The effects of delapril in combination with indapamide on glomerular filtration rate in elderly hypertensive patients.

We performed a placebo-controlled trial on the effects of a combined antihypertensive treatment with delapril, a new nonsulfhydryl angiotensin-converting enzyme inhibitor, and indapamide, a sulfonamide diuretic. We studied 28 elderly patients aged 65-85 years (mean age, 69 +/- 1 years) who took 30 mg delapril in combination with 1.25 mg indapamide once daily for 24 weeks. In the present study (performed simultaneously with our trial on the effects of delapril/indapamide on left ventricular mass in elderly patients with hypertension and on the same patients), we report the effects of this drug combination on glomerular filtration rate. Sitting arterial pressure (mean +/- SE) decreased from 156 +/- 1. 5/101 +/- 1 mm Hg at baseline to 133 +/- 1/73 +/- 1 mm Hg at the end of the 24-week treatment period (p < 0.0001). No significant changes in heart rate or episodes of orthostatic hypotension were observed. Glomerular filtration rate increased from 91.8 +/- 4.42 mL/min at baseline to 106.3 +/- 4.5 mL/min (p < 0.001) at the end of treatment. Our results show that the combination of delapril and indapamide is effective in the elderly hypertensive patient, with a favorable effect on the prevention of deterioration of kidney function.     

Angiotensin II receptor blocker telmisartan: effect on blood pressure profile and left ventricular hypertrophy in patients with arterial hypertension

In this open-label, non-comparative study, the anti-hypertensive efficacy and effect on left ventricular hypertrophy (LVH) of 24 weeks' treatment with once-daily telmisartan 40-80 mg was evaluated in 24 patients with mild-to-moderate hypertension and LVH. Patients were titrated to the higher dose of study drug at week 4 if they did not achieve blood pressure normalization (i.e. systolic blood pressure [SBP]/diastolic blood pressure [DBP] remained > or = 140/90 mmHg). The anti-hypertensive action of telmisartan was assessed using clinic cuff measurements and 24-h ambulatory blood pressure monitoring, and left ventricular mass index (LVMI) was determined by two-dimensional echocardiography at baseline and after 24 weeks of therapy. Telmisartan significantly reduced mean 24-h, daytime and night-time SBP and DBP compared with baseline after 12 and 24 weeks of therapy. Target blood pressure levels, defined as SBP/DBP < 140/90 mm Hg, were achieved in 16 (69.6%) patients at the end of the treatment period. After 24 weeks of telmisartan treatment, LVMI decreased from 151.6 +/- 5.4 to 135.1 +/- 5.9 g/m2. In conclusion, anti-hypertensive treatment with telmisartan for 24 weeks produced significant reductions in blood pressure and regression of LVH, as assessed by LVMI, in patients with hypertension and LVH.     

Regression of left ventricular hypertrophy with losartan potassium therapy in patients with hypertension

The aim of this study was to assess the effects of losartan potassium, an angiotensin II receptor antagonist, on systolic blood pressure; diastolic blood pressure; and left ventricular dimensions, functions, and mass index (LVMI) in patients with mild-to-moderate essential hypertension. Twenty patients aged 40 to 65 years with either uncontrolled or previously untreated hypertension and echocardio-graphically documented left ventricular hyptertrophy (LVH) defined by LVMI >130 g/m² for men and >110 g/m² for women were included in the study. Blood pressure measurements were taken at 2-week intervals. Blood samples were taken before treatment and after 3 months of treatment for determination of lipid concentrations and other laboratory variables used to monitor safety, and two-dimensional M-mode and Doppler echocardiographic measurements were obtained. Losartan was associated with a statistically significant reduction of mean systolic blood pressure from 173 ± 6 mm Hg to 135 ± 10 mm Hg and diastolic blood pressure from 100 ± 4 mm Hg to 82 ± 7 mm Hg without a change in heart rate. Significant decreases were identified in interventricular septal and left ventricular posterior wall thicknesses (from 12.5 ± 0.8 mm to 11.5 ± 0.8 mm and 12.1 ± 1.0 mm to 11.1 ± 0.8 mm, respectively). LVMI decreased from 138.8 ± 18.7 g/m² to 126.0 ± 21.8 g/m² after 3 months of treatment. Left ventricular dimensions and ejection fraction did not change significantly compared with baseline values. The Doppler echocardiographic assessment of mitral E/A ratio, which is a marker of diastolic function, increased significantly from baseline. Except for a significant increase in mean serum lactate dehydrogenase activity, laboratory findings (including serum lipid concentrations) remained constant. No clinical adverse effects attributable to losartan were observed. Results of this study suggest that losartan is an effective, well-tolerated drug that reduces LVH, improves left ventricular diastolic functions, and controls systolic and diastolic blood pressures in patients with mild-to-moderate essential hypertension.     

