The influence of isotonic exercise on cardiac hypertrophy in arterial hypertension: impact on cardiac function and on the capacity for aerobic work.

Intense physical training through isotonic exercises has controversial effects in individuals with moderate to severe hypertension. In this study, normotensive Wistar rats and rats with renovascular hypertension (Goldblatt II) were subjected to intense physical exercise involving two 50-min swimming sessions per day for a period of 12 weeks. At the end of the study, we evaluated the effect of training on arterial pressure, the capacity for aerobic work and cardiac function. Our results demonstrate that intense physical training has no effect on the arterial blood pressure of normotensive rats or of animals with moderate renovascular hypertension. Hypertensive animals with cardiac hypertrophy require a greater period of training in order to attain the same capacity for aerobic work as normotensive rats. This difference may result from an inability of the former animals to increase cardiac compliance, thereby impeding more extensive usage of the Frank-Starling mechanism to subsequently increase the systolic cardiac performance. Cardiac hypertrophy induced by exercise did not summate with that induced by arterial hypertension. Physical exercise normalized the end-diastolic left ventricular pressure in hypertensive animals without any corresponding increase in the compliance of the chamber. The first derivative of left ventricular pulse pressure (+/- dP/dt) was greater in the hypertensive trained group than in the hypertensive sedentary rats. These observations suggest that a systolic dysfunction of the left ventricle involving an elevated residual volume secondary to arterial hypertension may be corrected by physical exercise such as swimming.

Hemodialysis versus continuous ambulatory peritoneal dialysis: effects on the heart.

In this study we compared the influence of 2 different modalities of treatment, CAPD and hemodialysis, on the prevalence and severity of left ventricular hypertrophy and cardiac arrhythmias of chronic renal failure patients. We compared 27 patients on the CAPD program with 27 patients on the chronic hemodialysis matched for sex, age, and duration of dialysis treatment. The prevalence of hypertension was significantly lower in CAPD than in hemodialysis patient (41% vs. 81%, p = 0.0023). Blood pressure levels were also lower in CAPD than in hemodialysis patients (systolic pressure 124.9 +/- 4.7 vs. 154.8 +/- 4.6 mm Hg, p < 0.0001; diastolic pressure 77.5 +/- 2.9 vs. 93.3 +/- 2.8 mm Hg, p = 0.0001). Left ventricular hypertrophy (LVH) was present in 52% of CAPD and in 93% of hemodialysis patients (p = 0.0008). Severe cardiac arrhythmias (Lown 3-4) occurred in only 4% of CAPD and in 33% of the hemodialysis group (p = 0.0149). The lower frequency of LVH in CAPD might explain the lower incidence of severe arrhythmias.

[Reversal of left ventricular hypertrophy after the use of benazepril]. / Reversão de hipertrofia ventricular esquerda após o uso de benazepril.

PURPOSE: To assess the effects of benazepril (ACE inhibitor) on arterial blood pressure (ABP) and left ventricular mass index (LVMI). METHODS: Nineteen patients (7 men, 12 women) with mean age 38.2 +/- 10.2 years, with mild to moderate hypertension were evaluated. Besides raised blood pressure, the necessary inclusion criterion was the presence of left ventricular hypertrophy detected by echocardiogram. After a wash-out period, all patients were given placebo followed by the active drug benazepril at a dose of 10 mg once a day. For those patients who did not achieve a satisfactory control of the blood pressure (BP) 25 mg of chlorthalidone was added. All patients underwent 180 days of benazepril treatment. RESULTS: The ABP was gradually controlled as follow: at seated position the systolic BP changed from 156.05 +/- 5.07 mmHg to 129 +/- 3.74 mmHg (p < 0.001) and the diastolic BP from 99.74 +/- 1.59 mmHg to 81.8 +/- 2.27 mmHg (p < 0.001). At orthostatic position the systolic BP changed from 156.9 +/- 5.35 mmHg to 124.28 +/- 5.33 mmHg (p < 0.001) and the diastolic BP from 101.7 +/- 1.34 to 81.36 +/- 2.81 (p < 0.001). The heart rate did not change significantly during the study. The LVMI decreased significantly from 182.4 +/- 9.2g/m2 to 122.6 +/- 4.2g/m2 (p < 0.001). CONCLUSION: Our data revealed that 100% of the patients achieved satisfactory degrees of LVMI regression and in 34% there was a normalization of it.

