The dependence of the cardiac effects of nifedipine on the responses of the peripheral vascular system

To elucidate the mechanisms of reduction of left ventricular end-diastolic pressure by nifedipine in certain individuals, we evaluated cardiac and peripheral hemodynamic responses in 32 patients after they were randomly assigned to nifedipine (20 mg sublingually) or to placebo treatment. Forearm plethysmography was performed during cardiac catheterization with micromanometers. No hemodynamic parameters were changed after placebo. Left ventricular end-diastolic pressure declined by 14% (p less than .02) after nifedipine in patients with impaired left ventricular function, but was unchanged in those with normal function; indexes of peripheral venous hemodynamics (forearm venous tone, forearm volume change) were not affected. In those patients with abnormal left ventricular function, forearm vascular resistance decreased 36% and forearm blood flow increased 31% (p less than .0005 for both), while neither changed in those with normal function. Cardiac output increased by 10% in patients with impaired left ventricular function but was unchanged in the remainder, while calculated total systemic resistance fell by 24% in those with abnormal left ventricular function (p less than .002 for both). Thus, reduction of left ventricular preload by nifedipine is not attributable to venous pooling, but rather this beneficial effect appears to be attributable to improved left ventricular systolic function in response to afterload reduction, particularly in patients with impaired left ventricular function.     

西洋参叶二醇组皂苷对大鼠实验性心室重构的保护作用

目的观察西洋参叶二醇组皂苷(PQDS)对大鼠实验性心室重构的保护作用。方法结扎大鼠腹主动脉建立压力超负荷性心室重构模型。将Wistar雄性大鼠随机分为假手术组、重构模型组、阳性药贝那普利(10mg/kg)组及PQDS50、100mg/kg组。给药6w后测定心肌形态学及血流动力学参数,通过光学显微镜观察心肌病理变化。结果PQDS能明显降低心室重构大鼠的心室重量及心脏系数,明显升高收缩压(SBP)、舒张压(DBP)及平均动脉压(MAP),降低左室舒张末压(LVEDP),能抑制心肌纤维增粗,改善心肌间质水肿,其作用效果与血管紧张素转化酶抑制剂贝那普利相当。结论PQDS可能通过改善心室重构大鼠的左心收缩和舒张功能发挥防治心室重构的作用。     

Comparative study of acute and chronic effects of nifedipine in patients with secondary pulmonary hypertension

The effects of nifedipine in a single dose of 10 mg on the pulmonary circulation and the selected right and left ventricular function indices were studied in a group of 10 patients with secondary pulmonary hypertension (mean systolic pressure 55.2 mm Hg). In 8 patients hemodynamic studies were repeated after seven days treatment (3 x 10 mg). Acute treatment with nifedipine resulted in a reduction in mean systolic arterial pressure by 21.8%, diastolic by 12.2% and systemic resistance by 25.5%, and in an increase in cardiac index by 14.3%. After 7 days a similar pattern of changes was observed, however with less intensity: systolic pressure was reduced by 10.3% diastolic by 5.5%, and systemic resistance by 17.1%. Pulmonary artery wedge pressure did not change after a single dose, and mean pulmonary artery pressures showed a tendency toward lower levels: systolic by 8.9% and diastolic by 8.6%, whereas total pulmonary resistance decreased markedly (by 22.7%), as well as pulmonary vascular resistance. Right ventricular filling pressure was reduced. After chronic treatment we found a further slight fall in the pulmonary arterial pressure. Although per cent changes were similar to those in the arterial pressure, alterations in the mean values were not statistically significant. The total pulmonary resistance remained reduced. While analysing the changes in the pulmonary circulation and right ventricular indices it should be noted that they were less intense and less homogeneous than the left ventricular function parameters. Some of the patients showed certain similarities in the direction and intensity of changes in the hemodynamic indices of the pulmonary circulation in the acute and chronic experiment.     

