Multiple injuries in peacetime and wartime estimate of severity of injury by the Injury Severity Score and Polytraumaschlüssel

The aim of this study was to evaluate the efficacy and tolerability of valsartan, a new angiotensin II receptor antagonist, versus atenolol in the treatment of severe primary hypertension. A total of 103 adult out-patients were randomised to receive either valsartan 160 mg or atenolol 100 mg once daily for 6 weeks. If necessary, additional blood pressure (BP) control could be provided as add-on therapy. Both valsartan and atenolol decreased mean sitting diastolic BP (DBP) and mean sitting systolic BP (SBP): least squares mean change from baseline in DBP; valsartan, -20.0 mm Hg; atenolol, -20.4 mm Hg: in SBP; valsartan, -30.0 mm Hg; atenolol, -25.5 mm Hg. There was no statistically significant difference between the treatment groups. Add-on hydrochlorothiazide (HCTZ) 25 mg was required by 97.2% of patients receiving atenolol and 83.6% of patients receiving valsartan; additional verapamil SR 240 mg was also required by 58.3% of patients receiving atenolol and 64.2% receiving valsartan. Valsartan was well tolerated, with a comparable incidence of treatment-related adverse experiences in both groups. In conclusion valsartan 160 mg is as well tolerated and effective as atenolol 100 mg in lowering BP in severely hypertensive patients.     

Regression of left ventricular hypertrophy in hypertensive patients after 1 year of treatment with rilmenidine: a double-blind, randomized, controlled (versus nifedipine) study

OBJECTIVE: To assess the effect of 1-year treatment with rilmenidine, an oxazoline compound that exerts its antihypertensive effects through binding to imidazoline receptors in the brainstem, on left ventricular hypertrophy (LVH) secondary to essential, mild-to-moderate hypertension [supine diastolic blood pressure (DBP)95-115 mmHg]. METHODS: We performed a double-blind, randomized, controlled (versus slow-release nifedipine) trial. Adjustment of treatment took place every month (M) between inclusion (MO) and an evaluation after 6 months (M6), then during M9 and after 1 year (M12) to achieve supine DBP values < or = 90 mmHg. Patients were dropped from our study if they had DBP> 95mmHg during two consecutive visits or DBP>115 mmHg on one occasion. The daily dosage of rilmenidine was 1 mg, and could be increased to 2 mg/day. The daily dosage of slow-release nifedipine was started from the beginning at the maximum dosage of 40 mg/day, so that there was no true adjustment of treatment despite the allocation of patients to a different unit in the case of DBP> 95 mmHg. The primary criterion was the change in left ventricular mass index (LVMI, g/m2), assessed by echocardiography, between MO and M12 for patients who completed the trial. RESULTS: After a 1-month placebo run-in period, 76 patients were selected and 73 were included (35 treated with rilmenidine and 38 treated with nifedipine). Fifteen patients withdrew from the study and two completed the study with a major deviation from protocol, leaving 56 patients (24 treated with rilmenidine and 32 treated with nifedipine) for a per-protocol analysis. Baseline demographic characteristics and history of arterial hypertension for the rilmenidine and nifedipine groups were similar, for included patients and for those taken into account for the per-protocol analysis. Between MO and M12, DBP in members of the per-protocol population was adequately controlled for those in the rilmenidine group (102.7+/-4.6 versus 88.5+/-7.1 mmHg, respectively) and for those in the nifedipine group (102.7+/-5.1 versus 85.6+/-79 mmHg, respectively). During MO, LVMI of patients in the rilmenidine group (176.9+/-41.3 g/m2) was slightly higher than that of patients in the nifedipine group (172.6+/-35.1 g/m2). During M12, LVMI was observed to have decreased both for patients in the rilmenidine group (to 154.8+/-40.2 g/m2, a decrease of 22.1+/-23.3 g/m2, P< 0.001) and for those in the nifedipine group (to 145.6+/-36.4 g/m2, a decrease of 26.9+/-29.5 g/m2, P< 0.001) but the difference between these two groups was not significant (P= 0.5). CONCLUSION: One-year treatment with a daily dosage of 1 or 2 mg rilmenidine achieves a significant reduction of left ventricular mass, which is not statistically different than that occurring with a daily dosage of 40 mg of slow-release nifedipine.     

Angiotensin-converting enzyme inhibition prolongs survival and modifies the transition to heart failure in rats with pressure overload hypertrophy due to ascending aortic stenosis