Funçäo ventricular de animais submetidos a ablaçäo da massa renal: efeito do controle da pressäo arterial / Ventricular function in animals subjected to renal mass ablation: effect of blood pressure control

A determinaçäo da hipertrofia ventricular na insuficiência renal crônica é multifatorial. Foram estudadas a pressäo arterial da cauda, peso cardíaco, máxima pressäo desenvolvida e as relaçöes pressäo-volume de animais com ablaçäo de5/6 de massa renal, cuja pressäo arterial se mantinha elevada (IRC; n=16) ou que recebiam furosemida na dose de 16mg/Kg para controlar a pressäo (IRC-F; n=17). Animais submetidos a cirurgia fictícia serviram como controles (SHAM; n=15). Os animais que sofreram ablaçäo da massa renal apresentavan níveis de creatinina sérica maiores do que os näo-operados )IRC = 1,81 ñ 0,05; IRC - F = 1,75 ñ 0,08; SHAM = 0,72 ñ 0,09; p 0,001). A massa cardíaca estava aumentada nos grupos IRC hipertenso (0,99 ñ 0,02g) e normotenso (1,01 ñ 0,02g) comparativamente ao SHAM (0,84 ñ 0,01) [p < 0,01]. A máxima pressäo desenvolvida durante a oclusäo transitória da aorta foi semelhante nos três grupos (IRC = 221,2 ñ 7,04; IRC-F = 255,7 ñ 10,01; SHAM = 239,9 ñ 5,5 mmHg, n.s.). Entretanto, o volume diastólico final operacional dos grupos IRC-H e IRC-N (91,4 ñ 9,44; 70,9 ñ 6,22µl, respectivamente) eram significativamente maiores do que o observado no grupo SHAM (28,75 ñ 3,12µL, p < 0,001). Portanto, a HVE induzida pela uremia näo é dependente da hipertensäo arterial que acompanha esta condiçäo. Ainda, o rendimento sistólico dos animais com hipertrofia é semelhante ao dos animais normais, mas, aparentemente, depende de uma maior utilizaçäo do mecanismo de Frank-Starling para seu funcionamento normal

[Ventricular function in animals undergoing renal mass ablation. Effect of blood pressure control]. / Função ventricular de animais submetidos a ablação da massa renal. Efeito do controle da pressão arterial.

The causes of left ventricular hypertrophy (LVH) in chronic renal failure are multifactorial. The tail arterial pressure, heart weight, maximum developed pressure and pressure-volume relationship in animals with 5/6 nephrectomy (CRF, n = 16) and CRF animals who received furosemide by oral gavage (CRF-F, n = 17) were studied. All CRF animals increased their blood pressure (Basal: 117.2 +/- 0.8; 6th week: 184.8 +/- 2.9, p < 0.001) but in those treated with furosemide the blood pressure stayed within normal levels (Basal: 118.23 +/- 1.3; 6th week = 118.8 +/- 1.6, p = 0.5734). SHAM animals served as control (SHAM, n = 15). All CRF and CRF-F animals increased their levels of serum creatinine (CRF = 1.81 +/- 0.05; CRF-F = 1.75 +/- 0.05; SHAM = 0.72 +/- 0.09 mg/dL p < 0.001). Cardiac weight was elevated in CRF and CRF-F when compared with SHAM rats. The operational maximum developed pressure was similar in the three groups (CRF = 221.2 +/- 7.04; CRF-F = 255.7 +/- 10.1; SHAM = 239.9 +/- 5.5 mmHg, n.s.). However, the end-diastolic volume was significantly increased in both CRF and CRF-F when compared with SHAM rats (CRF = 91.4 +/- 9.44; CRF-F = 70.9 +/- 6.22; SHAM = 28.75 +/- 3.12 microL. p < 0.001). These data demonstrate that LVH in chronic renal failure is not dependent of the arterial hypertension, that accompanies this condition. Moreover, the systolic work of LVH animals is similar to that of normal animals, but a greater utilization of Frank-Starling mechanism to maintain normal ventricular function is needed.