Long-term treatment of chronic heart failure by an inhibitor of angiotensin converting enzyme

We studied the hemodynamic, echocardiographic, phonomechanographic and hormonal changes during acute (25 mg) and chronic (6 months--75 to 225 mg/day) treatment of 10 patients with congestive cardiac failure due to cardiomyopathy with dilatation with SQ 14 225 (Captopril). The following changes were observed after the single dose: an increase in cardiac output (p less than 0,001), in stroke volume (p less than 0,01), a reduction in heart rate (p less than 0,01), in peripheral resistance (p less than 0,001) and pulmonary capillary pressure (p less than 0,001). There were no significant changes in end systolic or end diastolic left ventricular internal diameter. Plasma renin activity increased (p less than 0,001); there was a concurrent fall in serum aldosterone (NS): the plasma concentration of converting enzyme decreased (p less than 0,001). There was a correlation between the increase in peripheral resistance under basal conditions and the basal plasma renin activity (R = 0,72, p less than 0,02). The decrease in peripheral resistance after captopril also correlated with basal plasma renin activity (R = 0,89, p less than 0,01). After six months continuous therapy, the hemodynamic effect was sustained and was accompanied by a significant symptomatic improvement. Left ventricular internal end systolic and end diastolic diameters decreased (p less than 0,01 and p less than 0,01 respectively). The pre-ejectional period decreased (p less than 0,05). Serum aldosterone fell significantly (p less than 0,001) as did plasma renin activity (p less than 0,01); the serum level of converting enzyme remained low with respect to its initial value. These results show that captopril may be useful in severe cardiac failure without tolerance during long-term administration. No renal or hematological toxicity was observed in this group of patients.     

Systemic and regional hemodynamic and humoral effects of nitrendipine in essential hypertension

The hemodynamic effects of 3 months of nitrendipine therapy were evaluated in 14 patients with mild to moderate essential hypertension. Nitrendipine reduced systolic and diastolic pressures from 145 +/- 4/95 +/- 3 to 119 +/- 3/78 +/- 2 mm Hg, respectively, (p less than 0.001) through a fall in total peripheral resistance index (46 +/- 4 to 34 +/- 3 units/m2, p less than 0.001) without associated reflex cardiac stimulation. This antihypertensive effect was related directly to the height of pretreatment arterial pressure (r = -0.67, p = 0.006) but not to age or pretreatment plasma renin activity. Renal and forearm blood flow increased, vascular resistance decreased, and glomerular filtration rate remained stable. In addition, nitrendipine reduced left ventricular mass index (133 +/- 7 to 116 +/- 5 g/m2, p = 0.003) and wall thickness, changes that were accompanied by improvement in diastolic as well as systolic (ejection fraction and fractional fiber shortening rate) left ventricular functions. Intravascular volume did not expand with reduction in pressure. This study provides new information concerning the long-term hemodynamic effects and associated echocardiographic changes with nitrendipine. It also provides the first regional hemodynamic data in essential hypertensive patients detailing forearm and splanchnic changes and renal blood flow increase during prolonged treatment.     

Separation of afterload reduction and a direct beneficial cardiac effect of nifedipine in congestive cardiomyopathy

To assess whether the calcium antagonist nifedipine has a specific, direct effect on left ventricular diastolic function separate from its vasodilatory action, we studied 10 patients with idiopathic congestive cardiomyopathy (ages 28-69, New York Heart Association Class III or IV) at 30 min, 2 h, and 6 h after administration of 10 mg of sublingual nifedipine. Hemodynamic parameters were assessed with Swan-Ganz catheter and two-dimensional echo images were processed with computer-assisted analysis (Quantic 1200) to obtain left ventricular chamber areas and an index of rapid diastolic filling. Indices of left ventricular systolic performance (cardiac index and left ventricular area change fraction) improved during the early (30 min and 2 h) observation periods as afterload (estimated by systolic blood pressure and systemic vascular resistance) was reduced (p less than .05 vs. baseline). Pulmonary capillary wedge pressure fell from 17 mmHg to 11 mmHg and rapid diastolic filling index increased from .28 (% area change/ms) to .37 (% area change/ms) (p less than .05 vs. baseline) during the early observation periods. Indices of left ventricular systolic performance and afterload had returned to baseline at the late (6 h) observation period. However, pulmonary capillary wedge pressure remained reduced significantly at 10 mmHg after 6 h (p less than .05 vs. baseline). Preload (estimated by left ventricular end-diastolic chamber area) did not vary throughout the study period. Reduction of pulmonary capillary wedge pressure at 6 h, despite return of afterload reduction to baseline and no change in preload, suggests improved left ventricular chamber compliance after sublingual nifedipine, not related to alteration of left ventricular loading conditions.     

