Remodeling of Wall Mechanics and the Myogenic Mechanism of Rat Intramural Coronary Arterioles in Response to a Short-Term Daily Exercise Program: Role of Endothelial Factors

PURPOSE: Exercise elicits early adaptation of coronary vessels enabling the coronary circulation to respond adequately to higher flow demands. We hypothesized that short-term daily exercise induces biomechanical and functional remodeling of the coronary resistance arteries related to pressure. METHODS: Male rats were subjected to a progressively increasing 4-week treadmill exercise program (over 60 min/day, 1 mph in the final step). In vitro pressure-diameter measurements were performed on coronary segments (119 +/- 5 mum in diameter at 50 mm Hg) with microarteriography. The magnitude of the myogenic response and contribution of endogenous nitric oxide and prostanoid production to the wall mechanics and pressure-diameter relationship were assessed. RESULTS: Arterioles isolated from exercised ani mals - compared to the sedentary group - had thicker walls, increased distensibility, and a decreased elastic modulus as a result of reduced wall stress in the low pressure range. The arterioles of exercised rats exhibited a more powerful myogenic response and less endogenous vasoconstrictor prostanoid modulation at higher pressures, while vasodilator nitric oxide modulation of diameter was augmented at low pressures (\u3c 60 mm Hg). CONCLUSIONS: A short-term daily exercise program induces remodeling of rat intramural coronary arterioles, likely resulting in a greater range of coronary autoregulatory function (constrictor and dilator reserves) and more effective protection against great changes in intraluminal pressure, contributing thereby to the optimization of coronary blood flow during exercise

The Beta-1-Receptor Blocker Nebivolol Elicits Dilation of Cerebral Arteries by Reducing Smooth Muscle [Ca2+]i

RATIONALE: Nebivolol is known to have beta-1 blocker activity, but it was also suggested that it elicits relaxation of the peripheral arteries in part via release of nitric oxide (NO). However, the effect of nebivolol on the vasomotor tone of cerebral arteries is still unclear. OBJECTIVE: To assess the effects of nebivolol on the diameter of isolated rat basilar arteries (BA) in control, in the presence of inhibitors of vasomotor signaling pathways of know action and hemolysed blood. METHODS AND RESULTS: Vasomotor responses were measured by videomicroscopy and the intracellular Ca2+ by the Fura-2 AM ratiometric method. Under control conditions, nebivolol elicited a substantial dilation of the BA (from 216±22 to 394±20 μm; p CONCLUSIONS: Nebivolol seems to have an important dilator effect in cerebral arteries, which is mediated via several vasomotor mechanisms, converging on the reduction of smooth muscle Ca2+ levels. As such, nebivolol may be effective to improve cerebral circulation in various diseased conditions, such as hemorrhage

Ischaemic heart disease in women: are there sex differences in pathophysiology and risk factors?: Position Paper from the Working Group on Coronary Pathophysiology and Microcirculation of the European Society of Cardiology

Cardiovascular disease (CVD) is the leading cause of death in women, and knowledge of the clinical consequences of atherosclerosis and CVD in women has grown tremendously over the past 20 years. Research efforts have increased and many reports on various aspects of ischaemic heart disease (IHD) in women have been published highlighting sex differences in pathophysiology, presentation, and treatment of IHD. Data, however, remain limited. A description of the state of the science, with recognition of the shortcomings of current data, is necessary to guide future research and move the field forward. In this report, we identify gaps in existing literature and make recommendations for future research. Women largely share similar cardiovascular risk factors for IHD with men; however, women with suspected or confirmed IHD have less coronary atherosclerosis than men, even though they are older and have more cardiovascular risk factors than men. Coronary endothelial dysfunction and microvascular disease have been proposed as important determinants in the aetiology and prognosis of IHD in women, but research is limited on whether sex differences in these mechanisms truly exist. Differences in the epidemiology of IHD between women and men remain largely unexplained, as we are still unable to explain why women are protected towards IHD until older age compared with men. Eventually, a better understanding of these processes and mechanisms may improve the prevention and the clinical management of IHD in wome

Delayed Care and Mortality Among Women and Men with Myocardial Infarction

Background-Women with ST-segment-elevation myocardial infarction (STEMI) have higher mortality rates than men. We investigated whether sex-related differences in timely access to care among STEMI patients may be a factor associated with excess risk of early mortality in women. Methods and Results-We identified 6022 STEMI patients who had information on time of symptom onset to time of hospital presentation at 41 hospitals participating in the ISACS-TC (International Survey of Acute Coronary Syndromes in Transitional Countries) registry (NCT01218776) from October 2010 through April 2016. Patients were stratified into time-delay cohorts. We estimated the 30-day risk of all-cause mortality in each cohort. Despite similar delays in seeking care, the overall time from symptom onset to hospital presentation was longer for women than men (median: 270 minutes [range: 130-776] versus 240 minutes [range: 120-600]). After adjustment for baseline variables, female sex was independently associated with greater risk of 30-day mortality (odds ratio: 1.58; 95% confidence interval, 1.27-1.97). Sex differences in mortality following STEMI were no longer observed for patients having delays from symptom onset to hospital presentation of (odds ratio: 0.77; 95% confidence interval, 0.29-2.02). Conclusions-Sex difference in mortality following STEMI persists and appears to be driven by prehospital delays in hospital presentation. Women appear to be more vulnerable to prolonged untreated ischemia

