin inhibitors in addressing cytokine release syndrome (CRS) and neurotoxicity secondary to CAR-T therapy. METHODOLOGY: The authors conducted a bibliographic review in which 10 articles were analyzed. These included cut-off studies, case reports, and clinical trials involving 11 cancer centers and up to 475 patients over 18 years of age. RESULTS: Tocilizumab is the only interleukin inhibitor approved to address CRS secondary to CAR-T therapy due to its efficacy and safety. Other inhibitors, such as siltuximab and anakinra, could be useful in combination with tocilizumab for preventing severe cytokine release and neurotoxicity. In addition, the new specific inhibitors could be effective in mitigating CRS without affecting the cytotoxic efficacy of CAR-T therapy. CONCLUSION: More lines of research should be opened to elucidate the true implications of these drugs in treating the side effects of CAR-T therapy.

Evaluation of the Effectiveness of Breastfeeding as a Factor in the Prevention of Breast Cancer.

BACKGROUND & OBJECTIVE: As cancer is one of the main causes of fatal illnesses in the world, and breast cancer is responsible for an elevated number of deaths in women, it is important to implement measures to prevent this disease. METHOD: In order to assess the influence of breastfeeding in preventing breast cancer in women, forteen prospective cohort articles are included in this study, and their methodological quality has been assessed through the Newcastle Ottawa quality assessment scale cohort studies. After determining the risk of bias for each case study, those with fewer systematic errors and therefore greater validity, have been selected to demonstrate the relationship they propose exists between breastfeeding and breast cancer. RESULTS: 50% percent of the research included found that breastfeeding does not reduce the risk of breast cancer, while the other 50% argue that it is a protective factor. However, with regards to quality, the case studies that conclude that breastfeeding is not associated with breast cancer have more evidential support. CONCLUSION: It is difficult to establish whether or not breastfeeding prevents breast cancer, given the diversity of conclusions in the literature. Nevertheless, the findings of this study reinforce the importance of developing strategies to improve long-term women's health in the field of prevention.

Circadian Variations and Associated Factors in Patients with Ischaemic Heart Disease.

Circadian rhythms have been identified in cardiovascular diseases, and cardiovascular risk factors can modify the circadian rhythm. The purpose of this study was to describe the onset of ischaemic heart disease symptomatology in relation to the date and time, the day of the week of presentation, the season, AMI location and severity and the level of influence of individual patient characteristics in a retrospective cross-sectional study involving 244 ischaemic heart disease patients from the intensive care unit of La Ribera Hospital (Spain). The onset of pain was more frequent in the morning, the season with the highest frequency of ischaemic events was winter, and the lowest incidence was during weekends. Regarding the severity of ischaemic heart disease, the circadian rhythm variables of weekdays vs. weekends and seasons did not show a significant association. The length of hospital stay was associated with the onset of pain in the afternoon. The onset of pain at night was associated with the subendocardial location of the infarction. In conclusion, living in a Mediterranean country, the Spanish population showed a circadian pattern of AMI, where the onset of pain has an influence on AMI location and on the length of hospital stay and is the same in patients with different individual risk factors.

Salivary IL-6 Concentration Is Associated with Frailty Syndrome in Older Individuals.

BACKGROUND: One of the physiological changes that is most closely associated with frailty is the increase in pro-inflammatory cytokines, and IL-6 in particular. Most studies have demonstrated this association using blood samples. We analyzed the relationship between frailty syndrome, individual frailty criteria, and IL-6 levels obtained by saliva tests. METHODS: A cross-sectional pilot study was performed among women institutionalized in nursing homes. Frailty was defined as having three or more of the following components: low lean mass, weakness, self-reported exhaustion, low activity level, and slow walking speed; prefrailty was defined as having one or two of those components. RESULTS: There was a significant and positive correlation between the frailty score and salivary IL-6 concentration. Regarding the associations between IL-6 and individual dichotomized frailty criteria, there were significant differences in salivary IL-6 concentration in two frailty criteria: weight loss (p = 0.002) and low physical activity (p = 0.007). Receiver operating characteristic curve analysis showed that IL-6 concentration significantly (p < 0.05) (although moderately) discriminated patients that progressed in the frailty syndrome (the area under the curve value was 0.697 with 95% CI 0.566-0.827). CONCLUSIONS: Salivary IL-6 concentration can be used as potential biomarker of frailty syndrome and as a tool to monitor the effects of interventions in frail individuals.

Nurse-led and Interdisciplinary Secondary Cardiovascular Prevention Programmes: Spanish Cohort of the EUROACTION Project.