Mechanisms for improvement of cardiac performance by nifedipine in an acute mitral regurgitation in dogs

To elucidate the mechanisms of the beneficial hemodynamic action of nifedipine in congestive heart failure, the systolic and diastolic hemodynamic parameters were evaluated for 30 min after sublingual administration of 20 mg of nifedipine in 12 dogs with acute mitral regurgitation (group 1) and in 5 dogs without mitral regurgitation (group 2, sham operation group). An additional 6 dogs with mitral regurgitation were followed for 30 min without nifedipine (group 3). Nifedipine lowered both arterial pressure and systemic vascular resistance, increased coronary blood flow and stroke volume significantly in both groups 1 and 2. The left ventricular developed tension was increased by nifedipine only in group 1, probably due to the geometric changes in the expanded left ventricle in failure, secondary to left ventricular preload and afterload reduction. Nifedipine had no effects on ventricular relaxation properties in this study. This study suggests that the mechanisms responsible for the improvement of cardiac performance induced by nifedipine in heart failure caused by an acute mitral regurgitation are essentially a reduction in left ventricular afterload and an increase in left ventricular contractility secondary to afterload reduction.     

Hemodynamics of the Mueller maneuver in man: right and left heart micromanometry and Doppler echocardiography

Ten subjects with normal hemodynamics were studied during elective cardiac catheterization with right and left heart multisensor micromanometry to assess hemodynamic responses to the Mueller maneuver. Simultaneous right and left circulatory hemodynamics and left ventricular, pulmonary arterial, and aortic pressures were recorded, in addition to pulmonary arterial and aortic flow velocities. Steady-state cardiac outputs were determined by thermal dilution. Aortic systolic and mean pressures were not significantly changed during the Mueller maneuver, in contrast to a lower diastolic (p = .019) and higher pulse pressure (p = .016). Mean right atrial pressure (+/- SE) decreased from 7 +/- 1 to -17 +/- 4 mm Hg (p = .0002) and the right atrial "x" descent was markedly accentuated. Left ventricular end-diastolic pressure decreased from 12 +/- 4 to -3 +/- 13 mm Hg (p = .0025). Systemic vascular resistance and left ventricular peak positive dP/dt were increased during the Mueller maneuver (p less than .02), cardiac output and stroke volume were reduced (p less than .05), and there was no significant change in heart rate. Right and left peak flow velocities showed a trend toward a bilateral decrease (right, p = .054; left, p greater than .1), and times to peak flow velocity were increased in the pulmonary artery (p = .007) and reduced in the aortic root (p = .03). Normal subjects were studied separately by pulsed Doppler echocardiography. During the sustained Mueller maneuver, the internal jugular and right ventricular dimensions decreased, and superior vena cava Doppler flow was reduced.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiovascular effects of caffeine in men and women

Caffeine increases blood pressure (BP). In men, acute BP elevations after caffeine intake are due to an increase in vascular resistance, with no change in cardiac output. The hemodynamic effects of caffeine have not been studied in women. Accordingly, BP and hemodynamic responses to caffeine were measured in a double-blind trial comparing age-matched men and women at rest and during mental stress. Caffeine (3.3 mg/kg, equivalent to 2 to 3 cups of brewed coffee) or placebo was given to separate groups of women (n = 21 and 21) and men (n = 16 and 19) (mean ages 29 and 27 years, respectively). BP, cardiac output, and vascular resistance were observed at rest, during a stressful public-speaking simulation, reading aloud, and recovery. Caffeine caused nearly identical systolic and diastolic BP elevations in women (4.5 and 3.3 mm Hg, respectively) and men (4.1 and 3.8 mm Hg, respectively). Men given caffeine versus placebo showed the expected elevation in vascular resistance throughout the remainder of the protocol (p <0.001), with no difference in cardiac output. In contrast, women responded to caffeine with increases in stroke volume (p <0.001) and cardiac output (p <0.001), with no difference in vascular resistance from women taking placebo. Men and women have similar BP responses to caffeine, but the BP responses may arise from different hemodynamic mechanisms. Women who consume a dietary dose of caffeine showed an increase in cardiac output, whereas men showed increased vascular resistance.     

