Tibor Fülöp

Increased Cyclooxygenase-2 Expression and Prostaglandin-Mediated Dilation in Coronary Arterioles of Patients With Diabetes Mellitus

Based on findings of experimental models of diabetes mellitus (DM) showing increased expression of vascular cyclooxygenase-2 (COX-2), we hypothesized that in patients with DM changes in COX-2–dependent prostaglandin synthesis affect vasomotor responses of coronary arterioles. Arterioles were dissected from the right atrial appendages obtained at the time of cardiac surgery of patient with DM(+) or without documented diabetes DM(−). Isolated arterioles (89±15 &mgr;m in diameter) were cannulated and pressurized (at 80 mm Hg), and changes in diameter were measured with video microscopy. After spontaneous tone developed [DM(−): 32±7%; DM(+): 37±5%; P=NS], arteriolar responses to bradykinin were investigated. Dilations to bradykinin (0.1 nmol/L to 1 &mgr;mol/L) were significantly (P<0.05) greater in DM(+) than DM(−) patients (10 nmol/L: 77±10% versus 38±14%). In both groups, dilations were similar to the NO-donor, sodium nitroprusside. In arterioles of DM(+), but not those of DM(−), patients bradykinin-induced dilations were reduced by the nonselective COX inhibitor indomethacin or by the selective COX-2 inhibitor NS-398 (DM(+) at 10 nmol/L: to 20±4% and 29±7%, respectively). Correspondingly, a marked COX-2 immunostaining was detected in coronary arterioles of DM(+), but not in those of DM(−) patients. We conclude that in coronary arterioles of diabetic patients bradykinin induces enhanced COX-2–derived prostaglandin-mediated dilation. These findings are the first to show that in humans diabetes mellitus increases COX-2 expression and dilator prostaglandin synthesis in coronary arterioles, which may serve to increase dilator capacity and maintain adequate perfusion of cardiac tissues.

Comparison of the New Cardioselective Beta-Blocker Nebivolol with Bisoprolol in Hypertension: The Nebivolol, Bisoprolol Multicenter Study (NEBIS)

AbstractObjective: The aim of the present study was to evaluate the antihypertensive efficacy of the highly beta1-selective adrenergic antagonist nebivolol in comparison with bisoprolol in the treatment of mild to moderate essential hypertension.nMethods: This multicenter, single-blind, randomized, parallel-group 16-week study involved a 4-week placebo run-in, followed by a 12-week treatment period (5 mg nebivolol or 5 mg bisoprolol). Patients (n = 273) eligible for the study had a sitting diastolic blood pressure (DBP) between 95 and 110 mm Hg and a systolic blood pressure (SBP) ≤180 mm Hg at the end of the placebo run-in period. The primary endpoint of the study was the percentage of responders achieving DBP normalization (≤90 mm Hg) or a DBP reduction of at least 10 mm Hg.nResults: The baseline SBP and DBP were similar in the two groups. Both SBP and DBP decreased gradually and significantly upon treatment. The two treatments had similar effects on the mean change from the baseline for both DBP (nebivolol −15.7 ± 6.4 mm Hg vs. bisoprolol −16.0 ± 6.8 mm Hg) and SBP. A high proportion of responders was noted in both groups (nebivolol 92.0% vs. bisoprolol 89.6%) and there was no significant difference between the treatments. The overall number and incidence of spontaneously reported adverse events were slightly, but not significantly lower for nebivolol (8 events; 5.8%) than for bisoprolol (12 events; 8.9%).nConclusions: The findings of the present trial indicate that 5 mg nebivolol once daily is an effective antihypertensive agent. It can therefore be recommended as a useful alternative first-line treatment option for the management of patients with mild to moderate essential hypertension.

