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Biomedical subjects

W P Leary

Publications and source records attributed to W P Leary.

At least 19 recordsLinked to original sources
PubMed1992

Effects of angiotensin-converting enzyme inhibitors on urinary excretions: interactions with diuretics.

The excretions of urinary sodium, potassium, magnesium, urate, and water after dosing with diuretics or the angiotensin-converting enzyme inhibitor perindopril are reported, as well as the results of other recent studies. Perindopril in low dose had no significant effect on any of these 24-hour urinary excretions and in high dose, in contrast to captopril and enalapril, does not increase magnesium loss. These effects were studied in healthy volunteers, which may not reflect urinary excretions in hypertensive patients.

Adolescent↗
PubMed1992

The effect of hexane on the ventricular fibrillation threshold of the isolated perfused rat heart.

This investigation was conducted to determine the influence of hexane on the ventricular fibrillation threshold of the isolated perfused rat heart and myocardial electrolyte levels. Ventricular fibrillation threshold was measured using the Langendorff perfusion apparatus. Heart rate was measured by a universal digital counter and the cardiac flow by collecting the outflow of the heating chamber below the heart into a graduated measuring cylinder. Magnesium and zinc were measured by atomic absorption spectrophotometry and potassium by flame photometry. Two groups of rats were studied; those in the experimental group were given 0.2 ml of hexane and the control group 0.2 ml olive oil subcutaneously for 90 days. Their hearts were removed under anaesthesia. Half of the experimental and control hearts were mounted on the Langendorff perfusion apparatus and the heart rate, coronary flow and ventricular fibrillation threshold were measured. The hearts of the other half were used to measure myocardial electrolyte levels. In the experimental group the ventricular fibrillation threshold decreased (4.72 (S.D. +/- 1.87) vs 9.48 (S.D. +/- 2.98); P less than 0.001). There was no change in the coronary flow and heart rate in between the groups. The mean myocardial potassium levels (2586 (S.D. +/- 162) vs 2968 (S.D. +/- 218) micrograms/g; P less than 0.001), magnesium levels (164 (S.D. +/- 28) vs 208 (S.D. +/- 18) micrograms/g; P less than 0.001) and zinc levels (19.6 (S.D. +/- 4) vs 33.8 (S.D. +/- 6.8) micrograms/g; P less than 0.001) were significantly lower in the hexane-treated group compared to controls. Hexane, a constituent of glue and benzine, is cardiotoxic; marked derangement in myocardial electrolytes and a reduced ventricular fibrillation threshold, indicating an increased myocardial vulnerability to arrhythmias, was noted in the experimental animals.

Animals↗
PubMed1992

Influence of ethyl alcohol when given alone or in combination with potassium and/or magnesium supplements on ventricular fibrillation threshold levels in laboratory rats.

Five groups of rats were studied in an investigation to determine whether changes in the ventricular fibrillation threshold (VFT) occur when ethyl alcohol (EtOH) is given alone or in combination with K+ and/or Mg2+ supplements; the first group (n = 20) served as controls, the second (n = 18) was given only EtOH, the third (n = 18) EtOH+KCl, the fourth (n = 16) EtOH+MgCl2, and the fifth (n = 18) EtOH+MgCl2 + KCl for a 9 month period. Two rats from each group were killed on each day. One rat heart was perfused using the Langendorff apparatus and the other used for tissue electrolyte analyses. A significant fall in the mean VFT (9.7 +/- SD 1.9 mA vs 4.5 +/- 1.6 mA; P less than 0.0001) was noted in the rats given EtOH solution as drinking water for 9 months, and a significant increase in the VFT levels was seen in the Mg(2+)-supplemented group (9.7 +/- 1.9 mA vs 18.9 +/- 4.1 mA; P less than 0.0001) and in the K+ + Mg2+ supplemented group (9.7 +/- 1.9 mA vs 15.8 +/- 1.3 mA; P less than 0.0001) compared to controls. In addition, an increase in the heart rate was observed in the group supplemented with Mg2+ (213 +/- 8 beats/min vs 231 +/- 10 beats/min; P less than 0.0001) as well as in the group supplemented with K+ + Mg2+ (213 +/- 8 beats/min vs 222 +/- 10 beats/min; P less than 0.002) compared to controls. There was no significant change in the coronary blood flow (CF) in any group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The effects of supra-therapeutic doses of rifampicin on liver function in the perfused rat liver.