Acute effects of intravenous nicardipine on hemodynamics and cardiac function in patients with a healed myocardial infarction and no evidence of congestive heart failure

Acute effects of intravenous nicardipine (10 micrograms/kg) on systemic hemodynamics and cardiac function were evaluated in 17 patients with a healed myocardial infarction and no evidence of congestive heart failure. Mean New York Heart Association functional class was 1.6 +/- 0.5 (mean +/- standard deviation). Aortic systolic pressure (p less than 0.001) and left ventricular end-diastolic pressure decreased (10 +/- 3 to 8 +/- 3 mm Hg, p less than 0.01), and systemic vascular resistance decreased significantly (p less than 0.001), whereas pulmonary and right atrial pressure and pulmonary arteriolar resistance did not change. Cardiac and stroke indexes showed biphasic changes. Although positive and negative maximal rate of left ventricular pressures decreased significantly (p less than 0.05 and p less than 0.01, respectively), they did not change significantly when aortic systolic pressure was corrected. There was a significant inverse correlation between the negative rate of left ventricular pressure/aortic systolic pressure before nicardipine infusion and its maximal percent increase after infusion (r = -0.56, p less than 0.05), indicating a beneficial effect on diastolic relaxation in patients with impaired diastolic function. Our data show that a low dose (10 micrograms/kg) of intravenous nicardipine exerts a favorable effect on impaired diastolic function, but depresses left ventricular pump function with much less effect on right heart circulation.     

Effects of nifedipine on intrinsic myocardial stiffness in man

To determine whether alteration of intrinsic myocardial stiffness is responsible for the reduction of left ventricular filling pressure and volume by nifedipine in patients with impaired baseline ventricular function, we evaluated the hemodynamic responses in 32 patients undergoing diagnostic cardiac catheterization. Micromanometric pressure and ventriculographic dimensional data were acquired before and 30 min after randomly assigned administration of nifedipine (20 mg sublingual) or placebo. A mathematical model requiring no assumptions about the stress-radius relationship or direct measurement of strain was used. No hemodynamic variables were changed after placebo. Left ventricular end-diastolic volume and pressure declined and cardiac output increased after nifedipine, particularly in subjects with impaired ventricular performance. Despite these salutary effects, intrinsic myocardial stiffness, elastic stiffness at a common level of stress, chamber stiffness, and rate of isovolumic relaxation were unchanged after nifedipine, even in patients with abnormal baseline ventricular function. The potent peripheral arteriodilator effect of nifedipine, rather than any direct myocardial or ventricular effects, appears to be responsible for the improved systolic and diastolic performance.     

Calcium antagonists in heart failure

Clinical experience with calcium antagonists in congestive heart failure has, to date, been mainly restricted to the use of nifedipine but there is either no or only a limited extent of information available on diltiazem and verapamil. In patients with acute and chronic congestive heart failure, single-dose administration of nifedipine was seen to lead to a decrease in systemic vascular resistance, left ventricular filling pressure and ventricular volumes as well as to an increase in stroke volume, ejection fraction and mean velocity of circumferential fiber shortening. These favorable effects could not be detected in eight patients during a three-week treatment phase with 80 mg nifedipine daily: resting blood pressure, cardiac volumes, echocardiographically-dimensions and exercise tolerance were unchanged as compared with placebo. In patients with ischemic heart disease and impaired ventricular function, in addition to an improvement in systolic function, single-dose nifedipine administration led to favorable effects on diastolic function with a shift of the diastolic pressure-volume relationship downward and to the diastolic pressure-volume relationship downward and to the left. In patients with severe aortic regurgitation, the observed increase in effective cardiac output affected by nifedipine was primarily attributable to an increase in heart rate. In the presence of an initially-elevated systemic vascular resistance, the regurgitation fraction decreased. In pulmonary hypertension, favorable hemodynamic effects have been reported after acute administration of verapamil as well as diltiazem and nifedipine. In individual cases, promising results in patients with primary pulmonary hypertension have been reported during long-term therapy with nifedipine provided that a favorable initial response could be documented.     

