Connexin 43 expression in human hypertrophied heart due to pressure and volume overload.

Left ventricular hypertrophy (LVH) is due to pressure overload or mechanical stretch and is thought to be associated with remodeling of gap-junctions. We investigated whether the expression of connexin 43 (Cx43) is altered in humans in response to different degrees of LVH. The expression of Cx43 was analyzed by quantitative polymerase chain reaction, Western blot analysis and immunohistochemistry on left ventricular biopsies from patients undergoing aortic or mitral valve replacement. Three groups were analyzed: patients with aortic stenosis with severe LVH (n=9) versus only mild LVH (n=7), and patients with LVH caused by mitral regurgitation (n=5). Cx43 mRNA expression and protein expression were similar in the three groups studied. Furthermore, immunohistochemistry revealed no change in Cx43 distribution. We can conclude that when compared with mild LVH or with LVH due to volume overload, severe LVH due to chronic pressure overload is not accompanied by detectable changes of Cx43 expression or spatial distribution.

Activation of electrical triggers of atrial fibrillation in hyperthyroidism.

CONTEXT: A shortening of the atrial refractory period has been considered as the main mechanism for the increased risk of atrial fibrillation in hyperthyroidism. However, other important factors may be involved. OBJECTIVE: Our objective was to determine the activity of abnormal supraventricular electrical depolarizations in response to elevated thyroid hormones in patients without structural heart disease. PATIENTS AND DESIGN: Twenty-eight patients (25 females, three males, mean age 43+/-11 yr) with newly diagnosed and untreated hyperthyroidism were enrolled in a prospective trial after exclusion of heart disease. Patients were followed up for 16 +/- 6 months and studied at baseline and 6 months after normalization of serum TSH levels. MAIN OUTCOME MEASURES: The incidence of abnormal premature supraventricular depolarizations (SVPD) and the number of episodes of supraventricular tachycardia was defined as primary outcome measurements before the start of the study. In addition, heart rate oscillations (turbulence) after premature depolarizations and heart rate variability were compared at baseline and follow-up. RESULTS: SVPDs decreased from 59 +/- 29 to 21 +/- 8 per 24 h (P = 0.003), very early SVPDs (so called P on T) decreased from 36 +/- 24 to 3 +/- 1 per 24 h (P < 0.0001), respectively, and nonsustained supraventricular tachycardias decreased from 22 +/- 11 to 0.5 +/- 0.2 per 24 h (P = 0.01) after normalization of serum thyrotropin levels. The hyperthyroid phase was characterized by an increased heart rate (93 +/- 14 vs. 79 +/- 8 beats/min, P < 0.0001) and a decreased turbulence slope (3.6 vs. 9.2, P = 0.003), consistent with decreased vagal tone. This was confirmed by a significant decrease of heart rate variability. CONCLUSION: Hyperthyroidism is associated with an increased supraventricular ectopic activity in patients with normal hearts. The activation of these arrhythmogenic foci by elevated thyroid hormones may be an important causal link between hyperthyroidism and atrial fibrillation.

Saline-cooled versus standard radiofrequency catheter ablation for infarct-related ventricular tachycardias.

BACKGROUND: Saline cooling of the electrode during radiofrequency (RF) ablation increases lesion size in animal models. If cooled RF also increases lesion size in human infarcts, it should facilitate the termination of ventricular tachycardia (VT). METHODS AND RESULTS: In 66 patients with VT due to prior infarction, 366 ablation sites, which were classified by entrainment and isolated potentials followed by ablation during VT with either standard RF energy (247 sites) or cooled RF (119 sites), were retrospectively reviewed to compare the efficacy for terminating VT. RF energy was applied at 259 isthmus sites, 62 bystander sites, 28 inner loop sites, and 17 outer loop sites. Compared with standard RF, cooled RF terminated VT more frequently at isthmus sites where an isolated potential was present (89% versus 54%, P=0.003), isthmus sites without an isolated potential (36% versus 21%, P=0.04), and at inner loop sites (60% versus 22%, P=0.04). Termination rates were similarly low for cooled and standard RF at bystander sites (14% versus 9%, P=0.56) and outer loop sites (13% versus 11%, P=0.93). CONCLUSIONS: Greater efficacy of cooled RF for terminating VT is consistent with the production of a larger lesion in human infarctions, which should facilitate successful ablation.

Catheter ablation in patients with multiple and unstable ventricular tachycardias after myocardial infarction: short ablation lines guided by reentry circuit isthmuses and sinus rhythm mapping.