BACKGROUND: We tested the hypotheses that long-term administration of the angiotensin-converting enzyme (ACE) inhibitor fosinopril will regress hypertrophy, modify the transition to heart failure, and prolong survival in rats with chronic left ventricular (LV) pressure overload due to ascending aortic stenosis. METHODS AND RESULTS: Aortic stenosis was created in weanling male Wistar rats by a stainless steel clip placed on the ascending aorta. Age-matched control animals underwent a sham operation (Sham group, n = 57). Six weeks after surgery, rats with aortic stenosis were randomized to receive either oral fosinopril 50 mg.kg-1.d-1 (Fos/LVH group, n = 38) or no drug (LVH group, n = 36) for 15 weeks. Pilot studies confirmed that this dosage produced significant inhibition of LV tissue ACE in vivo. Animals were monitored daily, and survival during the 15-week treatment period was assessed by actuarial analysis. At 15 weeks, in vivo LV systolic and diastolic pressures and heart rate were measured. To assess contractile function, the force-calcium relation was evaluated by use of the isovolumic buffer-perfused, balloon-in-LV heart preparation at comparable coronary flow rates per gram LV weight. Quantitative morphometry was performed. Mortality during the 15-week trial was significantly less in the Fos/LVH group than in the LVH group (3% versus 31%, P < .005). No deaths occurred in the Sham group. In vivo LV systolic pressure was similar between Fos/LVH and LVH hearts (223 +/- 10 versus 232 +/- 9 mm Hg) and significantly higher than the Sham group (99 +/- 3 mm Hg, P < .05). In vivo LV diastolic pressure was significantly lower in Fos/LVH hearts than in LVH hearts (10 +/- 2 versus 15 +/- 2 mm Hg), and both were significantly higher than in the Sham group (5 +/- 1 mm Hg, P < .05). Heart rate was similar among all groups. Despite equivalent elevation of LV systolic pressure, fosinopril resulted in regression of myocyte hypertrophy in Fos/LVH versus LVH (myocyte cell width, 14.8 +/- 0.5 versus 20.8 +/- 2.2 microns, P < .05) to normal levels (Sham, 16.3 +/- 0.9 microns). Quantitative morphometry demonstrated that the regression of LV myocyte hypertrophy in the Fos/LVH group was associated with a relative increase in the fractional volume of fibrillar collagen and noncollagen interstitium. In the isolated heart experiments, LV systolic developed pressure relative to perfusate [Ca2+] was significantly higher in Fos/LVH hearts than in LVH hearts. The improvement in systolic function was not related to any difference in myocardial high-energy phosphate levels, since LV ATP and creatine phosphate levels were similar in Fos/LVH and LVH hearts. CONCLUSIONS: In rats with ascending aortic stenosis, chronic ACE inhibition with fosinopril improved survival, decreased the extent of LV hypertrophy, and improved cardiac function despite persistent elevation of LV systolic pressure. The favorable effects of fosinopril may be related in part to inhibition of the effects of cardiac ACE on myocyte hypertrophy rather than to systemic hemodynamic mechanisms.     

Converting-enzyme inhibitor versus calcium antagonist in cyclosporine-treated renal transplants

The influence of antihypertensive treatment on the long-term evolution of arterial pressure and renal function was studied in a prospective controlled trial conducted in renal transplant recipients treated by cyclosporine. Within six months after transplantation, patients were randomly allocated to treatment by the angiotensin-converting enzyme inhibitor, lisinopril (ACEI, alone or associated with frusemide; N = 14), or the calcium antagonist, nifedipine (CA, alone or associated with atenolol; N = 11). Glomerular filtration rate (TcDTPA clearance) and effective renal plasma flow (hippuran clearance) as well as 24-hour urinary excretion of electrolytes and albumin were estimated at about 1 and 2.5 years of follow-up. Before initiation of antihypertensive therapy, the two groups were similar with regards to mean arterial pressure (119 +/- 2 vs. 120 +/- 4 mm Hg), effective renal plasma flow (285 +/- 26 vs. 248 +/- 33 ml/min/1.73 m2) and glomerular filtration rate (59 +/- 4 vs. 61 +/- 8 ml/min/1.73 m2 in the ACEI and CA groups, respectively). Both ACEI and CA treatments were associated with no change in renal function, a similar change in mean arterial pressure (ACEI -18 +/- 3; CA -13 +/- 5 mm Hg) and identical trough blood levels of cyclosporine. Urinary albumin excretion did not change significantly in any groups. Of interest, only in the ACEI group did filtration fraction significantly decrease (from 0.22 +/- 0.01% to 0.19 +/- 0.01% at final studies). These results indicate that in cyclosporine-treated transplant recipients, a satisfactory control of hypertension is obtained by chronic ACEI, which is as effective on arterial pressure as a combination of CA and atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Exercise echocardiography in postmenopausal hormone users with mild systemic hypertension

Rest and exercise echocardiography (at dynamic and isometric exercise) were performed in 30 postmenopausal women (aged 54 +/- 4 years) with borderline to mild hypertension. They were then divided into 2 groups: 17 women who started oral hormone replacement therapy (0.625 mg/day conjugated estrogens or 2 mg/day estradiol) and a control group of 13 nonusers. After 6 to 9 months, a second echocardiography was performed in 26 women (4 withdrew). There were only a few changes in values obtained in the 12 controls at the end of follow-up compared with baseline. Primarily, these changes included a slight decrease in systolic blood pressure at rest and on exercise. Several significant morphologic and hemodynamic alterations appeared in 14 hormone users. Left ventricular cavity dimensions and mass became smaller: mean end-diastolic diameter decreased from 45.9 +/- 3 mm at baseline to 44.4 +/- 3 mm at study termination (p = 0.007). The corresponding values for end-systolic diameter were 25.8 +/- 4 mm and 23.9 +/- 4 mm (p = 0.006); for left atrium diameter, it was 34.5 +/- 4 mm and 32.5 +/- 4 mm (p = 0.001); for left ventricular wall width, it was 19.9 +/- 2 mm and 19.3 +/- 2 mm (p = 0.02); for left ventricular mass, it was 197 +/- 28 g and 179 +/- 32 g (p = 0.006). The resting aortic blood flow velocity and acceleration increased: 119 +/- 18 cm/s before therapy versus 129 +/- 23 cm/s while on hormone substitution (p = 0.04), and 13.6 +/- 3 m/s2 versus 16.5 +/- 4 m/s2 (p = 0.008), respectively. Mean rest to peak exercise systolic blood pressure difference became smaller after hormones: 39 +/- 19 mm Hg versus 28 +/- 13 mm Hg (p = 0.03) during dynamic exercise, and 43 +/- 22 mm Hg versus 25 +/- 13 mm Hg (p = 0.004) during isometric exercise. The above data probably indicate that with hormone replacement therapy, there is an improvement in cardiac function both at rest and during exercise.     

