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Biomedical subjects

B G Firth

Publications and source records attributed to B G Firth.

At least 19 recordsLinked to original sources
PubMed1991

Congestive heart failure. New frontiers.

Congestive heart failure is a common syndrome with high mortality in its advanced stages. Current therapy includes the use of vasodilator drugs, which have been shown to prolong life. Despite current therapy, mortality remains high in patients with severe heart failure. Potent new inotropic vasodilators have improved ventricular performance but have not prolonged life in patients with end-stage heart failure. Serious arrhythmias are implicated in the sudden deaths of 30% to 40% of patients with severe heart failure, but the benefits of antiarrhythmic therapy have not been established. Upcoming trials will address this question. Ventricular remodeling and progressive dilatation after myocardial infarction commonly lead to congestive heart failure; early unloading of the ventricle with an angiotensin-converting enzyme inhibitor may attenuate these events. These findings support the concept that angiotensin-converting enzyme inhibitors may be useful in managing heart failure of all degrees of severity, including left ventricular dysfunction and end-stage heart failure. Part of the damage that may occur with acute myocardial infarction, particularly in this era of thrombolysis therapy, is reperfusion injury, which may be mediated by oxygen-derived free radicals. Better knowledge of the mechanisms and treatment of myocardial infarction, the leading cause of congestive heart failure, may help prevent or attenuate the development of this syndrome.

Anti-Arrhythmia Agents↗
PubMed1990

Left ventricular dilatation and failure post-myocardial infarction: pathophysiology and possible pharmacologic interventions.

An important antecedent to the development of late congestive heart failure is left ventricular dilatation and remodeling following myocardial infarction, which occurs in 30-40% of acute anterior transmural infarcts. Dilatation and remodeling commence within the first 24 hours following myocardial infarction and may be steadily progressive over months to years. Both the infarcted and uninfarcted regions of the myocardium are equally involved in the process. The remodeling process comprises left ventricular wall thinning (mainly due to cell slippage), chamber dilatation, and compensatory hypertrophy of the uninfarcted segment of the myocardium. The hypertrophy may initially be physiologic but may ultimately become a pathologic process, and thereby contribute to pump dysfunction. The possible reasons why the ventricular hypertrophy may ultimately be dysfunctional include alterations in local architecture and their sequelae alone or in concert with local changes in the beta-adrenergic, alpha-adrenergic, or renin angiotensin systems. At the present time, there are encouraging data to suggest that nitroglycerin, or the angiotensin converting enzyme inhibitor captopril, may ameliorate this process.

Animals↗
PubMed1990

Ethanol-induced coronary vasodilation in patients with and without coronary artery disease.

To assess the influence of ethanol on coronary arterial blood flow and dimensions, we measured coronary sinus blood flow in 35 subjects (23 men and 12 women, aged 38 to 69 years; (29 with and 6 without coronary artery disease) before and during a 15- to 30-minute intracoronary infusion of (1) 5% dextrose in water (n = 15, controls) or (2) 5% dextrose in water (n = 20). In the controls heart rate, arterial pressure, and coronary sinus blood flow were unchanged. In those receiving ethanol at a rate that produced a concentration in coronary sinus blood of 285 +/- 102 (mean +/- SD) mg/dl, heart rate-systolic arterial pressure product was unchanged; coronary sinus blood flow rose 27 +/- 36%, and coronary vascular resistance fell 17 +/- 22% (p less than 0.05 in comparison to baseline); arterial-coronary sinus oxygen content difference fell (p less than 0.05), and epicardial coronary arterial dimensions were unchanged. Thus intracoronary ethanol increases coronary blood flow and decreases resistance without inducing a change in epicardial coronary dimensions, suggesting that its effect results from dilatation of the intramyocardial resistance vessels.

Adult↗
PubMed1990

The prevention of congestive heart failure: left ventricular dilation and its management.

Left ventricular dilation and remodelling occur in 35-40% of anterior transmural myocardial infarcts and these events are important antecedents to the development of late congestive heart failure. This process commences within the first 24 hours following myocardial infarction and may be steadily progressive over months to years. Both the infarcted and the uninfarcted regions of myocardium are equally involved in the process. Thinning of the left ventricular wall occurs mainly as a result of cell slippage. In addition, compensatory hypertrophy occurs in the uninfarcted segment of the myocardium. While this hypertrophy may initially be physiological, it ultimately appears to become a pathological process and thereby contributes to pump dysfunction. At the present time there are encouraging data to suggest that nitroglycerin, administered in the setting of the acute infarction, or the angiotensin converting enzyme inhibitor captopril, may ameliorate this process. Whether a patent infarct related artery further limits dilation is uncertain and is currently under investigation.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Survival in congestive heart failure: have we made a difference?

