[Atrial natriuretic peptides: diagnostic and therapeutic potential]. / Die natriuretischen Peptide: Diagnostische und therapeutische Bedeutung.

The natriuretic family consists out of three molecules that share significant amino acid sequence homologies and a looped motif. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are similar in their abilities to promote natriuresis and diuresis, to inhibit the renin-angiotensin-aldosteroneaxis and to act as vasodilators. The understanding concerning the actions of the C-type natriuretic peptide is incomplete, but this new family member acts as a vasodilator. Plasma levels of ANP and BNP are elevated in patients with unstable angina, acute myocardial infarction, and with congestive heart failure. BNP may be superior to ANP as a prognosticator for risk stratification after myocardial infarction and is independent of left ventricular ejection fraction. ANP and BNP have little therapeutic potential while experimental work as well as clinical trials suggest that the inhibition of the catabolism of natriuretic peptides in particular in combination with ACE-inhibitors may be clinically beneficial.

Tetrahydrobiopterin improves endothelium-dependent vasodilation in chronic smokers : evidence for a dysfunctional nitric oxide synthase.

Conditions associated with impaired nitric oxide (NO) activity and accelerated atherosclerosis have been shown to be associated with a reduced bioavailability of tetrahydrobiopterin (BH4). We therefore hypothesized that BH4 supplementation may improve endothelial dysfunction of chronic smokers. Forearm blood flow (FBF) responses to the endothelium-dependent vasodilators acetylcholine (ACh; 0.75, 1.5, and 3.0 microg/100 mL tissue/min) or serotonin (5-HT; 0.7, 2.1, and 6.3 ng/100 mL tissue/min), to the inhibitor of endothelial nitric oxide synthase (NOS) N(G)-monomethyl-L-arginine (L-NMMA; 2, 4, and 8 micromol/min), and to the endothelium-independent vasodilator sodium nitroprusside (SNP; 0.1, 0.3, and 1.0 microg/100 mL tissue/min) were measured by venous occlusion plethysmography in controls and chronic smokers. Drugs were infused into the brachial artery, and FBF was measured before and during concomitant intra-arterial infusion of BH4, tetrahydroneopterin (NH4; another reduced pteridine), or the antioxidant vitamin C (6 and 18 mg/min). In control subjects, BH4 had no effect on FBF in response to ACh, 5-HT, and SNP. In contrast, in chronic smokers, the attenuated FBF responses to ACh and 5-HT were markedly improved by concomitant administration of BH4, whereas the vasodilator responses to SNP were not affected. L-NMMA-induced vasoconstriction was significantly reduced in smokers compared with controls, suggesting impaired basal NO bioactivity. BH4 improved L-NMMA responses in smokers while having no effect on L-NMMA responses in controls. Pretreatment with vitamin C abolished BH4 effects on ACh-dependent vasodilation. In vitro, NH4 scavenged superoxide created by the xanthine/xanthine oxidase reaction equipotent like BH4 but failed to modify ACh-induced changes in FBF in chronic smokers in vivo. These data support the concept that in addition to the free radical burden of cigarette smoke, a dysfunctional NOS III due to BH4 depletion may contribute at least in part to endothelial dysfunction in chronic smokers.

Initial experience with a hydrophilic-coated guidewire for recanalization of chronic coronary occlusions.

Chronic coronary occlusions are still a therapeutic challenge to the interventional cardiologist. New techniques such as laser wire have improved recanalization rates, but outcomes are still far from satisfactory. We report the results of a nonrandomized single-center investigation using a hydrophilic-coated guidewire (Terumo Crosswire). Between September 1996 and September 1998, 107 chronic occlusions in 106 patients were approached when previous attempts with conventional guidewires failed. Median occlusion duration in these cases was 4 months (range, 0.5-122); mean occlusion length was 19 +/- 11 mm (range, 5-60). Forty-five (42%) of these attempts were successful. Attempts were successful in 42% in the left anterior descending artery, in 30% in the left circumflex artery, in 48% in the right coronary artery, and in 43% in coronary artery bypass grafts. Success rates ranged from 56% for occlusions of less than 4-month duration to 18% for occlusions of more than 36-month duration. The success rate in TIMI 1-flow lesions was significantly higher than in TIMI 0 flow lesions, 85% vs. 36%. In a multivariate regression analysis, TIMI flow grade and occlusion age were independent predictors of success. There were no deaths or Q-wave myocardial infarctions; two cases of hemopericardium were treated successfully. In five cases, pericardial contrast staining due to vessel perforation occurred. Our results indicate that the Crosswire is an effective tool in the treatment of chronic coronary occlusions, even when recanalization attempts with conventional guidewires fail. Cathet. Cardiovasc. Intervent. 49:45-50, 2000.