The isolated liver perfusion model was used to study the effects of supra-therapeutic doses of rifampicin on hepatic gluconeogenesis and bromosulphthalein (BSP) clearance from the perfusate and biliary excretion of the dye in the rat. Three groups of rats randomly assigned to a control and two experimental groups were studied; those in the experimental groups were given 4 mg rifampicin per os daily for 90 days. The control group was untreated. The livers of the control and one experimental group were perfused with a medium containing pyruvate and subsequently these livers were perfused with a medium containing bromosulphthalein. The livers of the second experimental group were subjected to histological examination. The rate and the concentration of glucose was decreased, lactate levels and lactate: pyruvate ratios were increased in the experimental animals. The mean perfusate BSP and biliary excretion of the dye was decreased in the experimental group. Fatty change was present in the livers of rifampicin treated rats. This study demonstrates that the isolated liver model has proved to be both suitable and useful for the study of the effects of drugs and that chronic administration of supra-therapeutic doses of rifampicin to rats adversely affected liver function. It also produces histological evidence of hepatic damage in rats.

Animals↗
PubMed1991

Isradipine in the treatment of mild to moderate essential hypertension.

Male patients with supine diastolic blood pressures above 95 mmHg after placebo therapy received twice daily isradipine (Dynacirc; Sandoz) 1.25, 2.5 or 5.0 mg for 12 weeks. Blood pressures were measured every 14 days. Doses of 2.5 or 5 mg isradipine twice daily significantly reduced supine and erect mean systolic, mean diastolic and mean arterial pressures. Isradipine 1.25 mg twice daily reduced supine mean diastolic and mean arterial pressures only. A dose of 5 mg twice daily was accompanied by an increase in adverse reactions. The recommended dose of isradipine is 2.5 mg twice daily.

Antihypertensive Agents↗
PubMed1991

Time course of the blood pressure response to oral isradipine in uncomplicated mild-to-moderate essential hypertension.

Forty-five patients with supine diastolic blood pressures (DBPs) above 95 mm Hg at the end of a four-week placebo run-in period were randomized to receive either 1.25 mg, 2.5 mg, or 5 mg isradipine twice daily as monotherapy for 12 weeks. Blood pressures (BP) were measured every 14 days, always by the same observer and using standard techniques. The Montevideo Mathematical Model was used to determine the time course of the response to treatment in each dosage group. Of the 33 patients who completed the study, four of the 12 patients receiving 1.25 mg isradipine twice daily had their BP controlled by weeks 10 or 12 (supine DBP less than or equal to 90 mm Hg), seven of 11 by 2.5 mg twice daily, and five of 10 by 5 mg twice daily. Mean DBPs for each dosage group were significantly reduced by week 12 (P less than .015 in all groups). The Montevideo Model allows estimation of the time after onset of treatment by which BP is reduced by a given amount. This model indicated that, with 2.5 mg isradipine twice daily, a fall in mean arterial pressure of 10 mm Hg is to be expected within three weeks of initiating drug administration.

Administration, Oral↗
PubMed1991

Changes in myocardial electrolytes and ventricular fibrillation threshold induced by alcohol feeding in laboratory rats.

