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Biomedical subjects

C Michael White

Publications and source records attributed to C Michael White.

At least 73 records · Page 4Linked to original sources
PubMed2003

Effects of intravenous magnesium sulfate on the QT interval in patients receiving ibutilide.

STUDY OBJECTIVE: To determine the effect of intravenous magnesium sulfate on the QT and QTc intervals in patients receiving ibutilide for immediate chemical cardioversion of atrial flutter or fibrillation. DESIGN: Prospective, randomized, double-blind, placebo-controlled trial. SETTING: Hospital cardiology unit. PATIENTS: Twenty patients (mean age 72 +/- 14 yrs) with atrial fibrillation (12 patients) or atrial flutter (8 patients) who were scheduled to receive ibutilide. INTERVENTION: After determining that the patients' baseline QTc intervals were less than 440 msec and baseline serum magnesium levels were within normal limits (mean 2.1 +/- 0.29 mg/dl), the patients were randomly assigned to receive either a 10-minute infusion of magnesium sulfate 2 g in 50 ml of 0.9% sodium chloride or placebo immediately before ibutilide therapy. An additional 2 g of intravenous magnesium sulfate or placebo was given over 1 hour, 10 minutes after the first dose of ibutilide. MEASUREMENTS AND MAIN RESULTS: QT interval duration was measured manually in all 12 leads by using a 0.5-mm-scale precision ruler and magnifying lens. The QT interval increased 29% from baseline at 30 minutes after ibutilide therapy in the placebo group (p=0.007), but no significant change from baseline occurred in the magnesium sulfate group. The 30-minute QTc interval in the placebo group was 18% higher than the baseline value (p=0.01) but did not change significantly in the magnesium sulfate group. QTc changes from baseline were greater in the placebo group than in the magnesium sulfate group at 30 minutes (75 vs 19 msec, respectively, p=0.04). Magnesium sulfate reduced the risk of an ibutilide-induced QTc interval increase of greater than 30 msec or greater than 60 msec and reduced the risk of a QTc interval value of more than 500 msec by 65%, 60%, and 68%, respectively (p=0.07, p=0.175, and p=0.160). CONCLUSIONS: Prophylactic administration of intravenous magnesium sulfate prevents increases in the QT and QTc interval 30 minutes after the last infusion of ibutilide.

Aged↗
PubMed2003

Acute decompensated heart failure: a contemporary approach to pharmacotherapeutic management.

Hospital admissions for acute decompensated heart failure (ADHF) have increased precipitously during the past few decades and are projected to continue to increase in the future. To optimize patient outcomes and reduce the costs associated with this disorder, evidenced-based pharmacotherapy is essential. Continuous infusions of loop diuretic therapy rather than bolus dosing may enhance efficacy and reduce the extent of diuretic resistance. Nesiritide is a pharmacologically novel preload and afterload reducer but based on clinical trial evidence should be reserved for those unable to take or with resistance to intravenous nitrate therapy. Catecholamine- and phosphodiesterase-based inotropic therapies are efficacious, but the increased risk of arrhythmogenesis and the potential for negative survival effects limit their use. The experimental agent levosimendan is a positive inotropic agent but does not increase myocyte calcium concentrations as do catecholamines or phosphodiesterase inhibitors. Clinical trial evidence demonstrates a positive survival benefit for levosimendan versus dobutamine.

Acute Disease↗
PubMed2002

A comparison of two individual amiodarone regimens to placebo in open heart surgery patients.