BACKGROUND: Cardiovascular prevention and rehabilitation programmes (CVPRP) are a preventive tool, which can reverse unhealthy behaviours and improve risk factor management. They have been successfully implemented in a variety of settings in patients with coronary heart disease (CHD). OBJECTIVE: The objective of this study is to evaluate an interdisciplinary and nurse-led cardiovascular prevention and rehabilitation programme in patients with coronary heart disease. METHODS: Six pairs of hospitals were randomised between intervention (INT) and usual care (UC) patients. The interdisciplinary team in the intervention hospital carried out a 16-week CVPRP to reach European risk factor goals. The trial is registered as ISRCTN 71715857. RESULTS: The proportion of patients achieving European cardiovascular recommendations in Spain increased in the intervention hospital, mainly regarding fruit and vegetable consumption (INT 98% vs. UC 53%, p<0.001), oily fish consumption (INT 42% vs. UC 19.5%, p<0.001), self-reported physical activity (INT 31% vs. UC 12.4%, p=0.04), blood pressure (INT 69% vs. UC 47.1%) p< 0.05) and LDL concentrations (INT 86.1% vs. UC 67.6%, p=0.04). CONCLUSION: The EUROACTION nurse-led model of CVPR programme has shown that therapeutic goals in cardiovascular disease prevention are affordable and sustainable in everyday clinical practice. EUROACTION model adapted in Spain has produced a healthier lifestyle.

The Beneficial Effect of Physical Exercise on Inflammatory Makers in Older Individuals.

Old age is associated with a loss of motor functions and a general progressive decline in cognitive functions. Physical exercise is one of the ways in which inflammatory levels in general can be reduced, and therefore physical exercise can be considered a biological aging decelerator. In this article, we examine the relationships between physical exercise and inflammatory markers reported for the different physical exercise protocols that have been used in studies with older individuals, as well as the effects of these regimens. The different types of exercises programmed, and methods used to implement them were very heterogeneous in the articles we analysed. Both, the aerobic exercise and resistance training protocols produced a decrease in plasma levels of IL-6, CRP and TNF-α, and an increase of IL-10 plasma levels as a chronic effect. However, the acute-response of physical exercise appeared to be an initial increase in IL-6 expression and plasma IL-6 levels. Continuing with these exercise programs usually subsequently achieved a chronic response in which there was a decrease in both the basal levels of IL-6, CRP and TNF-α, and the IL-6 produced as acute responses. Regardless of the type of exercise performed, it seems that the exercise parameters, intensity, duration, subject variables, fitness, and level of inflammation are key factors in achieving the expected balance between proinflammatory and anti-inflammatory cytokines.

Psycho-Social Factors in Patients with Cardiovascular Disease Attending a Family-Centred Prevention and Rehabilitation Programme: EUROACTION Model in Spain.

BACKGROUND: Coronary heart disease (CHD) persists as the leading cause of death worldwide. Cardiovascular prevention and rehabilitation (CVPR) has an interdisciplinary focus, and includes not only in physiological components, but it also addresses psycho-social factors. METHODS: The study analysed the Spanish psycho-social data collected during the EUROACTION study. In Spain, two hospitals were randomised in the Valencia community. Coronary patients were prospectively and consecutively identified in both hospitals. The intervention hospital carried out a 16-week CVPR programme, which aimed to assess illness perceptions and establish healthy behaviours in patients and their partners. RESULTS: Illness perceptions were significantly and inversely associated with anxiety and depression. Low levels of anxiety were associated with better self-management of total cholesterol (p = 0.004) and low-density lipoprotein-cholesterol (p = 0.004). There was concordance at one year among patients and partners who participated in the programme related to anxiety (p < 0.001), fruit consumption (p < 0.001), and vegetable consumption (p < 0.001). CONCLUSIONS: The EUROACTION study emphasised the importance of assessing psycho-social factors in a CVPR programme and the inclusion of family as support in patients' changes in behaviour.

Lipid Profile Results after Cardiovascular Prevention Programme: Euroaction Model in Spain.

BACKGROUND: Cardiovascular prevention and rehabilitation programmes (CVPRP) are an established model of care designed to improve risk factor management. They have been successfully implemented in a variety of settings, in patients with coronary heart disease (CHD). OBJECTIVE: To assess the long term impact of a nurse-coordinated, multidisciplinary, CVPRP in patients with CHD in the reduction of lipid profile and medication prescription in clinical practice. METHODS: The study used an analytical, experimental, population based, prospective and longitudinal design. In Spain, the study was conducted in the Valencian Community, including two randomized hospitals. Coronary patients were prospectively and consecutively identified in both hospitals. The intervention hospital carried out an 8-week CVPRP. RESULTS: The proportion of patients achieving improved standards of preventive care increased in the intervention hospital compared with the usual care hospital, mainly regarding LDL-C concentrations. Furthermore, an increased prescription of statins was found in the intervention group. However, there were no statistically significant differences in triglycerides and glucose levels. CONCLUSION: The EUROACTION nurse-led CVPRP enabled coronary patients to control lipid profile to the European targets. A large proportion of patients were prescribed statin therapy as cardioprotective medication with favorable changes in medication for coronary patients. To improve the potential for cardiovascular prevention, we need local preventive cardiology programmes adapted to the health policy of individual countries.

