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Biomedical subjects

Y A Weiss

Publications and source records attributed to Y A Weiss.

At least 37 records · Page 2Linked to original sources

Pindolol availability in hypertensive patients with normal and impaired renal function.

Intravenous and oral pharmacokinetics of pinlolol were studied in 18 hypertensive patients-9 with normal renal function and 9 with impaired renal function. Analysis of data showed that a linear two-compartment model was suitable to describe the pindolol kinetics. Compared with patients with normal renal function, patients with chronic renal failure exhibited: (1) unchanged transfer rate constants and distribution volumes and (2) decreased total body clearance with decreased renal clearance and unchanged nonrenal clearance. Analysis of oral data by the Loo-Riegelman method showed that the pindolol absorption kinetic was not first order. Compared with patients with normal renal function, patients with chronic renal failure exhibited decreased fraction of dose effectively absorbed and increased initial rate of absorption. The initial rate of absorption was inversely correlated with the creatinine clearance. The study disclosed evidence that absorption was modified in chronic renal failure.

Administration, Oral↗

Volume-dependent parameters in essential hypertension.

Blood pressure, renal blood flow, total blood volume (TBV), plasma renin activity, and vascular reactivities to angiotensin and norepinephrine were studied in 48 normotensive subjects and 106 essential, sustained, hypertensive patients with normal renal function, balanced sodium intake, and urinary output. A significant negative pressure-volume relationship was observed in normal subjects. Among the hypertensive patients, some were inside the 95% confidence limits of the normal curve and the others were above, indicating a disturbance in the pressure-volume relationship. A quantitative evaluation of the pressure-volume disturbance was proposed and discussed. The blood pressure of each hypertensive patient corresponded to two different blood volume values: the renal valve and the theoretical value extrapolated from the normal curve. The difference between the two values was called deltaTBV and was positive in hypertensive patients. The deltaTBV value was negatively correlated with the renal blood flow, the creatinine clearance, the plasma renin activity, and the vascular reactivities to angiotensin and norepinephrine (P less than 0.0001). The parameters were not correlated with the real blood volume. This study demonstrates quantitatively a pressure-volume disturbance in essential hypertension. This disturbance is strongly correlated with the renal function and the renin-angiotensin system changes.

Blood Pressure↗

Baroreflex sensitivity and cardiopulmonary blood volume in normotensive and hypertensive patients.

Baroreflex sensitivity and cardiopulmonary blood volume were determined in 95 men, including normotensive and hypertensive subjects with normal renal function and balanced sodium intake and urinary output. Baroreflex sensitivity was estimated by determining the slope of the regression line relating the increase of systolic pressure to the cardiac slowing after transient rises of arterial pressure. A technique of gradual atropinisation was used to evaluate the parasympathetic mediated component of the reflex. With this method, it was possible to calculate the exact atropine dose abolishing the reflex sensitivity. This index was not dependent on age. It was negatively correlated to the diastolic pressure in normotensive patients but not in hypertensive patients. The ratio between the cardiopulmonary and the total blood volume was considered as an index of sympathetic venous tone. This ratio was positively correlated to the diastolic pressure in normotensive patients, but not in hypertensive patients. This study strongly suggests that a precise sympathetic-parasympathetic balance existed in the normotensive patients. This balance was disrupted in the hypertensive patients pointing to abnormalities in the autonomic nervous system of permanently hypertensive patients.

Adult↗

Central hemodynamics and cardiac output control in essential hypertensive patients.

Central hemodynamics were determined in 202 men including 101 normotensive and 101 permanent essential hypertensive patients of the same age. Cardiac output was identical in the two groups while blood pressure and total peripheral resistance were significantly different. Strong differences between the two groups are revealed by a systematic correlation study: (i) correlations of blood pressure (with respectively heart rate and total blood volume) were significant in the normotensive group but not in the hypertensive group; (ii) correlations of cardiac output (with respectively heart rate and total blood volume) were significant in both groups; (iii) correlations of renal blood flow (with respectively cardiac output and blood pressure) were significant in the hypertensive group but not in the normo tensive group. This study provided evidence that the volume and neural pressure controls are impaired in hypertensive patients while the cardiac output control is maintained and, suggested the existence of adaptive mechanisms involving the kidney in the maintenance of normal cardiac output in permanent essential hypertensive patients.