The effect of sodium on hemodynamic changes during coronary angiography with nonionic contrast media

To investigate the effect of sodium on cardiac hemodynamics, sodium chloride was added to nonionic contrast media to a 0.9% concentration and was compared with the standard media iohexol, iopamidol, and ioversol. Left coronary angiography was performed in 10 closed-chest, atrial-paced dogs with 10 ml injections of each preparation in a randomized and blinded fashion. The maximum changes in left ventricular systolic pressure, mean aortic pressure, left ventricular and diastolic pressure, and maximal rise of left ventricular pressure were measured. The left ventricular systolic pressure and mean aortic pressure decreased by 17 +/- 7 mm Hg and by 12 +/- 5 mm Hg with iohexol plus 0.9% NaCl, but only by 5 +/- 4 mm Hg and by 4 +/- 3 mm Hg with iohexol alone (p less than 0.001). The left ventricular and end diastolic pressure increased by 2.2 +/- 0.6 mm Hg with iohexol plus 0.9% NaCl, but did not change with iohexol alone (p less than 0.001). Left ventricular dp/dt decreased by 204 +/- 161 mm Hg/sec with iohexol plus 0.9% NaCl but increased by 392 +/- 122 mm Hg/sec with iohexol alone (p less than 0.001). Similar results were obtained from experiments with iopamidol versus iopamidol plus 0.9% NaCl and ioversol versus ioversol plus 0.9% NaCl. Ioversol plus 5% dextrose or ioversol plus 2.1% choline chloride (isomolar to ioversol plus 0.9% NaCl) produced a significant increase in left ventricular systolic pressure and left ventricular dp/dt (versus ioversol plus 0.9% NaCl, p less than 0.001). Thus, sodium, but not the osmolality or chloride, contributed to the negative inotropic effect of the contrast media.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical application of the nitroglycerin lingual spray

The effect of sublingually administered nitrate spray was investigated with noninvasive methods. During 3 months, 82 patients were entered into the study: 40 with angina pectoris, 15 with acute myocardial infarction, 18 with hypertensive crisis, and 9 with left ventricular failure or acute pulmonary edema. The hemodynamic effects of two jets of nitroglycerin spray (0.8 mg Nitrolingual spray; Pohl-Boskamp, Hohenlocksted, Germany) was measured on heart rate, blood pressure, and flow velocity at baseline and 1, 5, and 10 minutes after drug administration. Flow velocities were measured through the left ventricular outflow tract and the mitral valve (early diastolic wave and atrial wave) with bedside Doppler echocardiography. The time to improvement and occurrence of adverse events was analyzed. Heart rate was constant after the therapy (75 +/- 8, 75 +/- 10, 75 +/- 10, and 75 +/- 9 beats per min; not significant), and systolic blood pressure decreased significantly 1 minute after administration and remained decreased throughout the examination (135 +/- 27, 124 +/- 21, 125 +/- 19, and 124 +/- 22 mm Hg, respectively; p < 0.001). The diastolic blood pressure was also significantly decreased (82 +/- 17, 79 +/- 14, 78 +/- 12, 78 +/- 14 mm Hg; p < 0.001). A significant increase in flow velocities in the left ventricular outflow tract was detected (90 +/- 8, 101 +/- 10, and 114 +/- 13 cm/s; p < 0.001) concomitantly with a significant increase in the early diastolic flow (46 +/- 4, 65 +/- 6, and 76 +/- 8 cm/s; p < 0.001) and the atrial wave (101 +/- 9, 110 +/- 10, and 118 +/- 9 cm/s; p < 0.001). This increase of flow velocity was less pronounced through the mitral valve than through the left ventricular outflow tract.     

Effects of nisoldipine and lisinopril on left ventricular mass and function in diabetic nephropathy

