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Biomedical subjects

T D Giles

Publications and source records attributed to T D Giles.

At least 19 recordsLinked to original sources
PubMed1992

Importance of long-acting angiotensin-converting enzyme inhibitors for congestive heart failure.

The renin-angiotensin system (RAS) has both localized and systemic effects in the pathophysiology of heart failure. These may lead to structural changes in the heart and blood vessels as well as to more disseminated symptomatology, including vasoconstriction and both salt and water retention. In association with other neurohormonal mechanisms, such as the sympathetic nervous system, these latter effects result in an elevated work load for the heart. The increase in neurohormonal activity, seen in some patients with heart failure, may result in a loss of circadian variation in heart rate and blood pressure and deprive the heart of a needed reduction in work load during the night. The suppression of such neurohormonal activity through the use of long-acting angiotensin-converting enzyme (ACE) inhibitors, such as lisinopril, provides a means of controlling such symptoms. In comparison with short-acting ACE inhibitors, such long-acting suppression of the RAS may have a number of advantages. These include a more sustained increase in exercise duration, improvement in left ventricular ejection fraction, and, speculatively, a better influence on patient mortality.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Future uses of ambulatory blood pressure monitoring: implications for therapy.

Ambulatory blood pressure monitoring can play a significant role in evaluating the effects of treatment on the circadian cardiovascular pattern of patients with ischemic heart disease and/or congestive heart disease. In ischemic heart disease, drug therapy should be designed to reduce heart rate and blood pressure throughout the 24-hour cycle, including the early morning surge. Beta-blocking agents appear to accomplish these reductions. In congestive heart failure, some patients maintain their circadian variation while others do not, leaving them without the normal period of cardiac rest during the nighttime hours. Therapy should be designed to reduce this cardiac overload, and vasodilating agents appear to accomplish this. Ambulatory monitoring is especially useful in monitoring the effectiveness of drug interventions throughout the 24-hour cycle.

Ambulatory Care↗
PubMed1992

Remodeling and reparation of the cardiovascular system.

Growth or altered metabolism of nonmyocyte cells (cardiac fibroblasts, vascular smooth muscle and endothelial cells) alters myocardial and vascular structure (remodeling) and function. However, the precise roles of circulating and locally generated factors such as angiotensin II, aldosterone and endothelin that regulate growth and metabolism of nonmyocyte cells have yet to be fully elucidated. Trials of pharmacologic therapy aimed at preventing structural remodeling and repairing altered myocardial structure to or toward normal in the setting of hypertension, heart failure and diabetes are reviewed. It is proposed that these are therapeutic goals that may reduce cardiovascular morbidity and mortality. Although this hypothesis remains unproved the primary goal of therapy should be to preserve or restore tissue structure and function.

Animals↗
PubMed1992

Comparative effects of nitrendipine and hydrochlorothiazide on calciotropic hormones and bone density in hypertensive patients.

The effects of the calcium antagonist nitrendipine and the diuretic hydrochlorothiazide on plasma calciotropic hormone concentrations and lumbar bone density were compared during the treatment of hypertension in a randomized, double-blind, 8 week parallel study, followed by a 52 week open label study. There were 32 subjects with stable essential hypertension (sitting diastolic blood pressure > or = 95 mm Hg and < or = 115 mm Hg without medication) without evidence of renal insufficiency or active heart disease. They were randomly assigned to receive either 10 mg nitrendipine twice daily or 50 mg hydrochlorothiazide daily. In order to reach and maintain target blood pressure (diastolic blood pressure < or = 95 mm Hg) during the open label period, the nitrendipine dose was titrated up to 30 mg twice daily, and additional antihypertensive drugs, of differing classes, were added as necessary. Blood samples were analyzed for concentrations of calcium, parathyroid hormone, and calcitonin, and lumbar bone density was determined by dual photon absorptiometry, at the baseline and at 24 and 52 weeks of antihypertensive drug therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Failure of interleukin-2 to alter systolic blood pressure in Dahl salt-sensitive rats.

The effect of interleukin-2 (IL-2) on systolic blood pressure in Dahl salt-sensitive rats was investigated. The treatment group received human IL-2 injections (5000 units/kg). Control animals received subcutaneous saline injections. Both groups of animals were placed on a diet containing 1.5% sodium the day of the first injection and maintained on that diet for the duration of the study. Systolic blood pressure increased in both the IL-2 treated and the control groups (P = .0001) over 7 weeks. The increase in SBP was the same for both groups (P = .8823 for between group differences). At the end of 7 weeks, when SBP in both groups was elevated to a similar degree, the IL-2 group and the control group were each administered 5000 units/kg of IL-2. SBP in both groups remained elevated, showing no decrease over the next two weeks. These results indicate that perhaps unlike in SHR, IL-2 does not alter systolic blood pressure in Dahl salt-sensitive rats.

