Myocardial work in patients with heart failure and ischemic cardiomyopathy according to the mode of coronary revascularization.

BACKGROUND: The association of percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) on myocardial function, as reflected in myocardial work (MyW) parameters, in patients with ischemic cardiomyopathy and heart failure (HF) is unknown. METHODS: We analyzed data from 68 patients who were hospitalized with chronic HF due to ischemic cardiomyopathy and stratified them according to the mode of revascularization. All patients underwent a 2D speckle tracking echocardiography exam performed by the same expert sonographer and had complete MyW data including global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE). RESULTS: The mean age of patients was 70 ± 10 years and 86.8% were men. The mean left ventricular ejection fraction (LVEF) in overall cohort was 31.6 ± 9.5%. Both subgroups did not significantly differ in terms of baseline LVEF, comorbidities, and pharmacotherapy. Compared with those who received PCI, patients revascularized with CABG had significantly greater GWI (821 vs. 555 mmHg%, p = 0.002), GCW (1101 vs. 794 mmHg%, p = 0.001), GWE (78 vs. 72.6%, p = 0.025), and global longitudinal strain (-8.7 vs. -6.7%, p = 0.004). Both patient subgroups did not significantly differ with respect to GWW (273 vs. 245 mmHg%, p = 0.410 for CABG and PCI, respectively) and survival during the median follow-up of 18 months (log-rank p = 0.813). CONCLUSION: Patients with HF and ischemic cardiomyopathy revascularized with CABG had greater myocardial work performance when compared with those revascularized with PCI. This might suggest a higher degree of functional myocardial revascularization associated with the CABG procedure.

Diagnostic and therapeutic pathways for the malignant left atrial appendage: European Heart Rhythm Association physician survey.

AIMS: Patients with atrial fibrillation who despite taking oral anti-coagulant therapy (OAT) suffer a stroke or systemic embolism (SSE) without vascular cause or who develop left atrial appendage (LAA) thrombus (LAAT) should be considered as having malignant LAA. The optimal treatment strategy to reduce SSE risk in such patients is unknown. The aim of the study is to investigate the diagnostic and therapeutic pathways for malignant LAA practiced in European cardiac centres. METHODS AND RESULTS: An 18-item online questionnaire on malignant LAA was disseminated by the European Heart Rhythm Association (EHRA) Scientific Initiatives Committee. A total of 196 physicians participated in the survey. There seems to be high confidence in transoesophageal echocardiography (TEE) imaging, considering LAAT diagnosis. Switching to another direct oral anti-coagulant (DOAC) is the preferred initial step for the treatment of malignant LAA followed by a switch to vitamin K antagonist (VKA), low-molecular-weight heparin, or continued/optimized DOAC dosage, whereas LAA closure is the last option. Left atrial appendage closure is a viable option in patients with embolic stroke despite OAT and no evidence of thrombus at TEE (empty LAA) after comprehensive diagnostic measures to exclude other sources of embolism. CONCLUSION: This EHRA survey provides a snapshot of the contemporary management of patients diagnosed with malignant LAA. Currently, the majority of patients are treated on an outpatient basis with either shifting from VKA to DOAC or from one DOAC to another. Left atrial appendage closure in this population seems to be reserved for patients with higher bleeding risk or complications of malignant LAA, such as stroke.

Association of inflammatory biomarkers and disease activity with subclinical myocardial dysfunction in psoriatic arthritis.