BACKGROUND: This study compares the ability of two oral amiodarone regimens to reduce the risk of atrial fibrillation (AF) as compared with the placebo among elderly open heart surgery (OHS) patients receiving beta blockade. METHODS: This is a randomized, double-blinded, placebo-controlled trial of 220 patients undergoing OHS. Patients (average age, 73 years) received 7 g of oral amiodarone more than 10 days starting 5 days before OHS (slow load; n = 56), a 6 g oral amiodarone regimen more than 6 days starting 1 day before OHS (fast load; n = 64), or matching placebo in one of the two previously mentioned regimens (n = 100). RESULTS: Patients receiving the slow load amiodarone regimen had a significant reduction in the risk of AF (48.4%; p = 0.013), AF lasting more than 24 hours (76.5%; p = 0.003), symptomatic AF (90.0%; p = 0.002), and recurrent AF (64.5%; p = 0.025) as compared with the placebo. Patients receiving the fast load amiodarone regimen had significant reductions in the risk of AF lasting more than 24 hours (52.6%; p = 0.038) and symptomatic AF (65.0%; p = 0.024), but the incidence of any AF or any recurrence of AF only showed a trend toward significance (34.0% and 45.5%; p = 0.054 and 0.09, respectively). CONCLUSIONS: Oral amiodarone in a slow loading regimen provides significant suppression of all AF factors and can be used when a patient has started it at least 5 days before OHS. If a patient has less than 5 days before OHS, the fast loading regimen is an efficacious alternative as it provides significant benefits in preventing AF from lasting more than 24 hours and for preventing symptomatic AF. Both regimens were well tolerated and safe in elderly patients receiving beta blockade according to the hospital's standard protocol.

Adrenergic beta-Antagonists↗
PubMed2002

The effects of hydroxy-methyl-glutaryl co-enzyme A reductase inhibitors on platelet thrombus formation.

BACKGROUND: Hydroxy-methyl-glutaryl co-enzyme A reductase inhibitors (HMG CoA RIs) markedly improve the lipid profile of patients with hypercholesterolemia, but the magnitude and time course of the effect of these drugs on other risk factors for atherosclerosis are not well defined. METHODS: We employed a random assignment, double-blind design to compare the effect of 8 weeks of HMG CoA RI therapy with either pravastatin (40 mg QD; n=12) or simvastatin (20 mg QD; n=12) with placebo (n=13) on serum lipids, platelet thrombus formation (PTF), and markers of inflammation and thrombosis in patients with coronary artery disease. PTF was measured using a validated ex vivo perfusion chamber system. RESULTS: Total and LDL cholesterol decreased 20.3 +/- 12.7% and 31.4 +/- 16.5% in the HMG CoA RI group and were unchanged with placebo (P<0.01). Triglycerides also decreased 15.3 +/- 22.5% with HMG CoA RI therapy, but increased 8.4 +/- 30.0% with placebo (P=0.01). PTF increased 54.1 +/- 89.0% with placebo and decreased 8.0 +/- 46.82% with HMG CoA RI treatment (P<0.01). CONCLUSIONS: HMG CoA RI therapy with pravastatin or simvastatin reduces PTF after only 8 weeks of therapy. Such lipid effects may contribute to the prompt reduction in cardiovascular events noted in some clinical trials.

Aged↗
PubMed2002

The effect of head-upright tilt table testing for vasovagal syncope on P-wave duration.

Fluid shifts in vasovagal syncope may be reflected in electrocardiographic P-wave duration. We examined the effect of head-upright tilt-table testing (HUT) on P-wave duration among patients with positive or negative HUT. P-wave duration was measured at baseline and several post-HUT time points. In patients with a positive HUT, the test was immediately discontinued. P-wave duration measurements obtained at the completion of the test or when symptoms occurred were compared to baseline measurements. The P-wave duration among patients with a positive HUT was significantly reduced at the onset of symptoms as compared to baseline (-14.0 ms, P = .0054) and 2-minute tilt measurements (-11.3 ms, P = .0246). P-wave duration measurements were not reduced in patients experiencing a negative HUT at any follow-up time. We showed a significant reduction in P-wave duration among patients experiencing positive HUT that suggests a dynamic relationship between atrial volume and P-wave duration.

Adult↗
PubMed2002

Effect of intravenous testosterone on myocardial ischemia in men with coronary artery disease.