Relation between smoking in reproductive-age women and disorders in reproduction]

BACKGROUND: Genotype-phenotype correlation studies consistently have shown that mutations are prognosticators in patients with hypertrophic cardiomyopathy (HCM). While Arginine (Arg)719Tryptophan (Trp) mutation in the beta-myosin heavy chain (MyHC) gene is associated with a high incidence of sudden cardiac death (SCD), the Valine (Val)606Methionine (Met) mutation in the same gene is associated with a near normal life expectancy. It is unknown whether the prognostic significance of mutations is reflective or independent of their hypertrophic expressivity. We determined the indices of left ventricular hypertrophy (LVH) in patients with beta-MyHC mutations associated with high, moderate, and low incidence of SCD. METHODS: Mutations were identified by chemical cleavage (Val606Met and Glu930Lys) or polymerase chain reaction (PCR) and MspI restriction mapping (Arg719Gln). Left ventricular mass was determined using 2-D echocardiograms, and was indexed (LVMI) for body surface area. The extent of LVH was determined using a semiquantitative point score method that takes into account the extent of involvement of the septum, apex, and lateral wall of the left ventricle. RESULTS: The Arg719Trp, Glu930Lys, and Val606Met mutations were associated with high (14/29, 48%), moderate (3/16, 19%), and low (1/11, 9%) risk of premature death, respectively. Concordant with the incidence of premature death, the LVMI was the greatest (148.0 +/- 37 g/m2) in patients with the Arg719Trp mutation, the smallest (111.7 +/- 19 g/m2) in patients with the Val606Met mutation, and in between (127.1 +/- 15 g/m2) in patients with the Glu930Lys mutation (p = 0.023). Similarly, the LVH score was also greater in patients with the Arg719Trp mutation than in those with the Val606Met mutation (5.92 +/- 2.3 vs 3.2 +/- 1.5, respectively, p = 0.015). A trend toward a greater septal thickness was also present in patients with the Arg719Trp compared to the Val606Met mutations (20.7 +/- 6.8 mm vs 16.2 +/- 2.6 mm, p = 0.077). CONCLUSION: Hypertrophic cardiomyopathy patients with the malignant Arg719Trp mutation have more extensive hypertrophy than those with the benign Leu606Val mutation. This findings suggests that the prognostic significance of beta-MyHC mutations is reflective of their hypertrophic expressivity.     

Characteristics of 9194 patients with left ventricular hypertrophy: the LIFE study. Losartan Intervention For Endpoint Reduction in Hypertension

-Losartan was the first available orally administered selective antagonist of the angiotensin II type 1 receptor developed for the treatment of hypertension. The Losartan Intervention For Endpoint (LIFE) Reduction in Hypertension Study is a double-blind, prospective, parallel group study designed to compare the effects of losartan with those of the beta-blocker atenolol on the reduction of cardiovascular morbidity and mortality. Patients with essential hypertension, aged between 55 and 80 years, and ECG-documented left ventricular hypertrophy (LVH) were included. Altogether, 9223 patients in Scandinavia, the United Kingdom, and the United States were randomized from June 1995 through April 1997, and 9194 remain after exclusion of a study center at which irregularities were discovered. This population of hypertensives (mean systolic/diastolic blood pressure, 174.4/97.8 mm Hg) with LVH comprises women (54.1%) and men, mostly retired from active work (mean age, 66.9 years), with a high prevalence of overweight (mean body mass index, 28.0 kg/m2), diabetes mellitus (12.3%), lipid disorders (18.0%), and symptoms or signs of coronary heart disease (15.1%). There were fewer current smokers (<17%) than in the general population, and approximately 7% were nonwhite. Almost 30% of participants had been untreated for at least 6 months when screened for the study. Only 1557 persons who entered the placebo run-in period of 14 days were excluded, predominantly because of sitting blood pressures above or below the predetermined range of 160-200/95-115 mm Hg and ECG-LVH criteria not met. By application of simple 12-lead ECG criteria for LVH (Cornell voltage QRS duration product formula plus Sokolow-Lyon voltage read by a core laboratory), hypertensive patients with LVH with an average 5-year coronary heart disease risk of 22.3% according to the Framingham score were identified. This population is now being treated (goal, <140/90 mm Hg) in adherence with the protocol for at least 4 years after final enrollment (ie, through April 2001) and until at least 1040 patients suffer myocardial infarction, stroke, or cardiovascular death.     