We examined the role of adipokines and pro-inflammatory cytokines in psoriatic arthritis-associated subclinical myocardial dysfunction, and the relationship between these variables and psoriatic arthritis (PsA) disease activity. Fifty-five PsA patients without cardiovascular risk factors and 25 controls underwent standard and speckle tracking echocardiography with global longitudinal strain (GLS) calculated. Standard anthropometric data and Disease Activity in Psoriatic arthritis (DAPSA) scores were recorded, with low disease activity defined as DAPSA ≤ 14 and moderate and high disease activity DAPSA > 14. Standard biochemical tests, adiponectin, resistin, leptin, tumor necrosis factor (TNF) alfa, interleukin 17 A (IL-17A), B lymphocyte chemoattractant (BLC), and monokine induced by intereferon gamma (MIG) were analyzed. Median age was 53.0 (46.0-61.0), median PsA duration 6.0 (4.0-13.0) years and median DAPSA score 25.5 (13.0-41.5). Lower GLS, tricuspid annular plane systolic excursion (TAPSE) and left ventricular ejection fraction (LVEF) were found in moderate and high PsA disease activity compared to low PsA disease activity and controls. PsA patients with GLS < 20 had higher body mass index (BMI), DAPSA score and uric acid levels, and lower adiponectin levels. Although patients with GLS < 20 had higher IL-17A levels, it was not statistically significant (P = 0.056). However, when we included healthy controls and analyzed differences based on a GLS cut-off of 20% in the entire population, the difference in IL-17A became statistically significant, 0.17 pg/mL (0.06-0.32) vs. 0.43 pg/mL (0.23-0.65), P = 0.017. The association between DAPSA score and GLS and IL-17 remained significant in multivariate analysis. Moreover, the association between GLS and IL-17 and adiponectin was significant after adjustment for age and BMI. Patients with moderate and high PsA disease activity have reduced myocardial function, lower adiponectin, and higher IL-17A levels.

Left Ventricular Systolic Function After 3 Months of SGLT2 Inhibitor Therapy in Heart Failure Patients with Reduced Ejection Fraction.

Not much is known about the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on echocardiographic parameters of left ventricular (LV) systolic function in patients with heart failure and reduced ejection fraction (HFrEF).We prospectively included 59 outpatients with HFrEF: 41 patients received SGLT2i with OMT (SGLT2i+ group), whereas eighteen patients received OMT without SGLT2i (SGLT2i- group). Myocardial work index (MWI), 3D ejection fraction (3D LVEF), and global longitudinal strain (GLS) were measured at baseline and after 3 months following treatment. At 3-month follow-up, the SGLT2i+ group showed significantly greater improvement in MWI than the SGLT2i- group. In both groups, there was a significant improvement in 3D LVEF and LV GLS, circulating NT-proBNP levels, and NYHA functional class, with significantly greater improvement in the SGLT2i+ group.In conclusion, the addition of SGLT2i to fully optimized background medical therapy resulted in a greater improvement of LV systolic function among outpatients with HFrEF.

Impact of SGLT2 Inhibitor Therapy on Right Ventricular Function in Patients with Heart Failure and Reduced Ejection Fraction.

Background: The impact of sodium-glucose cotransporter-2 inhibitors (SGLT2is) in addition to optimal medical therapy (OMT) on the right ventricular (RV) systolic function using advanced echocardiographic analysis among outpatients with heart failure and a reduced ejection fraction (HFrEF) has thus far been poorly investigated. Methods: This was a single-center, prospective, single-blinded study in which an echocardiographic expert was blinded to the allocation of the treatment. A total of 36 outpatients with HFrEF were randomized to either OMT or OMT+SGLT2i. Both groups underwent an echocardiographic examination of the RV systolic function at the baseline and at the 3-month follow-up (3mFU). Results: The patients in both groups did not significantly differ with respect to the relevant baseline comorbidities, therapy, and clinical characteristics. The patients receiving OMT+SGLT2i showed a significant improvement from the baseline to the 3mFU in all the measured RV echocardiographic parameters, while for the OMT group, a significant improvement after the 3mFU was observed for TAPSE and s'. The mean percent change from the baseline to the 3mFU was significant when comparing OMT+SGLT2i to the OMT group concerning RV FWS (+91% vs. +28%, p = 0.039), TR maxPG (-27% vs. +19%, p = 0.005), and TR Vmax (-17% vs. +13%, p = 0.008), respectively. Conclusions: Adding SGLT2i to OMT in patients with HFrEF resulted in a greater improvement in the RV systolic function from the baseline to the 3mFU compared to the OMT alone.