Congestive heart failure (CHF) affects approximately 400,000 new patients each year in the United States, resulting in death in more than 50% within five years, with traditional therapy including digitalis and diuretics. The aging of the population will only serve to aggravate this problem. Surgical treatment of CHF is a viable option in a minority of cases; a total of no more than 2,000 heart transplantation procedures were performed in the United States in 1988. Therefore, if survival is to improve in patients with CHF, effective alternative medical therapy may need to be added to or substituted for more traditional therapy. Vasodilator therapy with the angiotensin-converting enzyme inhibitors captopril and enalapril, or the combination of hydralazine and isosorbide dinitrate, improves survival in patients with severe heart failure when added to treatment with digitalis and diuretics. Nevertheless, the mortality rate remains extremely high once this stage of the disease process is reached. The prevention of left ventricular dilatation and remodeling, before the occurrence of overt heart failure, is the focus of much attention. Interventions that limit or interrupt the disease process at an even earlier stage will be necessary to make a major impact on survival.

Heart Failure↗
PubMed1989

Cardiorenal effects of atrial natriuretic factor administration in congestive heart failure: natriuresis and diuresis without hemodynamic alterations.

The effects of low bolus dose (70 +/- 6 micrograms [mean +/- SEM]) atrial natriuretic factor (ANF) administration was assessed in 16 patients with chronic congestive heart failure. Measurements were made for at least 60 minutes before and after the dose of ANF. There was a significant increase in urine flow rate (0.81 +/- 0.06 to 1.81 +/- 0.23 ml/min, p less than 0.01), sodium excretion rate (56 +/- 14 to 80 +/- 23 microEq/min, p less than 0.01), fractional excretion of sodium (1.23 +/- 0.49 to 1.63 +/- 0.60 percent, p less than 0.01) and potassium excretion rate (35 +/- 7 to 42 +/- 6 microEq/min, p less than 0.02). However, no significant alterations in renal plasma flow or glomerular filtration rate were observed. Furthermore, there was no significant correlation between the change in urine flow rate or sodium excretion rate and the change in renal plasma flow or glomerular filtration rate, respectively. In addition, there was no significant effect on cardiac index, mean aortic or left ventricular filling pressures, or systemic vascular resistance. There also was no discernible relationship between the response to ANF and the baseline concentrations of plasma ANF, aldosterone, or plasma renin activity. Thus, in patients with congestive heart failure, low dose ANF boluses may produce an increase in urine flow rate and sodium excretion rate that is independent of renal plasma flow or glomerular filtration rate. This suggests a meaningful direct renal tubular effect of exogenous ANF in this setting.

Adult↗
PubMed1988

Left ventricular dysfunction due to chronic right ventricular pressure overload. Resolution following percutaneous balloon valvuloplasty for pulmonic stenosis.

Left ventricular dysfunction due to chronic right ventricular pressure overload is well documented in experimental animals, but is controversial in humans. Whether left ventricular dysfunction resolves following the relief of chronic right ventricular pressure overload has not been studied. In this report, rapid improvement in both right and left ventricular function following successful percutaneous balloon valvuloplasty is described in a patient with severe isolated valvular pulmonic stenosis and biventricular dysfunction. It appears that: (1) geometric distortion played a major role in his reversible left ventricular dysfunction, and (2) severe biventricular dysfunction should not be a contraindication to valvuloplasty for valvular pulmonic stenosis.

Adult↗
PubMed1988

Congestive heart failure.

Congestive heart failure (CHF) is not a single entity but a symptom complex that may represent the consequence of mechanical abnormalities, myocardial abnormalities, and/or disturbances of cardiac rhythm. In turn, it affects virtually every organ system in the body. This review focuses on CHF due to systolic dysfunction of the left ventricle, which comprises the majority of cases of this condition. Recent data suggest that CHF may be the most frequent primary diagnosis in patients on medical services in nonmilitary hospitals in this country: it affects approximately 2% of the United States population, or some 4 million people. The mortality rate for CHF is also worse than for many forms of cancer; thus, new therapeutic alternatives are imperative. In order to devise new therapeutic strategies, a detailed understanding of the pathophysiology of this condition is required. The relative advantages and disadvantages of various pharmacologic and nonpharmacologic approaches are considered in detail. Certain medications, such as the angiotensin converting enzyme (ACE) inhibitors, have been shown to improve survival, and heart transplantation is clearly life-saving for those who are eligible for this therapy. However, the real challenge is to devise strategies to prevent the occurrence of heart failure, or interrupt its progress at a very early stage.

Blood Volume↗
PubMed1988

The multifacetted role of angiotensin converting enzyme inhibitors in congestive heart failure.