Parenteral isradipine reduces blood pressure in hypertensive crisis.

The efficacy and tolerability of an infusion of isradipine, a calcium antagonist of the dihydropyridine type, were tested in patients in hypertensive crisis. Ten patients with symptomatic and significant elevations in blood pressure were infused for 12 h with isradipine at 1.2, 2.4, 4.8, and 7.2 micrograms/kg/h (3 h of each infusion level). No untoward effects or adverse reactions were noted. No alterations were observed on electrocardiographic tracings, and blood pressure was significantly reduced only at doses of 7.2 micrograms/kg/h. Thus, isradipine as an infusion is useful and safe for hypertensive crisis, starting at a rate of 7.2 micrograms/kg/h. Higher doses may yet prove to be safe, well tolerated, and even more efficacious.

Reversal of left ventricular hypertrophy with isradipine induces diminution of cardiac arrhythmias.

The left ventricular hypertrophy (LVH) of hypertension is often associated with ventricular arrhythmias, which may increase the risk of cardiovascular mortality. Our study was therefore designed to assess whether pharmacological reversal of LVH was associated with the diminution of LV ectopic beats. The antihypertensive agent selected for the study was the dihydropyridine calcium antagonist isradipine (2.5 to 5.0 mg/day orally), which induces rapid regression of LVH. A marked temporal association was observed between regression of LV mass and reductions in the total number of ventricular extrasystoles and in paired beats. Furthermore, there was a diminution of the complexity of the form of ventricular ectopic beats during antihypertensive treatment. No changes in serum electrolytes were documented to account for this control of cardiac arrhythmias. We conclude that the reversal of LVH obtained with isradipine is accompanied by control of the ventricular arrhythmias in hypertensive patients. It is possible that this cardioprotective action may be associated non-specifically with the reduction in LV mass, although a drug- or class-specific action cannot be ruled out.

Risk factors for the occurrence of cardiac arrhythmias in patients on continuous ambulatory peritoneal dialysis.

In order to evaluate the risk factors for the occurrence of ventricular arrhythmias (VA) in continuous ambulatory peritoneal dialysis (CAPD), we studied 47 patients by echocardiography, dipyridamole-thallium tests, and biochemical profile. We observed that the group with VA had a greater cardiac mass index dependent only on an increased left ventricular internal diameter. Septum and posterior wall thickness, as well as biochemical variables, were not associated with the presence of VA in CAPD patients. In addition, altered myocardial perfusion was not associated with VA in these patients.

[Captopril in the treatment of patients with congestive heart failure. Its bicycle ergometry evaluation]. / Captopril no tratamento de pacientes com insuficiência cardíaca congestiva. Avaliação cicloergométrica.

PURPOSE: To analyze the physical performance of the patients with congestive heart failure (CHF), grades I and II of the New York Heart Association (NYHA), submitted to ergometric test: 1) under conventional treatment with digitalis and diuretic; 2) with an angiotensin converting enzyme inhibitor, captopril, associate with conventional treatment; 3) using captopril associated with digitalis or diuretic. METHODS: A randomized double blind study was performed in 20 patients with CHF (I and II-NYHA) submitted to ergometric test in different therapeutic phases. The initial workload was 5 watts and load was increased until the appearance of limiting symptoms. RESULTS: The introduction of captopril to the conventional treatment for CHF or associated with digitalis or diuretic promotes significant increase in the duration of the physical exercise, in the oxygen consumption and in the total workload during the ergometric test. CONCLUSION: In the initial forms of CHF, captopril provides better physical performance when compared with conventional treatment and the diuretic treatment can be changed for the angiotensin converting enzyme inhibitor with equal efficacy.