Isotope dilution analysis of bromate in drinking water matrixes by ion chromatography with inductively coupled plasma mass spectrometric detection.

Bromate is a disinfection byproduct in drinking water which is formed during the ozonation of source water containing bromide. This paper describes the analysis of bromate via ion chromatography-inductively coupled plasma mass spectrometry. The separation of bromate from interferences such as bromide and brominated haloacetic acids is achieved using a PA-100 column in combination with a 5 mM HNO3 + 25 mM NH4NO3 mobile phase. Polyatomic ions are observed on masses 79 and 81 in a synthetic phosphate matrix and in ozonated drinking waters. These polyatomic ions have been tentatively identified as PO3+ and H2PO3+. These polyatomic ions do not interfere with the detection of bromate because phosphate elutes prior to bromate. A polyatomic ion is observed on mass 81 in a synthetic sulfate matrix and in ozonated drinking waters. This polyatomic ion has been tentatively identified as HSO3+ and does not interfere with the detection of bromate because sulfate elutes after bromate. Isotope dilution analysis produces a relative standard deviation (RSD) of approximately 5% for both enriched isotopic additions at sample concentrations of 10 ng/g. The RSD associated with the direct analysis of bromate is 3.2% at sample concentrations of 10 ng/g. The bromate concentrations determined in ozonated drinking waters via isotope dilution analysis are within 10% of the concentrations determined via direct analysis for sample concentrations above 2 ng/g. The detection limit for the direct analysis of bromate via IC-ICPMS is 0.3 ng/g.

Protection of side-branches in coronary lesions with a new stent design.

Side-branches often complicate stenting of coronary lesions. We investigated a new stent, characterized by four wider cells in its center, which can be expanded up to 3.5 mm and which are meant to be placed over the ostium of a major side-branch. Forty-seven consecutive patients with lesions involving 48 side-branches received one side-branch stent each. Stent deployment was successful in all patients. Twenty-five side-branches needed additional treatment. Nineteen side-branches received a PTCA, and 6 additional side-branches were stented. Postinterventional CK-(creatine kinase) elevation was observed in 3 patients (6%). One additional patient was sent for CABG on the day of the procedure due to loss of a stent intended to be placed into the side-branch. The investigated stent proved to be a safe and effective tool to treat this complex subgroup of stenoses in the presence of favorably preserved flow in the side-branches, with a low incidence of periprocedural complications.

Long-term nitroglycerin treatment is associated with supersensitivity to vasoconstrictors in men with stable coronary artery disease: prevention by concomitant treatment with captopril.

OBJECTIVES: We examined whether long-term nitroglycerin (NTG) treatment leads to an increase in sensitivity to vasoconstrictors. To assess a potential role of the renin-angiotensin system in mediating this phenomenon, we treated patients concomitantly with the angiotensin-converting enzyme (ACE) inhibitor captopril. BACKGROUND: The anti-ischemic efficacy of organic nitrates is rapidly blunted by the development of nitrate tolerance. The underlying mechanisms are most likely multifactorial and may involve increased vasoconstrictor responsiveness. METHODS: Forearm blood flow and vascular resistance were determined by using strain gauge plethysmography. The short-term responses to intraarterial angiotensin II (1, 3, 9 and 27 ng/min) and phenylephrine (an alpha-adrenergic agonist drug, 0.03, 0.1, 0.3 and 1 microg/min) were studied in 40 male patients with stable coronary artery disease. These patients were randomized into four groups receiving 48 h of treatment with NTG (0.5 microg/kg body weight per min) or placebo with or without the ACE inhibitor captopril (25 mg three times daily). RESULTS: In patients treated with NTG alone, the maximal reductions in forearm blood flow in response to angiotensin II and phenylephrine were markedly greater (-64 +/- 3% and -53 +/- 4%, respectively) than those in patients receiving placebo (-41 +/- 2% and -42 +/- 2%, respectively). Captopril treatment completely prevented the NTG-induced hypersensitivity to angiotensin II and phenylephrine (-33 +/- 3% and -35 +/- 3%, respectively) but had no significant effect on blood flow responses in patients without NTG treatment (-34 +/- 2% and -37 +/- 3%, respectively). CONCLUSIONS: We conclude that continuous administration of NTG is associated with an increased sensitivity to phenylephrine and angiotensin II that is prevented by concomitant treatment with captopril. The prevention of NTG-induced hypersensitivity to vasoconstrictors by ACE inhibition indicates an involvement of the renin-angiotensin system in mediating this phenomenon.

Speciation of selenium and arsenic compounds by capillary electrophoresis with hydrodynamically modified electroosmotic flow and on-line reduction of selenium(VI) to selenium(IV) with hydride generation inductively coupled plasma mass spectrometric detection.