Adaptation of Vasomotor Function of Human Coronary Arterioles to the Simultaneous Presence of Obesity and Hypertension

Objectives—We hypothesized that simultaneous presence of obesity and hypertension activates adaptive vascular mechanisms affecting dilations of human coronary arterioles. Methods and Results—Agonist-induced dilations were assessed in isolated pressurized coronary arterioles from patients (n=38) who underwent cardiac surgery. Among normotensives we found that dilations to bradykinin (BK) and the NO-donor, sodium-nitroprusside (SNP) were reduced in obese subjects (BK, 10−7 mol/L, lean:90±4%, obese:64±7%; SNP, 10−6 mol/L, lean:89±7%, obese:76±5%). However, among hypertensives, both BK- and SNP-induced dilations were significantly enhanced in obese patients, when compared with lean individuals (BK, lean:71±7%, obese:85±3%; SNP, lean:60±6%, obese:83±2%). Correspondingly, in hypertensive patients, but not in those of normotensives, a positive correlation was found between body mass index (BMI) and BK-induced (P=0.036, r=0.46), and also SNP-evoked (P=0.031, r=0.44) coronary dilations. Moreover, in additional 55 hypertensive patients flow-mediated (FMD) and nitroglycerin (NTG)-induced dilations of the brachial artery were assessed. In obese hypertensive individuals, FMD- and NTG-induced dilations were greater (FMD:6.2±0.7%, NTG:17.2±0.9%), than in lean hypertensive patients (FMD:3.7±0.6%, NTG:13.6±1.1%). Correspondingly, FMD- and NTG-induced dilations were positively correlated with BMI (P=0.020, r=0.31 and P=0.033, r=0.29, respectively). Conclusions—These findings are the first to suggest that obesity may lead to activation of adaptive vascular mechanisms to enhance the dilator function of coronary and peripheral arterial vessels in hypertensive patients.

Clinical aspects of changes in water and sodium homeostasis in the elderly

The population of elderly individuals is increasing worldwide. With aging, various hormonal and kidney changes occur, both affecting water homeostasis. Aging is a risk factor for chronic kidney disease (CKD) and many features of CKD are reproduced in the aging kidney. Dehydration and hyperosmolarity can be triggered by diminished thirst perception in this population. Elderly with dementia are especially susceptible to abnormalities of their electrolyte and body water homeostasis and should be (re-)assessed for polypharmacy. Hypo- and hypernatremia can be life threatening and should be diagnosed and treated promptly, following current practice guidelines. In severe cases of acute symptomatic hyponatremia, a rapid bolus of 100 to 150xa0ml of intravenous 3% hypertonic saline is appropriate to avert catastrophic outcomes; for asymptomatic hyponatremia, a very gradual correction is preferred. In summary, the body sodium (Na+) balance is regulated by a complex interplay of environmental and individual factors. In this review, we attempt to provide an overview on this topic, including dehydration, hyponatremia, hypernatremia, age-related kidney changes, water and sodium balance, and age-related changes in the vasopressin and renin-angiotensin-aldosterone system.

Holistic polar map for integrated evaluation of cardiac imaging results

Polar map display (PM) is a comprehensive interpretation of the left ventricle. This is a non-rigid registration of the left ventricle originally for the visual and quantitative analysis of tomographic myocardial perfusion scintigrams. In this scheme the maximal-count circumferential profiles of well-defined short- and long-axis planes are plotted to a map showing the distribution of the perfusion tracer onto a two-dimensional polar representation. The usual coronary artery distribution is often indicated on the PMs of SPECT studies by referring to the regions of the three main coronary branches, nevertheless, the individual variations may differ extensively. We set out to develop an Access (Microsoft)-based computer program that permits an integrated evaluation of the imaging results (coronary angiography, echocardiography and SPECT) on patients with coronary artery disease. This semi-quantitative registration of the coronary tree to a PM focused on the relation between the supplying coronary branches and the myocardial regions of the 16-segment left ventricular evaluating model. All the recorded anatomical and functional data were related to these 16 left ventricular segments, which allowed the direct comparison and holistic synthesis of the results. Two projections were taken into consideration for generation of the coronary PM: from the right anterior oblique projections, the left anterior descendent (LAD)/right coronary artery (RCA) border was assessed through the comparison of the left and right coronary angiograms. The terminations of the visually detected end-arteries showed the separation of the myocardial beds supplied by the two branches. The border of the myocardial beds on the polar map was determined on the vertical axis of the local coordinate system. The RCA/ left circumflex (LCx) separation can be determined from the left anterior oblique view. In this projection, the left ventricular septal edge was delineated by the LAD, while the LCx indicated the lateral epicardial surface. The individual coronary artery circulation was typified from among 12 variations in the Holistic Coronary Care program. With this determination of the individual coronary circulation, the lesion-associated segments are generated automatically by the software. The lesion-associated regions are defined as the myocardial bed of a diseased artery distal to the lesion. The PMs generated from the coronary angiographic results were compared with those of 99Tc-labelled MIBI single photon emission computed tomography (SPECT) in order to test the accuracy of the localizing method. The overlap between the segments associated with the coronary lesion and the stress perfusion defects (<80% relative MIBI activity during stress tests) was analyzed in 10 patients with (sub)total coronary occlusion after myocardial infarction. The distributions of the segments with stress perfusion defects on MIBI SPECT gave positive and negative predictive values of coronary occlusion of 0.94 and 0.8, respectively. According to the 16-segment wall motion analysis by echocardiography, the positive and negative predictive values of coronary occlusion for wall motion abnormality were 0.82 and 0.76, respectively. While the distal part of the subtended region usually demonstrated a higher degree perfusion abnormality than the proximal part, the high positive predictive value proved that, during the stress condition, the perfusion defect could be detected in practically all the subtended regions. The low negative predictive value of the coronary lesion for the wall motion abnormality was associated with the remodeling of the entire left ventricle.