Right ventricular free wall strain in acutely decompensated heart failure patients with ischemic and non-ischemic cardiomyopathy.

AIMS: Right ventricular (RV) dysfunction is a predictor of adverse outcomes among patients with HF with reduced ejection fraction (HFrEF); however, differences in RV parameters in HFrEF patients with ischemic (ICM) and non-ischemic cardiomyopathies (NICM) are not well understood. We investigated echocardiographic characteristics, including RV strain, in patients with acute decompensated heart failure (ADHF) and compared patients with ICM and NICM etiology. METHODS: Consecutive patients who presented with ADHF and NYHA class III-IV were prospectively enrolled if they had LVEF < 40% and history of ICM or NICM. All patients underwent clinical exam, laboratory evaluation and 2-D echocardiographic assessment of the left ventricular (LV) and RV function, LV and RV global longitudinal strain (LVGLS, RVGLS), and RV free wall strain (RVfwLS). RESULTS: Of 84 patients, 44 had ICM and 40 NICM. The groups had similar blood pressure, NT-proBNP, and echocardiographic parameters of LV function including LVGLS. Absolute RVGLS values were lower than RVfwLS values in both groups. Patients with NICM had significantly lower RVfwLS, but not RVGLS, compared to patients with ICM (-13% to -17%, p = 0.006). Similar differences in RVfwLS were seen in patients in NYHA class III (NICM vs ICM: -13% and -17%, respectively, 95% CI: -8.5 to -.5) and NYHA class IV (NICM vs ICM: -13.8% and -17%, respectively, 95% CI: -6.4 to -.59). CONCLUSION: Among patients hospitalized with ADHF, patients with nonischemic etiology compared with the patients with ICM, have more severe RV dysfunction measured by RVfwLS, despite similar extent of LV impairment and the same functional limitation class.

Left-Ventricular Function After 3 Months of Sacubitril-Valsartan in Acute Decompensated Heart Failure.

There is limited data on the effect of sacubitril-valsartan on the echocardiographic parameters in acute decompensated heart failure (ADHF). We prospectively enrolled 68 consecutive patients with ADHF who received sacubitril-valsartan (N = 34, S/V group) or angiotensin inhibition-based therapy (N = 34, ACEi/ARB group). Two-dimensional echocardiography with speckle tracking (2D-STE) was performed at baseline and after 3 months of treatment. Changes in 2D-STE parameters, including global longitudinal strain (GLS), were compared between the groups by t test and ANCOVA. Baseline characteristics were similar between the groups. Following 3 months of treatment, LVEF and GLS significantly improved in the S/V group (mean LVEF from 27 to 34.5% and GLS from - 6.6 to - 9.4%) but not in ACEi/ARB group. The improvement in LVEF and GLS was more prominent in patients with non-ischemic cardiomyopathy. In patients with ADHF 3-month treatment with sacubitril-valsartan, compared to guideline directed medical therapy without sacubitril, improves LVEF and GLS. Graphical Abstract A typical change in GLS in a patient with acute decompensated heart failure after 3 months of sacubitril-valsartan.

Disturbed Fatty Acid Oxidation, Endoplasmic Reticulum Stress, and Apoptosis in Left Ventricle of Patients With Type 2 Diabetes.

