Shmuel Oren

Arterial and venous compliance in obese and nonobese subjects

Arterial compliance and central blood volume were evaluated in obese and nonobese patients with and without hypertension. Arterial compliance was lower in the hypertensive group, although obese subjects, regardless of their blood pressure, had higher arterial compliance. The ratio of central blood volume to total blood volume was highest in hypertensive patients, whether obese or lean, indicating increased venoconstriction.

Diagnosis and treatment of cervical tuberculous lymphadenitis

PURPOSE This study presents the long-term results of treatment of a series of patients with tuberculous mycobacterial lymphadenitis of the head and neck. PATIENTS Twenty-one patients were seen in a 10-year period. The median age at onset was of 41.2 years (range, 4 to 79 years), and the male-to-female ratio was 11:10. Sixteen patients were of Ethiopian origin, 3 from the former USSR, and 2 were Israeli women (1 of Indian and 1 of Morrocan origin). Symptoms started between 2 weeks and 6 months before presentation (mean, 5.8 weeks). Most patients had negative chest radiographs, a variable response to the tuberculin skin test, and a negative culture for mycobacterial organisms. RESULTS Fine-needle aspiration (FNA) of the cervical lymph nodes was the most reliable method to confirm the bacteriologic agent causing the lymphadenopathy. Acid-fast bacilli smears of the aspirate were positive in all but 3 patients, whereas histologic examination of the lymph nodes gave diagnostic results in only two thirds of cases examined. All patients were treated with antituberculous chemotherapy. Sixteen patients also underwent surgical excision of their cervical lymph nodes, and all of them showed a complete response to the combined treatment. The remaining patients reacted to chemotherapy alone with complete cure. One patient died of gastric carcinoma, and the only acquired immune deficiency syndrome (AIDS) patient died a year later of cytomegalovirus encephalitis. CONCLUSION The most reliable indicator of cervical mycobacterial infection is an acid-fast smear from the FNA specimen. Antituberculous chemotherapy, with or without surgical excision of the involved cervical lymph nodes, is the method of choice for treatment of this disease.

Left ventricular filling in the systemic hypertension of obesity.

Cardiac structure and systolic as well as diastolic functions were evaluated by 2-dimensional M-mode echocardiography in lean and obese patients who were either hypertensive or normotensive. Diastolic function, as assessed by diminished normalized early peak filling rate and prolonged duration of rapid filling, was decreased in hypertensive patients compared with normotensive patients (p = 0.02). When compared with lean patients with similar blood pressure levels, obese patients exhibited a lower normalized peak filling rate (p = 0.0014) but no difference in duration of rapid filling. A significant correlation was observed between the normalized peak filling rate and either body mass index or left ventricular (LV) mass (r = 0.355 and r = -0.32, respectively; p less than 0.001). Obese patients had greater LV end-diastolic and systolic dimensions (p less than 0.005 and p less than 0.02, respectively), LV wall thickness (p less than 0.05) and LV mass (p less than 0.007) than lean patients. Impairment of LV filling was most pronounced in obese hypertensive patients. It is concluded that the burden on the left ventricle imposed by obesity causes cardiac enlargement and impairment of LV filling regardless of levels of arterial pressure.

Disparate hemodynamic and sympathoadrenergic responses to isometric and mental stress in essential hypertension

The hemodynamic and sympathoadrenergic responses during isometric handgrip and mental arithmetic tests were compared in 18 patients with mild essential hypertension. Mean blood pressure increased significantly after both maneuvers (27% during isometric stress and 10.7% during mental stress), but the increase was significantly higher during isometric stress (p less than 0.001). Both stressors increased the heart rate (p less than 0.001) and cardiac output (p less than 0.001). However, the total peripheral resistance behaved differently, for it increased during isometric stress (p less than 0.05) and remained unchanged during mental stress. Both stressors increased the epinephrine levels (p less than 0.005), but only isometric stress increased the norepinephrine levels (p less than 0.001). It is concluded that both stressors increase cardiac output by way of an increase in heart rate, but isometric stress also increases total peripheral resistance and thus causes a greater increase in arterial pressure. Isometric stress activates both the adrenergic and noradrenergic systems, thereby accounting for the exaggerated response in arterial pressure, whereas mental stress stimulates the adrenergic system only.