OBJECTIVE: To compare the effects of the calcium channel blocker, nisoldipine, and the ACE inhibitor, lisinopril, on left ventricular mass (LVM) and systolic function in type 1 diabetic patients with diabetic nephropathy. RESEARCH DESIGN AND METHODS: M-mode echocardiography was performed in 50 hypertensive type 1 diabetic patients with diabetic nephropathy enrolled in a 1-year, randomized, double-blind, parallel study of antihypertensive treatment with nisoldipine CC (20-40 mg/day) or lisinopril (10-20 mg/day). Ambulatory 24-h blood pressure was measured with the Takeda TM 2420 device (A & D, Tokyo, Japan) every 3 months. Three patients dropped out and seven patients were excluded due to technical difficulties. RESULTS: The 24-h diastolic blood pressure was reduced from 83 to 80 mmHg in the nisoldipine group (P = 0.06) and from 85 to 80 mmHg in the lisinopril group (P = 0.02). The decline in systolic blood pressure was not significant with any of the two treatments, and no difference in reduction of blood pressure was seen between groups. LVM corrected for body surface area (LVMI) was comparable between groups at baseline and increased from 96 +/- 5 to 107 +/- 6 g/m2 (mean +/- SEM; P = 0.007) in the nisoldipine group and from 95 +/- 4 to 103 +/- 5 g/m2 (P = 0.03) in the lisinopril group. The mean difference between the change in LVMI in the two groups was 2.9 (95% CI 6.8 to 12.7) g/m2. The prevalence of left ventricular hypertrophy rose from 18 (95% CI 6-30) to 30% (16-44) during the study period. A multiple linear regression analysis revealed that after 1 year of treatment, LVMI increased with higher systolic blood pressure level and declining glomerular filtration rate (R2 = 0.25). Fractional shortening was within normal range at baseline, 42 +/- 1 vs. 41 +/- 1% with nisoldipine and lisinopril, respectively, and did not change during follow-up. CONCLUSIONS: Antihypertensive treatment with nisoldipine or lisinopril to bring diastolic blood pressure level within the normal target range does not hinder a rise in LVMI in type 1 diabetic patients with diabetic nephropathy.     

Effect of antihypertensive treatment on the prevalence of ventricular arrhythmias among patients with isolated systolic hypertension without left ventricular hypertrophy

Background: The high incidence of ventricular arrhythmias in patients with hypertension and left ventricular hypertrophy (LVH) is well documented. However, few studies have been conducted on the prevalence of ventricular arrhythmias in patients with isolated systolic hypertension without LVH.Objectives: The objectives of this study were to (1) determine the prevalence of ventricular arrhythmias in patients with systolic hypertension without LVH and (2) estimate the effect of a perindopril/indapamide combination, which does not have an antiarrhythmic effect, on the incidence of ventricular arrhythmias.Methods: Patients with newly diagnosed isolated systolic hypertension (systolic blood pressure [SBP] >160 mm Hg) and a control group of normotensive patients were enrolled. During the 2-week washout period, patients underwent physical examination (including blood pressure measurements), ambulatory electrocardiography monitoring, echocardiography, and laboratory urine and blood tests. Absence of LVH was confirmed by echocardiographic examination. The group of hypertensive patients received 1 tablet of 2 mg perindopril/0.625 mg indapamide per day for a total of 4 weeks. Physical examinations and ambulatory electrocardiographic monitoring were repeated after treatment.Results: A total of 60 hypertensive (mean age, 63.1 years; mean SBP, 176.8 ± 3.1 mm Hg; mean diastolic blood pressure, 82.6 ± 2.9 mm Hg) and 60 normotensive patients were enrolled. Ambulatory electrocardiographic monitoring indicated that 18 of the 60 hypertensive patients (30%) had ventricular arrhythmias: 17 had ventricular premature contractions (>100/24 h) and 1 had ventricular tachycardia plus ventricular premature contractions. In the control group, 7 of 60 subjects (11.7%) had ventricular premature contractions. The difference between the 2 groups in incidence of ventricular arrhythmias was significant (P < 0.01). After treatment, mean SBP decreased to 136.1 ± 3.2 mm Hg, and ventricular premature contractions were found in 9 of 60 hypertensive patients (15%) (P < 0.02 vs pretreatment).Conclusions: The results of this study suggest that in patients with isolated systolic hypertension without LVH, (1) the prevalence of ventricular arrhythmia is higher than in normotensive patients and (2) treatment with perindopril/indapamide decreases the incidence of ventricular arrhythmias.     

Assessment of the antihypertensive efficacy of various doses of delapril by office and ambulatory blood pressure measurement: The DEFIND study