Chronic heart failure is a common complication in patients with type 2 diabetes mellitus (T2DM). T2DM is associated with disturbed metabolism of fat, which can result in excessive accumulation of lipids in cardiac muscle. In the current study, we assessed mitochondrial oxidation of carbohydrates and fatty acids, lipid accumulation, endoplasmic reticulum (ER) stress, and apoptosis in diabetic left ventricle. Left ventricular myocardium from 37 patients (a group of patients with diabetes and a group of patients without diabetes [ejection fraction >50%]) undergoing coronary artery bypass graft surgery was obtained by subepicardial needle biopsy. The group with diabetes had a significantly decreased rate of mitochondrial respiration fueled by palmitoyl-carnitine that correlated with blood glucose dysregulation, while there was no difference in oxidation of pyruvate. Diabetic myocardium also had significantly decreased activity of hydroxyacyl-CoA dehydrogenase (HADHA) and accumulated more lipid droplets and ceramide. Also, markers of ER stress response (GRP78 and CHOP) and apoptosis (cleaved caspase-3) were elevated in diabetic myocardium. These results show that, even in the absence of contractile failure, diabetic heart exhibits a decreased mitochondrial capacity for ß-oxidation, increased accumulation of intracellular lipids, ER stress, and greater degree of apoptosis. Lower efficiency of mitochondrial fatty acid oxidation may represent a potential target in combating negative effects of diabetes on the heart.

2D speckle tracking echocardiography of the right ventricle free wall in SCUBA divers after single open sea dive.

The presence of circulating gas bubbles and their influence on pulmonary and right heart hemodynamics was reported after uncomplicated self-contained underwater breathing apparatus (SCUBA) dive(s). Improvements in cardiac imaging have recently focused great attention on the right ventricle (RV). The aim of our study was to evaluate possible effects of a single air SCUBA dive on RV function using 2D speckle tracking echocardiography in healthy divers after single open sea dive to 18 meters of seawater, followed by bottom stay of 47 minutes with a direct ascent to the surface. Twelve experienced male divers (age 39.5 ± 10.5 years) participated in the study. Echocardiographic assessment of the right ventricular function (free wall 2 D strain, tricuspid annular planes systolic excursion [TAPSE], lateral tricuspid annular peak systolic velocity [RV s`] and fractional area change [FAC]) was performed directly prior to and 30, 60, 90 and 120 minutes after surfacing. Two-dimensional strain of all three segments of free right ventricular wall showed a significant increase in longitudinal shortening in post-dive period for maximally 26% (basal), 15.4% (mid) and 16.3% (apical) as well as TAPSE (11.6%), RV FAC (19.2%), RV S` (12.7%) suggesting a rise in systolic function of right heart. Mean pulmonary arterial pressure (mean PAP) increased post-dive from 13.3 mmHg to maximally 23.5 mmHg (P = .002), indicating increased RV afterload. Our results demonstrated that single dive with significant bubble load lead to increase in systolic function and longitudinal strain of the right heart in parallel with increase in mean PAP.

Early Changes in Platelet Size and Number in Patients with Acute Coronary Syndrome.

A strong relationship exists between acute coronary syndrome (ACS) and platelets (PLTs) volume. Mean platelet volume (MPV) is a parameter of PLT functions and a marker for increased PLT activation. The aim of this study was to determine early changes in number of total PLT and MPV in different manifestation of ACS and to find out predictive value of MPV in the spectrum of ACS. This was a prospective study. One hundred thirty-four ACS patients were enrolled, 76 of them finished the study. PLT and MPV in patients with unstable angina, non-ST elevation, and ST elevation myocardial infarctions were determined on arrival and 1, 3, 72 hours, and 7 days after the admission to hospital. There was decrease in PLT and MPV in all three groups after 3 hours of arrival in hospital in comparison with admission values. In the later time period (72 hours and 7 days), there was an increase in PLT and MPV only in patients with acute myocardial infarction (AMI). We have revealed completely new dynamics in early changes in MPV and PLT count in patients with AMI. Biphasic changes were found in early phase after admission to the hospital. Fast response in these parameters raises new questions about their origin.

Intrapulmonary arteriovenous anastomoses in humans with chronic obstructive pulmonary disease: implications for cryptogenic stroke?