Adaptation, Physiological↗

Relationship of plasma renin activity and aldosterone levels with hemodynamic functions in essential hypertension.

Correlates of plasma renin activity and plasma aldosterone levels with hemodynamic functions were studied in 47 male patients with untreated, permanent essential hypertension. All subjects had a normal creatinine clearance and received a diet of 110 mEq/day of sodium. Supine plasma renin activity was directly correlated with cardiac index (P less than.01) and cardiopulmonary blood volume (P=.01). Percentage changes in plasma renin activity and total peripheral resistance in response to upright position were positively correlated (P less than.001). Supine plasma aldosterone level was directly correlated with stroke index (P less than .001) and negatively correlated with hear rate (P less than .05). No significant correlation of aldosterone level was observed with the other measurements, including plasma renin activity. The study points to the neural sympathetic control of plasma renin activity in essential hypertension and suggests the existence of some interrelationships between aldosterone level and cardiac performance.

Adult↗

[A new approach of the hemodynamics of human essential hypertension. Study of the control of cardiac output].

The smoothing technique is used in this part II to study the cardiac output control in normotensive and hypertensive subjects. It is proved that: 1. cardiac frequency and total blood volume are both determinants of cardiac output in the normotensives; 2. in the hypertensives, blood volume is the main factor, the role of the frequency becomes negligible; 3. at high pressures, the part of the blood volume in the body-weight increases, suggesting an overhydration phenomenon in essential human hypertension.

Blood Volume↗

Isoproterenol sensitivity and total body clearance of propranolol in hypertensive patients.

The isoproterenol sensitivity (dose-response curve) and the total body clearance of propranolol were measured in 80 men including 15 normal subjects and 65 essential hypertensive patients (20 borderline and 45 permanent hypertensives). The critical dose of isoproterenol was found to be directly correlated to weight (P less than 0.01), age (P less than 0.001), and basal diastolic arterial pressure (P less than 0.001). A partial correlation coefficient study showed that the diastolic arterial pressure was of greater influence than weight and age. The total body clearance of propranolol was inversely related to the basal diastolic arterial pressure (P less than 0.0001) in hypertensive patients. The study provides evidence that the level of basal diastolic arterial pressure could influence the beta-receptor responsiveness and the beta-adrenergic blockade in hypertensive patients.

Adult↗

Comparison of the pharmacokinetics of intravenous dl-propranolol in borderline and permanent hypertension.

In borderline and permanent hypertensives after rapid i.v. injection of dl-propranolol 0.2 mg/kg plasma levels were measured and were fitted to a two-compartment open-model. In borderline patients, characterized by a high basal cardiac output (CO), plasma levels were always lower than in permanent hypertensives. The biological half-life was reduced and the central volume of distribution, volume of distribution at pseudo-equilibrium and total clearance (TC) were markedly increased. In the overall population, there was a significant positive correlation between CO and TC. Rapid achievement of a predetermined plateau in each group constituted experimental proof of the validity of the two-compartment open-model for kinetic analysis of propranolol i.v. If kinetic parameters from permanent hypertensive were applied to borderline hypertensives a lower plateau was obtained. Thus, in so far as beta-blockade is related to plasma level of propranolol, an increased intravenous dose may be required in patients with high CO.

Cardiac Output↗

Control of cardiac output in essential hypertension.

Cardiac and renal hemodynamics and cardiopulmonary and total blood volume were determined in 202 men, 101 with normotension and 101 of the same age with chronic essential hypertension, normal renal function and balanced sodium intake and urinary output. Cardiac output was identical in the two groups, whereas blood pressure and total peripheral resistance were significantly different. The two groups exhibited strong differences in the correlation study: (1) Correlations of blood pressure with, respectively, heart rate, cardiopulmonary blood volume and total blood volume were significant in the normotensive group but not in the hypertensive group. (2) Correlations of cardiac output with, respectively, heart rate, cardiopulmonary blood volume and total blood volume were significant in both groups. (3) Correlations of renal blood flow with, respectively, cardiac output, blood pressure and total blood volume were significant in the hypertensive group but not in the normotensive group. This study provides evidence that: (1) the volume and neural control of blood pressure are disrupted in hypertension whereas control of cardiac output is maintained; and (2) adaptive mechanisms involving renal function are necessary to the maintenance of normal cardiac output in patients with essential hypertension.