This study was undertaken to compare and verify the antihypertensive effects of various delapril doses versus placebo on office and ambulatory blood pressure (BP). After a 2-wk placebo period, 303 patients with mild to moderate essential hypertension were randomized in a double-blind study to 8 wk of treatment with placebo, or delapril 7.5 mg twice daily, delapril 15 mg twice daily, delapril 30 mg twice daily, or delapril 30 mg once daily. BP changes versus baseline and rates of normalized office systolic blood pressure (SBP) > 140 mm Hg and diastolic blood pressure (DBP) > 90 mm Hg, as well as responder office SBP > 140 mm Hg or reduction ≥20 mm Hg and office DBP > 90 mm Hg or reduction ≥10 mm Hg, were calculated. In the intention-to-treat population (n=296), office SBP and DBP reductions were more notable with 30 mg twice daily (15.6/11.5 mm Hg) and 15 mg twice daily (14.8/12.5 mm Hg) than with other delapril regimens (30 mg once daily: 11.8/10.5 mm Hg; 7.5 mg twice daily: 12.9/10.1 mm Hg) and placebo (P< .05 for DBP;P< .01 for SBP). The same was true for frequency of responders (63.8% and 60.3%; P≤.05 vs placebo) and normalized patients (58.6% and 53.4%;P< .05 vs placebo). Analysis of ambulatory BPs confirmed the accuracy of office BPs. Drug-related adverse events occurred in 3.4% to 6.7% of patients given delapril and in 6.5% of those given placebo. The lowest effective dose of delapril, 15 mg twice daily, may be recommended as the initial dose for patients who begin treatment with this agent.     

Coronary angiography during acute myocardial infarction in dogs: comparison of the hemodynamic effects of ionic and nonionic contrast media

We compared the hemodynamic effects during coronary angiography of three nonionic contrast media, iopamidol, iohexol, and ioversol, with each other as well as with the standard ionic contrast medium containing 66% diatrizoate meglumine and 10% diatrizoate sodium (Hypaque-76) in the presence of a left anterior descending coronary artery occlusion in dogs. In 13 opened-chest anesthetized dogs, we recorded the maximal change in left ventricular systolic pressure (LVSP), mean aortic pressure (MAP), left ventricular diastolic pressure (LVDP) and rate of rise in left ventricular pressure (LV dp/dt) during left main coronary artery injections of 10 ml each of Hypaque-76, iopamidol, iohexol, and loversal 1 hour after left anterior descending coronary artery occlusion. The changes in LVSP and MAP were, respectively, -29 +/- 12 mm Hg and -21 +/- 11 mm Hg with Hypaque-76, 3 +/- 6.6 mm Hg and -0.2 +/- 3.6 mm Hg with iopamidol, 4.8 +/- 8.6 mm Hg and 0.5 +/- 4 mm Hg with iohexol, and -0.8 +/- 6 mm Hg and -1.5 +/- 33 mm Hg with ioversal (p less than 0.001). The change in LVDP was 5.4 +/- 4.4 mm Hg with Hypaque-76 but -1.5 +/- 3.1 mm Hg with iopamidol, -1.7 +/- 2.4 mm Hg with iohexol, and -0.5 +/- 2.5 mm Hg with ioversol (p less than 0.001). The LV dp/dt decreased 682 +/- 318 mm Hg/sec with Hypaque-76, but increased 412 +/- 297 mm Hg/sec with iopamidol, 350 +/- 214 mm Hg/sec with iohexol, and 293 +/- 191 mm Hg/sec with ioversol (p less than 0.001). Thus, each nonionic agent produced significantly fewer hemodynamic abnormalities than Hypaque-76. There was no significant difference between any of the nonionic agents on any hemodynamic parameter. These agents may be preferable in patients with acute myocardial infarction or significantly impaired myocardial function.     

老年原发性高血压患者动态脉压与左心室质量指数关系的研究

目的探讨老年原发性高血压动态脉压与左心室质量指数（LVMI）的关系。方法收集2012年1月一12月住院的110例老年原发性高血压患者的临床资料。所有患者均已行动态血压检测,并行超声心动图检查,依据24h动态血压结果计算动态脉压,依据超声心动图结果计算LVMI,按照脉压〈60mmHg（1mmHg=0．133kPa）以及≥60mmHg将患者分为A组（n=70）和B组（n=40）,比较两组患者的LVMI等指标,并采用多重线性逐步回归分析动态脉压与LVMI的关系。结果B组患者的24h平均收缩压、动态脉压较A组明显增高（P〈0．001）;B组患者的室间隔厚度、左心室后壁厚度、左心室质量、LVMI均高于A组（P〈0．05）;Pearson相关分析显示：动态脉压与LVMI呈正相关（r=0．33,P〈0．001）;多重线性逐步回归显示：动态脉压是LVMI增加的危险因素（β=0．90,P〈0．001）。结论老年原发性高血压患者动态脉压与LVMI呈正相关,动态脉压是老年原发性高血压患者左心室结构损害的重要危险因素。     

Reducing ventilation frequency during cardiopulmonary resuscitation in a porcine model of cardiac arrest