Capillary electrophoresis (CE) with hydride generation inductively coupled plasma mass spectrometry was used to determine four arsenicals and two selenium species. Selenate (SeVI) was reduced on-line to selenite (SeIV) by mixing the CE effluent with concentrated HCl. A microporous PTFE tube was used as a gas-liquid separator to eliminate the 40Ar37Cl and 40Ar35Cl interference from 77Se and 75As, respectively. The direction of the electroosmotic flow during CE was reversed with hydrodynamic pressure, which allowed increased freedom of buffer choice. For conventional pressure injection, method detection limits for SeIV and SeVI based on seven replicate injections were 10 and 24 pg, respectively. Recoveries of SeIV and SeVI in drinking water were measured.

Comparison of conventional and transesophageal echocardiography with magnetic resonance imaging for anatomical mapping of thoracic aortic dissection. A dual noninvasive imaging study with anatomical and/or angiographic validation.

Thirty-five consecutive patients with clinically suspected aortic dissection were subjected to a dual noninvasive imaging protocol using comprehensive echocardiography and ECG-triggered MRI with multi-slice spin echo and cine sequences in random order. The purpose of this dual imaging study was to compare the diagnostic accuracy of two-dimensional and color-coded Doppler echocardiography using the conventional transthoracic (TTE) and the transesophageal approach (TEE) with magnetic resonance imaging (MRI) for the exact morphologic evaluation and anatomical mapping of the thoracic aorta. The results of each diagnostic method were validated independently against the 'gold standard' of intraoperative findings (n = 17), necropsy (n = 4) or contrast angiography (n = 22). Compared to conventional transthoracic echocardiography both TEE and MRI were more reliable in detecting aortic dissections (TTE vs TEE: p < 0.02; TTE vs MRI: p < 0.01) and associated epiphenomena. Moreover, the reliability of TTE decreased significantly from proximal to distal segments of the aorta, e.g. from the ascending segment to the arch (p < 0.05) and to the descending aorta (p < 0.005), whereas the sensitivities of both TEE and MRI were excellent irrespective of the site of dissection. With regard to epiphenomena such as thrombus formation and entry location, MRI emerged as the optimal method for detailed morphologic information in all segments of the aorta. No serious side effects were encountered with either method. Thus, in patients with suspected acute or subacute aortic dissections the echocardiographic assessment should include the transesophageal approach for significant improvement of the moderate sensitivity and specificity of TTE. Both TEE and MRI are non-traumatic, safe and diagnostically accurate to identify and classify acute and subacute dissections of the thoracic aorta irrespective of their location. MRI provides superb anatomical mapping of all type A and B dissections and more detailed information on the site of entry and thrombus formation than TEE. These features of TEE and MRI may render retrograde contrast angiography obsolete in the setting of thoracic aortic dissection and may encourage surgical interventions exclusively on the basis of noninvasive imaging.

Noninvasive estimation of regurgitant flow rate and volume in patients with mitral regurgitation by Doppler color mapping of accelerating flow field.

OBJECTIVES: This study was designed to examine the accuracy of proximal accelerating flow calculations in estimating regurgitant flow rate or volume in patients with different types of mitral valve disease. BACKGROUND: Flow acceleration proximal to a regurgitant orifice, observed with Doppler color flow mapping, is constituted by isovelocity surfaces centered at the orifice. By conservation of mass, the flow rate through each isovelocity surface equals the flow rate through the regurgitant orifice. METHODS: Forty-six adults with mitral regurgitation of angiographic grades I to IV were studied. The proximal accelerating flow rate (Q) was calculated by: Q = 2 pi r2.Vn, where pi r2 is the area of the hemisphere and Vn is the Nyquist velocity. Radius of the hemisphere (r) was measured from two-dimensional or M-mode Doppler color recording. From the M-mode color study, integration of accelerating flow rate throughout systole yielded stroke accelerating flow volume and mean flow rate. Mitral regurgitant flow rate and stroke regurgitant volume were measured by using a combination of pulsed wave Doppler and two-dimensional echocardiographic measurements of aortic forward flow and mitral inflow. RESULTS: The proximal accelerating flow region was observed in 42 of 46 patients. Maximal accelerating flow measured from either two-dimensional (372 +/- 389 ml/s) or M-mode (406 +/- 421 ml/s) Doppler color study tended to overestimate the mean regurgitant flow rate (306 +/- 253 ml/s, p < 0.05). Mean Doppler accelerating flow rate correlated well with mean regurgitant flow rate (r = 0.95, p < 0.001), although there was a tendency toward slight overestimation of mean regurgitant flow by mean accelerating flow in severe mitral regurgitation. However, there was no significant difference between the mean accelerating flow rate (318 +/- 304 ml/s) and the mean regurgitant flow rate (306 +/- 253 ml/s, p = NS) for all patients. A similar relation was found between accelerating flow stroke volume (78.27 +/- 62.72 ml) and regurgitant flow stroke volume (76.06 +/- 59.76 ml) (r = 0.95, p < 0.001). The etiology of mitral regurgitation did not appear to affect the relation between accelerating flow and regurgitant flow. CONCLUSIONS: Proximal accelerating flow rate calculated by the hemispheric model of the isovelocity surface was applicable and accurate in most patients with mitral regurgitation of a variety of causes. There was slight overestimation of regurgitant flow rate by accelerating flow rate when the regurgitant lesion was more severe.