BACKGROUND: Extensive lines of radiofrequency (RF) lesions through infarct (MI) can ablate multiple and unstable ventricular tachycardias (VTs). Methods for guiding ablation that minimize unnecessary RF applications are needed. This study assesses the feasibility of guiding RF line placement by mapping to identify a reentry circuit isthmus. METHODS AND RESULTS: Catheter mapping and ablation were performed in 40 patients (MI location: inferior, 28; anterior, 7; and both, 5) with an electroanatomic mapping system to measure the infarct region and ablation lines. The initial line was placed in the MI region either through a circuit isthmus identified from entrainment mapping or a target identified from pace mapping. A total of 143 VTs (42 stable, 101 unstable) were induced. An isthmus was identified in 25 patients (63%; 5 with only stable VTs, 5 with only unstable VTs, and 15 with both VTs). Inducible VTs were abolished or modified in 100% of patients when the RF line included an isthmus compared with 53% when RF had to be guided by pace mapping (P=0.0002); those with an isthmus identified received shorter ablation lines (4.9+/-2.4 versus 7.4+/-4.3 cm total length, P=0.02). During follow-up, spontaneous VT decreased markedly regardless of whether an isthmus was identified. VT stability and number of morphologies did not influence outcome. CONCLUSIONS: A 4- to 5-cm line of RF lesions abolishes all inducible VTs in more than 50% of patients. Less ablation is required if a reentry circuit isthmus is identified even when multiple and unstable VTs are present.

The N + 1 difference: a new measure for entrainment mapping.

OBJECTIVES: The purpose of this study was to develop and test a new entrainment mapping measurement, the N + 1 difference. BACKGROUND: Entrainment mapping is useful for identifying re-entry circuit sites but is often limited by difficulty in assessing: 1) changes in QRS complexes or P-waves that indicate fusion, and 2) the postpacing interval (PPI) recorded directly from the stimulation site. METHODS: In computer simulations of re-entry circuits, the interval from a stimulus that reset tachycardia to a timing reference during the second beat after the stimulus was compared with the timing of local activation at the site during tachycardia to define an interval designated the N + 1 difference. The N + 1 difference was compared with the PPI-tachycardia cycle length (TCL) difference in simulations and at 65 sites in 10 consecutive patients with ventricular tachycardia (VT) after myocardial infarction and at 45 sites in 10 consecutive patients with atrial flutter. RESULTS: In simulations, the N + 1 difference was equal to the PPI-TCL difference. During mapping of VT and atrial flutter, the N + 1 difference correlated well with the PPI-TCL difference (r > or = 0.91, p < 0.0001), identifying re-entry circuit sites with sensitivity of > or = 86% and specificity of > or = 90%. Accuracy was similar using either the surface electrocardiogram or an intracardiac electrogram (Eg) as the timing reference. CONCLUSIONS: The N + 1 difference allows entrainment mapping to be used to identify re-entry circuit sites when it is difficult to evaluate Egs at the mapping site or fusion in the surface electrocardiogram.

Multi atrial maco-re-entry circuits in adults with repaired congenital heart disease: entrainment mapping combined with three-dimensional electroanatomic mapping.

OBJECTIVES: We sought to characterize re-entry circuits causing intra-atrial re-entrant tachycardias (IARTs) late after the repair of congenital heart disease (CHD) and to define an approach for mapping and ablation, combining anatomy, activation sequence data and entrainment mapping. BACKGROUND: The development of IARTs after repair of CHD is difficult to manage and ablate due to complex anatomy, variable re-entry circuit locations and the frequent co-existence of multiple circuits. METHODS: Forty-seven re-entry circuits were mapped in 20 patients with recurrent IARTs refractory to medical therapy. In the first group (n = 7), ablation was guided by entrainment mapping. In the second group (n = 13), entrainment mapping was combined with a three-dimensional electroanatomic mapping system to precisely localize the scar-related boundaries of re-entry circuits and to reconstruct the activation pattern. RESULTS: Three types of right atrial macro-re-entrant circuits were identified: those related to a lateral right atriotomy scar (19 IARTs), the Eustachian isthmus (18 IARTs) or an atrial septal patch (8 IARTs). Two IARTs originated in the left atrium. Radiofrequency (RF) lesions were applied to transect critical isthmuses in the right atrium. In three patients, the combined mapping approach identified a narrow isthmuses in the lateral atrium, where the first RF lesion interrupted the circuit; the remaining circuits were interrupted by a series of RF lesions across a broader path. Overall, 38 (81%) of 47 IARTs were successfully ablated. During follow-up ranging from 3 to 46 months, 16 (80%) of 20 patients remained free of recurrence. Success was similar in the first 7 (group 1) and last 13 patients (group 2), but fluoroscopy time decreased from 60 +/- 30 to 24 +/- 9 min/procedure, probably related to the increasing experience and ability to monitor catheter position non-fluoroscopically. CONCLUSIONS: Entrainment mapping combined with three-dimensional electroanatomic mapping allows delineation of complex re-entry circuits and critical isthmuses as targets for ablation. Radiofrequency catheter ablation is a reasonable option for treatment of IARTs related to repair of CHD.