BACKGROUND: Studies on the effect of estrogen on atherosclerotic coronary artery disease (CAD) risk in women have produced conflicting results. Similar confusion, but fewer data, exists on the effect of testosterone on CAD risk in men. METHODS: We used 99mTc sestamibi single-photon emission computed tomography (SPECT) myocardial perfusion imaging to examine the acute effect of intravenous testosterone in 32 men (mean age, 69.1 +/- 6.4 years) with provocable myocardial ischemia on standard medical therapy. Patients performed 3 exercise (n = 18) or adenosine (n = 16) stress tests during the infusion of placebo or 2 doses of testosterone designed to increase testosterone 2 or 6 times baseline. RESULTS: Serum testosterone increased 137 +/- 58% and 488 +/- 113%, and estradiol levels increased 27 +/- 46% and 76 +/- 57%, (P <.001 for all) during the 2 testosterone infusions. There were no differences among the placebo or testosterone groups in peak heart rate, systolic blood pressure, maximal rate pressure product, perfusion imaging scores, or the onset of ST-segment depression. CONCLUSIONS: Acute testosterone infusion has neither a beneficial nor a deleterious effect on the onset and magnitude of stress-induced myocardial ischemia in men with stable CAD.

Aged↗
PubMed2002

The immediate and short-term effect of successful percutaneous coronary intervention on repolarization in acute myocardial infarction patients.

OBJECTIVES: The primary objective was to assess the immediate and short-term impact of successful percutaneous coronary intervention (PCI) on QT dispersion (QT disp) and corrected QT dispersion (QTc disp). Secondarily, the impact of PCI on QT and QTc disp within different infarct-related arteries and the impact of successful PCI in these different arteries were evaluated. METHODS: Patients (n = 140, age 61.6 +/- 12.9, 69% male) undergoing direct primary PCI for acute MI were evaluated. Twelve-lead ECGs were obtained before (baseline), immediately after (0 h), 24hours after, and 3 days after PCI. The QT and QTc interval in each of the 12-leads were measured and the shortest interval was subtracted from the longest to derive the QT disp and QTc disp, respectively. RESULTS: Angiography showed blockages in the left anterior descending, right coronary artery, and circumflex in 37.1, 48.9, and 15.0% of patients, respectively. Overall, 97 patients achieved successful reflow. QT and QTc disp were significantly improved in the group with successful reflow at each follow-up time after PCI versus baseline and corresponding values in the unsuccessful reflow group. QT disp was improved among patients with successful reflow irrespective of which infarct artery was responsible for the acute myocardial infarction. CONCLUSIONS: Successful reflow with PCI is associated with a rapid reduction in QT disp and QTc disp that is maintained for at least 3 days after the event. Conversely, unsuccessful reflow was not associated with significant reductions in QT or QTc disp.

Aged↗
PubMed2002

Electrocardiographic and hemodynamic effects of Panax ginseng.

OBJECTIVE: To determine whether Panax ginseng ingestion can acutely or chronically alter electrocardiographic parameters: PR, QRS, QT, QTc, and RR intervals, and QT and QTc interval dispersion. Effects of P. ginseng on blood pressure and heart rate also were evaluated. METHODS: This is a prospective, randomized, double-blind, placebo-controlled study of healthy adults at the University of Connecticut. Thirty subjects were randomly allocated to receive 28 days of therapy with either P. ginseng extract 200 mg or placebo. Baseline 12-lead electrocardiograms (ECGs) were obtained. Subsequent ECGs were performed following study drug ingestion at 50 minutes, 2 hours, and 5 hours on days 1 and 28. Blood pressure readings were taken with each ECG. RESULTS: P. ginseng ingestion increased the QTc interval by 0.015 seconds on day 1 at 2 hours compared with the placebo group (p = 0.03). It also reduced diastolic blood pressure from 75 +/- 5 mm Hg at baseline to 70 +/- 6 mm Hg at the same time point (p = 0.02). The observed effects are not believed to be clinically significant. No other statistically significant changes were found in electrocardiographic or hemodynamic variables on days 1 or 28. CONCLUSIONS: P. ginseng, at doses of 200 mg of the extract daily, increases the QTc interval and decreases diastolic blood pressure 2 hours after ingestion in healthy adults on the first day of therapy.