Pharmacological modifications of the stretch-induced effects on ventricular fibrillation in perfused rabbit hearts.

Stretch induces modifications in myocardial electrical and mechanical activity. Besides the effects of substances that block the stretch-activated channels, other substances could modulate the effects of stretch through different mechanisms that affect Ca(2+) handling by myocytes. Thirty-six Langendorff-perfused rabbit hearts were used to analyze the effects of the Na(+)/Ca(2+) exchanger blocker KB-R7943, propranolol, and the adenosine A(2) receptor antagonist SCH-58261 on the acceleration of ventricular fibrillation (VF) produced by acute myocardial stretching. VF recordings were obtained with two epicardial multiple electrodes before, during, and after local stretching in four experimental series: control (n = 9), KB-R7943 (1 microM, n = 9), propranolol (1 microM, n = 9), and SCH-58261 (1 microM, n = 9). Both the Na(+)/Ca(2+) exchanger blocker KB-R7943 and propranolol induced a significant reduction (P < 0.001 and P < 0.05, respectively) in the dominant frequency increments produced by stretching with respect to the control and SCH-58261 series (control = 49.9%, SCH-58261 = 52.1%, KB-R7943 = 9.5%, and propranolol = 12.5%). The median of the activation intervals, the functional refractory period, and the wavelength of the activation process during VF decreased significantly under stretch in the control and SCH-58261 series, whereas no significant variations were observed in the propranolol and KB-R7943 series, with the exception of a slight but significant decrease in the median of the fibrillation intervals in the KB-R7943 series. KB-R7943 and propranolol induced a significant reduction in the activation maps complexity increment produced by stretch with respect to the control and SCH-58261 series. In conclusion, the electrophysiological effects responsible for stretch-induced VF acceleration in the rabbit heart are reduced by the Na(+)/Ca(2+) exchanger blocker KB-R7943 and by propranolol but not by the adenosine A(2) receptor antagonist SCH-58261.

The Effects of Exercise on IL-6 Levels and Cognitive Performance in Patients with Schizophrenia.

Exercise plays an important role in brain plasticity, leading to improvements in cognitive function and delaying the cognitive deterioration of healthy people. These effects can be observed in individuals with schizophrenia through improvements in their performance in cognitive tasks and a decrease in the symptomology of the disease. In this review we examine the current evidence for the roles that exercise and the immune system play in patients with schizophrenia, and specifically analyze the interleukin-6 (IL-6) pathway as a potential mechanism resulting in these positive effects. Inflammation and high levels of IL-6 are associated with both the severity of schizophrenia and the cognitive impairment suffered throughout the disease. Performing regular exercise can modulate IL-6 by lowering its basal levels and by causing lower acute increases in the plasma levels of this cytokine in response to exercise (an anti-inflammatory response to physical exertion). Although there is evidence for the positive effects of physical exercise on schizophrenia, more studies will be required to better understand how variation in different exercise parameters affects both the acute and chronic plasma levels of IL-6.

Analyzing the electrophysiological effects of local epicardial temperature in experimental studies with isolated hearts.

As a result of their modulating effects upon myocardial electrophysiology, both hypo- and hyperthermia can be used to study the mechanisms that generate or sustain cardiac arrhythmias. The present study describes an original electrode developed with thick-film technology and capable of controlling regional temperature variations in the epicardium while simultaneously registering its electrical activity. In this way, it is possible to measure electrophysiological parameters of the heart at different temperatures. The results obtained with this device in a study with isolated and perfused rabbit hearts are reported. An exploration has been made of the effects of local temperature changes upon the electrophysiological parameters implicated in myocardial conduction. Likewise, an analysis has been made of the influence of local temperature upon ventricular fibrillation activation frequency. It is concluded that both regional hypo- and hyperthermia exert reversible and opposite effects upon myocardial refractoriness and conduction velocity in the altered zone. The ventricular activation wavelength determined during constant pacing at 250 ms cycles is not significantly modified, however. During ventricular fibrillation, the changes in the fibrillatory frequency do not seem to be transmitted to normal temperature zones.

Apoptosis and Mobilization of Lymphocytes to Cardiac Tissue Is Associated with Myocardial Infarction in a Reperfused Porcine Model and Infarct Size in Post-PCI Patients.