[Treatment of hypertensive crisis in outpatients with sublingual isradipine]. / Tratamento da crise hipertensiva em pacientes ambulatoriais com isradipina sublingual.

PURPOSE: Evaluate the efficacy and tolerability of isradipine, a new dihydropyridine calcium antagonist in the therapy of outpatients hypertensive crisis. PATIENTS AND METHODS: Twenty seven patients with mean age of 37.2 +/- 2.5 years (ages ranging from 18 to 59 years old) of different races (14 white, 13 not white); 15 men and 12 women, with diastolic blood pressure over 130 mmHg and without signs of recent target organ damage were studied. The patients were divided in three groups according to the used dosage of Isradipine tablets by sublingual route. Group I (n = 10): 1.25 mg; Group II (n = 10): 2.5 mg and Group III (n = 7): 5.0 mg. Arterial blood pressure levels and heart rate were determined before the drug administration and every 30 minutes until 120 minutes after dosing. RESULTS: Mean arterial blood pressure (MABP) decrease significantly in all patients from 153.43 +/- 4.3 to 124.0 +/- 2.3 mmHg after 60 minutes and to 118.0 +/- 2.1 mmHg after 120 minutes (p < 0.001). Heart rate did not show significant changes with the drug. Clinical significant side effects were not observed. The comparative analysis of MABP curves did not show significant differences among the groups I, II and III. However, a tendency of a greater decrease in MABP was observed in the patients of group III. CONCLUSION: Isradipine tablets in the dosages of 1.25, 2.5 and 5.0 mg by sublingual route is effective and well tolerated in the treatment of ambulatorial patients with hypertensive crisis.

Severe hypertension induces disturbances of renal autoregulation.

To study if the severity of hypertension could be associated with disturbances of the autoregulation of renal blood flow and glomerular filtration, we compared the renal hemodynamic and functional responses to acute blood pressure reductions of a group of patients with moderate essential hypertension (n = 10) with those of a group of patients with severe hypertension (n = 10). Blood pressure was reduced to normal levels by a stepwise infusion of sodium nitroprusside, and effective renal blood flow (by 131I-hippuran), glomerular filtration rate (by endogenous creatinine clearance), and filtration fraction were determined. After acute blood pressure normalization, effective renal blood flow and glomerular filtration rate were significantly reduced in patients with severe hypertension (-41.6 +/- 8.3% and -44.7 +/- 6.8%, respectively; p less than 0.01 for both) but not in those with moderate hypertension (+4.9 +/- 9.1% and +6.2 +/- 13.3%, respectively; NS). Filtration fraction remained unchanged in both groups. These results show that severe but not moderate essential hypertensive patients have a displacement to the right of the lower limit of the renal autoregulation curve due to impaired vasodilation to maintain adequate renal blood flow during acute reductions of blood pressure. This impairment may be due to anatomic or functional defects of preglomerular vessels, or to both. Furthermore, the inability to maintain adequate glomerular filtration in these circumstances shows that patients with severe hypertension also have an impaired ability to adjust postglomerular vasomotor tone in the face of reductions in glomerular blood flow.

Lung and myocardial thallium-201 kinetics in resting patients with congestive heart failure: correlation with pulmonary capillary wedge pressure.