The diagnosis of thoracic aortic dissection by noninvasive imaging procedures.

BACKGROUND AND METHODS: This study was designed to assess the safety and reliability of new noninvasive imaging methods as compared with aortography in the diagnosis of dissection of the thoracic aorta. One hundred ten patients with clinically suspected aortic dissection followed a diagnostic protocol that included transthoracic and transesophageal color-flow Doppler echocardiography (TTE and TEE), contrast-enhanced x-ray computed tomography (CT), and magnetic resonance imaging (MRI). Imaging results were compared in a blinded fashion and validated independently against intraoperative findings in 62 patients, autopsy findings in 7, and the results of contrast angiography in 64. RESULTS: The sensitivities of MRI, TEE and x-ray CT for detecting dissection were similar, at 98.3, 97.7, and 98.3 percent, respectively; TTE had a sensitivity of only 59.3 percent (P < 0.005). The specificities of both TTE (83.0 percent) and TEE (76.9 percent) were lower than those of x-ray CT (87.1 percent) and MRI (97.8 percent; P < 0.05), mainly as a result of false positive findings in the ascending aorta. MRI and x-ray CT were more sensitive than TTE in detecting the formation of thrombus in the entire thoracic aorta (P < 0.05), but were not superior to TEE in this regard. CT was not effective in detecting an entry site or aortic regurgitation, but MRI and TEE accurately identified both. Two patients died during or soon after CT and TEE, and three died between retrograde angiography and surgery. CONCLUSIONS: A noninvasive diagnostic strategy using MRI in all hemodynamically stable patients and TEE in patients who are too unstable to be moved should be considered the optimal approach to detecting dissection of the thoracic aorta. Comprehensive and detailed evaluation can thus be reduced to a single noninvasive diagnostic test in the investigation of suspected dissection of the thoracic aorta.

[Measuring electric impedance of organs--methodologic principles]. / Messung der elektrischen Impedanz von Organen--Methodische Grundlagen.

Ischemia causes changes in organ tissue (e.g. during operation or transplantation) which may finally lead to irreversible injury, so that the organ can no longer be resuscitated. To the extent that these changes affect the electrical properties of the tissue they are manifested in the impedance spectrum. As an example, the course of impedance of a HTK-protected porcine liver is presented in the frequency range of 0.1 Hz to 10 MHz, which includes two dispersion--alpha- and beta-dispersion. Using a suitable electrical equivalent circuit analogue to the structure of the liver, the behavior of the alpha- and beta-dispersion is explained on the basis of gap junction closure and narrowing of the extracellular space due to cell swelling.

Impedance spectroscopy: a method for surveillance of ischemia tolerance of the heart.

UNLABELLED: During myocardial ischemia the phase angle phi of the complex electric impedance of myocardial tissue at 5 kHz AC exhibits a characteristic behaviour, the progress of which depends on the cardioplegic method applied. By extending the frequency range to 200 Hz and 10 MHz and by analyzing in addition to phase and magnitude also real and imaginary part of the impedance it was possible to elucidate which ischemic changes in the myocardium are responsible for the course of phi (5 kHz). This method we call impedance spectroscopy. Canine hearts were cardioplegically perfused with either the standard solution HTK[4] or the solution HTK[4] + 50 mumol/l Ca++. During the following ischemia at 25 degrees C energy-rich phosphate level, the ultrastructure, the real part, imaginary part and phase angle of the impedance between 200 Hz and 10 MHz were analyzed. RESULTS: phi (5 kHz) displays very similar characteristics during the ischemic period to those of the real part of the impedance at 200 Hz, Re (200 Hz). Re (200 Hz) increases, when--according to electron microscopic findings--an intracellular myocardial edema begins to develop. The changes of Re(200 Hz) are always smaller, however, than those of phi (5 kHz). This indicates that phi (5 kHz) increases in the course of ischemia not only as a consequence of confinement of the extracellular space by myocardial cellular edema but also because of changes of passive electrical characteristics of the myocardial cell membranes.(ABSTRACT TRUNCATED AT 250 WORDS)