Risk perception of NSAIDs in South Dakota in comparison with Slovakia and Greece.

AIM: Adverse effects (ADRs) of non-steroidal anti-inflammatory drugs (NSAIDs) represent a public health problem. To decrease the negative effect on the population, an improvement of risk awareness is crucial. We aimed to evaluate the risk perception and the use of NSAIDs in South Dakota in comparison with Slovakia and Greece. METHOD: A structured questionnaire evaluating NSAID use in 185 patients in a hospital in South Dakota. RESULTS: 95.7 % of respondents reported the use of analgesics. On 1-10 visual analogue scale, perceived risk of NSAIDs was 4.27±2.46, similar to Greece (4.36±2.41, p=0.360), but significantly higher than in Slovakia (3.8±1.9, p=0.038). Only 12.4 % were familiar with gastrointestinal ADRs and only 1.1 % were aware of cardiovascular risk. Although 57.8 % were informed about ADRs by their doctor or pharmacist, only 33.0 % were informed spontaneously, without actively asking. Providers in South Dakota were informing patients spontaneously more often than in Slovakia (15.9 %, p≤0.001) and on par with Greece (36.3 %, p=0.631). CONCLUSIONS: Public awareness about NSAID risk is dangerously low. Only a third of providers are informing patients about possible risks spontaneously (Tab. 6, Ref. 15) Keywords: non-steroidal anti-inflammatory drugs, risk perception, adverse effects, cardiovascular risk, gastrointestinal risk.

Novel Use of an Orbital Atherectomy Device for In-Stent Restenosis: Lessons Learned.

We present a case of a 67-year-old man with stage III chronic kidney disease, uncontrolled diabetes mellitus, coronary artery disease, and high surgical risk who presented with two episodes of acute coronary syndrome attributed to in-stent restenosis (ISR) associated with heavily calcified lesions. In this case, we were able to improve luminal patency with orbital atherectomy system (OAS); however, withdrawal of the device resulted in a device/stent interaction, causing failure of the device. Given limitations in current evidence and therapies, managing ISR can be a technical and cognitive challenge. Balloon expansion of the affected region often provides unsatisfactory results, possibly related to significant calcium burden. OAS could be an efficacious way of reestablishing luminal patency in ISR lesions, as these lesions are often heavily calcified.

Does aspirin attenuate the beneficial effects of angiotensin-converting enzyme inhibition in heart failure?

Ischemic heart disease is the most common underlying cause of congestive heart failure, and thus aspirin (acetylsalicylic acid [ASA]) and angiotensin-converting enzyme (ACE) inhibitors are commonly used together for treatment in this setting. The issue of possible attenuation of the effect of ACE inhibitors by ASA has been an area of intense debate. Currently, it is perceived that a significant part of the beneficial effect of ACE inhibitors is related to augmentation of bradykinin levels, which among other effects stimulate the release of prostacyclin. Aspirin, on the other hand, inhibits the production of prostacyclin by blocking cyclooxygenase. Prostaglandins play an important endogenous vasodilatory role and counteract the enhanced peripheral vasoconstriction state in congestive heart failure. Thus, the counteracting effect of ASA on the augmentation of prostacyclin synthesis by ACE inhibitors could result in a potential reduction of the beneficial effects of the ACE inhibitor's and could be of great importance. This article reviews reports from large clinical trials pertaining to this issue and relates their findings to the currently available theoretical bases for support of the counteracting effect of ASA on augmentation of prostacyclin synthesis by ACE inhibitors. The clinical implications of such an interaction are discussed.

Effect of endothelin-3 on blood pressure in conscious spontaneously hypertensive [SHR] and DOCA-salt hypertensive rats.

The aim of the study was to investigate blood pressure responses and changes in heart rate after bolus administration of endothelin-3 [ET-3] in conscious, freely moving SHR and WKY rats and DOCA-salt hypertensive and normotensive Wistar rats. The effect of ET-3 on blood pressure and heart rats was investigated for four doses equal to 250 ng, 500 ng, 1000 ng and 2000 ng of ET-3. Our study shows that in experimental models of hypertension changes in blood pressure were predominantly characterized by the pronounced hypotensive phase with no significant raises in blood pressure. In normotensive animals cardiovascular responses to ET-3 were biphasic, with initial depressor phase followed by long-lasting, significant pressor effect.