INTRODUCTION: American Heart Association/American College of Cardiology guidelines recommend a compression-to-ventilation ratio (C/V ratio) of 15:2 during cardiopulmonary resuscitation (CPR) for out-of-the-hospital cardiac arrest. Recent data have shown that frequent ventilations are unnecessary and may be harmful during CPR, since each positive-pressure ventilation increases intrathoracic pressure and may increase intracranial pressure and decrease venous blood return to the right heart and thereby decrease both the cerebral and coronary perfusion pressures. HYPOTHESIS: We hypothesized that reducing the ventilation rate by increasing the C/V ratio from 15:2 to 15:1 will increase vital-organ perfusion pressures without compromising oxygenation and acid-base balance. METHODS: Direct-current ventricular fibrillation was induced in 8 pigs. After 4 min of untreated ventricular fibrillation without ventilation, all animals received 4 min of standard CPR with a C/V ratio of 15:2. Animals were then randomized to either (A) a C/V ratio of 15:1 and then 15:2, or (B) a C/V ratio of 15:2 and then 15:1, for 3 min each. During CPR, ventilations were delivered with an automatic transport ventilator, with 100% oxygen. Right atrial pressure, intratracheal pressure (a surrogate for intrathoracic pressure), aortic pressure, and intracranial pressure were measured. Coronary perfusion pressure was calculated as diastolic aortic pressure minus right atrial pressure. Cerebral perfusion pressure was calculated as mean aortic pressure minus mean intracranial pressure. Arterial blood gas values were obtained at the end of each intervention. A paired t test was used for statistical analysis, and a p value < 0.05 was considered significant. RESULTS: The mean +/- SEM values over 1 min with either 15:2 or 15:1 C/V ratios were as follows: intratracheal pressure 0.93 +/- 0.3 mm Hg versus 0.3 +/- 0.28 mm Hg, p = 0.006; coronary perfusion pressure 10.1 +/- 4.5 mm Hg versus 19.3 +/- 3.2 mm Hg, p = 0.007; intracranial pressure 25.4 +/- 2.7 mm Hg versus 25.7 +/- 2.7 mm Hg, p = NS; mean arterial pressure 33.1 +/- 3.7 mm Hg versus 40.2 +/- 3.6 mm Hg, p = 0.007; cerebral perfusion pressure 7.7 +/- 6.2 mm Hg versus 14.5 +/- 5.5 mm Hg, p = 0.008. Minute area intratracheal pressure was 55 +/- 17 mm Hg . s versus 22.3 +/- 10 mm Hg . s, p < 0.001. End-tidal CO(2) with 15:2 versus 15:1 was 24 +/- 3.6 mm Hg versus 29 +/- 2.5 mm Hg, respectively, p = 0.001. Arterial blood gas values were not significantly changed with 15:2 versus 15:1 C/V ratios: pH 7.28 +/- 0.03 versus 7.3 +/- 0.03; P(aCO(2)) 37.7 +/- 2.9 mm Hg versus 37.6 +/- 3.5 mm Hg; and P(aO(2)) 274 +/- 36 mm Hg versus 303 +/- 51 mm Hg. CONCLUSIONS: In a porcine model of ventricular fibrillation cardiac arrest, reducing the ventilation frequency during CPR by increasing the C/V ratio from 15:2 to 15:1 resulted in improved vital-organ perfusion pressures, higher end-tidal CO(2) levels, and no change in arterial oxygen content or acid-base balance.     

Combination Treatment with Sustained-Release Verapamil and Indapamide in the Treatment of Mild-to-Moderate Hypertension

A multicenter study of the treatment of mild and moderate hypertension compared three once-daily regimens for efficacy and safety: Group I, verapamil sustained release (SR) 240 mg; Group II, verapamil SR 480 mg; and Group III, combination therapy of verapamil SR 240 mg plus indapamide 2.5 mg. After a 3-week placebo washout period and a 2-week preliminary treatment period with verapamil SR 240 mg daily, those patients with diastolic blood pressures of <95 mm Hg were excluded from further study; 137 remaining patients with sitting diastolic blood pressure of 95--115 mm Hg, representing "incomplete" responders to verapamil SR 240 mg, were randomized in a double-blind fashion to one of the three treatment groups for a duration of 16 weeks. Efficacy was assessed after 16 weeks of double-blind therapy or at end point. All three treatments significantly reduced sitting diastolic and systolic blood pressure from baseline levels. Compared with Group I (verapamil SR 240 mg daily), there was a significant reduction (p < 0.05) in Group II combination therapy of 8.6 mm Hg systolic and 3.0 mm Hg diastolic and a significant reduction (p < 0.05) in Group II (verapamil SR 480 mg daily) of 7.6 mm Hg systolic and 3.9 mm Hg diastolic BP. Patients who had the least change in blood pressure (diastolic blood pressure decreases of <5 mm Hg) to lead-in verapamil SR 240 mg daily, prior to randomization, tended to have a greater response to combination therapy than to verapamil SR 480 mg. Adverse experiences leading to withdrawal from the study occurred in 21% of patients receiving verapamil SR 480 mg daily (Group II). There was a significantly greater withdrawal from Group II than the other two treatment groups (8.5% from Group III and 4% from Group I). This trial demonstrated that adding indapamide 2.5 mg to the incomplete responders of verapamil SR 240 mg enhances efficacy and was well tolerated.     

