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Biomedical subjects

V Papademetriou

Publications and source records attributed to V Papademetriou.

68 records · Page 4Linked to original sources

Effect of diuretic therapy on ventricular arrhythmias in hypertensive patients with or without left ventricular hypertrophy.

Recent studies have suggested that hypertensive patients with ECG evidence of left ventricular hypertrophy (LVH) may have increased risk of sudden death when treated with diuretics. In the present study echocardiography was used as a more sensitive index for the presence of LVH. Thirty-one patients with uncomplicated hypertension underwent 48-hour ambulatory ECG monitoring both before any treatment and after 4 weeks of hydrochlorothiazide, (HCTZ), 100 mg daily. In 18 patients with left ventricular posterior wall thickness (LVPWT) greater than or equal to 13 mm (average = 14.4 +/- 0.2 mm) on echocardiogram, plasma potassium decreased from 4.1 +/- 0.3 to 3.3 +/- 0.4 mEq/L with HCTZ (p less than 0.01). Premature ventricular contractions (PVCs) averaged 5.7 +/- 9.9/hr at baseline and 7.1 +/- 16.6/hr following HCTZ (p = NS). The total number of couplets was 29 before and 13 after HCTZ, while four brief runs of ventricular tachycardia occurred only before treatment. In the remaining 13 patients with LVPWT less than or equal to 12 mm (average = 11.2 +/- 0.1 mm), plasma potassium decreased from 4.1 +/- 0.3 to 3.4 +/- 0.5 mEq/L with HCTZ (p less than 0.01). The average number of PVCs was 4.3 +/- 8.0/hr after HCTZ (p = NS). One couplet and one 3-beat run of ventricular tachycardia occurred before and one 3-beat run of ventricular tachycardia after HCTZ. Although more complex arrhythmias were noted in the LVH group, the differences were not statistically significant. These results indicate that thiazide therapy does not increase ventricular arrhythmias either in patients with or without LVH.

Adult↗

How dangerous are diuretics?

The proposal that thiazide diuretics may increase cardiovascular risk receives no support from recent data. Current evidence does not indicate that diuretic-induced hypokalaemia is associated with increased ventricular arrhythmias. This evidence includes continuous electrocardiographic monitoring--which is the most sensitive technique for quantitating cardiac arrhythmias. In contrast to earlier reports, more recent studies found no evidence for increased arrhythmias during the period of hypokalaemia, or for decreased arrhythmic activity after correction of hypokalaemia. Similarly, studies claiming increased sudden death in patients on diuretic treatment have not been substantiated by the results of other large-scale trials. Elevation of serum cholesterol concentrations with thiazide appears to be a short term phenomenon since most studies indicate the elevation reverts to baseline during long term treatment. Thiazide diuretics remain as one of our most effective antihypertensive agents. Fears of their increasing the incidence of ventricular arrhythmias due to hypokalaemia, or constituting a risk factor for atherosclerosis by elevating serum cholesterol concentrations, appear largely unsubstantiated.

Antihypertensive Agents↗

Effectiveness of potassium chloride or triamterene in thiazide hypokalemia.

Potassium chloride was compared with triamterene in a crossover trial involving 16 hypertensive patients with overt diuretic-induced hypokalemia. Potassium chloride, 24 to 96 mEq/day, normalized the plasma potassium (PK) level at 3.5 mEq/L or more in only eight of the patients. The average increase in PK level was 0.58 mEq/L. Triamterene, 50 to 200 mg daily, normalized PK level in ten of the patients. The average increase in PK level was 0.72 mEq/L, which was not significantly different than that with potassium therapy. Some patients who responded to potassium did not respond to triamterene, and vice versa. Most of the administered potassium was excreted in the urine even with persisting hypokalemia. Addition of triamterene to diuretic therapy resulted in a small but statistically significant increase in plasma creatinine level.

Adult↗

Early changes in plasma and urinary potassium in diuretic-treated patients with systemic hypertension.

Two groups of patients with uncomplicated systemic hypertension were studied. Group 1 included 11 patients who had overt hypokalemia with diuretic drug treatment, and group 2 included 11 patients who remained normokalemic. After baseline studies without treatment were performed, both groups received hydrochlorothiazide, 50 mg twice daily. Plasma potassium (PK) was significantly reduced within the first day of treatment and stabilized by day 7 in both groups. The average decrease in PK was 1.0 +/- 0.1 mEq/liter (p less than 0.01) in the first group and 0.6 +/- 0.2 mEq/liter (p less than 0.01) in the second group. Cumulative losses of K were approximately 200 mEq in the hypokalemic group and were minimal in the normokalemic group as assessed by 24-hour urinary collections. Patients in the hypokalemic group also had a greater reduction in body weight and blood pressure. Supplementation with KCl, 96 mEq/day, or triamterene, 200 mg/day, in 9 hypokalemic patients resulted in an increase of PK to approximately 3.5 mEq/liter leveling off by day 7, and a cumulative K retention of approximately 200 mEq. Thus, overt thiazide-induced hypokalemia was associated with small and biologically unimportant losses of K from body stores. With replacement therapy the estimated amount of retained K was also small.