Metrological analysis of measuring systems in testing an anticipatory reaction to the position of a moving object

This study compared the effects of angiotensin converting enzyme (ACE) inhibitors captopril versus enalapril on left ventricular (LV) muscle mass and LV systolic and diastolic function in 58 patients with primary glomerulonephritis and moderate chronic renal failure. The design was a 6-8 week titration phase and 6-month maintenance phase. Mean myocardial mass calculated by M-mode echocardiography in the captopril group was 153 +/- 26 g/m2 before, and 130 +/- 14 g/m2 after 6 months of treatment, in enalapril group 147 +/- 22 g/m2 before, and 126 +/- 23 g/m2 after 6 months of treatment (p < 0.05). LV ejection fraction, early and late transmitral flow velocities and early to late LV inflow velocities ratio were not significantly affected by both ACE inhibitors.     

Diltiazem slow-release and left-ventricular hypertrophy: a volumetric approach of left ventricular mass using magnetic resonance imaging

AIMS: This study was designed to assess the changes in left ventricular mass (LVM) in hypertensive patients with left ventricular hypertrophy under drug therapy with once-daily slow-release diltiazem. Magnetic resonance imaging (MRI) was used for this purpose because of its higher reproducibility than M-mode or two-dimensional echocardiography. METHODS: Patients suffering from essential hypertension were included if their baseline LVM index (LVMI) was > or = 105 g/m2 in male or > or = 85 g/m2 in female patients, ie, equal or higher to the median values observed in hypertensive patients in our institution. MRI consisted in a true short-axis, electrocardiogram (ECG) gated spin-echo slice acquisition at baseline, after 3 and 6 months of therapy (M0, M3, and M6). Data were stored on magnetic tapes and read subsequently under blind conditions and the control of an external auditor. RESULTS: Thirty-five patients were included. Of these, 14 patients (40%) were not previously treated. Inter- and intra-observer variability for LVMI measurement were 5.6 +/- 4.3% and 2.1 +/- 3.0%, respectively. Mean baseline LVMI was 110 +/- 16 g/m2 in male and 96 +/- 16 g/m2 in female patients. It decreased by 3.6% at M3 (P = 0.05) and by 6.0% at M6 (P = 0.02). A trend towards a greater LVMI reduction was observed in previously untreated patients. CONCLUSION: This study confirms that MRI is a reproducible technique for the measurement of LVM. It demonstrates a significant reduction in LVMI as early as the 3rd month of therapy in hypertensive patients treated with once-daily sustained release (SR) diltiazem, although baseline LVMI in the majority of participating patients was only moderately increased.     

Left ventricular concentric remodelling and carotid structural changes in essential hypertension

AIM: Left ventricular concentric remodelling defines a modified left ventricular geometry in the presence of a normal left ventricular mass; it is an early and frequent adaptation in arterial hypertension. The present study was designed to evaluate the extent of carotid structural changes in essential hypertensives with left ventricular remodelling. PATIENTS AND METHODS: Two groups of hypertensive patients, who had never previously received anti-hypertensive treatment, 14 with left ventricular concentric remodelling (group I, relative wall thickness 0.48 +/- 0.02) and 48 with normal left ventricular geometry (group II, relative wall thickness 0.37 +/- 0.04) underwent clinical and laboratory examination, echocardiography, carotid artery ultrasonography and 24 h ambulatory blood pressure monitoring (ABPM). The left ventricular dimensions and mass were obtained according to the Penn convention. The intima-media thickness (IMT) of the posterior wall of both common carotid arteries was measured 5, 10 and 20 mm caudally to the bulb and the average value was used for analysis. RESULTS: In both groups age (group I 44 +/- 9 years; group II 40 +/- 9 years), body surface area (group I 1.85 +/- 0.2 m2; group II 1.80 +/- 0.2 m2), duration of hypertension (group I 4.4 +/- 4; group II 3.8 +/- 3.9 years), metabolic parameters and smoking habits were similar. Both clinic and 24 h ABPM values were higher in group I (clinic 157 +/- 12/102 +/- 5; 24 h ABPM 145 +/- 10/95 +/- 7 mmHg) than they were in group II (clinic 146 +/- 11/97 +/- 5; 24 h ABPM = 134 +/- 10/87 +/- 8 mmHg, P < 0.01). The left ventricular mass index (LVMI) and IMT were found to be slightly but significantly greater in group I than they were in group II (LVMI 106 +/- 7 versus 98 +/- 12 g/m2, P < 0.05; IMT 0.68 +/- 0.13 versus 0.61 +/- 0.10 mm, P < 0.05). A significant correlation was found between LVMI and common carotid IMT in the whole group of hypertensive patients (r = 0.43, P < 0.01). CONCLUSIONS: Our results indicate that left ventricular concentric remodelling does not represent the only early cardiovascular change in arterial hypertension but rather is associated often with carotid intima-media thickening.     