What is the central question of this study? Do individuals with chronic obstructive pulmonary disease have blood flow through intrapulmonary arteriovenous anastomoses at rest or during exercise? What is the main finding and its importance? Individuals with chronic obstructive pulmonary disease have a greater prevalence of blood flow through intrapulmonary arteriovenous anastomoses at rest than age-matched control subjects. Given that the intrapulmonary arteriovenous anastomoses are large enough to permit venous emboli to pass into the arterial circulation, patients with chronic obstructive pulmonary disease and an elevated risk of thrombus formation may be at risk of intrapulmonary arteriovenous anastomosis-facilitated embolic injury (e.g. stroke or transient ischaemic attack). The pulmonary capillaries prevent stroke by filtering venous emboli from the circulation. Intrapulmonary arteriovenous anastomoses are large-diameter (≥50 µm) vascular connections in the lung that may compromise the integrity of the pulmonary capillary filter and have recently been linked to cryptogenic stroke and transient ischaemic attack. Prothrombotic populations, such as individuals with chronic obstructive pulmonary disease (COPD), may be at increased risk of stroke and transient ischaemic attack facilitated by intrapulmonary arteriovenous anastomoses, but the prevalence and degree of blood flow through intrapulmonary arteriovenous anastomoses in this population has not been fully examined and compared with age-matched healthy control subjects. We used saline contrast echocardiography to assess blood flow through intrapulmonary arteriovenous anastomoses at rest (n = 29 COPD and 19 control subjects) and during exercise (n = 10 COPD and 10 control subjects) in subjects with COPD and age-matched healthy control subjects. Blood flow through intrapulmonary arteriovenous anastomoses was detected in 23% of subjects with COPD at rest and was significantly higher compared with age-matched healthy control subjects. Blood flow through intrapulmonary arteriovenous anastomoses at rest was reduced or eliminated in subjects with COPD after breathing hyperoxic gas. Sixty per cent of subjects with COPD who did not have blood flow through the intrapulmonary arteriovenous anastomoses at rest had blood flow through them during exercise. The combination of blood flow through intrapulmonary arteriovenous anastomoses and potential for thrombus formation in individuals with COPD may permit venous emboli to pass into the arterial circulation and cause stroke and transient ischaemic attack. Breathing supplemental oxygen may reduce this risk in COPD. The link between blood flow through intrapulmonary arteriovenous anastomoses, stroke and transient ischaemic attack is worthy of future investigation in COPD and other populations.

The effects of low-dose epinephrine infusion on spleen size, central and hepatic circulation and circulating platelets.

In several conditions associated with adrenergic stimulation, an increase in peripheral count of larger platelets has been observed, but the mechanism remained elusive. Larger platelets have greater prothrombotic potential and increase the risk of acute thrombotic events. The human spleen retains one-third of total body platelets, with mean volume (MPV) about 20% greater than that of circulating platelets. We aimed to answer whether low-dose epinephrine infusion results in spleen contraction and MPV increase. We undertook the continuous ultrasonic measurements of spleen volume, hepatic and central circulation with concurrent blood sampling in response to intravenous infusion of epinephrine (6 min of 0·06 µg kg(-1) per min, followed by 3 min of 0·12 µg kg(-1) per min) in nine healthy young subjects. The spleen volume started to decrease immediately after the onset of infusion, in the presence of substantial decreases in peripheral resistance and mean blood pressure and increases in heart rate and cardiac output. The majority of spleen emptying, approximately 25%, (95% CI 71·3-299·7) was observed 1 min after infusion onset, the hepatic vein flow peaked at the end of infusion for 28·4% (95% CI 1074·6-407·9), while increases in platelet count for approximately 31% (95% CI 187·8-314·8) and MPV for 4·4% (95% CI 7·3-10·9) lagged until 1 min after infusion cessation. We suggest that spleen is a dynamic reservoir of large platelets, which are mobilized even by low-dose epinephrine infusion in conditions of decreased blood pressure.