Blood Pressure↗

Diuretic-induced hypokalemia in uncomplicated systemic hypertension: effect of plasma potassium correction on cardiac arrhythmias.

Sixteen patients with diuretic-induced hypokalemia underwent 24-hour ambulatory electrocardiographic monitoring during and after correction of hypokalemia. Plasma potassium averaged 2.83 +/- 0.08 mEq/liter before and 3.73 +/- 0.06 mEq/liter after correction with potassium chloride, triamterene or both. Premature atrial contractions decreased in 6 patients, increased in 6 and remained unchanged in 4. There was no improvement in ventricular ectopic activity after plasma potassium correction. Ventricular ectopic activity improved in 5 patients, worsened in 10 and remained unchanged in 1. Ventricular tachycardia was not observed in either phase. Plasma magnesium remained normal throughout. The investigators conclude that in patients with uncomplicated hypertension, correction of diuretic-induced hypokalemia does not significantly reduce the occurrence of spontaneous atrial or ventricular ectopic activity.

Adult↗

Treatment of severe hypertension with intravenous labetalol.

The effectiveness of repeated intravenous injections of labetalol in reducing blood pressure (BP) was evaluated in patients with severe hypertension. The subjects were 10 patients who were 29 to 61 yr old and who had diastolic blood pressure (DBP) of 125 mm Hg or higher. Repeated injections titrated from 20 to 80 mg were given at 15-min intervals until there was a reduction in DBP of 30 mm Hg or until 300 mg had been administered. The average reduction of BP ranged from 201 +/- 5/132 +/- 1 to 157 +/- 6/108 +/- 4 mm Hg (mean +/- SEM). Four patients responded with a reduction in DBP of 30 mm Hg or more with total doses of 60 to 220 mg. Of the remaining six who received the full dose, in four there was a 20 to 29 mm Hg reduction in DBP, in one there was a 10 mm Hg fall, and in one there was no reduction. There was a positive correlation between age and response to intravenous labetalol. No severe side effects were encountered. Intravenous labetalol is useful and well tolerated in patients with severe hypertension.

Adult↗

Enhancing activity of various immunoaugmenting agents on the delayed-type hypersensitivity response in mice.

Six immunoaugmenting agents were tested in the delayed-type hypersensitivity reaction (DTH) in normal BALB/c X DBA/2 mice. The agents tested, levan, lentinan, mannozym, maleic anhydride divinyl ether, polyriboinosinic-polycytidylic acid-poly-L-lysine, and highly purified L-cell interferon, gave significant increases in the DTH response above the sheep red blood cell control. The schedule of doses for each agent corresponded with previous experiments from this laboratory of the maximum natural killer cell activity, macrophage activation, and interferon induction. Highly purified L-cell interferon was capable of eliciting a significant DTH response when given 4 hr after the initial challenge with sheep erythrocytes. In addition, lambda-carrageenan, a macrophage-cytotoxic agent which can render the macrophage inactive, was found to suppress the DTH response to levels slightly above phosphate-buffered saline controls. The carrageenan-induced suppression of the DTH response could be abrogated by coadministration with immunoaugmenting agents to levels attained with the immunoaugmenting agents alone.

Adjuvants, Immunologic↗

Immune response modifying activity in mice of polyinosinic: polycytidylic acid stabilized with poly-L-lysine, in carboxymethylcellulose [poly-ICLC].

Poly-ICLC, a polyinosinic: polycytidylic acid stabilized with poly-L-lysine in carboxymethyl-cellulose was tested in mice for its immunoregulatory activity. Poly-ICLC was found to enhance T cell responsiveness but not B cells. It augmented the delayed type hypersensitivity response significantly. The results indicate Poly-ICLC to be a T cell stimulator. Macrophage tumoricidal activity was markedly enhanced both in vitro and in vivo after exposure to Poly-ICLC. Natural killer cell cytotoxicity was significantly augmented in vivo. Both macrophage and natural killer cell activity was maintained for over 3 days after only one treatment. The extended period of tumor cell cytotoxicity, exhibited by macrophages and natural killer cells, may correlate to Poly-ICLC induction of early and high levels of interferon which are maintained in the serum for a longer period of time.