Increased lung thallium-201 activity occurs with exercise in patients with severe coronary artery disease as a result of increased pulmonary capillary wedge pressure. No study has shown resting lung kinetics in chronic congestive heart failure. To better understand the relationship between lung and myocardial thallium uptake and pulmonary capillary wedge pressure, this study was performed. Resting lung and myocardial thallium uptake, expressed as a ratio, were compared with simultaneous pulmonary capillary wedge pressure in 16 patients with congestive heart failure and cardiomyopathy, all New York Heart Association class IV. There were no variations in pulmonary capillary wedge pressure throughout the study protocol. There was a significant reduction in the lung/myocardium thallium ratio from 10 to 60 minutes (0.83 +/- 0.30 to 0.59 +/- 0.17; p less than 0.001). At 60 minutes after thallium injection there was a linear correlation between the lung/myocardium ratio and capillary wedge pressure with an r value of 0.62 (p less than 0.01). Thus thallium-201 washout is rapid despite persistence of pulmonary capillary wedge pressure elevation, indicating that clearance does not imply resolution of congestive heart failure. In addition, a significant but imprecise correlation was found between capillary pressure and the lung/myocardium ratio. Rapid changes in lung activity during the early postinjection period may limit the clinical use of the lung/myocardium ratio.

Isradipine in the treatment of hypertensive crisis in ambulatory patients.

In order to investigate the efficacy of isradipine in the treatment of hypertensive crisis, we treated three groups of patients who had diastolic blood pressure (DBP) greater than 120 mm Hg, and who were without signs of acute target-organ damage. Isradipine was given sublingually in doses of 1.25 mg (group 1; n = 10), 2.5 mg (group 2; n = 10), and 5 mg (group 3; n = 7). Mean arterial pressure (MAP) was reduced in all patients [from 153.4 +/- 4.3 to 124.0 +/- 2.3 mm Hg at 60 min, and to 118.0 +/- 2.1 mm Hg at 2 h after administration (p less than 0.001)]. The heart rate (HR) did not change significantly (from 82.4 +/- 3.7 to 84.0 +/- 6 beats/min; NS). No significant differences were noted in the overall responses of the three groups; however, blood pressure reduction was more rapid in the group receiving 5 mg compared with the other two dosages. These results show that isradipine given sublingually is effective in reducing the elevated blood pressure of a hypertensive crisis and is not accompanied by limiting side effects. Isradipine's onset of action is early (approximately 30 min after dosing) and reaches its maximum blood pressure response within 2 h of administration. No dose-dependent reductions in blood pressure were observed with the dosage range employed in this study.

Regression of left ventricular hypertrophy in the short-term treatment of hypertension with isradipine.

This was a study of the effectiveness of isradipine, a calcium antagonist of the dihydropyridine group, in reversing left ventricular hypertrophy (LVH) in patients with mild-to-moderate hypertension. Mean arterial pressure was effectively reduced at 90 days of treatment (from 129.5 +/- 2.0 to 111.5 +/- 2.8 mm Hg; P less than .001). The electrocardiographic Romhilt-Estes score for LVH showed early reduction at 45 days of treatment (from 7.1 +/- 0.6 to 5.1 +/- 0.4 points; P less than .001), and further diminutions were observed at 90 days of treatment (3.8 +/- 0.4 points; P less than .01). The echocardiographically determined left ventricular mass indices confirmed these findings (from 175.0 +/- 8.9 to 141.7 +/- 5.5 and to 124.8 +/- 4.2 g/m2; P less than .001) for 45 and 90 days, respectively. The results indicate that isradipine is effective in reducing left ventricular mass and that these reductions are observed early in the course of treatment.

Reversal of left ventricular hypertrophy following treatment of hypertension with isradipine.