Cardiac adaptation to obesity and hypertension after heart transplantation.

Obesity and hypertension frequently develop after heart transplantation. The cardiac adaptation to obesity and hypertension was studied by determining hemodynamic and echocardiographic indexes in 10 obese hypertensive patients (body mass index greater than or equal to 27.8 kg/m2 in men or greater than or equal to 27.3 kg/m2 in women) matched by mean arterial pressure, age and gender with 10 nonobese hypertensive patients 1 year after cardiac transplantation. Cardiac output was 30% greater (p less than 0.02) and systemic vascular resistance 25% lower (p less than 0.01) in the obese than in the nonobese patients. Right ventricular systolic and pulmonary artery systolic, diastolic and mean pressures were also significantly higher (p less than 0.05) in the obese patients. Left ventricular end-diastolic diameter was 25% greater (p less than 0.05), left ventricular mass 28% greater (p less than 0.02) and left ventricular end-diastolic volume 20% higher (p less than 0.01) in the obese subjects. Left ventricular ejection fraction was significantly lower in the obese than in the nonobese subjects (34% vs. 51%, p less than 0.05). These results indicate that the cardiac adaptation to obesity and hypertension after heart transplantation consists of left ventricular dilation and an increase in left ventricular mass associated with an increased cardiac output and lower peripheral vascular resistance. These adaptive changes that occur in obese hypertensive patients after heart transplantation might increase the long-term risk of graft failure, as suggested by their lower left ventricular ejection fraction 1 year after transplantation.     

Acute effects of parenteral beta-blockade on regional ventricular function of infarct and noninfarct zones after reperfusion therapy in humans.

Although the mechanism is unknown, clinical trials have suggested that intravenous beta-adrenergic blockade may prevent early cardiac rupture after myocardial infarction. Previous studies have examined effects of beta-blockers on global left ventricular function after myocardial infarction; however, few data exist regarding their immediate effects on regional function or in patients after successful reperfusion. Therefore, 65 patients in whom thrombolysis with or without coronary angioplasty achieved reperfusion at 4.6 +/- 1.7 h from symptom onset were studied. Low osmolarity contrast ventriculograms were obtained immediately before and after administration of 15 mg of intravenous metoprolol (n = 54) or placebo (n = 11). Intravenous metoprolol immediately decreased heart rate (from 92 to 76 beats/min, p less than 0.0001), increased left ventricular diastolic volume (from 150 to 163 ml, p less than 0.001) and systolic volume (from 72 to 77 ml, p less than 0.0005) but did not change systolic and diastolic pressures. Although there was no difference in ejection fraction after metoprolol, centerline chord analysis revealed reduced noninfarct zone motion (from 0.41 to 0.12 SD/chord, p less than 0.05), improved infarct zone motion (from -3.1 to -2.9 SD/chord, p less than 0.01) and smaller circumferential extent of hypokinesia (from 30 to 27 chords, p less than 0.05). Patients with dyskinesia of the infarct zone had the most striking improvement in infarct zone wall motion. Because these changes occurred immediately after beta-blockade, they could not be attributed to myocardial salvage. No significant changes in heart rate, left ventricular volumes or regional wall motion were apparent in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relation between serum nifedipine concentration and hemodynamic effects in nonobstructive hypertrophic cardiomyopathy