Adolescent↗
PubMed2002

Amlodipine versus Angiotensin-receptor blockers for nonhypertension indications.

OBJECTIVE: To review the efficacy and safety data of amlodipine and the angiotensin-receptor blockers (ARBs), focusing on heart failure, angina, percutaneous coronary intervention (PCI), and renal protection. DATA SOURCE: A MEDLINE search (1966-December 2001) was completed using amlodipine, angiotensin-receptor antagonist, losartan, valsartan, candesartan, and telmisartan as key words. English-language articles were identified and included. STUDY SELECTION AND DATA EXTRACTION: All identified articles were evaluated. Articles representative of the subject matter of our review were included. DATA SYNTHESIS: Amlodipine and the ARBs lower blood pressure to a similar extent. Amlodipine is an effective antianginal agent, whereas ARBs are not. However, amlodipine is not effective in the treatment of heart failure; ARBs may be useful in this setting. ARBs are also effective in preserving renal function and may provide some protection from restenosis in patients who have had a PCI. The ARBs may also be useful in preventing both diabetic and nondiabetic nephropathy. CONCLUSIONS: Concomitant disease states should be considered when choosing between an ARB and amlodipine for the management of hypertension.

Amlodipine↗
PubMed2002

An economic analysis of amiodarone versus placebo for the prevention of atrial fibrillation after open heart surgery.

STUDY OBJECTIVE: To determine if the additional costs of oral amiodarone in patients undergoing open heart surgery would be offset by reductions in the frequency of atrial fibrillation. DESIGN: Piggyback cost analysis of the data from a randomized, double-blind, placebo-controlled trial. SETTING: Urban academic hospital. PATIENTS: Two hundred twenty elderly patients (> or = 60 yrs old) undergoing open heart surgery. INTERVENTION: Hospital costs of open heart surgery in patients given amiodarone for the prevention of atrial fibrillation and in prespecified subgroups were compared with those for patients given placebo (i.e., standard care with beta-blockers alone). MEASUREMENTS AND MAIN RESULTS: Total hospital costs incurred were $15,565 +/- $9832 and $16,126 +/- $8043 in the amiodarone and placebo groups, respectively (p=0.12). General ward, intensive care unit, operating room, pharmacy, and costs in all other departments were similar between the groups (p>0.05 for all comparisons). Because costs were similar but amiodarone was more effective than placebo, amiodarone was cost-effective compared with placebo. Amiodarone remained cost-effective compared with placebo regardless of the following subgroup characteristics: rapid or slow loading strategy, no history of atrial fibrillation or heart failure, age older than 70 years, and no tolerance to preoperative beta-blockers. Moreover, in the one-way sensitivity analysis, the findings remained robust to changes in effectiveness and cost of amiodarone. CONCLUSION: Routine prophylaxis with amiodarone is cost-effective compared with placebo. Future studies should examine the cost-effectiveness of selective prophylaxis, and primary cost-effectiveness studies should be conducted to validate these findings.

Aged↗
PubMed2002

Effect of diuresis on P-wave duration and dispersion.

STUDY OBJECTIVE: To evaluate the effects of changing volume status on P-wave duration and dispersion in patients with decompensated heart failure. DESIGN: Prospective analysis. SETTING: Hospital cardiology unit. PATIENTS: Twenty-one patients with symptoms of decompensated heart failure who were treated with diuretics on admission. INTERVENTION: Twelve-lead electrocardiograms were obtained at baseline and after diuresis. Average, minimum, and maximum P-wave duration and P-wave dispersion (minimum minus maximum duration) were determined. MEASUREMENTS AND MAIN RESULTS: P-wave duration was measured manually in all 12 leads by using a 0.5-mm-scale precision ruler and magnifying lens. After 40+/-23 hours of diuresis, 3+/-1 L of fluid was removed. A significant correlation was found between average P-wave duration and amount of fluid removed (r = -0.59, p=0.015). Also, average and maximum P-wave duration were significantly decreased with diuresis (p=0.001 and 0.022, respectively). No other P-wave variables were significantly affected. CONCLUSIONS: Diuresis may attenuate electrophysiologic changes caused by fluid overload.