Cerebral oxygenation following epinephrine infusion.

Evidence suggests that the autonomic nervous system may actively regulate the cerebral vasculature. In this study, central hemodynamics and brain oxy-hemoglobin, deoxy-hemoglobin and total hemoglobin changes (bO2Hb, bdHb and bTHb) were monitored during infusion of epinephrine (0.06 µg/kg/min over 6 min, and 0.12 µg/kg/min for 3 min) in 12 men. Epinephrine decreased mean arterial pressure (MAP) and total peripheral resistance (TPR), while heart rate (HR), stroke volume (SV) and cardiac output (CO) increased, but did not affect bO2Hb, bdHb or bTHb. However, upon the cessation of epinephrine infusion an increase in both Oxy- and Total Hb occurred which peaked at 3 min post infusion (+6.0±4.6 and +4.9±4.8 µmol/L respectively, P<0.05) and persisted for 20 min post infusion (+1.5±2.2 and +1.8±2.7 µmol/L respectively, P<0.05). No evidence was found for reduction in cerebral oxygenation during a cold-pressor test. The results of the present study demonstrated that clinical doses of epinephrine result in a delayed increase in cortical blood volume due to an increase in Oxy-Hb, consistent with vasodilation.

Venous and arterial bubbles at rest after no-decompression air dives.

PURPOSE: During SCUBA diving, breathing at increased pressure leads to a greater tissue gas uptake. During ascent, tissues may become supersaturated, and the gas is released in the form of bubbles that typically occur on the venous side of circulation. These venous gas emboli (VGE) are usually eliminated as they pass through the lungs, although their occasional presence in systemic circulation (arterialization) has been reported and it was assumed to be the main cause of the decompression sickness. The aims of the present study were to assess the appearance of VGE after air dives where no stops in coming to the surface are required and to assess their potential occurrence and frequency in the systemic circulation. METHODS: Twelve male divers performed six dives with 3 d of rest between them following standard no-decompression dive procedures: 18/60, 18/70, 24/30, 24/40, 33/15, and 33/20 (the first value indicates depth in meters of sea water and the second value indicates bottom time in minutes). VGE monitoring was performed ultrasonographically every 20 min for 120 min after surfacing. RESULTS: Diving profiles used in this study produced unexpectedly high amounts of gas bubbles, with most dives resulting in grade 4 (55/69 dives) on the bubble scale of 0-5 (no to maximal bubbles). Arterializations of gas bubbles were found in 5 (41.7%) of 12 divers and after 11 (16%) of 69 dives. These VGE crossovers were only observed when a large amount of bubbles was concomitantly present in the right valve of the heart. CONCLUSIONS: Our findings indicate high amounts of gas bubbles produced after no-decompression air dives based on standardized diving protocols. High bubble loads were frequently associated with the crossover of VGE to the systemic circulation. Despite these findings, no acute decompression-related pathology was detected.

Glossopharyngeal insufflation induces cardioinhibitory syncope in apnea divers.

Apnea divers increase intrathoracic pressure voluntarily by taking a deep breath followed by glossopharyngeal insufflation. Because apnea divers sometimes experience hypotension and syncope during the maneuver, they may serve as a model to study the mechanisms of syncope. We recorded changes in hemodynamics and sympathetic vasomotor tone with microneurography during breath holding with glossopharyngeal insufflation. Five men became hypotensive and fainted during breath holding with glossopharyngeal insufflation within the first minute. In four divers, heart rate dropped suddenly to a minimum of 38 ± 4 beats/min. Therefore, cardioinhibitory syncope was more common than low cardiac output syncope.

Effects of successive air and trimix dives on human cardiovascular function.