Adult↗

The pressure-volume relationship in normotensive and permanent essential hypertensive patients.

1. Blood pressure, blood volume and renal blood flow were determined in 101 men; forty-three were normal subjects and fifty-eight were untreated permanent essential hypertensive patients with normal renal function and equilibrated sodium balance. 2. A significant negative pressure-volume relationship was observed overall. The relationship could be expressed as a hyperbola whose slope expressed the reduction in blood volume per unit rise in pressure: the higher the blood pressure, the lower the slope. Thus essential hypertensive subjects have a smaller decrement in blood volume per unit rise in pressure than normal subjects. 3. The relation between change in blood volume and change in pressure was confirmed in each individual by defining for each a ration deltaV/deltaP, statistically identical with the hyperbolic slope dV/dP. The deltaV/deltaP ratio was found to be well correlated with the renal blood flow and the creatinine clearance. No correlation existed between the total blood volume and these two renal parameters. 4. It is concluded that the present study demonstrates a blood volume regulation disturbance in essential hypertension and provides evidence from human studies that a renal defect accompanies high blood pressure.

Adult↗

The spectrum of pressor-response to norepinephrine in normotensive and hypertensive patients.

The pressor-response to norepinephrine was determined in the whole body circulation of 15 normal subjects and 86 untreated essential hypertensive patients. The slope, the threshold-dose and the critical-dose were calculated from the log dose-response curve. In the overall population (101 subjects) a slight correlation (r = +0.20 less than 0.05) was observed between the basal diastolic arterial pressure and the threshold-dose. In contrast, highly significant parabolic correlations (r = +0.46 less than 0.00001) were observed between the diastolic arterial pressure and the slope or the critical dose. When diastolic arterial pressure was above 100 mmHg, the slope increased while the blood pressure increased. This result suggests either a decreased sympathetic tone or an adaptative structural change of the arterial wall. When diastolic arterial pressure was under 100 mmHg, the slope decreased while the blood pressure increased. This observation points to an enhanced sympathetic activity in mild blood pressure.

Adult↗

Vascular reactivity to norepinephrine and hemodynamic parameters in borderline hypertension.

Pressor response to norepinephrine, cardiopulmonary blood volume, and hemodynamic parameters were studied in 41 borderline hypertensive patients in comparison with 42 permanent essential hypertensive patients and 28 normal subjects. Borderline hypertensive subjects had high cardiac index (p less than 0.0001), normal total peripheral resistance, and low total blood volume (p less than 0.005). The ratio between cardiopulmonary blood volume (CPBV) and total blood volume (TBV) was significantly higher in comparison with normal subjects (p less than 0.01) and permanent hypertensive subjects subjects (p less than 0.0001). The pressor dose of norepinephrine was elevated (p less than 0.0001) and was directly correlated with the basal values of the cardiac output (p less than 0.005), the cardiopulmonary blood volume (p less than 0.001), and the CPBV/TBV ratio (p less than 0.01). None of these results was observed in permanent hypertensive subjects: the only significant result was a negative correlation between the pressor dose of norepinephrine and the basal diastolic arterial pressure (p less than 0.0001). This study provides evidence that the cardiac output elevation in borderline hypertensive subjects was related to increased venous return and enhanced sympathetic venous tone.

Adult↗

Altered blood volume regulation in sustained essential hypertension: a hemodynamic study.