Characterization of the angiotensin II receptor antagonist TCV-116 in healthy volunteers.

The purpose of this study was to assess the inhibitory effect of TCV-116, an orally active angiotensin II (Ang II) antagonist, on the pressor action of exogenous Ang II and to determine the compensatory rise in plasma renin activity and Ang II levels. Twenty-three male volunteers were treated for 8 days in a double-blind fashion with either placebo or TCV-116 (1, 2, or 4 mg PO daily) and challenged on the first, fourth, and eighth days with repeated bolus injections of Ang II. An additional 4 subjects received 8 mg PO daily in a single-blind fashion. The inhibitory effect on the systolic blood pressure response to Ang II was long lasting and clearly dose related. Six hours after 4 mg TCV-116, the systolic blood pressure response to a given dose of Ang II was reduced to 40 +/- 4% and 35 +/- 8% of baseline value on days 1 and 8, respectively. TCV-116 induced a dose-related increase in plasma renin activity and Ang II levels that was more pronounced on the eighth than on the first day of drug administration. Despite this compensatory mechanism, the relation between the time-integrated systolic blood pressure response to Ang II and the time-integrated CV-11974 levels, the active metabolite of TCV-116, was not different between days 1 and 8. In conclusion, TCV-116 appears to be a well-tolerated, orally active, potent, and long-lasting antagonist of Ang II in men.

Long-term nitric oxide synthase inhibition and distensibility of carotid artery in intact rats.

The goal of the present study was to evaluate the effect of long-term nitric oxide synthase inhibition by NG-nitro-L-arginine-methyl ester (L-NAME) on the morphology and viscoelastic properties of the carotid arteries in rats. Twelve-week-old Wistar-Kyoto rats were treated for 6 weeks with either the nitric oxide synthase inhibitor L-NAME (0.4 g/L in drinking water; L-NAME rats, n = 13) or tap water (control rats, n = 13). Age-matched spontaneously hypertensive rats (SHR, n = 14) received tap water for the same period. The internal diameter of the common carotid artery was measured continuously with an echo-tracking device with the rats under anesthesia with halothane. Intra-arterial pressure was monitored on the contralateral side. L-NAME rats exhibited arterial pressures similar to those of SHR. The distensibility pressure-curve determined in L-NAME rats was a direct continuation of that obtained in control rats. In contrast the distensibility in SHR was increased (P < .01, SHR versus L-NAME rats). Carotid artery cross-sectional area and left ventricular weight index were increased similarly in SHR and L-NAME rats compared with control rats. Thus the hypertension caused by long-term nitric oxide synthesis inhibition was not associated with the increased arterial distensibility observed in SHR despite similar blood pressure elevations, similar arterial hypertrophy, and consequently similar wall stress. This suggests a role for nitric oxide in regulating the mechanical behavior of arteries exposed to high blood pressure.

Chronic nitric oxide synthase inhibition and carotid artery distensibility in renal hypertensive rats.

The goal of the present study was to examine the viscoelastic properties of the carotid artery in genetically identical rats exposed to similar levels of blood pressure sustained by different mechanisms. Eight-week old male Wistar rats were examined 2 weeks after renal artery clipping (two-kidney, one clip [2K1C] Goldblatt rats, n = 53) or sham operation (n = 49). One half of the 2K1C and sham rats received the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 1.48 mmol/L) in their drinking water for 2 weeks after the surgical procedure. Mean blood pressure increased significantly in the 2K1C-water (182 mm Hg), 2K1C-L-NAME (197 mm Hg), and sham-L-NAME (170 mm Hg) rats compared with the sham-water rats (127 mm Hg). Plasma renin activity was not altered by L-NAME but significantly enhanced after renal artery clipping. A significant and similar increase in the cross-sectional area of the carotid artery was observed in L-NAME and vehicle-treated 2K1C rats. L-NAME per se did not modify cross-sectional area in the sham rats. There was a significant upward shift of the distensibility-pressure curve in the L-NAME- and vehicle-treated 2K1C rats compared with the sham-L-NAME rats. L-NAME treatment did not alter the distensibility-pressure curve in the 2K1C rats. These results demonstrate that the mechanisms responsible for artery wall hypertrophy in renovascular hypertension are accompanied by an increase in arterial distensibility that is not dependent on the synthesis of nitric oxide.