INTRODUCTION: The use of trimix (a mixture of oxygen, helium, and nitrogen) has significantly increased among the diver population. However, data indicating how trimix dives at most common depths affect the cardiovascular function are sparse. The purpose of this study was to investigate the cardiovascular effects of trimix dives and compare them with air dives and to determine whether the repetition of dives in successive days affects their extent. METHODS: Nine professional divers performed four dives in consecutive days where the dive depth was progressively increased to the maximum of 55 m. Divers used air in the first dive, nitrox 25 in the second, and trimix 20/30 in the third and fourth dives. Echocardiography was performed before and after each dive. RESULTS: After each dive, a significantly decreased left ventricular ejection fraction and fractional shortening and an increased end-systolic volume without a change in end-diastolic volume were found, indicating a depressed systolic function of the left side of the heart. Assessment of the ratio between pulmonary artery acceleration time and right ventricular ejection time (used as an indicator of pulmonary artery pressure (PAP)) revealed an increase in PAP after all the dives. No physiologically relevant cumulative effects of the multiple dives or signs of acclimatization were found. CONCLUSIONS: The current study shows that the cardiovascular effects of trimix dives do not differ from those of the dives with compressed air. However, it suggests that even a very safe and conservative trimix diving profile exerts significant cardiovascular effects.

Changes in platelet size and spleen volume in response to selective and non-selective beta-adrenoceptor blockade in hypertensive patients.

1. The spleen contains approximately one-third of all the body's platelets. These platelets are relatively larger and haemostatically more active than platelets in the systemic circulation and can be released into the systemic circulation by stimulation of alpha-adrenoceptors or inhibition of beta-adrenoceptors. In the present study, we evaluated the effects of selective (bisoprol) and non-selective (carvedilol) beta-blockers agents on mean platelet volume (MPV) and spleen size in hypertensive patients at rest and after exercise. 2. Blood pressure, heart rate, platelet count, MPV and spleen volume were measured in 18 newly diagnosed hypertensive patients, as well as in nine healthy control subjects, subjected to treadmill exercise test at their first visit and, for the hypertensive group, after 15 and 30 days of treatment with the selective beta(1)-adrenoceptor antagonist bisoprolol 5 mg/day (n = 9) or the non-selective alpha(1)-, beta(1)- and beta(2)-adrenoceptor antagonist carvedilol 25 mg/day (n = 9). 3. Increases in resting MPV values with concomitant decreases in spleen volume were found after 15 and 30 days treatment with either bisoprolol or carvedilol. The pronounced decrease in splenic volume after exercise and the increased MPV and platelet counts seen at first visit were halved after 15 and 30 days of treatment with either drug. 4. We conclude that in hypertensive patients treated with either selective or non-selective beta-blockers, the spleen contracts and MPV increases, which may increase the risk of atherothrombosis.

Effects of indomethacin on cerebrovascular response to hypercapnea and hypocapnea in breath-hold diving and obstructive sleep apnea.

We tested whether breath hold divers (BHD) and obstructive sleep apnea (OSA) subjects had similar middle cerebral artery velocity (MCAV) responses to hypercapnea and hypocapnea. We analyzed changes in MCAV (cm/s) in response to hypocapnea and hyperoxic hypercapnea during placebo or after 90 min of oral indomethacin (100 mg) in BHD (N=7) and OSA (N=7). During control hypercapnea MCAV increased for 54.4% in BHD and 48.4% in OSA. Indomethacin blunted the MCAV increase in response to hypercapnea in BHD (P=0.02), but not in OSA. Indomethacin attenuated the mean arterial pressure response in BHD, but not in OSA. The blunted MCAV responses to hypercapnea with indomethacin in BHD, but not in OSA patients suggests that (a) the normal contribution of local vasodilating mechanisms to the cerebrovascular responses to hypercapnea is absent in OSA patients and (b) exposure to chronic/repeated apneas is not causal per se in limiting the contribution of vasodilating mechanisms to the cerebrovascular responses to hypercapnea in OSA.