In order to complement earlier short-term observations, we studied the effects of isradipine (1.25 or 2.5 mg twice daily) on blood pressure as well as its action in reversing cardiac hypertrophy in 25 moderately hypertensive patients. We observed that the treatment produced short-term (3 month) and longer-term (9 month) control of blood pressure [decreases in mean arterial pressure (MAP) from 128 +/- 2.3 to 112 +/- 2.7 mm Hg and to 105.5 +/- 2.9 mm Hg; p less than 0.001] while heart rate remained constant throughout the study (from 76.6 +/- 2.3 to 74.7 +/- 2.4 beats/min; NS). Reversal of left ventricular hypertrophy (LVH) obtained after 3 months of treatment (LV mass index from 173.7 +/- 8.8 to 135.7 +/- 4.5 g/m2; p less than 0.001) was accentuated with continued therapy (to 131.0 +/- 4.0 and 124.4 +/- 3.1 g/m2 at 6 and 9 months, respectively; p less than 0.01). These results indicate that significant regression of LVH can be obtained with short-term treatment of hypertension with isradipine and that this effect will be fully obtained with longer-term (9 month) therapy.

Left ventricular hypertrophy as a risk factor for arrhythmias in hemodialysis patients.

The contribution of left ventricular hypertrophy in determining ventricular arrhythmias (VAS) was studied in 81 chronic renal failure patients in chronic hemodialysis using two-dimensional echocardiographic and electrocardiogram Holter monitoring. The prevalence of LVH was 93% (96% in hypertensive and 87% in normotensive patients). The prevalence of VA was 48%. These arrhythmias were associated with increased cardiac mass, lack of potassium supplementation to the hemodialysis bath, and low K+ and PaO2 during dialysis. Severe forms of VA occurred in 19 of 78 patients, and the risk factors for this occurrence were (a) largely increased cardiac mass indices (exceeding in more than 40% the upper limit of normal for each sex) and (b) prolonged periods of time in hemodialysis treatment (34 +/- 5.5 vs. 17 +/- 2.7 months, p less than 0.05). Changes in potassium or oxygen content of the blood were not significantly associated with the occurrence of severe forms of VA.

Dipyridamole-thallium tests are predictive of severe cardiac arrhythmias in patients with left ventricular hypertrophy.

In a population of patients with chronic renal failure (CRF) and a high prevalence of left ventricular hypertrophy (LVH) undergoing chronic hemodialysis, we investigated the association between the results of dipyridamole-thallium tests (DTTs) and the occurrence of ventricular arrhythmias. We observed a positive significant association between positive DTTs and the occurrence of severe forms of ventricular arrhythmias. A significant association was also observed between the presence of severe LVH and the occurrence of severe ventricular arrhythmias. However, no association was found between the presence of LVH and the positivity of the DTT. As most of our patients with positive DTTs had unimpaired coronary circulations, we conclude that positive DTTs, although falsely indicative of impaired myocardial blood supply, does have an important clinical relevance, indicating increased risk of morbidity (and, possibly, mortality) due to ventricular arrhythmias in a population of CRF patients submitted to chronic renal function replacement program.

Pump performance after regression of cardiac hypertrophy following treatment of hypertension with isradipine.

In view of the possibility that cardiac hypertrophy may be reversed by isradipine, we studied the effect of two different doses of isradipine (1.0 and 7.0 mg/kg per day) on relative cardiac weight in the rat. These doses have proved equipotent in lowering the blood pressure of the two-kidney, one clip model of hypertension. Untreated hypertensive rats had significantly greater cardiac weights than the untreated controls (3.16 +/- 0.06 versus 2.31 +/- 0.05 mg/g, P less than 0.001). Hypertrophy was still present in the group treated with isradipine at 1.0 mg/kg per day (3.17 +/- 0.07 versus 2.30 +/- 0.03 mg/g; P less than 0.001) but not with 7.0 mg/kg per day (2.55 +/- 0.17 versus 2.37 +/- 0.11 mg/g; NS). Functional studies revealed that reversal of cardiac hypertrophy did not affect cardiac performance compared with the ventricles with increased mass. These results suggest that reversal of left ventricular hypertrophy with isradipine is dependent on complex mechanisms, possibly unrelated to the unloading of the heart.