Increased central body fat deposition precedes a significant rise in resting blood pressure in male offspring of essential hypertensive parents: a 5 year follow-up study.

OBJECTIVES: As long as offspring of essential hypertensive parents (OHyp) are lean, their blood pressure usually remains within normal limits. The mechanism(s) transforming this 'genetically dysregulated normotension' into hypertension are unclear. We hypothesized that OHyp are not only genetically prone to develop hypertension, but may also have a particular propensity to accumulate central body fat. DESIGN: A 5-year follow-up cohort study. SETTING: University Hospital in Switzerland. PARTICIPANTS: Seventeen young (25 +/- 1 years, mean +/- SD), lean healthy normotensive male OHyp and 17 age- and sex-matched offspring of normotensive parents (ONorm) paired for baseline blood pressure with the OHyp. MAIN OUTCOME MEASURES: Resting and exercise blood pressure, body weight, body mass index (BMI) and waist-to-hip ratio were assessed at baseline and after 5 years. RESULTS: At baseline, body weight, BMI, waist-to-hip ratio and blood pressure did not differ significantly between OHyp and ONorm. At follow-up, body weight was increased in both groups (from 73.9 +/- 6.0 to 77.7 +/- 8.1 kg in OHyp, P = 0.008, and from 71.5 +/- 6.9 to 73.5 +/- 6.6 kg in ONorm, P = 0.03). BMI followed a similar pattern. In contrast, waist-to-hip ratio increased in OHyp (from 0.84 +/- 0.03 to 0.87 +/- 0.03, P = 0.012), but not in ONorm (from 0.84 +/- 0.03 to 0.84 +/- 0.04, P = 0.79) and was therefore higher in OHyp at follow-up (P = 0.011, OHyp versus ONorm). Peak systolic blood pressure during dynamic exercise also rose at 5 years in the OHyp (from 182 +/- 10 to 214 +/- 17 mmHg, P = 0.0001) while resting systolic blood pressure only tended to do so (from 121 +/- 7 to 128 +/- 12 mmHg, P = 0.07). In ONorm, resting and peak dynamic exercise systolic blood pressure remained unchanged (119 +/- 11 versus 121 +/- 9 mmHg, baseline versus follow-up, P = 0.40, and 186 +/- 12 versus 196 +/- 22 mmHg, P = 0.10, respectively). Thus, systolic peak exercise blood pressure was significantly (P = 0.014) elevated at follow-up in OHyp compared to ONorm, while resting systolic blood pressure only tended (P = 0.06) to do so. CONCLUSIONS: Initially lean normotensive OHyp have a disparate long-term course of central body fat as compared to ONorm. Thus, OHyp are not only genetically prone to develop hypertension, but they also have a particular propensity to accumulate central body fat, even before a distinct rise in resting blood pressure occurs. The exaggerated blood pressure response to exercise observed at follow-up in the OHyp represents another marker that confers them a greater risk of developing future hypertension.

Endothelial function of the mesenteric arteriole and mechanical behaviour of the carotid artery in rats with insulin resistance and hypercholesterolaemia.

OBJECTIVE: To examine whether insulin resistance and hypercholesterolaemia in obese Zucker rats are associated with a modification of the mechanical behaviour of a conductance (carotid) artery and with an altered endothelium-dependent response to acetylcholine of a small resistance (mesenteric) artery. DESIGN: Male obese Zucker rats, 6-8 months old, were compared with age-matched lean heterozygous and control Zucker rats. METHODS: The mechanical behaviour of the carotid artery was examined in anaesthetized rats by simultaneously monitoring the internal diameter with an A-mode ultrasonic echo-tracking device and the intra-arterial pressure with a computerized data-acquisition system. Furthermore, histometric measurements of the carotid artery were carried out after death. The response to acetylcholine was examined in vitro with a Mulvany dual myograph on precontracted isolated segments of the third-generation mesenteric artery. RESULTS: Obese Zucker rats exhibited high plasma insulin and cholesterol levels. Blood pressure was the same in the obese and control animals. There was no hypertrophy or change in the mechanical behaviour of the carotid arterial wall. Heart weight was slightly higher in the obese rats than in the controls, but smaller in relation to body weight. The relaxation to acetylcholine was significantly attenuated in isolated small mesenteric arteries obtained from the obese strain. CONCLUSION: Hyperinsulinaemia and hypercholesterolaemia in obese Zucker rats are associated with an abnormal response to acetylcholine in the mesenteric arterioles. This metabolic state does not, however, alter the mechanical behaviour or the geometry of the carotid artery.