Three groups of rats were studied in an investigation to determine the influence of alcohol on myocardial electrolytes and the ventricular fibrillation threshold (VFT) levels. Drinking water was provided ad libitum; the control group received water while the other 2 groups drank a water-ethanol solution, constituted in a ratio of 75: 25, for periods of 3 and 9 months, respectively. Two rats from each of the experimental groups, together with a control rat were killed on each experimental day. One heart was studied on the Langendorff preparation and the other used for tissue electrolyte analysis. The mean myocardial Mg2+ levels (233 +/- 28 micrograms/g vs 148 +/- 23 micrograms/g and 233 +/- 28 micrograms/g vs 107 +/- 15 micrograms/g; p less than 0.0001), K+ levels (3260 +/- 437 micrograms/g vs 1779 +/- 312 micrograms/g and 3260 +/- 437 micrograms/g vs 1195 +/- 205 micrograms/g; p less than 0.0001) and Zn2+ levels (32.7 +/- 6.8 micrograms/g vs 14.0 +/- 4 micrograms/g and 32.7 +/- 6.8 micrograms/g vs 4.2 +/- 3.4 micrograms/g; p less than 0.0001) were significantly lower in alcohol fed rats than the controls. In addition, a significant fall in the mean VFT levels (10.1 +/- 1.94 mA vs 6.27 +/- 2.17 mA, p less than 0.001) was noted in rats given water: alcohol solution for 9 months. This study reveals that chronic exposure to alcohol induces a deficiency of myocardial Mg2+, K+ and Zn2+, and an increase in myocardial irritability in laboratory rats.

Animals↗
PubMed1990

Comparison of felodipine and hydrochlorothiazide for the treatment of mild to moderate hypertension in black Africans.

A double-blind, parallel-group study was performed to assess the antihypertensive effects and tolerability of felodipine and hydrochlorothiazide (HCT) in black patients with mild to moderate uncomplicated hypertension [entry supine diastolic blood pressure (DBP) of 96-116 mm Hg]. The medicines were given as monotherapy and the additional effect of metoprolol was assessed in patients unresponsive to felodipine or HCT alone. After a 4-week placebo period, 45 patients were randomly allocated to treatment with felodipine (21) or HCT (24). Initial doses of felodipine 2.5 mg or HCT 12.5 mg twice daily were doubled after 1 week and doubled again after week 4 in cases with supine DBP above 90 mm Hg. At week 8, metoprolol 100 mg twice daily was added to the regimen of uncontrolled patients (supine DBP greater than 90 mm Hg) and maintained for the remaining 4-week trial period. Felodipine significantly reduced supine and erect systolic BP (SBP) and DBP after 4, 8, and 12 weeks of treatment. Responses to HCT were similar although standing diastolic BP at week 4 and standing SBP at week 8 were not significantly reduced. After 4 weeks, the mean fall in supine DBP was significantly greater for the felodipine than the HCT group. Eight patients on felodipine and 14 in the HCT group required additional metoprolol to achieve BP control. A significantly greater number of adverse effects were associated with HCT than felodipine treatment. Monotherapy with felodipine produced a more rapid control of hypertension, was more frequently effective, and was associated with a lower incidence of side effects than HCT.

Adult↗
PubMed1989

Renal excretory actions of antihypertensive agents. Effects of rilmenidine.

The acute renal excretory actions of several antihypertensive agents were assessed in healthy volunteers. Rilmenidine (1 mg) did not affect water and electrolyte balance. Beta-adrenergic blockers had little effect upon urinary composition, whereas diuretics caused significant urinary losses of fluid, sodium, potassium, and magnesium as expected. The vasodilators ketanserin and flosequinan did not affect water and electrolyte excretion. Ketanserin increased urate output in common with angiotensin-converting enzyme inhibitors, which may act as facultative diuretics. Combining the angiotensin-converting enzyme inhibitor captopril (100 mg) or rilmenidine (1 mg) with hydrochlorothiazide (25 mg) had little influence upon the known actions of the diuretic. When the beta-blocker pindolol (10 mg) was given with the diuretic clopamide (5 mg), beneficial effects were noted; potassium and magnesium losses were markedly reduced, whereas the natriuretic and diuretic effects of clopamide were unchanged. These short-term studies in healthy volunteers provide useful pointers to some possible pharmacodynamic effects of antihypertensive drugs in patients.