Association between blood pressure and circulating hormonal factors with left ventricular mass in patients with essential hypertension older than 55 years of age

BACKGROUND: The prevalence of left ventricular hypertrophy (LVH) is higher in elderly patients with hypertension than in normotensive patients. The factors relationed herewith are not well known. The first purpose was to analyse the relationship between the levels of blood pressure (BP) recorded by ambulatory blood pressure monitoring (ABPM) and the left ventricular mass index (LVMI) in a group of untreated patients older than 55 years with essential hypertension. Our second purpose was to observe the relationship between the concentration of several circulating hormones and the left ventricular mass index. SUBJECTS AND METHODS: The study included 31 untreated patients with mild to moderate essential hypertension and 37 healthy normotensives. Both groups were of similar age, sex and body mass index. We determined for both groups the casual arterial pressure (CAP), ambulatory BP monitoring (ABPM) throughout 24 h, daytime (07.00-23.00 h), nighttime (23.00-07.00 h), left ventricular mass index (LVMI) (following Devereux's formula) and circulating levels of endothelin-1, aldosterone, renine, free adrenaline and noradrenaline. RESULTS: The ILVM in hypertensive patients was 139.6 +/- 35.9 g/m2 and in 124.0 +/- 31.8 g/m2 in normotensive (p < 0.05). The percentage of patients with LVH was 63 and 43%, respectively (p < 0.05). The LVMI in hypertensive patients was correlated with the diastolic CAP (97 +/- 7 mmHg) (r = 0.41; p < 0.05), unlike with the systolic CAP (164 +/- 18 mmHg). The ILVM in normotense patients was not associated neither with the systolic CAP (126 +/- 10 mmHg) nor with the diastolic (79 +/- 6 mmHg). In hypertensive patients we found a slight association between the LVMI and the systolic ABPM (130 +/- 14 mmHg) during nighttime (r = 0.41; p < 0.05). The rest of average ambulatory BP and the hormonal values at study did not show a correlation with the LVMI in both groups. CONCLUSIONS: A slight correlation exists between BP (casual and determined with ambulatory blood pressure monitoring throughout 24 hours) and the left ventricular mass index in mild to moderate untrated hypertensive patients older than 55 years. We did not observe correlations between the circulating levels of endothelin-1, renin, aldosterone, free adrenaline and noradrenaline and the left ventricular mass. The average ventricular mass and the number of subjects with ventricular hypertrophy was significantly increased in hypertensives than in normotensives.     

Pulmonary artery size and clinical outcome after the modified Fontan operation

The maximum cross-sectional area of the central pulmonary arteries indexed to the body surface area (pulmonary artery index [PAI]) was measured preoperatively from angiograms in 173 patients evaluated for a Fontan-type operation between 1981 and June 1989. Of these, 34 patients underwent another palliative procedure, 8 primarily on the basis of small pulmonary arteries (PAI, 106 to 167 mm2/m2). The mean PAI of this group was significantly smaller than the mean PAI of the remaining 139 patients who underwent a Fontan operation (136 +/- 20 versus 310 +/- 113 mm2/m2) (p < 0.001). The patients who underwent a Fontan operation were evaluated according to three overlapping end points: (1) hospital death or takedown of repair (12.2%), (2) early failure (cumulative death or takedown of repair within 6 months of operation) (16.5%), and (3) early failure or persistent effusions (33.8%). With regard to these end points, no significant difference in pulmonary artery size could be found between patients having a favorable or unfavorable outcome. However, among a low-risk subset of 30 patients with tricuspid atresia, those with "early failure or persistent effusions" had significantly smaller pulmonary arteries than those with a good outcome (PAI, 185 +/- 47 versus 276 +/- 83 mm2/m2) (p < 0.01). The postoperative transpulmonary gradient of the 8 patients with the smallest pulmonary arteries who underwent a Fontan operation (all PAIs < 170 mm2/m2) was significantly greater than that of the rest of the study group (9.88 +/- 2.3 versus 8.13 +/- 2.3 mm Hg) (p < 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term effect of lisinopril and atenolol on kidney function in hypertensive NIDDM subjects with diabetic nephropathy

The aim of our study was to evaluate whether inhibition of ACE (lisinopril 10-20 mg/day) can reduce the rate of decline in kidney function more than reducing blood pressure with conventional antihypertensive treatment (atenolol 50-100 mg/day), usually in combination with a diuretic. We performed a prospective, randomized, parallel study for 42 months, double blind for the first 12 months and single blind thereafter. Forty-three (21 lisinopril and 22 atenolol) hypertensive NIDDM patients with diabetic nephropathy were enrolled. Data from 36 patients (17 lisinopril and 19 atenolol, 60 +/- 7 years of age, 27 men) who completed at least 12 months of the study period are presented. At baseline, the two groups were comparable: glomerular filtration rate (51Cr-EDTA plasma clearance) was 75 +/- 6 and 74 +/- 8 ml x min(-1) x 1.73 m(-2), mean 24-h ambulatory blood pressure (A&D TM2420) was 110 +/- 3 and 114 +/- 2 mmHg, and 24-h urinary albumin excretion rate was 961 (range 331-5,727) and 1,578 (476-5,806) mg/24 h in the lisinopril and atenolol groups, respectively. The mean follow-up time was similar, 37 and 35 months in the lisinopril and atenolol groups, respectively. Mean ambulatory blood pressure was equally reduced in the two groups, 12 +/- 2 and 10 +/- 2 mmHg in the lisinopril and atenolol groups, respectively. Glomerular filtration rate declined in a biphasic manner with a faster initial (0 to 6 months) change of 1.25 +/- 0.49 and 0.81 +/- 0.29 ml x min(-1) x month(-1) followed by a slower sustained decline (6 to 42 months) of 0.59 +/- 0.10 and 0.54 +/- 0.13 ml x min(-1) x month(-1) in the lisinopril and atenolol groups, respectively. No significant differences were observed in either initial or sustained decline in glomerular filtration rate between the two groups. Urinary albumin excretion was reduced (% reduction of baseline) more in the lisinopril than in the atenolol group, at 55 (95% CI 29-72) and 15% (-13 to 34), respectively (P = 0.01). In conclusion, the relentless decline in kidney function characteristically found in hypertensive NIDDM patients with diabetic nephropathy can be reduced equally effectively by two antihypertensive treatments, the beta-blocker atenolol and the ACE inhibitor lisinopril.     