Animals↗
PubMed1992

Hemodynamic and neurohumoral responses to intravenous nicorandil in congestive heart failure in humans.

Nicorandil is a vasodilator drug that combines potassium channel opening properties with nitrate effects. The resulting potent and unique vasodilating properties suggest a potential therapeutic role in congestive heart failure. We therefore studied the acute hemodynamic and neurohumoral responses to nicorandil, given as single intravenous bolus doses of 158, 251, 398, or 630 micrograms/kg, to 22 patients with chronic congestive heart failure (ejection fraction less than 40%). Hemodynamic responses occurred within 5 min of dosing and terminated within 240 min. The heart rate was significantly increased only at 5 min after the 158 micrograms/kg dose, and was unchanged after all other doses. The mean arterial pressure was reduced only by the 398 and 630 micrograms/kg doses. The pulmonary capillary wedge pressure and right atrial pressure were significantly reduced by all doses within the initial 30 min; this reduction in pulmonary capillary wedge pressure was better sustained over time by the two larger doses, whereas the reduction in right atrial pressure was sustained only by the 158 micrograms/kg dose. The cardiac index was reduced by the 158 micrograms/kg dose, but increased after 251, 398, and 630 micrograms/kg of nicorandil. Plasma nicorandil concentrations were positively correlated with changes in cardiac index, systemic arterial pressure, pulmonary capillary wedge pressure, heart rate, and systemic vascular resistance. When measured 1 h after dosing, plasma immunoreactive ANF decreased, norepinephrine concentrations did not change, and plasma renin activity increased, but only at the 630 micrograms/kg dose level.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Antihypertensive therapy and cardiovascular risk. Are all antihypertensives equal?

The lack of success of antihypertensive drug therapy in decreasing cardiovascular events has caused close examination of the influence of antihypertensive drugs on cardiac risk factors. Striking differences exist in the pharmacological profiles of antihypertensive drug classes and subclasses as well as in the influences of the drugs on electrolyte, lipid, and glucose metabolism. Differences also exist in the effects of the drugs on left ventricular hypertrophy. These differences in the effects of antihypertensive drugs on cardiac risk factors may assist in explaining the lack of a favorable effect on cardiovascular events in previous clinical trials. However, prospective trials are necessary to demonstrate that treatment of hypertension with drugs that have a more favorable effect on cardiac risk factors will reduce cardiac events (i.e., myocardial infarction, heart failure, and sudden death).

Antihypertensive Agents↗
PubMed1991

Angiotensin-converting enzyme inhibition, cell growth, and left ventricular hypertrophy in hypertension.

Left ventricular hypertrophy is now recognized as an important risk marker in cardiovascular morbidity and mortality. Left ventricular hypertrophy is an integral component of the complex pathophysiology of primary hypertension and results from mechanical, neurohumoral, and genetic factors. The renin-angiotensin system is involved with the production of left ventricular hypertrophy, not only through the effects on systemic arterial blood pressure but also by both direct and indirect effects on myocardial cell growth. The angiotensin-converting enzyme (ACE) inhibitors are effective drugs for reducing blood pressure in primary hypertension. ACE inhibitor therapy is also associated with regression of left ventricular hypertrophy and restoration of normal diastolic and systolic left ventricular function. Regression of left ventricular hypertrophy is associated with improved prognosis. Thus, when left ventricular hypertrophy regression is a goal of antihypertensive treatment, the ACE inhibitors are effective drugs.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Evaluation of labetalol in elderly patients with essential hypertension.

