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.

Effects of endothelium-derived nitric oxide on cerebral circulation during normoxia and hypoxia in the rat.

The aim of this study was to determine the effects of endogenous nitric oxide (NO) on cerebral blood flow (CBF) and cerebrovascular resistance (CVR) under conditions of normoxia and hypoxia. Experiments were performed on anesthetized, mechanically ventilated Wistar rats. CBF was measured using the intracarotid 133Xe injection technique. NO formation was inhibited by NG-monomethyl-L-arginine (L-NMMA). Administration of L-NMMA (100 mg kg-1 i.v.) during normoxia resulted in an increase in mean arterial blood pressure from 113 +/- 4 to 145 +/- 4 mm Hg (p less than 0.001), a decrease in CBF of 21% (from 91 +/- 4 to 75 +/- 5 ml 100 g-1 min-1, p less than 0.001), and an increase in CVR of 53% (from 1.3 +/- 0.1 to 2.0 +/- 0.2 mm Hg ml-1 100 g min, p less than 0.001). These effects were reversed by i.v. administration of 300 mg kg-1 of L-arginine but not D-arginine. Moreover, the administration of L-NMMA abolished the enhancement of CBF and the diminution in CVR observed during intracarotid infusion of acetylcholine (ACh). The increase in CBF and decrease in CVR during hypoxia in the group of rats that received L-NMMA were similar to that in the control group, although CBF and CVR levels attained during hypoxia in both groups were different. The results show that NO is involved in the maintenance of basal CBF and CVR, and is responsible for the ACh-elicited increase in CBF and the decrease in CVR in rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of NG-nitro-L-arginine on pressor action of arginine vasopressin in normotensive (WKY) and spontaneously hypertensive (SHR) rats.

In order to find out whether the pressor effect of arginine vasopressin (AVP) is limited by release of nitric oxide (NO) and whether it is altered in hypertension, blood pressure (MAP) and heart rate (HR) responses to i.v. administration of AVP were compared in conscious normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats under control conditions and during blockade of NO synthesis induced by i.v. administration of NG-nitro-L-arginine (L-NOARG). In control experiments AVP elicited significant elevations of MAP in WKY and SHR. The maximum increases in WKY and SHR amounted 26 +/- 3 and 16 +/- 3 mmHg, respectively, and did not differ significantly from each other. In WKY increase of MAP was associated with significant bradycardia. Administration of AVP in this strain during blockade of NO synthesis resulted in significantly smaller increase of blood pressure (13 +/- 5 mmHg) than under control conditions (p < 0.001), and in nonsignificant changes of HR. In SHR AVP caused a progressive significant decrease of blood pressure associated with transient tachycardia. The results indicate that blockade of NO synthesis does not enhance but reduces increase of blood pressure in WKY and transforms the pressor action of this peptide into the hypotensive effect in SHR. This phenomenon is discussed in relevance to the possible unfavorable effects of AVP on coronary and/or cerebral circulation during blockade of NO formation.

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.

Acute hemodynamic effects and angina improvement with enhanced external counterpulsation.

Enhanced external counterpulsation (EECP) is an effective noninvasive treatment for coronary artery disease. The mechanism of action is felt to be hemodynamic. The complex hemodynamic effects have been simply quantified by calculating a previously described effectiveness ratio (ER). The EECP Clinical Consortium, a clinical registry of 37 centers, prospectively enrolled 395 chronic stable angina patients (79 women, 316 men, mean age 66 years) to examine the relation of the ER to posttreatment improvement in Canadian Cardiovascular Society angina class (CCS). Women and the elderly underwent planned subgroup analysis. The ER was calculated during the first and last hours of a 35-hour course of EECP treatment. After EECP, CCS improved by at least 1 class in 88% of patients, 87% of men and 92% of women (p = NS), and in 89% of patients < or = 66 years and 88% of patients > 66 years old (p = NS). The initial and final ER were similar in patients with and without improvement in CCS. Significant first-hour ER differences were seen between men and women (0.96 +/- 0.03 vs 0.76 +/- 0.04, p<0.005), and between ages < or = 66 and > 66 years old (1.04 +/- 0.04 vs 0.81 +/- 0.03, p<0.0001). However, all subgroups responded equally well to EECP treatment. EECP is effective in improving CCS in chronic stable angina patients; it has comparable effects in men and women and across a broad range of ages. The hemodynamic effect of EECP (ER) does not predict improvement in CCS and may indicate that other factors, such as neurohormonal changes, may have a significant role in mediating the observed EECP benefits.

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.

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)

Direct coronary stenting without balloon or device pretreatment: acute success and long-term results.

Improvements in coronary stents have made planned direct coronary stenting technically feasible, though safety, acute success, cost-effectiveness, and long-term results remain to be determined. Sequential patients eligible for direct stenting were prospectively characterized and treated with either direct or secondary stenting. Major adverse cardiovascular events (MACE) such as cardiac death, myocardial infarction (MI), target vessel ischemia, or revascularization (TVR) were followed for 6 months post-PCI. Enrollment included 128 direct (1.38 lesions/patient) and 69 secondary (1.39 lesions/patient) stented patients. Direct stenting was successful in 99% (with 5% crossover to secondary stenting) without major procedural complications and with a similar rate of vessel wall dissection or no-reflow phenomenon (2.3% vs. 2.1%; P > 0.05) as the secondary stenting group. There was a trend toward less postprocedural CPK-MB elevation in the nonacute MI patients with direct vs. secondary stenting (3% vs. 11%, respectively). At 6 months, there were no statistically significant differences in overall MACE. Direct stenting has a high success rate, low complication rate, and durable long-term results. Procedural cost and time savings, less contrast use and radiation exposure make direct stenting attractive in properly selected patients.