Decreased hypotensive responsiveness to nitric oxide donor S-nitroso N-acetyl-DL-penicillamine (SNAP) in spontaneously hypertensive (SHR) rats.

The aim of the study was to compare hemodynamic effects of intravenously (i.v.) applied nitric oxide (NO) donor S-nitroso N-acetyl-DL-Penicillamine (SNAP) in conscious spontaneously hypertensive (SHR) to those observed in normotensive Wistar Kyoto (WKY) rats. The study was performed on 7 SHR and 8 WKY instrumented with polyethylene catheters inserted to the abdominal aorta and vena cava for blood pressure (MAP) and heart rate period (HRp) monitoring, and for i.v. administration of SNAP (0.05, 0.1, 0.2, 0.5, 1.0, 2.0, 5.0, 10.0, 20.0, 40.0 and 75.0 microM/kg of body weight). The following differences were found between SHR and WKY rats: 1) the threshold dose of SNAP, eliciting significant decrease of MAP was markedly higher in SHR (1.0 microM/kg b.w.) than in WKY (0.2 microM/kg b.w.), 2) SHR responded with significantly smaller maximum decreases of MAP to administration of 1.0, 2.0, 5.0 and 10.0 microM/kg b.w. of SNAP and with smaller heart rate acceleration to administration of 10.0, 40.0 and 75.0 microM/kg b.w. of SNAP, 3) in SHR MAP decreased progressively, the greatest decline being observed after administration of the highest dose (75 microM/kg b.w.) of SNAP while in WKY the log dose/delta MAP response curve reached plateau beginning with 2 microM/kg b.w. of SNAP, 4) the slopes and intercepts of the regression lines describing relationship between MAP and HRp after administration of SNAP were significantly different in SHR and WKY rats (P < 0.01). The results indicate that SHR are significantly less sensitive to hypotensive effects of NO generated from moderate doses of SNAP.

Current clinical applications of heart rate variability.

Heart rate variability (HRV) has become a popular method for the studies of physiologic mechanisms responsible for the control of heart rate fluctuations, in which the autonomic nervous system appears to play a primary role. Depression of HRV has been observed in many clinical scenarios, including autonomic neuropathy, heart transplantation, congestive heart failure, myocardial infarction (MI), and other cardiac and noncardiac diseases. However, it is important to realize that clinical implication of HRV analysis has been clearly recognized in only two clinical conditions: (1) as a predictor of risk of arrhythmic events or sudden cardiac death after acute MI, and (2) as a clinical marker of evolving diabetic neuropathy. Recently, its role in evaluation and management of heart failure has also been recognized. It is pertinent to recognize the limitations of HRV as far as its clinical utility at present is concerned. The methodology of HRV had remained poorly standardized until the recent publication of the Special Report of the Task Force of ESC/NASPE, and thus has been presenting difficulty in comparing earlier existing data. Also, determination of the exact sensitivity, specificity, and predictive value of HRV, as well as the normal values of standard measures in the general population, still require further investigation before better standards can be set for existing and future clinical applications. This article reviews the major concepts of HRV measurements, their clinical relevance, and the recent advances in this field.

Structure and oxygen mobility in mayenite (Ca12Al14O33): a high-temperature neutron powder diffraction study.

The structure of mayenite, Ca(12)Al(14)O(33), was investigated by neutron powder diffraction up to 1323 K. It has been described previously as a calcium-aluminate framework, in which 32 of the 33 oxygen anions are tightly bound, containing large cages, 1/6 of them being filled randomly by the remaining 'free' oxygen. At ambient temperature excess oxygen was found, corresponding to the composition Ca(12)Al(14)O(33.5) which was attributed to the presence of hydroxide, peroxide and superoxide radicals in the cages. Above 973 K these are lost under vacuum conditions and the composition becomes stoichiometric. From the refined structural parameters it is concluded that the structure is more adequately described as a relatively stable aluminate framework consisting of eightfold rings of AlO(4) tetrahedra with disordered Ca and 'free' O distributed within. At high temperatures the density of the 'free' oxygen is extremely spread out, with the expansion being related to the high ionic conductivity of this material. Since no continuous density distribution between adjacent cages was found and the 'free' O forms bonds with part of the Ca, the diffusion proceeds via a jump-like process involving exchange of the 'free' oxygen with framework oxygen. The results confirm the recent theoretical predictions of Sushko et al.