Labetalol was evaluated in a multicenter, placebo-controlled study of elderly patients (greater than or equal to 60 years) with mild to moderate essential hypertension. After a placebo-washout period, doses were titrated from 100 mg BID to a maximum of 400 mg BID over a 6-week period. Once blood pressure control (standing diastolic blood pressure [SDBP] less than 90 mm Hg and greater than or equal to 10 mm Hg reduction from baseline) was achieved or the maximum allowable dosage had been given, the dosage remained the same until the end of the study. The titration phase was followed by a 4-week maintenance period. Blood pressure control was achieved in 37/54 (69%) of the patients who were treated with labetalol compared with 21/58 (36%) of the patients who received placebo (P less than .001). Twenty-nine (78%) of those controlled on labetalol responded to doses of 200 mg or less BID, and there was no significant difference between groups with respect to orthostatic blood pressure changes. Adverse experiences were generally mild and occurred with similar frequency in the labetalol and placebo groups; six patients who received labetalol and five who received placebo withdrew from the study due to adverse experiences, but in only one case (labetalol) was the adverse experience considered drug-related. In summary, labetalol effectively and safely lowered diastolic blood pressure in the elderly without producing significant orthostatic changes.

Aged↗
PubMed1991

Prolonged hemodynamic benefits from a high-dose bolus injection of human atrial natriuretic factor in congestive heart failure.

The physiologic and potential pharmacologic roles of atrial natriuretic factor in congestive heart failure have remained confusing. We have evaluated the hemodynamic responses to human atrial natriuretic factor [ANF (102-126)] given as bolus intravenous doses of 2.0 or 4.5 micrograms/kg to 12 patients with congestive heart failure. Responses were monitored with pulmonary and systemic arterial catheters in place. By 30 minutes after 4.5 micrograms/kg ANF (n = 6), heart rate decreased from 97 +/- 16 to 91 +/- 15 beats/min, right atrial pressure from 14 +/- 4 to 12 +/- 3 mm Hg, and pulmonary capillary wedge pressure from 33 +/- 3 to 23 +/- 2 mm Hg (all p less than 0.05); responses persisted for 120 minutes. Mean arterial pressure, cardiac index, stroke volume index, and pulmonic and systemic vascular resistances did not change significantly. The 2.0 micrograms/kg ANF dose produced similar responses, but only heart rate and right atrial pressure decreased significantly. No clinically important side effects were noted. High-dose ANF bolus doses can be administered simply and safely and improve hemodynamic parameters in chronic heart failure. Therefore ANF does have pharmacologic activity in heart failure and may have therapeutic potential.

Aged↗
PubMed1991

Benefits of prolonged angiotensin-converting enzyme inhibition in congestive heart failure.

Normal individuals have time-dependent variations in cardiovascular function, most of which are circadian (once daily). They include changes in heart rate, systemic arterial blood pressure, cardiac output, blood volume, and viscosity. There are also changes in neuroendocrine function, including the sympathetic and parasympathetic nervous systems and the renin-angiotensin system. These variations have important consequences for the heart, since haemodynamic and neuroendocrine alterations determine cardiac work load; heart rate, blood pressure, and sympathetic nervous system activity are highest during the waking hours and lowest during sleep. Cardiovascular mortality and morbidity are associated with these changes. Patients with congestive heart failure undergo changes in neurohumoral cardiovascular regulation that increase the work load of the heart as a result of increases in heart rate and peripheral vascular resistance. Moreover, a normal circadian variation is lost, causing blood pressure and heart rate to remain increased at night, depriving the heart of a period of rest. In addition, these patients have an ability to increase blood flow to exercising skeletal muscle, limiting exercise tolerance, as well as the consequences of elevated ventricular filling pressures. These time-dependent variations in the pathophysiological processes of congestive heart failure have implications for pharmacological therapy. In particular, vasodilator therapy should be administered to provide optimal unloading of the heart throughout the day. Vasodilator therapy should also provide antagonism to those factors that limit blood flow to working skeletal muscle, so that the physical ability is not intermittently compromised during the trough effect of the drug. Criteria for establishing the efficacy of drugs for the treatment of congestive heart failure should include an analysis of peak and trough effects.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Comparison of lisinopril and captopril in the treatment of left ventricular congestive heart failure--influence of duration of action on efficacy and safety.

Data from the lisinopril-captopril comparison trial (6), as well as other data (1, 8, 14, 10) indicate that both long- and short-acting ACEI are effective and safe for the treatment of CHF. An improved effect on LV function and signs and symptoms of CHF as a result of more prolonged unloading of the heart by long-acting ACEI is suggested by the lisinopril-captopril comparison trial, but requires confirmation. An effect on renal function is expected with ACEI treatment of CHF, i.e., increase in BUN and serum creatinine; the greater increase in BUN by lisinopril as compared to captopril reflects more the potency and duration of action of the drug rather than a more serious diverse consequence. In patients with renal insufficiency (serum creatinine greater than 1.6 mg/dl), the more potent, longer-acting ACEI may be required. Advanced CHF, i.e. Class III-IV (NYHA), is a clear indication for the use of ACEI, both for improvement in symptoms and mortality. Indication for ACEI treatment of patients with less severe heart failure awaits the results on ongoing clinical trials.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Hemodynamic and renal effects of atrial natriuretic peptide in congestive heart failure.