Therapeutic strategy with total coronary artery occlusions.

Patients with a coronary artery occlusion are more likely to be revascularized surgically or to be treated conservatively than patients without occlusion. A higher prevalence of patients with multivessel coronary artery disease (CAD), particularly with 3-vessel CAD, in the group with occlusion may account in part for this difference in management.

Evidence rather than costs must guide use of the implantable cardioverter defibrillator.

Randomized controlled trials have shown superior survival rates with implantable cardioverter defibrillators (ICDs) compared with antiarrhythmic drugs in survivors of cardiac arrest and life-threatening ventricular tachyarrhythmias, as well as in high-risk patients with ischemic heart disease and inducible ventricular tachycardia (VT). Current defibrillators are small and implanted with techniques similar to standard pacemakers. They provide high-energy shocks for ventricular fibrillation (VF) and rapid VT, antitachycardia pacing for monomorphic VT, and antibradycardia pacing. Limited evidence suggests that ICD therapy is cost-effective when compared with other widely accepted treatments. The use of ICDs is likely to continue to expand in the future. Ongoing clinical trials will define further prophylactic indications of the ICD and clarify its cost-effectiveness ratio in different clinical settings.

Low-dose thrombolysis for thrombosed prosthetic heart valve.

This report describes two cases of successful fibrinolysis of thrombosed tricuspid and mitral valve prostheses (Carbomedics; Austin, Texas) with low-dose urokinase therapy corresponding to only one third of the dose usually recommended.

Diastolic dysfunction precedes myocardial hypertrophy in the development of hypertension.

BACKGROUND: Left ventricular (LV) hypertrophy and impaired diastolic function may occur early in systemic hypertension, but longitudinal studies are missing. METHODS: We performed an echocardiographic follow-up study in young initially normotensive male offspring of hypertensive (OHyp) (n = 25) and normotensive (ONorm) (n = 17) parents. Blood pressure (BP), LV mass, and mitral inflow were determined at baseline and after 5 years. Pulmonary vein flow pattern assessment and septal myocardial Doppler imaging were additionally performed at follow-up. RESULTS: At follow-up, BP was not significantly different between the two groups (128 +/- 11/84 +/- 10 v 123 +/- 11/81 +/- 5 mm Hg, OHyp v ONorm) but five OHyp had developed mild hypertension. LV mass index remained unchanged and was not different between the two groups at follow-up (92 +/- 17 v 92 +/- 14 g/m2). Diastolic echocardiographic properties were similar at baseline, but, at follow-up, the following differences were found: mitral E deceleration time (209 +/- 32 v 185 +/- 36 msec, P < .05) and pulmonary vein reverse A wave duration (121 +/- 15 v 107 +/- 12 msec, P < .05) were prolonged in the OHyp as compared to the ONorm. Compared to the normotensive subjects, the five OHyp who developed hypertension had more pronounced alterations of LV diastolic function, that is, significantly higher mitral A (54 +/- 7 v 44 +/- 9 cm/sec, hypertensives v normotensives, P < .05), lower E/A ratio (1.31 +/- 0.14 v 1.82 +/- 0.48, P < .05), increased systolic-to-diastolic pulmonary vein flow ratio (1.11 +/- 0.3 v 0.81 +/- 0.16, P < .005), longer myocardial isovolumic relaxation time (57 +/- 7 v 46 +/- 12 msec, P < .05) as well as smaller myocardial E (10 +/- 1 v 13 +/- 2 cm/sec, P < .05) and E/A ratio (1.29 +/- 0.25 v 1.78 +/- 0.43, P < .05), despite similar LV mass (91 +/- 16 v 93 +/- 18 g/m2). CONCLUSIONS: Over a 5-year follow-up, initially lean, normotensive, young men with a moderate genetic risk for hypertension, developed Doppler echocardiographic alterations of LV diastolic function compared to matched offspring of normotensive parents. These alterations were more pronounced in the OHyp who developed mild hypertension and occurred without a distinct rise in LV mass.