Cardiac and renal hemodynamics and total blood volume were determined in 28 normal subjects and 60 patients with untreated essential well-established hypertension. Endogenous creatinine clearance was within normal ranges and sodium intake was 110 mEq/day. A significant negative volume-resistance relationship was observed both in normal subjects (P less than 0.005) and hypertensive patients (P less than 0.001). In comparison with the normal curve, the hypertensive curve has two characteristics: 1) the curve was reset on the right-hand side and, 2) the slope was significantly shallower, indicating a reduced ability to decrease the volume per unit rise in resistance. By using the normal curve as a reference system, a quantitative evaluation of the blood volume disturbance was proposed. In hypertensives, the value of the total peripheral resistance could correspond to two different values of the total blood volume: the real value and the theoretical value extrapolated from the normal curve. The difference between the two values was called "relative variation in blood volume" and was used as a mathematical model. In hypertensives, the real blood volume was significantly reduced (P less than 0.001) while a significant "relative increase" in total blood volume was observed (P less than 0.001). This "relative increase" was directly correlated with the diastolic arterial pressure (r=0.064; P less than 0.00001) and was inversely related to the renal blood flow (r=-0.54; P less than 0.0001) and the creatinine clearance. Such correlations were not observed with the real blood volume. In agreement with Guyton's theory, this study highly suggests that sustained hypertension is related to an increase in blood volume relative to the capacity of the circulatory system and that a renal defect is necessary for the blood pressure elevation mechanism.

Adult↗

Anti-hypertensive adrenergic-blocking agents: effects on sodium balance, the renin-angiotensin system and haemodynamics.

1. The changes in plasma volume, haemodynamic variables, plasma renin activity and plasma aldosterone were studied in forty-one hypertensive patients after administration of adrenergic-blocking agents. Four drugs were used: alpha-methyldopa (fourteen patients), guanethidine (ten patients), clonidine (nine patients) and reserpine (eight patients). Drugs were administered orally during 7 days' hospitalization on a normal sodium diet (110 mmol/day). 2. The four drugs had similar effects: a significant decrease in blood pressure, a significant increase in plasma volume and no change in stroke volume. 3. With alpha-methyldopa and guanethidine, heart rate, plasma renin activity and plasma aldosterone were unchanged. 4. With reserpine and clonidine, heart rate and plasma renin activity were significantly decreased, whereas plasma aldosterone did not change significantly. 5. This study suggests that the decrease in plasma renin activity was related to the lowering of the heart rate rather than to sodium retention and that adrenergic-blocking agents can impair the normal relationship between stroke index and plasma volume, between plasma volume and plasma renin activity, and between plasma renin activity and plasma aldosterone.

Adult↗

The stroke volume in juvenile borderline hypertension.

Hemodynamic changes in supine and upright position and during exercise were studied in 144 men including 37 normal subjects and 107 patients with borderline hypertension. Borderline hypertensives were classified in 4 groups, according to the basal level of heart rate and stroke index. In the first two groups, stroke index was normal, but heart rate was either decreased (Group I) or elevated (Group II): supine total peripheral resistance was superior (Group I; p less than 0.02) or equal (Group II) to normal values; plasma volume was normal or slightly decreased; hemodynamic response to tilt test closely approximated the normal; impaired adaptation of cardiac index and stroke index to exercise was observed in Group II (p less than 0.001). In the other two groups, stroke index was significantly elevated (p less than 0.0001) but heart rate was either decreased (Group III) or increased (Group IV); supine total peripheral resistance values were decreased (p less than 0.001); plasma volume was equally reduced (p less than 0.001); abnormal percentile increase in diastolic arterial pressure (p less than 0.02; p less than 0.001) and total peripheral resistance during tilt test were observed; during exercise, only the patients of Group IV had an impaired adaptation of cardiac index (p less than 0.001) and total peripheral resistance (p less than 0.02). The study provide evidence that in boderline hypertension i) a high basal level of stroke volume is associated with a reduced plasma volume and an imparied adaptation of total peripheral resistance during tilt, ii) a high basal level of heart rate is associated with an impaired adapatation of cardiac output during exercise, and iii) only patients having an increase in both heart rate and stroke volume exhibited a specific hemodynamic pattern including: reduction of plasma volume, impaired adaptation of cardiac output during exercise, impaired adaptation of total peripheral resistance during tilt and exercise.

Adult↗