Reduction in left ventricular mass in patients with systemic hypertension treated with enalapril, lisinopril, or fosenopril.

There are still conflicting data as to whether reduction in LV mass is beneficial. In the present study, no deterioration in LV systolic function occurred in patients in whom regression of LV mass was achieved. Impairment in LV compliance has been shown in hypertensive patients, even in the presence of preserved systolic function and normal LV mass. In our study, improvement in diastolic function was observed only in patients whose LV mass decreased, and it was related to reduction in mass and not to a decrease in mean arterial pressure. Therefore, we suggest that because diastolic function is the first activity to deteriorate in hypertensive patients, it may be the first activity to improve, and this improvement may be related to reduction in LV mass with ACE inhibitors.

Cardiovascular effects of isradipine in essential hypertension

The immediate and short-term cardiovascular effects of oral isradipine therapy were evaluated in 11 patients with mild to moderate systemic hypertension. Isradipine, 5 mg administered orally, induced a significant reduction in arterial pressure from 165 +/- 6/88 +/- 3 mm Hg to 140 +/- 5/76 +/- 2 mm Hg (p less than 0.001) within 2.5 hours by a decrease in total peripheral resistance associated with an increase in heart rate and cardiac output. Contrary to the acute effect, oral therapy with isradipine for 3 months reduced arterial pressure through a decrease in total peripheral resistance but without causing an increase in heart rate or cardiac output or activation of the sympathetic nervous system. Isradipine slightly reduced left ventricular mass and improved cardiac systolic function and left ventricular filling. Renal blood flow increased, and renal vascular resistance (p less than 0.01) and total blood volume (p less than 0.002) decreased without a change in either sodium excretion or body weight. Thus, isradipine, when given for 3 months, decreased arterial pressure by reducing total peripheral resistance without activation of reflexive mechanisms. Its favorable effects on systemic hemodynamics, total blood volume, renal blood flow, and cardiac structure and function suggest isradipine to be an excellent choice for antihypertensive therapy.

Immediate and short-term cardiovascular effects of fosinopril, a new angiotensin-converting enzyme inhibitor, in patients with essential hypertension

Immediate and short-term cardiovascular effects of a new angiotensin-converting enzyme inhibitor, fosinopril, were assessed in 10 patients with mild to moderate essential hypertension. Administration of a 10 mg oral dose of fosinopril reduced mean arterial pressure (p less than 0.001) as a result of a 24% fall in total peripheral resistance (p less than 0.001). Short-term therapy (12 weeks) maintained the decrease in mean arterial pressure (p less than 0.05) by decreasing total peripheral resistance (p less than 0.01), without reflexive cardiac stimulation or expanding intravascular volume. Renal vascular resistance decreased (p less than 0.05) while renal blood flow, glomerular filtration rate and filtration fraction remained unchanged. The response pattern to mental, isometric and orthostatic stress was similarly unchanged. Left ventricular mass diminished by 11% (p less than 0.01); myocardial contractility was unaffected. Afterload was reduced (p less than 0.05), and velocity of circumferential fiber shortening and stroke volume increased (p less than 0.05). Thus, arterial pressure reduction produced by fosinopril was associated with improved systemic and renal hemodynamics and reduced left ventricular mass.

Effect of Weight Loss on Blood Pressure, Arterial Compliance, and Insulin Resistance in Normotensive Obese Subjects

Background:Obesity is characterized by insulin resistance and hyperinsulinemia that may elevate arterial pressure due to sympathetic overactivity and volume overload. The aim of the study is to measure hemodynamic parameters and metabolic variables in obese normotensive subjects. Methods:Twenty-four normotensive, overweight subjects from our medical staff were enrolled. They had personal and group meetings with a physician, dietician, and psychologist to improve their compliance with regard to physical activity and personal low-calorie diet. In addition, each subject was given orlistat 120 mg three times daily for 12 weeks. Noninvasive hemodynamic parameters including arterial compliance were measured using radial artery pulse wave analysis, at the beginning and 1 month after taking the last dose of Orlistat, and insulin resistance was calculated using HOMA score. Results:At the end of the 3-month period, the average weight was reduced from 89.5 ± 12 kg to 81.5 ± 9 kg. The systolic arterial pressure was reduced from 128 ± 12 mm Hg to 121 ± 10 mm Hg and diastolic arterial pressure was reduced from 75.4 ± 9 mm Hg to 69.6 ± 7 mm Hg. Arterial compliance measurements showed significant improvement in large artery compliance from 13 ± 4 to 15.8 ± 3.6 while no change occurred in small arteries. The insulin sensitivity assessed by HOMA score improved significantly from 6.5 ± 4.5 to 4.8 ± 3.1 with weight reduction. Conclusions:Our data show that weight loss is accompanied by lowering of blood pressure, even in normotensive obese patients. This weight loss brings about an improvement in insulin resistance and a rise in large artery compliance, whereas no change occurs in small artery compliance.