Relationship between the prescriber's instructions and compliance with antibiotherapy in outpatients treated for an acute infectious disease.

Antibiotics are frequently prescribed in everyday practice for the management of acute microbial infections. The present study was designed to assess the relationship between the prescriber's instructions and the patient's adherence to a prescribed schedule of twice-daily doses of antibiotic for at least 5 days to treat an infectious disease. The trial was conducted by ten practicing physicians on ambulatory patients. Compliance with the antibiotic regimen was evaluated using a microelectronic device, the Medication Event Monitoring System (MEMS). Seventy patients were prescribed an antibiotic in twice-daily doses for 5 to 14 days (mean = 8). Data were available for analysis from 68 of them, aged 18 to 84 years (mean = 44). The "taking compliance" for the whole story group, which corresponded to the ratio of the number of times the bottle was opened and the total number of doses prescribed during the monitoring period, was nearly perfect at 99.6%. However, only 32.6% of the medications was taken within 1 hour before or after the 12-hour interval expected to be optimal for a twice-daily regimen. It therefore seems highly desirable that physicians give more detailed recommendations to their patients regarding the drug regimens they prescribe.

DDD-pacing-induced cardiomyopathy following AV node ablation for persistent atrial tachycardia.

Ventricular rate control by catheter ablation of the AV node and pacing in patients with persistent atrial tachycardia has been reported to improve left ventricular function. However, this approach requires careful selection of the pacing mode. We report a patient who underwent AV node ablation for persistent multiple atrial tachycardias, and who then had a non-mode-switching pacemaker implanted. Because of an inappropriately programmed relatively high upper rate limit, the patient developed left ventricular dysfunction after 6 years. This resolved after programming the pacemaker to VVI at 70 bpm.

[Ventricular tachycardia--etiology, mechanisms and therapy]. / Kammertachykardien--Atiologie, Mechanismen, Therapie.

Prevention and therapy of cardiovascular diseases have undergone enormous changes over the last decades. However, ventricular tachycardias (VT) still pose a major problem in a number of cardiac patients. Analysis of the etiology and mechanism of the tachycardia is of paramount importance for initiation of specific therapies. The morphology of VTs on the surface ECG can be either polymorphic or monomorphic. Polymorphic VTs have a constantly changing QRS-morphology due to the variable ventricular activation, without specific origin. This kind of VT is mainly caused by an acute, often reversible condition, such as ischemia or QT-prolongation. These VTs are potentially malignant, they cannot be treated by catheter ablation. In contrast, monomorphic VTs have a constant QRS-morphology, indicative of repetitive ventricular depolarisation in the same activation sequence. This kind of VT is either caused by focal abnormal activity (triggered activity, automaticity, micro-reentry) or by an arrhythmogenic substrate (macro-reentry). Focal idiopathic VTs usually have a benign prognosis and catheter ablation is potentially curative. The majority of ventricular arrhythmias, however, are substrate-related reentry tachycardias, most commonly based on an infarct scar Therapy of first choice for these patients is the treatment with an implantable Cardioverter/Defibrillator (ICD). Catheter ablation is indicated in case of drug refractory recurrent VTs triggering repeated ICD therapies. The different therapeutic strategies are not alternative but complementary options in many patients.

Angiotensin II antagonists DuP 753 and TCV 116.

BACKGROUND: Acute blockade of the renin-angiotensin system with the parenterally active angiotensin II antagonist saralasin has been shown to effectively lower blood pressure in a large fraction of patients with essential hypertension and to improve haemodynamics in some patients with congestive heart failure. It is now possible to chronically antagonize angiotensin II at its receptor using non-peptide angiotensin II inhibitors such as losartan (DuP 753/MK-954) or TCV 116. EFFECT OF NON-PEPTIDE ANGIOTENSIN II ANTAGONISTS: When administered by mouth, DuP 753 and TCV 116 induce dose-dependent inhibition of the pressor response to exogenous angiotensin II. This effect is closely related to circulating levels of the corresponding active metabolites E3174 and CV11974. Preliminary studies performed in hypertensive patients suggest that losartan lowers blood pressure to an equivalent extent to an angiotensin converting enzyme (ACE) inhibitor. CONCLUSIONS: Further investigation is required to show whether these new angiotensin II antagonists compounds compare favourably with ACE inhibitors.