Effect of low-dose scopolamine on autonomic control of the heart.

BACKGROUND: In low doses, scopolamine paradoxically enhances parasympathetic outflow to the heart. The mechanisms which mediate this action are not fully understood. Moreover, there are conflicting data regarding the potential role of sympathetic activity. This study in 17 healthy individuals was designed to characterize the influence of low dose transdermal scopolamine on the gain of the baroreflex and respiratory heart rate reflex and to determine the role of sympathetic activity. METHODS: The effect of scopolamine was analyzed in the time and frequency domain by computing heart rate variability indices. The gains of the respiratory heart rate reflex and the baroreflex were estimated simultaneously by means of a cardiovascular system identification approach using an optimized autoregressive moving average algorithm. Measurements were repeated in the upright posture to assess the influence of enhanced sympathetic activity. In six subjects ambulatory ECGs were recorded to determine whether there are diurnal variations of the effect of scopolamine. RESULTS: Scopolamine enhances vagal modulation of heart rate through both the respiratory-heart rate reflex and the baroreflex, as the gains of both were augmented by the drug in the supine and in the upright postures. CONCLUSIONS: Scopolamine increases parasympathetic cardiac control by augmenting the gain of the respiratory-heart rate and baroreflex. This action is not attenuated in the upright posture when sympathetic tone is increased.

Blood pressure responses to substances interfering with nitric oxide formation, cyclooxygenase and converting enzyme activities and vasopressin V1 receptors blockade in conscious spontaneously hypertensive and normotensive rats.

The aim of the study was to investigate to what extent inhibition of nitric oxide (NO) formation, cyclooxygenase and converting enzyme activities and vasopressin V1 receptors blockade affects the cardiovascular system in conscious, freely moving normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. The experiments were performed on 33 WKY and on 33 SHR. In series 1 (8 WKY and 8 SHR) animals received bolus injection of N omega-nitro-L-arginine - NLA (10 mg/kg), in series 2 (6 WKY and 6 SHR) bolus injection of indomethacin (10 mg/kg). In series 3 (8 WKY and 8 SHR) the animals received captopril as initial bolus (1 mg/kg) followed by constant infusion (1 mg/kg/min), in series 4 (11 WKY and 11 SHR) vasopressin V1 receptor antagonist 1-(1-mercapto-4-methylcyclohexaneacetic acid)-8-arginine-vasopressin (MeCAAVP) was infused (1.52 micrograms/kg/min). In series 1 in WKY NLA elicited a long-lasting, significant increase in mean blood pressure (max 46 +/- 3 mmHg at 40 min). In SHR mean blood pressure raises were not significant (max 22 +/- 6 mmHg). In series 2, both in WKY and SHR, indomethacin elicited only transient, nonsignificant increases in mean blood pressure. In series 3, the mean blood pressure fall during the captopril infusion was more pronounced in SHR than in WKY (45 +/- 2 mmHg vs 13 +/- 2 mmHg respectively). In series 4 vasopressin V1 receptor blockade caused a nonsignificant fall in mean blood pressure, both in WKY and SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Modulation of the effect of endothelin-3 on blood pressure by atrial natriuretic peptide in conscious spontaneously hypertensive (SHR) and normotensive (WKY) rats.

Endothelin (ET) exerts direct vasoconstrictory effects and stimulates release of vasoactive substances. It has been demonstrated that ET stimulates the release of atrial natriuretic peptide (ANP) both under in vitro and in vivo conditions. The present study aimed at elucidating whether the cardiovascular effects of endothelin-3 (ET-3) in normotensive (WKY) and spontaneously hypertensive (SHR) rats are modulated by ANP. The experiments were performed on 17 conscious WKY and 17 SHR rats. The effects of i.v. administration of 1 microgram of ET-3 on blood pressure (BP) and heart rate (HR) were investigated under control conditions and during ANP infusion (0.3 microgram/kg/min). In both strains ET-3 elicited a transient significant hypotensive effect followed by an increase in BP. BP fall was significantly greater and pressor effect significantly smaller in SHR than in WKY. In WKY, but not in SHR rats, both hypotensive and pressor phases were significantly attenuated during ANP administration. The results are evidence of differential involvement of endogenous blood pressure regulating factors in the cardiovascular effects of ET-3 in WKY and SHR rats during ANP infusion.