The relation between nifedipine concentration and hemodynamic effects after sublingual administration of 10 or 20 mg was examined in 13 patients with nonobstructive hypertrophic cardiomyopathy (HC). Serum nifedipine concentrations were determined by gas chromatography and were not related to dose. Peripheral vascular resistance decreased as a function of nifedipine concentration (r = -0.63, p less than 0.001); this was associated with a concentration-related increase in heart rate (r = 0.56, p less than 0.001) and in cardiac index (r = 0.50, p less than 0.001). However, evidence for a pure vasodilator effect of nifedipine was inconsistent, in that the change in stroke volume index with nifedipine was not significant. Although stroke volume index increased at nifedipine concentrations between 60 and 120 ng/ml (38 +/- 6 to 42 +/- 4 ml/m2, p less than 0.01), it decreased at concentrations greater than 120 ng/ml (40 +/- 3 to 38 +/- 4 ml/m2, p less than 0.01). Moreover, pulmonary artery wedge pressure increased at nifedipine concentrations greater than 120 ng/ml (11 +/- 2 to 16 +/- 4 mm Hg, p less than 0.001), suggesting either depressed left ventricular (LV) systolic function or reduced LV filling. To investigate these possible mechanisms, LV systolic and diastolic function was studied during catheterization with a nonimaging scintillation probe in 6 of the 13 patients. In these subjects, heart rate was held constant by atrial pacing.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inhibition of p38 mitogen-activated protein kinase attenuates left ventricular dysfunction by mediating pro-inflammatory cardiac cytokine levels in a mouse model of diabetes mellitus

Aims/hypothesis We investigated the effect of SB 203580, a pharmacological inhibitor of p38 mitogen-activated protein kinase (MAPK), on cardiac inflammation, cardiac fibrosis, and left ventricular function using an animal model of diabetic cardiomyopathy. Materials and methods Diabetes mellitus was induced by streptozotocin (50 mg/kg i.p. for 5 days) in 20 C57/BL6J mice. Diabetic mice were treated daily with the p38 MAPK inhibitor SB 203580 (1 mg/kg daily, n=10) or with placebo (n=10) and were compared to non-diabetic controls. Left ventricular function was measured by pressure–volume loops after 8 weeks of diabetes mellitus. The parameters for systolic function were the end systolic pressure–volume relationship (ESPVR) and the left ventricular end systolic pressure. The parameters for diastolic function were the left ventricular end diastolic pressure and the end diastolic pressure–volume relationship (EDPVR). Cardiac tissue was analysed by ELISA for the protein content of the cytokines TNF-α, IL6, IL1-β, and TGF-β1. Phosphorylation of MAPK p38 was analysed by western blot, and the total cardiac collagen content was analysed by Sirius red staining. Results Left ventricular dysfunction was documented by impaired ESPVR and EDPVR. Cardiac cytokine levels and cardiac fibrosis were increased in diabetic animals compared to controls. Treatment with the p38 inhibitor normalised cardiac cytokine levels and improved systolic function, but did not change cardiac fibrosis and diastolic dysfunction compared to placebo. Conclusions/interpretation Pharmacological inhibition of p38 MAPK prevents cardiac inflammation and attenuates left ventricular dysfunction in diabetic cardiomyopathy.     

Intake of tuna or other broiled or baked fish versus fried fish and cardiac structure, function, and hemodynamics

Fish intake is associated with improved cardiovascular health, including a lower risk of arrhythmic death, atrial fibrillation, and heart failure. However, the physiologic effects that may produce these cardiovascular benefits are not well-established. We investigated the cross-sectional associations between a usual dietary intake of fish during the previous year and cardiac structure, function, and hemodynamics as determined by physical examination and 2-dimensional, Doppler, and M-mode transthoracic echocardiography among 5,073 older adults enrolled in the Cardiovascular Health Study. On multivariate-adjusted analyses, consumption of tuna or other broiled or baked fish was associated with a lower heart rate (p < 0.001), lower systemic vascular resistance (p = 0.002), and greater stroke volume (p < 0.001). Tuna/other fish intake was also associated with a higher E/A ratio (p = 0.004), a measure of more normal diastolic function. In contrast, fried fish or fish sandwich (fish burger) intake was associated with left ventricular wall motion abnormalities (p = 0.02), a reduced ejection fraction (p < 0.001), lower cardiac output (p = 0.04), a trend toward a larger left ventricular diastolic dimension (p = 0.07), and higher systemic vascular resistance (p = 0.003). In conclusion, in this large population-based study, the intake of tuna or other broiled or baked fish was associated with improved cardiac hemodynamics, but fried fish intake was associated with structural abnormalities indicative of systolic dysfunction and potential coronary atherosclerosis. These findings suggest potential specific physiologic mechanisms that may, in part, account for the effects of fish intake on cardiovascular health.     