Heart remodeling in case of isolated systolic arterial hypertension

Examination of 32 patients with isolated systolic arterial hypertension (office blood pressure 171.9 = -3.3/79.7 +/- 0.2 mm Hg) and 54 ones with systolic/diastolic hypertension) 179.8 +/- 3.9/114.8 +/- 1.9 mm Hg) showed that the former are characterized by isolated hypertrophy of interventricular septum, the latter by symmetric hypertrophy of the septum and free left ventricular wall. Septal hypertrophy affects the initial phase of diastolic filling of the left ventricle as appears from longer time of isovolume relaxation and low peak rate of early transmitral blood flow; it does not influence diastolic function of the right ventricle. Hypertrophy of the free left ventricular wall disturbs the final stage of early diastolic filling of both right and left ventricles manifest as increased duration of their slowed early filling.     

Efficacy and safety of delapril plus manidipine compared with enalapril plus hydrochlorothiazide in mild to moderate essential hypertension: results of a randomized trial

BACKGROUND: The use of combination therapy is required to achieve blood pressure targets in 40% to 75% of patients with hypertension. There have been few studies comparing the efficacy and tolerability of the new fixed combination of the angiotensin-converting enzyme (ACE) inhibitor delapril 30 mg and the calcium channel antagonist manidipine 10 mg with those of a standard combination of another ACE inhibitor and a diuretic. OBJECTIVE: The aim of this study was to compare the antihypertensive efficacy and tolerability of delapril 30 mg given alone or with manidipine 10 mg with those of enalapril 20 mg given alone or with hydrochlorothiazide (HCTZ) 12.5 mg in patients with mild to moderate essential hypertension. METHODS: This was a multicenter, active-controlled, parallel-group trial. After an initial 2-week placebo run-in period, patients aged 18 to 75 years with diastolic blood pressure (DBP) > or =90 and < or =109 mm Hg were randomized in a 2:1 ratio to receive delapril or enalapril for 8 weeks. After the initial 8 weeks, nonresponders (DBP > or =85 mm Hg) received an additional 8 weeks of treatment with a fixed combination of delapril + manidipine or enalapril + HCTZ; patients whose DBP was normalized continued their initial monotherapy through the end of the study. The primary efficacy variable was the change in sitting DBP at the end of treatment. Secondary efficacy variables were the percentage of patients whose DBP was normalized (DBP Z:85 mm Hg) and the percentage of responders (> or =10-mm Hg reduction in DBP or DBP <85 mm Hg). RESULTS: One hundred sixty patients (84 men, 76 women) were randomized to receive delapril (n = 106) or enalapril (n = 54). After 16 weeks of treatment, the mean (SD) reduction in DBP was similar with the 2 treatments (delapril, -14 [8] mm Hg; enalapril, -15 [8] mm Hg). In the delapril and enalapril groups, DBP was normalized in a respective 55 (51.9%) and 29 (53.7%) patients, and 77 (72.6%) and 38 (70.4%) were responders; there was no significant difference between groups. Tolerability was also similar in both groups--10 (9.4%) patients in the delapril group and 5 (9.3%) in the enalapril group experienced adverse events that were judged related to treatment. CONCLUSIONS: The results of this study suggest that delapril alone or combined with manidipine is well tolerated and as effective as enalapril alone or combined with HCTZ in lowering blood pressure in patients with mild to moderate essential hypertension.     