Adolescent↗
PubMed1988

Diltiazem compared with hydrochlorothiazide in the treatment of mild-to-moderate essential hypertension.

The efficacy of diltiazem (DTZ) (Tilazem; Parke-Davis) 90-180 mg twice daily was compared with that of hydrochlorothiazide (HCT) 25-50 mg once daily in the monotherapy of mild-to-moderate essential hypertension using a double-blind, double-dummy technique. Twenty-nine patients were randomly assigned to two groups and after a 4-week placebo period treated with HCT 25 mg once daily or DTZ 90 mg twice daily for 12 weeks. Dosage was doubled at week 8 in non-responders. Cross-over of therapy took place after a 4-week placebo washout. Both drugs effectively reduced raised arterial pressures with little change in pulse rate. HCT caused a slight elevation of the mean serum urate level. The study confirms that diltiazem offers an effective well-tolerated monotherapy for essential hypertension.

Adult↗
PubMed1987

Angiotensin I converting enzyme inhibitors and the renal excretion of urate.

Hyperuricaemia carries with it a high risk of tophi development affecting connective tissue in kidney, skin and joints, its overt clinical expression being gout. Diuretics, which are invariably prescribed in congestive heart failure and widely used for the treatment of essential hypertension, may cause hyperuricaemia and predispose to gout by inducing renal retention of urate. The angiotensin I converting enzyme inhibitors captopril and enalapril have been found to augment renal urate excretion both in normal volunteers and in hypertensive patients. Current evidence appears to indicate that the uricosuric effect of captopril and enalapril could be due to the rises in renin and angiotensin I these drugs elicit by angiotensin I converting enzyme inhibition, and/or to pharmacological actions not related, at least directly, to the renin-angiotensin-aldosterone system. Serum urate levels have been significantly reduced by monotherapy with captopril in hypertensive patients suffering from hyperuricaemia. Diuretic-induced hyperuricaemia in hypertensive patients can be prevented or counteracted by the administration of captopril and enalapril. Available clinical data support the argument that captopril and enalapril should be used as first choice drugs for the treatment of hyperuricaemic hypertensive patients. When diuretic-induced hyperuricaemia develops in patients suffering from congestive heart failure, captopril or enalapril should be added to the therapeutic regime in doses capable of countering the shift in plasma urate concentration, provided the clinical condition of the patients permits such additional pharmacological treatment. Therapy with captopril and enalapril should preferably be instituted in a gradual manner, especially in patients with hyperuricaemia, in order to prevent the precipitation of urate in the kidney and in the urinary tract.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1987

HLA-A, B, DR, and DQ antigens in black patients with severe chronic rheumatic heart disease.

To determine whether genetic factors could be involved in the pathogenesis of rheumatic heart disease, we performed HLA-A and HLA-B typing in 120 black patients with severe chronic rheumatic heart disease requiring cardiac surgery, and HLA-DR and HLA-DQ typing in 103 and 97 of these patients, respectively. The HLA typing was done by a standard microlymphocytotoxicity method. Patients were 12 to 60 years old (mean 27.6 +/- 14.5). No differences in HLA-A, HLA-B, and HLA-DQ frequencies between patients and controls were noted. HLA-DR 1 antigen was present in 12.6% of patients compared with 2.7% of normal control subjects (corrected p less than .045; relative risk = 5.2) and the HLA-DRw6 antigen was present in 31.1% of patients compared with 15% of control subjects (corrected p less than .045; relative risk = 2.6). These findings suggest that genetically determined immune-response factors may play a role in the pathogenesis of severe chronic rheumatic heart disease.

Adolescent↗