Left ventricular filling and stress response pattern in essential hypertension

PURPOSE To evaluate whether impaired left ventricular filling determines the hemodynamic responses to isometric and orthostatic stress in a population with mild essential hypertension. PATIENTS AND METHODS The study population consisted of 32 patients with essential hypertension who were subdivided into those with preserved left ventricular filling (15 patients) and those with impaired left ventricular filling (17 patients). Echocardiograms were obtained before hemodynamic assessment was performed. Isometric stress and head-up tilt tests were done with a recovery period of at least 10 minutes between each to allow for blood pressure and heart rate to return to baseline. Hemodynamic reassessment was performed during the last minute of each test and at the end of the recovery period. Plasma epinephrine, norepinephrine, and dopamine levels were determined by radioenzymatic method. RESULTS Isometric stress increased mean arterial pressure by 30% (p less than 0.0001) by an increase in cardiac output (p less than 0.0001) and total peripheral resistance (p less than 0.0001) associated with an increase in plasma catecholamine levels (p less than 0.0001). Patients with preserved left ventricular filling had an increase in arterial pressure predominantly through an elevation in cardiac output (17%, p less than 0.0001) associated with a small increase in plasma norepinephrine levels (p less than 0.05) and in peripheral resistance (11%, p less than 0.05). In contrast, patients with impaired left ventricular filling had an increase in arterial pressure mainly through an increase in peripheral resistance (25%, p less than 0.0001) that was associated with a 45% elevation in plasma norepinephrine levels (p less than 0.0001). Orthostatic stress (passive head-up tilt) caused an exaggerated decrease in stroke volume (p less than 0.01) and cardiac output (p less than 0.01) in patients with impaired left ventricular filling when compared with those with preserved diastolic function. CONCLUSION Impaired left ventricular filling blunts the response of the heart to isometric and orthostatic stress. As a consequence, hypertensive patients with impaired ventricular filling respond to these stressors with enhanced sympathetic stimulation and exaggerated vasoconstriction.

Disparate cardiovascular response to stress tests during isradipine and fosinopril therapy

Optimal antihypertensive therapy should control blood pressure at rest and during stress while preserving the physiologic hemodynamic response. In patients with mild to moderate hypertension, the hemodynamic profile and catecholamine response at rest, during isometric, mental, and orthostatic stresses were compared before and 12 weeks after angiotensin-converting enzyme inhibition or calcium channel blockade. Antihypertensive therapy was titrated either with the angiotensin-converting enzyme inhibitor fosinopril (10 to 40 mg; n = 9) or with the calcium antagonist isradipine (5 to 20 mg; n = 10) until diastolic blood pressure < 90 mm Hg was achieved. Groups were comparable in race, sex, body mass index, pretreatment mean arterial pressure and response to isometric stress (25% increase in mean arterial pressure) before treatment. At rest, total peripheral resistance was reduced to the same extent (18%) in both groups. After fosinopril, the percent increase in stroke volume was higher and heart rate lower than with isradipine. During isometric stress, the percent increase in mean arterial pressure and cardiac output was higher, with isradipine (p < 0.05) reaching pretreatment levels. Plasma catecholamines were also higher with isradipine (p < 0.05), increasing by 100% with plasma norepinephrine compared with 16% before treatment. During orthostatic stress significant reductions in mean arterial pressure and stroke volume were observed after isradipine but not after fosinopril. Neither medication significantly modified the response to mental stress. Our data suggest that despite a comparable reduction in total peripheral resistance at rest, fosinopril preserves a more physiologic hemodynamic response to isometric and orthostatic stress than isradipine.(ABSTRACT TRUNCATED AT 250 WORDS)