Animals↗

The immunomodulatory effect on BM 12.531 (azimexon) on normal or tumored mice: in vitro and in vivo studies.

The effect of BM 12.531 (BM) treatment on normal or tumored mice was studied under both in vitro and in vivo experimental conditions. It was found that BM treatment of mice that received 500 R of whole body irradiation caused a highly significant (P < 0.001) increase in the prolongation of the mean survival time. BM was found to significantly increase (P < 0.01) the delayed-type hypersensitivity reaction of normal mice. BM treatment was found to moderately increase both in vivo and in vitro activated macrophages. However, BM was found to be extremely effective in significantly increasing the mean survival times of lung carcinoma-bearing or leukemic mice.

Animals↗

Enhanced macrophage and natural killer cell antitumor activity by various molecular weight maleic anhydride divinyl ethers.

A series of Maleic anhydride divinyl ether (MVE) polyanions, synthesized with molecular weight ranging from 12500 to 52600, were found capable of enhancing macrophage tumoricidal activity of MBL-2 leukemia cells. These agents also augmented Natural Killer cell activity against the YAC lymphoma and M109 adenocarcinoma cell lines.

Adenocarcinoma, Bronchiolo-Alveolar↗

Augmentation of cytotoxicity by splenic cells of pregnant or human chorionic gonadotropin-treated normal mice.

The natural killer (NK) activity, of an allogeneic tumor system, was found to be enhanced by the total splenic population of either pregnant or normal female BALB/c mice treated with human chorionic gonadotropin (HCG). The splenic population of the early pregnant (9-10 days) mice resulted in a statistically significant increase in NK activity over nonpregnant controls at all effector/target ratios tested. The mid (12-13 days) and the late (15-16 days) pregnant groups also significantly enhanced NK activity above control values at effector/target ratios of 100:1, 50:1 and 25:1. The i.v. administration of carrageenan into pregnant mice abolished the increased NK activity suggesting a putative role for the macrophage in this system. HCG administered to normal female BALB/c mice resulted in enhanced NK activity similar to that seen for the pregnant mice. This augmented NK activity does not appear to be effected by either the number or the timing of HCG administration. The augmentation of NK activity of HCG treated mice was also detected in a syngeneic system utilizing 51Cr labeled M109 tumor target cells and BALB/c effector cells.

Animals↗

The modulatory effect of exogenously added prostaglandin E1 or E2 on the delayed-type hypersensitivity reaction of normal or tumored mice.

The effect of exogenously added prostaglandin (PG) E1 or E2 over concentration ranges of from 1 x 10(-4) to 1 x 10(-9)M were studied in order to determine their effect on the delayed-type hypersensitivity (DtH) reaction of normal or tumored mice. PGE1 or PGE2 generally caused a stimulation over the control values of normal mice as detected by the footpad swelling assay. However, PGE1 or PGE2 at all concentrations tested were found to significantly inhibit the DtH reaction of CD2F1 tumored mice.

Alprostadil↗

Acute and short-term effects of new calcium antagonist in hypertension.

Nitrendipine (Bay e 5009) is a new calcium antagonist antihypertensive agent similar in structure and function to nifedipine. Nitrendipine was tested in a range of single and repeated doses in 10 adult males with uncomplicated mild to moderate hypertension. The treatment goal was reduction of diastolic blood pressure to 90 mm Hg or less. The dose that achieved goal blood pressure ranged between 10 and 30 mg. Systolic and diastolic blood pressure began to fall within 15 minutes following ingestion of single oral doses of nitrendipine. The maximum effect of the drug was achieved in 60 to 90 minutes and remained at approximately this level for 6 to 8 hours. The average reduction in supine diastolic was more than twice as great as the fall in systolic blood prere began to fall within 15 minutes following ingestion of single oral doses of nitrendipine. The maximum effect of the drug was acheived in 60 to 90 minutes and remained at approximately this level for 6 to 8 hours. The average reduction in supine diastolic was more than twice as great as the fall in systolic blood pressure. With continuous doses given three times daily, all patients' blood pressures were as low or lower than the maximal effect observed after single doses. The reduction in blood pressure was sustained for the full 3 weeks of treatment. There was a sustained small increase in pulse rate averaging 6 beats/min. The drug was generally well tolerated by most patients. Mild to moderate headache that resolved with continued treatment was the most frequent side effect. This preliminary trial indicates that nitrendipine is an effective antihypertensive agent that merits further study.

Antihypertensive Agents↗