ST-segment elevation myocardial infarction (STEMI) is the most severe outcome of coronary artery disease. Despite rapid reperfusion of the artery, acute irrigation of the cardiac tissue is associated with increased inflammation. While innate immune response in STEMI is well described, an in-depth characterization of adaptive immune cell dynamics and their potential role remains elusive. We performed a translational study using a controlled porcine reperfusion model of STEMI and the analysis of lymphocyte subsets in 116 STEMI patients undergoing percutaneous coronary intervention (PCI). In the animal model, a sharp drop in circulating T lymphocytes occurred within the first hours after reperfusion. Notably, increased apoptosis of circulating lymphocytes and infiltration of proinflammatory Th1 lymphocytes in the heart were observed 48 h after reperfusion. Similarly, in STEMI patients, a sharp drop in circulating T lymphocyte subsets occurred within the first 24 h post-PCI. A cardiac magnetic resonance (CMR) evaluation of these patients revealed an inverse association between 24 h circulating T lymphocyte numbers and infarction size at 1-week and 6-month post-PCI. Our translational approach revealed striking changes in the circulating and tissue-infiltrating T lymphocyte repertoire in response to ischemia-reperfusion. These findings may help in developing new diagnostic and therapeutic approaches for coronary diseases.

[Time-frequency analysis of ventricular fibrillation. An experimental study]. / Análisis tiempo-frecuencia de la fibrilación ventricular. Estudio experimental.

INTRODUCTION AND OBJECTIVES: The analysis of frequency variability during ventricular fibrillation has yielded inconsistent results. We used an experimental model of ventricular fibrillation, with a short timescale, to analyze variations in frequency and their associated spatial distribution. METHODS: Epicardial recordings of ventricular fibrillation were made in 10 perfused isolated rabbit heart preparations using a multiple electrode system (i.e., 240 unipolar electrodes). Both spectral and time-frequency analysis were used to derive the dominant frequency in the anterolateral wall of the left ventricle. RESULTS: Linear regression analysis showed that there was a good correlation between the dominant frequency obtained using the two signal analysis methods: frequency (spectral analysis) = 1.01 x frequency (time-frequency analysis) -- 0.4 (r=0.9; P< .0001; standard error of the estimate, 2.2 Hz). In all cases except one, the dominant frequency exhibited a significant temporal variation on a short timescale (time-frequency analysis); the coefficient of variation was between 0.19 (0.06) and 0.24 (0.07) (NS). In all cases, there were significant differences between regions. The location at which the frequency was highest varied according to the timepoint considered, though it was predominantly in the apical or anterior zone. CONCLUSIONS: In the absence of external modulating factors, the frequency of ventricular fibrillation exhibits temporal and spatial variations which can be observed at short timescales. In the free wall of the left ventricle, the dominant frequency is highest in the apical and anterior zones, and the maximum frequencies are most often found in these zones.

Experimental Study of the Effects of EIPA, Losartan, and BQ-123 on Electrophysiological Changes Induced by Myocardial Stretch.

INTRODUCTION AND OBJECTIVES: Mechanical response to myocardial stretch has been explained by various mechanisms, which include Na(+)/H(+) exchanger activation by autocrine-paracrine system activity. Drug-induced changes were analyzed to investigate the role of these mechanisms in the electrophysiological responses to acute myocardial stretch. METHODS: Multiple epicardial electrodes and mapping techniques were used to analyze changes in ventricular fibrillation induced by acute myocardial stretch in isolated perfused rabbit hearts. Four series were studied: control (n = 9); during perfusion with the angiotensin receptor blocker losartan (1 µM, n = 8); during perfusion with the endothelin A receptor blocker BQ-123 (0.1 µM, n = 9), and during perfusion with the Na(+)/H(+) exchanger inhibitor EIPA (5-[N-ethyl-N-isopropyl]-amiloride) (1 µM, n = 9). RESULTS: EIPA attenuated the increase in the dominant frequency of stretch-induced fibrillation (control=40.4%; losartan=36% [not significant]; BQ-123=46% [not significant]; and EIPA=22% [P<.001]). During stretch, the activation maps were less complex (P<.0001) and the spectral concentration of the arrhythmia was greater (greater regularity) in the EIPA series: control=18 (3%); EIPA = 26 (9%) (P < .02); losartan=18 (5%) (not significant); and BQ-123=18 (4%) (not significant). CONCLUSIONS: The Na(+)/H(+) exchanger inhibitor EIPA attenuated the electrophysiological effects responsible for the acceleration and increased complexity of ventricular fibrillation induced by acute myocardial stretch. The angiotensin II receptor antagonist losartan and the endothelin A receptor blocker BQ-123 did not modify these effects.