Pre-ESRD Dementia and Post-ESRD Mortality in a Large Cohort of Incident Dialysis Patients

Background: Conservative management may be a desirable option for elderly, fragile, or demented patients who reach end-stage renal disease (ESRD), yet some patients with dementia are placed on renal replacement therapy nonetheless. Methods: From a nationwide cohort of 45,076 US veterans who transitioned to ESRD over 4 contemporary years (October 1, 2007 to September 30, 2011), we identified 1,336 (3.0%) patients with International Classification of Diseases, Ninth Revision, Clinical Modification code-based dementia diagnosis during the prelude (predialysis) period. We examined the association of prelude dementia with all-cause mortality within the first 6 months following transition to dialysis, using a propensity-matched cohort and Cox proportional hazards models. Results: In the entire cohort, the overall mean ± standard deviation age at baseline was 72 ± 11 years, 95% were male, 23% were African-American, and 66% were diabetic. There were 8,080 (18.5%) deaths (mortality rate, 412; 95% confidence interval [CI], 403-421/1,000 patient-years) in the dementia-negative group, and 396 (29.6%) deaths (mortality rate, 708; 95% CI, 642-782/1,000 patient-years) in the dementia-positive group in the entire cohort in the first 6 months after dialysis initiation. Presence of dementia was associated with higher risk of all-cause mortality (adjusted hazard ratio, 1.25; 95% CI, 1.12-1.38) compared to dementia-free patients in the first 6 months after dialysis initiation. Conclusion: Pre-ESRD dementia is associated with increased risk of early post-ESRD mortality in veterans transitioning to dialysis.

99mTc-MIBI SPECT assessment of the effects of aneurysm resection on the left ventricular morphology

Objective — 99mTc-MIBI SPECT is a widely used myocardial perfusion investigation technique, but few data are available concerning its use to assess the morphological characteristics of a left ventricular aneurysm (LVA) before and after LVA resection. Methods and results — Pre- and postoperative rest 99mTc-MIBI SPECT images were analysed in order to characterize the features of LVAs and the changes in the 3D scintigraphic parameters after apical LVA resection in 6 patients. In the middle horizontal slice an angle was defined to quantify the apical divergence associated with the LVA. After resection, the changes in the divergence angles (DA) were measured as were the changes in the left ventricular volumes (LVV) by volumetric calculations. The mean DA decreased from an average of 38.5° ± 11.32° preoperatively to 24° ± 11.84° postoperatively (p = 0.03). The mean LVV also decreased significantly: from 443 ± 87 ml to 317 ± 74 ml (p = 0.003). The resectable LVAs were associated with a very low isotope uptake in the apical segments (< 20% relative activity).A DA < 20° was also characteristic of anatomical LVA in all patients. A regression curve plotting divergence angle and the number of left ventricular segments below 20% relative activity showed a significant correlation between them (r = 0.86, p = 0.003). Conclusions — The significant decreases of DA and LVV after resection reflect favourable morphological changes in the left ventricle (reverse remodelling).We consider 99mTc-MIBI SPECT a useful method for apical LVA detection, it allows an analysis of the morphological (and indirectly the functional) results of the surgery.