Comparative study of spirapril (quadropril) and amlodipine efficacy. Results of randomized trial in patients with mild to moderate arterial hypertension

AIM: To compare in the non-blind randomised parallel study the efficiency of quadropril and amlodipine in the treatment of mild to moderate arterial hypertension. MATERIAL AND METHODS: A total of 80 patients (57.6 +/- 1.0 years) were included in this study. The patients were randomised in two groups, 40 patients each. Patients of group 1 received monotherapy with quadropril, while those of group 2 were treated with amlodipine. The treatment duration was 8 weeks in both groups. Quadropril was given in a fixed dose of 6 mg once daily. The initial dose of amlodipine was 5 mg/day. In case of insufficient effect the dose was elevated to 10 mg/day. The efficacy was evaluated by changes in blood pressure (BP) measured at rest. Moreover, in 50 randomly chosen patients 24-h monitoring of BP was performed at the start and end of the treatment. RESULTS: In the quadropril group baseline systolic BP reached 158.6 +/- 2.1 mm Hg, diastolic BP--101.8 +/- 0.8 mm Hg, heart rate was 74.3 +/- 1.6 beats/min. In the amlodipine group baseline systolic BP was 159.9 +/- 2.4 mm Hg, diastolic BP--101.8 +/- 1.0 mm Hg, heart rate was 71.3 +/- 1.0 beats/min. Systolic BP decreased at the end of quadropril therapy to 138.5 +/- 2.2 mm Hg, diastolic BP to 88.1 +/- 1.4 mm Hg. No significant change of the heart rate was observed. Under 5 mg of amlodipine systolic BP decreased to 137.9 +/- 2.5 mm Hg and diastolic BP to 87.1 +/- 1.6 mm Hg. Heart rate increased to 73.3 +/- 2.2 beats/min. Under therapy with 10 mg amlodipine systolic BP decreased to 145.9 +/- 3.8 mm Hg, diastolic BP to 89.7 +/- 3.4 mm Hg. Heart rate increased to 77.3 +/- 4.0 beats/min (p < 0.01). The hypotensive effect of quadropril remained stable while the effect of amlodipine decreased by the 8th week of therapy (p < 0.01). Side effects were observed significantly more often in the amlodipine group, then in the quadropril group. The main quadropril side effect was cough. Side effects observed in the amlodipine group were edemas, tachycardia, weakness. CONCLUSION: Both quadropril and amlodipine demonstrated a comparable antihypertensive effect although in 11 of 40 patients in the amlodipine group a dose increase was necessary and tolerability of quadropril was better.     

Heart remodeling in patients with predialysis phase of chronic renal failure

AIM: To investigate remodeling of the heart in patients with predialysis phase of chronic renal failure (CRF). MATERIAL AND METHODS: Patients with predialysis phase of CRF (n = 61; serum creatinine 412.4 +/- 242.69 mumol/l), essential hypertension (EH) (n = 35) and healthy volunteers (n = 20) were assessed with echocardiography. The patients were not significantly different by the level of systolic and diastolic blood pressure, age and gender. RESULTS: Left ventricular mass index (LVMI) was increased in 53(86.9%) patients with CRF. LVMI was not different in patients with CRF and EH (189.9 +/- 71.35 vs. 165.0 +/- 41.83 g/m2; p = 0.3). Relative wall thickness was similar in patients with serum creatinine < 200 mumol/l and patients with more elevated serum creatinine (57.2 +/- 10.33 vs 58.31 +/- 13.33; p = 0.9). The ejection fraction lower than 50% was detected in 14(22.9%) patients with CRF. Multivariate regression analysis showed that LVMI was independently related to systolic blood pressure (p = 0.004) and level of hemoglobin (p = 0.004). Diastolic dysfunction (early and atrial peak filling velocities ratio < 1.0) was detected in 13(50%) from 26 investigated patients with CRF. The independent influence of hemoglobin on isovolumic relaxation time (p = 0.04) and early and atrial peak filling velocities ratio (p = 0.02) are shown. CONCLUSION: In patients with predialysis phase of CRF left ventricular hypertrophy (LVH) is extremely common including patients with mildly elevated serum creatinine. The treatment of patients with renal pathology and normal function must include measures not only to correct renal process but also to prevent development of LVH.     

缬沙坦对高血压患者左心室壁厚度和舒张功能的影响

目的观察缬沙坦的降压效果,及其对左心室壁厚度和舒张功能的影响。方法对55例高血压患者使用缬沙坦降压治疗6个月,观察其降压效果及对左心室功能影响。结果治疗6个月后患者血压明显下降,收缩压平均下降27.7 mm Hg(1 mm Hg=0.133 kPa),舒张压平均下降16.4 mm Hg,左心室壁厚度及左心室舒张末期内径也明显下降。结论缬沙坦降压效果较好,且不良反应轻微,并可逆转左心室肥厚及改善左心室舒张功能。     

Digitalis-Induced Increase in Aortic Regurgitation and the Contrasting Effects of Glucagon in the Sedated Dog