Aged↗
PubMed2002

Clinical pharmacokinetics and selective pharmacodynamics of new angiotensin converting enzyme inhibitors: an update.

The angiotensin converting enzyme (ACE) inhibitors are widely used in the management of essential hypertension, stable chronic heart failure, myocardial infarction (MI) and diabetic nephropathy. There is an increasing number of new agents to add to the nine ACE inhibitors (benazepril, cilazapril, delapril, fosinopril, lisinopril, pentopril, perindopril, quinapril and ramipril) reviewed in this journal in 1990. The pharmacokinetic properties of five newer ACE inhibitors (trandolapril, moexipril, spirapril, temocapril and imidapril) are reviewed in this update. All of these new agents are characterised by having a carboxyl functional groups and requiring hepatic activation to form pharmacologically active metabolites. They achieve peak plasma concentrations at similar times (t(max)) to those of established agents. Three of these agents (trandolapril, moexipril and imidapril) require dosage reductions in patients with renal impairment. Dosage reductions of moexipril and temocapril are recommended for elderly patients, and dosages of moexipril should be lower in patients who are hepatically impaired. Moexipril should be taken 1 hour before meals, whereas other ACE inhibitors can be taken without regard to meals. The pharmacokinetics of warfarin are not altered by concomitant administration with trandolapril or moexipril. Although imidapril and spirapril have no effect on digoxin pharmacokinetics, the area under the concentration-time curve of imidapril and the peak plasma concentration of the active metabolite imidaprilat are decreased when imidapril is given together with digoxin. Although six ACE inhibitors (captopril, enalapril, fosinopril, lisinopril, quinapril and ramipril) have been approved for use in heart failure by the US Food and Drug Administration, an overview of 32 clinical trials of ACE inhibitors in heart failure showed that no significant heterogeneity in mortality was found among enalapril, ramipril, quinapril, captopril, lisinopril, benazepril, perindopril and cilazapril. Initiation of therapy with captopril, ramipril, and trandolapril at least 3 days after an acute MI resulted in all-cause mortality risk reductions of 18 to 27%. Captopril has been shown to have similar morbidity and mortality benefits to those of diuretics and beta-blockers in hypertensive patients. Captopril has been shown to delay the progression of diabetic nephropathy, and enalapril and lisinopril prevent the development of nephropathy in normoalbuminuric patients with diabetes. ACE inhibitors are generally characterised by flat dose-response curves. Lisinopril is the only ACE inhibitor that exhibits a linear dose-response curve. Despite the fact that most ACE inhibitors are recommended for once-daily administration, only fosinopril, ramipril, and trandolapril have trough-to-peak effect ratios in excess of 50%.

Age Factors↗
PubMed2002

A review of the pharmacologic and pharmacokinetic aspects of rosuvastatin.

Rosuvastatin is a new HMG-CoA reductase inhibitor with unique pharmacologic and pharmacokinetic properties. It has additional HMG-CoA reductase enzyme-binding interactions that cause tighter binding, has substantial active transport into hepatocytes, and has the lowest IC50 for sterol synthesis in hepatocytes. Rosuvastatin 10 mg and 80 mg dosages have superior low-density lipoprotein (LDL) cholesterol-lowering efficacy as compared to atorvastatin 10 mg and 80 mg. Rosuvastatin 10 mghas also been shown to have superior LDL reductions to 20 mg of both simvastatin and pravastatin. This agent can raise high-density lipoprotein (HDL) 8% to 12% and lower triglycerides by 10% to 35%. Rosuvastatin is a hydrophilic agent with poor penetration in extrahepatic tissue such as human umbilical vein endothelial cells and fibroblasts. It also has a low potential for cytochrome P450 drug interactions and can be dosed in the morning or night. In conclusion, rosuvastatin is an agent with molecular alterations that provide it with unique pharmacologic and phannacokinetic effects. As such, it is a novel and unique HMG-CoA reductase inhibitor for the treatment of hyperlipidemia.

Animals↗