Estrogen receptor alpha and beta expression in upper gastrointestinal tract with regulation of trefoil factor family 2 mRNA levels in ovariectomized rats

STUDY OBJECTIVE: To investigate the effect of short-term inhalation of nitric oxide (NO) on transpulmonary angiotensin II formation in patients with severe ARDS. DESIGN: Prospective, clinical study. SETTING: Anesthesiology ICU of a university hospital. PATIENTS: Ten ARDS patients who responded to inhalation of 100 ppm NO by decreasing their pulmonary vascular resistance (PVR) by at least 20 dyne x s x cm(-5) were included in the study. INTERVENTIONS AND MEASUREMENTS: In addition to standard treatment, the patients inhaled 0, 1, and 100 ppm NO in 20-min intervals. Fraction of inspired oxygen was 1.0. Hemodynamics were measured and recorded online. Mixed venous (pulmonary arterial catheter) and arterial (arterial catheter) blood samples were taken simultaneously for hormonal analyses at the end of each inhalation period. RESULTS: Pulmonary arterial pressure decreased from 33+/-2 mm Hg (0 ppm NO, mean+/-SEM) to 29+/-2 mm Hg (1 ppm NO, p<0.05), and to 27+/-2 mm Hg (100 ppm NO, p<0.05, vs 0 ppm). PVR decreased from 298+/-56 (0 ppm NO) to 243+/-45 dyne x s x cm(-5) (1 ppm NO, not significant [NS]), and to 197+/-34 dyne x s x cm(-5) (100 ppm NO, p<0.05, vs 0 ppm). Arterial oxygen pressure increased from 174+/-23 mm Hg (0 ppm NO) to 205+/-26 mm Hg (1 ppm NO, NS), and to 245+/-25 mm Hg (100 ppm NO, p <0.05, vs 0 ppm). Mean plasma angiotensin II concentrations were 85+/-20 (arterial) and 57+/-13 pg/mL (mixed venous) during 0 ppm NO and did not change during inhalation of 1 and 100 ppm NO. Mean transpulmonary plasma angiotensin II concentration gradient (=difference between arterial and mixed venous blood values) was 28+/-8 pg/mL (range, 0 to 69) during 0 ppm NO and did not change during inhalation of 1 and 100 ppm NO. Mean transpulmonary angiotensin II formation (transpulmonary angiotensin II gradient multiplied with the cardiac index) was 117+/-39 ng/min/m2 (range, 0 to 414) during 0 ppm NO and did not change during inhalation of 1 and 100 ppm NO. Mean arterial plasma cyclic guanosine monophosphate concentration was 11+/-2 pmol/mL (0 ppm NO), did not change during 1 ppm NO, and increased to 58+/-8 pmol/mL (100 ppm NO, p<0.05). Arterial plasma concentrations of aldosterone (142+/-47 pg/mL), atrial natriuretic peptide (114+/-34 pg/mL), angiotensin-converting enzyme (30+/-5 U/L), and plasma renin activity (94+/-26 ng/mL/h of angiotensin I) did not change. CONCLUSION: The decrease of PVR by short-term NO inhalation in ARDS patients was not accompanied by changes in transpulmonary angiotensin II formation. Our results do not support any relationship between transpulmonary angiotensin II formation and the decrease in PVR induced by inhaled NO.     

Effect of intensive treatment on diabetic nephropathy in patients with type I diabetes

We evaluated the long-term effect of an intensive treatment of diabetic nephropathy (anti-hypertensive drugs, low protein diet, multiple insulin injections to achieve a good metabolic control) on glomerular filtration rate (GFR) and albumin excretion rate (AER). Fourteen type I diabetic patients (mean age 45 +/- 9.5 years, mean duration of diabetes 23.5 +/- 7.3 years, 8 males/6 females) with glomerular filtration rate < 70 ml/min-1/1.73 m2 and albumin excretion rate > 30 micrograms/min were treated intensively for 36 months. This intensive treatment consisted of multiple insulin injections, antihypertensive therapy with ACE inhibitors and a low-protein diet (0.8 g/kg body wt/day.) Renal function was evaluated as GFR and AER. HbA1c mean value decreased significantly from 8.7 +/- 0.8% to 6.5 +/- 0.5% (P < 0.0002). GFR rose from 58 +/- 12 ml/min-1/1.73 m2 to 84 +/- 11 ml/min-1/1.73 m2 (P < 0.0008). AER decreased from 208 micrograms/min (range: 73 to 500) to 63.8 micrograms/min (range 15 to 180; P < 0.05). Systolic and diastolic blood pressure decreased respectively from 144 +/- 26 mm Hg to 120 +/- 15 mm Hg and from 89 +/- 9 mm Hg to 75 +/- 8 mm Hg (P < 0.01). We obtained a rise of GFR and a reduction of proteinuria after three years of this treatment. We suggest that this intensive treatment in all patients with early stage diabetic nephropathy may be effective in slowing the progression to renal failure.     