The hemodynamic and renal effects of anaritide (human atrial natriuretic peptide 102-126), a synthetic analog of atrial natriuretic peptide, were evaluated in 35 patients with chronic New York Heart Association class II to IV heart failure. There were 32 men and 3 women, aged 33 to 75 (mean +/- standard error of the mean 56 +/- 2) years. In the first phase of the study, right-sided heart catheterization was performed, and anaritide was administered as 1-hour infusions. The rate of the infusion varied among patients from 0.03 to 0.3 micrograms/kg/min. In response to anaritide, there were decreases in mean systemic arterial (94 +/- 2 to 87 +/- 2 mm Hg), right atrial (10 +/- 1 to 8 +/- 1 mm Hg), mean pulmonary arterial (33 +/- 2 to 28 +/- 2 mm Hg) and pulmonary artery wedge (22 +/- 2 to 15 +/- 2 mm Hg) pressures (all p less than 0.05). Cardiac index increased (2.39 +/- 0.15 to 2.62 +/- 0.15 liters/min/m2, p less than 0.05) and heart rate was unchanged. Systemic vascular resistance decreased significantly, but pulmonary vascular resistance was unchanged. There were increases in urine volume (1.6 +/- 0.2 to 2.3 +/- 0.4 ml/min), sodium excretion (47 +/- 13 to 74 +/- 20 muEq/min) and fractional excretion of sodium (0.41 +/- 0.11 to 0.59 +/- 0.14%, all p less than 0.05), while potassium excretion and creatinine clearance did not change. In the second phase of the study, patients received 2-hour infusions of anaritide (0.03 to 0.6 micrograms/kg/min) and placebo with noninvasive monitoring.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Intravenous captopril in congestive heart failure.

Hemodynamic and neurohumoral effects of intravenous captopril were studied in ten patients with severe chronic congestive heart failure (NYHA Functional Class III and IV). Incremental bolus doses of captopril, titrated to a maximum cumulative dose of 15 mg, were given at 10-minute intervals. Systemic arterial pressure, mean pulmonary capillary wedge pressure, systemic vascular resistance, mean pulmonary artery pressure, and heart rate decreased (P less than .05). Cardiac index and stroke volume index increased (P less than .05). Maximum hemodynamic effects occurred after cumulative doses of 7 mg and were seen within 30 minutes after initiation of therapy; responses persisted for 30-90 minutes after the last dose. Plasma renin activity increased, and plasma atrial natriuretic factor concentration decreased. No adverse effects were observed with the use of intravenous captopril. Thus, intravenous captopril produces rapid and favorable hemodynamic improvement in advanced heart failure patients.

Aged↗
PubMed1990

Efficacy of nicardipine in angina pectoris.

The dose-related efficacy and safety of nicardipine, a new calcium antagonist of the dihydropyridine class, was assessed by exercise tolerance testing in a randomized, double-blinded, placebo-controlled study in 19 patients with chronic, stable effort angina pectoris. Four patients were assigned to each of four treatment sequences receiving nicardipine three times daily in an extended Latin-Square study design. An increase in total exercise capacity, time to onset of angina and time to 1 mm ST segment depression was observed with nicardipine 90 mg/day compared to placebo (P less than .05). Gradual upward dose titration in 30 mg/day increments starting from 30 mg/day appeared to produce maximal increase in exercise capacity. Two patients developed adverse side effects attributable to the drug when administered nicardipine 90 mg/day directly from placebo.

Aged↗
PubMed1990

Clinical experience with lisinopril in congestive heart failure. Focus on the older patient.

Lisinopril, a long acting, non-sulfhydryl-containing angiotensin-converting enzyme inhibitor, produces an increase in exercise capacity and an improvement in symptoms when administered in a dose of 5 to 20 mg/day to patients with congestive heart failure. There is an increase in left ventricular ejection fraction, and the effectiveness of the drug is not diminished by impairment of renal function (serum creatinine greater than 71.6 mg/dl). Lisinopril is just as effective in older (greater than 65 years of age) patients as in younger patients and is well tolerated among patients of all age groups.

Age Factors↗