Effect of enalapril on left ventricular mass and performance in essential hypertension

The effect of enalapril on left ventricular (LV) morphology and function was studied in 12 hypertensive patients. The subjects were evaluated after 2 weeks of placebo and after 4 months of treatment with enalapril (20 or 40 mg once daily), using M-mode digitized echocardiograms. The drug reduced arterial blood pressure in all patients. Systemic vascular resistance decreased significantly without changes in cardiac output and heart rate. No patient had significant side effects. After treatment LV mass decreased significantly (233 +/- 46 to 204 +/- 37 g, p less than 0.01); the reduction was due to a decrease in septal and posterior wall thickness, without changes in LV diameter. LV systolic function remained unchanged, whereas peak lengthening rate of LV dimension, an index of LV diastolic function, increased significantly (4.05 +/- 1.8 to 5.11 +/- 1.8 s-1, p less than 0.01). After treatment the basal inverse correlation between peak shortening rate and wall stress did not change, the inverse correlation between peak lengthening rate and wall stress became closer and the basal inverse correlation between peak lengthening rate and LV mass disappeared. In conclusion, antihypertensive treatment with enalapril led to a significant regression of LV hypertrophy associated with improvement in LV diastolic performance and no deterioration of LV systolic function.     

Left ventricular mass and function before and after antihypertensive treatment

We have studied the effect of blood pressure control upon left ventricular mass and function. Twenty hypertensive patients without clinical or electrocardiographic signs of cardiac involvement were given sequentially: placebo for two weeks; captopril (250 mg/day) for eight weeks; and captopril (125 mg/day), alone or combined with chlorthalidone (25 mg/day), for eight weeks. M-mode echocardiography was performed at the end of placebo period, after eight and after 16 weeks active treatment. Blood pressure was significantly reduced (p less than 0.01) by therapy, the maximum decrease being observed at the end of the study. Similarly, interventricular septal thickness, posterior wall thickness and left ventricular mass index showed a significant reduction (P less than 0.01 at the eighth and P less than 0.001 at the 16th week), while no changes were detected in left ventricular function. Furthermore, both wall stress index at end-diastole and end-systolic stress were significantly lowered by treatment (at the 16th week P less than 0.01 and P less than 0.001, respectively). Baseline systolic blood pressure was inversely correlated with the ratio of the left ventricular radius to posterior wall thickness (r = -0.97, P less than 0.001) but no relation was found between post-treatment fall in either systolic or diastolic blood pressure and left ventricular mass index. After treatment more patients showed normal left ventricular wall thickness in relation to systolic blood pressure. We conclude that in uncomplicated hypertensive patients captopril, either alone or combined with chlorthalidone, can reverse left ventricular hypertrophy by decreasing both septal and posterior wall thickness.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic effects of antiarrhythmic drugs in acute myocardial infarction

The hemodynamic effects induced by an i.v. administration of Amiodarone (5 mg/Kg in 10 min + continuous infusion of 0.6 mg/min for 4-40 hrs), Propafenone (1-2 mg/Kg in 5 min + continuous infusion of 10-15 mcg/Kg/min for 24 hrs) and Mexiletine (250 mg in 15 min + 250 mg in 1 hr) have been evaluated in patients with acute myocardial infarction complicated by sinus tachycardia and hyperdynamic pattern, ventricular or supraventricular arrhythmias. The hemodynamic serial determinations have been comprehensive of: heart rate; systolic, diastolic and mean pressure; central venous pressure; arterial and wedge pulmonary pressure; cardiac output and cardiac index; vascular systemic resistences; left ventricular stroke work index; left ventricular mean ejection rate; double and triple product. In all of the three groups we observed: a reduction of cardiac index associated with an increase of left and right ventricular filling pressure and a reduction either of left ventricular stroke work index and left ventricular mean ejection rate; these hemodynamic changes were less significant after Mexiletine than after Amiodarone or Propafenone. These data confirm the negative inotropic effect of the three drugs; anyhow, these changes are usually well tolerated by patients affected by AMI with a sufficiently preserved ventricular function. The authors, however, reccommend an accurate hemodynamic monitoring of the effects of the drugs also to identify patients with a not overt ventricular failure which may become manifest after drug administration.