Systemic venous collateral development after the bidirectional cavopulmonary anastomosis. Prevalence and predictors

OBJECTIVES: To determine the prevalence of systemic venous collaterals after the bidirectional cavopulmonary anastomosis and the factors associated with their development. BACKGROUND: Systemic venous collaterals have been found after cavopulmonary anastomosis. Methods. Cardiac catheterization was performed in 103 patients before and after a bidirectional cavopulmonary anastomosis. RESULTS: After surgery, 51 venous collaterals were identified in 32 patients (31%). Collateral development was associated with an abnormal superior vena caval connection (56% incidence vs. 26% with a single right superior vena cava, p = 0.01) and postoperative factors including pulmonary artery distortion (53% incidence vs. 22% without distortion, p = 0.002); increased superior vena caval mean pressure (14 +/- 5 mm Hg versus 11 +/- 4 mm Hg with no collaterals, p = 0.0002); increased pulmonary artery mean pressure (13 +/- 4 mm Hg vs. 11 +/- 4 mm Hg with no collaterals, p = 0.02); lower right atrial mean pressure (5 +/- 2 mm Hg vs. 6 +/- 3 mm Hg with no collaterals, p = 0.04); and increased mean gradient between superior vena cava and right atrium (8 +/- 3 mm Hg vs. 5 +/- 4 mm Hg with no collaterals, p = 0.0002). Using multiple logistic regression, only this last factor was independently associated with collateral development with an odds ratio per 1 mm Hg of 1.33 (95% CI 1.12-1.58, p = 0.001) for their presence. CONCLUSIONS: Systemic venous collaterals occur frequently after a bidirectional cavopulmonary anastomosis and are found postoperatively when a significant pressure gradient occurs between cava and right atrium.     

Reduced periinfarction mortality as a result of long-term therapy with captopril but not hydralazine or propranolol in spontaneously hypertensive rats

Hypertension and left ventricular hypertrophy (LVH) are known to increase susceptibility to ventricular arrhythmias during and before myocardial ischemia and to increase the risk of periinfarction mortality. Although regression of LVH has been advocated as a therapeutic goal, little evidence exists to suggest that it can reduce periinfarction mortality, and if it does, by which mechanisms it may do this. In this study, we evaluated the effects of control of systemic arterial blood pressure, of regression of myocardial hypertrophy, and of cardiac fibrosis on the susceptibility to ventricular arrhythmias and periinfarction mortality in the spontaneously hypertensive rat (SHR) model of hypertension and LVH. After 12 weeks of treatment, captopril and hydralazine reduced systolic blood pressure to 93 +/- 14 and 126 +/- 13 mm Hg, respectively, as compared with 193 +/- 12 mm Hg, p < 0.05, in the untreated control SHR group. The decrease with propranolol (to 185 +/- 12 mm Hg) was of borderline significance. There was a significant decrease in inducibility of ventricular arrhythmias by programmed electrical stimulation with captopril (5%; p < 0.05). One hour after infarction, there was a trend toward reduced mortality in the rats treated with hydralazine, 9.5% (p = 0.20 vs. control; p = 0.10 vs. propranolol), and captopril, 5% (p = 0.08 vs. control; p = 0.010 vs. propranolol). However, only captopril reduced 3-h postinfarction mortality (40%; p = 0.022) compared with 72% in the control group. The results showed a significant decrease of the left ventricular weight/body weight ratio in the rats treated with hydralazine (2.6 +/- 0.2 mg/g; p < 0.05) and captopril (2.2 +/- 0.2 mg/g; p < 0.05) compared with the control group (2.8 +/- 0.2 mg/g). An assessment of cardiac fibrosis indicated that captopril decreased the volume percentage of collagen the most (2.01 +/- 0.53; p < 0.05), followed by propranolol (2.29 +/- 0.64; p < 0.05) and hydralazine (2.92 +/- 0.58; p < 0.05) versus controls (3.23 +/- 0.61). This study suggests that regression of myocardial hypertrophy or long-term normalization of arterial systolic blood pressure or both are the major determinants of very early mortality (within 1 h after infarction) and that later mortality (3 h after infarction) may be the result of a more complex interplay of regression of myocardial hypertrophy and fibrosis and of control of blood pressure.     

Inhibition of hypoxic pulmonary hypertension by heparins of differing in vitro antiproliferative potency