Sex-related Differences In Acute Coronary Care Among Patients With Myocardial Infarction: The Role Of Pre-hospital Delay

Background: We sought to investigate sex-related differences in access to care among patients with myocardial infarction (STEMI) in order to identify gender-related factors associated with outcomes. Methods: We studied 7457 patients enrolled in the ISACS-TC registry 2010-2014 (ClinicalTrials.gov NCT01218776). Outcome measures were: inhospital mortality, time delay to call emergency medical services (EMS), home-to-hospital delay using EMS, door-to-needle and door-to-balloon times and the overall time to treatment from symptom onset. Constant variables included in logistic regression analyses were: age, risk factors, severity of clinical presentation, reperfusion therapies, and concurrent acute medications. Time to treatment from symptom onset was used as dummy variable. Results: Women were less likely than men to receive care within the benchmark time for reperfusion therapy (time to treatment from symptom onset 60 min in 70.3% of women vs 29.7% of men. There were no significant differences in door-to-needle (median; 28 min vs 26 min) and door-to-balloon (median: 45 min vs 45 min) times. Major (z >4)determinants of poorer rates of reperfusion therapies included time to treatment from symptom onset >12 hours (adjusted OR: 5.37, CI: 4.58 - 6.31) Killip class > 2 (OR: 1.53, CI: 1.27-1.86) and history of prior heart failure (OR: 2.77, CI, 1.99 to 3.87). After adjustment, women had greater inhospital mortality rates than men (OR: 1.34, CI: 1.01-1.77). Sex differences in in-hospital mortality rates were no longer observed in the cohort, when time to treatment from symptom onset <12 hours was included in the multivariable analysis (OR: 1.31, CI: 0.98 -1.74). Conclusion: Sex differences in outcomes persist among STEMI patients, as fewer women receive timely reperfusion therapy. Pre-hospital delays in women experiencing STEMI remain unacceptably long

Sex-related Differences In Acute Coronary Care Among Patients With Myocardial Infarction: The Role Of Pre-hospital Delay

Background: We sought to investigate sex-related differences in access to care among patients with myocardial infarction (STEMI) in order to identify gender-related factors associated with outcomes. Methods: We studied 7457 patients enrolled in the ISACS-TC registry 2010-2014 (ClinicalTrials.gov NCT01218776). Outcome measures were: inhospital mortality, time delay to call emergency medical services (EMS), home-to-hospital delay using EMS, door-to-needle and door-to-balloon times and the overall time to treatment from symptom onset. Constant variables included in logistic regression analyses were: age, risk factors, severity of clinical presentation, reperfusion therapies, and concurrent acute medications. Time to treatment from symptom onset was used as dummy variable. Results: Women were less likely than men to receive care within the benchmark time for reperfusion therapy (time to treatment from symptom onset 60 min in 70.3% of women vs 29.7% of men. There were no significant differences in door-to-needle (median; 28 min vs 26 min) and door-to-balloon (median: 45 min vs 45 min) times. Major (z >4)determinants of poorer rates of reperfusion therapies included time to treatment from symptom onset >12 hours (adjusted OR: 5.37, CI: 4.58 - 6.31) Killip class > 2 (OR: 1.53, CI: 1.27-1.86) and history of prior heart failure (OR: 2.77, CI, 1.99 to 3.87). After adjustment, women had greater inhospital mortality rates than men (OR: 1.34, CI: 1.01-1.77). Sex differences in in-hospital mortality rates were no longer observed in the cohort, when time to treatment from symptom onset <12 hours was included in the multivariable analysis (OR: 1.31, CI: 0.98 -1.74). Conclusion: Sex differences in outcomes persist among STEMI patients, as fewer women receive timely reperfusion therapy. Pre-hospital delays in women experiencing STEMI remain unacceptably long

Covid-19 vaccines elicit effective IgG responses in an elderly thymus cancer patient with chemotherapy

The rising need for repeated booster vaccinations against SARS-CoV-2 infections raises the question of whether chronic immunosuppressive chemotherapies influence the efficacy of vaccination. Here, we present the case of a 70-year-old post-thymoma surgery patient who received Vepesid (etoposide, Xediton Pharmaceuticals Inc) chemotherapy for six months before vaccination with Comirnaty (Pfizer-BioNTech COVID-19 mRNA Vaccine). The first two vaccinations elicited only minimal increases of IgG antibodies specific against the receptor-binding domain (RBD) on the spike protein (S1), while the third vaccination was effective in providing high, slowly subsiding antibody titers over a 7-month period. The patient also developed a cellular immune response after the third vaccination. Also, measuring of anti-polyethylene glycol (PEG) IgM titers before and after vaccinations showed no immunogenicity for PEG. Later, a single dose of Sinopharm (China National Pharmaceutical Group) inactivated virus-type vaccine was administered, which also modestly increased the level of IgG. A symptomless COVID-19 infection, however, greatly increased the serum level of anti-RBD IgG, which later subsided. This case confirms that an effective immune response can be achieved with a series of COVID-19 vaccinations despite cytostatic treatment in an old thymus cancer surviving patient in the absence of adverse reactions