The hemodynamic and phasic ascending aortic flow changes induced by acetylstrophanthidin and glucagon were studied in closed-chest sedated dogs with aortic regurgitation. While the positive inotropic effect of both agents was reflected in an increase in peak rate of rise of left ventricular pressure, acetylstrophanthidin increased aortic regurgitation, while glucagon decreased it. With the former, left ventricular end-diastolic pressure rose from 20+/-6 to 27+/-6 mm Hg (P < 0.005), but fell from 18+/-4 to 11+/-3 mm Hg (P < 0.001) with glucagon. Acetylstrophanthidin increased systemic vascular resistance, aortic diastolic pressure, and diastolic regurgitant flow rate, and, heart rate and the duration of regurgitation per beat and per minute being unchanged, regurgitant flow per beat increased 32+/-15% (P < 0.001). Glucagon decreased regurgitant flow per beat 27+/-14% (P < 0.001) because of abbreviation of diastole associated with tachycardia, and because of reduction in regurgitant flow rate. Despite tachycardia, the duration of regurgitation per minute was unchanged, and the small fall in regurgitant blood flow per minute was not significant, but this pertained in the face of 47% increase in effective cardiac output (P < 0.001). In contrast, acetylstrophanthidin increased regurgitant flow per minute 28+/-14% (P < 0.001) without change in effective cardiac output. The increase in cardiac contractility, tachycardia, and systemic vasodilatation induced by glucagon preferentially enhanced forward blood flow, which led to reduction in left ventricular volume overload, while it increased cardiac output. Contrarily, acetylstrophanthidin increased aortic regurgitation and, despite its inotropic effect, increased left ventricular volume overload without an increase in cardiac output.     

Pulse blood pressure (according to 24-hour monitoring) and left ventricular myocardial structural changes in patients with hypertensive disease

AIM: To study a relationship of the magnitude of structural changes in the left ventricle (LV) to the mean daily pulse blood pressure (PBP) in patients with hypertensive disease (HD). MATERIALS AND METHODS: 70 male patients (mean age 49 +/- 1 years) with stages I (n = 54) to 11 (n = 16) HD. LV mass (LVM) was estimated by echocardiography according to the formula derived by R. B. Devereux et al. and normalized to body surface area [the LVM index (LVMI)]. The relative thickness index (RTI) for the posterior wall (PWRTI) and ventricular septum (VSRTI) was calculated as a ratio of the sum of PWRTI and VSRTI to the LV end-diastolic size. LVMI > 125 g/m2 was considered to be a criterion for LV hypertrophy (LVH). 24-hour blood pressure (BP) monitoring was performed with a Spacelabs-90207 device (USA). According to the 24-hour PBP value, the patients were divided into 2 groups: 1) those (n = 17) having PBP24 > 53 mm HG and 2) those (n = 53) having PBP24 < 53 mm Hg. RESULTS: Group 1 patients were found to have significantly higher LVMI, LV WRTI, and incidence of LVH and a complex of changes in the BP profile as higher values of 24-hour systolic, diastolic and mean BP, PBP, and BP variations. Multiple regression analysis revealed a highly significant contribution of PBP24 to the development of LVH. CONCLUSION: The pedictive value of PBP as an index that characterizes a dynamic pressure load in regard to LV structural changes is higher than that of mean BP as a static load index and a BP variation index.     

超声心动图评价吲达帕胺和氢氯噻嗪对高血压病患者心脏结构和功能的影响

目的　应用多普勒超声心动图评价吲达帕胺和氢氯噻嗪对于轻中度原发性高血压病患者心脏结构和功能的影响。方法　 63例轻中度高血压病患者随机双盲分为吲达帕胺组 (2 .5mg/d)、氢氯噻嗪组 (2 5mg/d)和未用药对照组。在用药前及用药后的 4周、6个月末行超声心动图检查评价心脏结构、左室功能。结果　两药均有逆转左室肥厚的趋势。 6个月后吲达帕胺组LVM和LVMI显著降低 ,LVMI从 (97.0 2± 15 .60 ) g/m2 降至 (73 .89± 16.70 ) g/m2 ,LVM从 (162 .75± 3 6.2 3 )g降至 (112 .7± 2 8.15 ) g ,P值分别 <0 .0 1和 <0 .0 5 ,与对照组比也显著降低 ,P <0 .0 1。 6个月时的LVMI和IVST在二药有显著性差异 ,P均 <0 .0 5。两药对舒张、收缩功能有改善趋势 ,氢氯噻嗪的作用稍强 ,但这些改变在与用药前和两药之间的比较中均无显著性意义。结论　吲达帕胺和氢氯噻嗪可轻度改善心脏收缩和舒张功能。吲达帕胺逆转左室肥厚的作用非常显著。