Heparin inhibits smooth-muscle cell (SMC) growth in vitro and inhibits the development of hypoxic pulmonary hypertension and vascular remodeling in vivo. We wondered whether preparations of heparin with different antiproliferative potency in vitro would differ in their ability to inhibit the development of hypoxic pulmonary hypertension in vivo. Two such heparins, a weakly antiproliferative lot of Elkins-Sinn (E-S) (% inhibition of SMC growth at 10 micrograms/ml = 13 +/- 9% [mean +/- SEM, n = 24]) and a more active lot from Upjohn (UJ) (% inhibition = 71 +/- 12% [n = 12, p < 0.05 versus E-S]), were infused subcutaneously (300 U.S.P. units/day; E-S 300 versus UJ 300) via an osmotic pump into guinea pigs exposed to hypoxia (10% O2) for 10 d, after which pulmonary artery pressure (PAP; mm Hg) and cardiac index (CI; ml/min/kg) were measured in room air. Hypoxic controls (HC) received saline. PAP increased from 11 +/- 1 mm Hg in normoxic controls (NC) (n = 5) to 24 +/- 1 mm Hg in HC (n = 8, p < 0.05). The PAP was lower in the E-S 300 (21 +/- 1; n = 7, p < 0.05 versus HC and NC) and even lower in the UJ 300-treated group (18 +/- 0.5; n = 7, p < 0.05 versus HC and NC). Total pulmonary vascular resistance (TPR; mm Hg/ml/min/kg) increased significantly from 0.038 +/- 0.002 in NC to 0.076 +/- 0.003 (p < 0.05) in HC. There was no difference in TPR between the HC and the E-S 300-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Electroneutral Na-coupled cotransporter expression in the kidney during variations of NaCl and water metabolism

The antiproteinuric effect of angiotensin converting enzyme (ACE) inhibition in insulin-dependent diabetes mellitus (IDDM) patients with diabetic nephropathy varies considerably. Therefore, we tested the potential role of an insertion (I)/deletion (D) polymorphism of the ACE gene on this early antiproteinuric responsiveness in an observational follow-up study. Sixty (II, N = 13; ID, N = 26 and DD, N = 21) young hypertensive IDDM patients suffering from diabetic nephropathy were investigated during three months before and for the initial six month period during ACE inhibition [captopril 44 (SD 22) mg/24 hr, no differences in drug dose between groups]. Blood pressure (MABP) and albuminuria (ELISA) were measured three (1 to 6) times before and three (1 to 13) times during ACE inhibition. At baseline the groups (II/ID/DD) had comparable (1) mean arterial blood pressure (MABP mm Hg) of 113 +/- 10/108 +/- 9/114 +/- 8, (2) albuminuria (geometric mean with 95% CI) 1394 (747 to 2608)/1176 (844 to 1797) and 1261 (827 to 2017) mg/24 hr, and (3) serum creatinine (geometric mean with 95% CI), 80 (68 to 93)/85 (76 to 97)/103 (85 to 119) mumol/liter, respectively. Angiotensin converting enzyme inhibition induced a significant reduction in MABP, albuminuria and kidney function in all three groups (II/ID/DD; P < 0.05): (1) MABP (mean +/- SD) 12 +/- 7/5 +/- 7/8 +/- 9 mm Hg (ANOVA, P = 0.02); (2) albuminuria [mean (95% CI)] 61 (34 to 77)/22 (3 to 37)/31 (13 to 46) %, (ANOVA, P < 0.01); and (3) increasing serum creatinine [mean (95% CI)] 8 (4 to 12)/9 (3 to 16)/8 (0 to 16) % (ANOVA, NS), respectively. Adjusting for differences in reduction in MABP did not change the association between decrease in albuminuria and ACE/ID genotypes (P < 0.01). A multiple linear regression analysis revealed that the ACE/ID polymorphism, albuminuria and MABP at baseline independently influenced the decline in albuminuria after initiation of ACE inhibition (R2 = 0.21, P < 0.01). A significant association between changes in MABP and albuminuria was demonstrated (R2 = 0.16, P < 0.01). Our data show that hypertensive albuminuric IDDM patients with the II genotype are particularly susceptible to commonly advocated renoprotective treatment.     

Pulmonary hypertension after transjugular intrahepatic portosystemic shunt: effects on right ventricular function

The short- and mid-term hemodynamic effects of transjugular intrahepatic portosystemic shunt (TIPS) were studied in 16 sedated cirrhotic patients. Indications included relapsing variceal bleeding (n = 10) and refractory ascites (n = 6). The decrease of porto-atrial pressure gradient (from 20.4 +/- 4.2 mm Hg to 10.1 +/- 2.4 mmHg; P < .05) was associated with an increase of mean pulmonary artery pressure (MPAP) (from 12.3 +/- 3.0 mm Hg to 20.3 +/- 5.3 mm Hg; P < .05) and of right atrial pressure (RAP) from 3.4 +/- 2.6 mm Hg to 8.3 +/- 3.7 mm Hg; P < .05), whereas right ventricular end-diastolic volume (RVEDVI) remained unchanged. The significant increase of cardiac index (CI) (from 4.5 +/- 1.2 L/min/m2 to 5.0 +/- 1.1 L/min/m2; P < .05) was essentially attributable to an increase of heart rate (HR) (from 81 +/- 11 to 88 +/- 10 beats/min; P < .05). Systemic vascular resistance (SVR) decreased (from 812 +/- 281 to 666 +/- 191 dynes/sec/cm5; P < .05), whereas pulmonary vascular resistance (PVR) increased (from 60.6 +/- 29.6 to 82.0 +/- 34.6 dynes/sec/cm5; P < .05). After transient shunt occlusion with a balloon catheter, all of the hemodynamic parameters returned to baseline values, except pulmonary artery pressure, which also decreased but remained significantly increased. One month after TIPS, pulmonary pressure remained elevated, and CI further increased. It is concluded that increased PVR is the major hemodynamic alteration occurring after TIPS placement. It correlates with the decrease of porto-atrial gradient and is probably mediated by both mechanical and neurohumoral factors.