The angiotensin converting enzyme (ACE) inhibitors constitute a major breakthrough in the medical management of congestive heart failure. The incidence of side effects with these agents is surprisingly low when they are used in the appropriate dosage. They produce sustained beneficial hemodynamic and symptomatic improvement in most patients with congestive heart failure and may produce greater symptomatic benefit than digoxin when given as second-line therapy to patients with heart failure on diuretics. Their neurohumoral effects generally are advantageous, resulting in normalization of sodium and potassium balance and a reduction in ventricular arrhythmias. The ACE inhibitors may improve survival in patients with congestive heart failure, and recent data suggest that they may prevent or delay the development of left ventricular dilatation and overt heart failure in patients with asymptomatic left ventricular dysfunction.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1987

Comparison of intravenous milrinone and dobutamine for congestive heart failure secondary to either ischemic or dilated cardiomyopathy.

Milrinone and dobutamine are positive inotropic agents with beneficial hemodynamic effects in patients with congestive heart failure. This study was undertaken to compare the effects of intravenous milrinone and dobutamine in patients with stable New York Heart Association class III or IV congestive heart failure and to test the hypothesis that intravenous milrinone is at least as beneficial as dobutamine in this setting. Seventy-nine patients were randomized to either dobutamine therapy at incremental doses of 2.5, 5, 7.5, 10, 12.5 and 15 micrograms/kg/min, or milrinone as a bolus of 50 or 75 micrograms/kg followed by an infusion of 0.5 to 1.0 micrograms/kg/min. Both agents significantly increased heart rate, cardiac index and stroke volume index and decreased pulmonary artery wedge pressure and systemic vascular resistance compared with baseline levels (p less than 0.01). During sustained infusion for 48 hours, no difference in hemodynamic effects was observed between the 2 drugs. Ventricular tachycardia occurred in 5 patients (3 taking milrinone, 2 taking dobutamine); 1 patient taking milrinone had ventricular fibrillation. Milrinone and dobutamine elicited similar beneficial hemodynamic results with relatively few adverse effects.

Cardiomyopathy, Dilated↗
PubMed1987

Replacement of the failing heart.

Heart transplantation is an effective means of treating patients with severe congestive heart failure. Following heart transplantation, the 1-year survival rate is now greater than 80%, and the 5-year survival rate is more than 60% at major medical centers. More than 1,200 heart transplants were performed in more than nine countries worldwide in 1985. The failure of medicare to pay for this procedure is no longer defensible on medical grounds. The argument in favor of medicare funding for heart transplantation is at least as compelling as that for kidney dialysis, the treatment of cancer, or AIDS. The limited availability of donor organs (at most, 1300-2000/year) is likely to place a finite constraint on the number of heart transplants that can and will be performed. Although combined heart-lung transplantation is feasible therapy for certain patients with severe pulmonary hypertension, the availability of suitable donors poses an even greater restriction on this procedure. Totally implantable ventricular assist devices are on the horizon. These devices have the potential for helping 17,000 to 35,000 patients annually at an estimated cost to society of $2.5 to $5 billion per annum. The development and use of such extremely expensive technology poses major socioeconomic and ethical questions for society.

Ethics, Medical↗
PubMed1986

Variability of right-sided cardiac oxygen saturations in adults with and without left-to-right intracardiac shunting.

In many catheterization laboratories and intensive care units, oxygen saturation of single blood specimens is measured from the superior vena cava (SVC), right atrium (RA) and pulmonary artery (PA) during right-sided catheterization, but variability of such single measurements in adults with and without intracardiac left-to-right shunting has not been assessed. Oxygen saturation of SVC, RA and PA single blood samples were measured in 1,031 adults (524 men, 507 women, aged 50 +/- 13 years [mean +/- standard deviation SD]). In the 980 patients without shunting, differences in saturation between SVC and RA, RA and PA and SVC and PA were 3.9 +/- 2.4%, 2.3 +/- 1.7%, and 4.0 +/- 2.5%, respectively, so that the normal limits of variability (mean +/- 2 standard deviations) for these saturation differences were 8.7%, 5.7% and 9.0%, respectively. Of the 51 patients with left-to-right shunting, these limits of variability of oxygen saturation correctly identified 46 (90%), and the 5 with shunting whose saturation differences were below these limits had small shunts (Qp/Qs ratios of 1.9 or less). Thus, assessment of oxygen saturation from single blood specimens obtained from the SVC, RA and PA offers excellent sensitivity (more than 90%), specificity (94 to 95%) and predictive accuracy (94% or more) in identifying patients with and without intracardiac left-to-right shunting. The sensitivity of these limits is especially high in patients with large shunts (Qp/Qs of 2 or more).

Adolescent↗
PubMed1986

Importance of the "atrial kick" in determining the effective mitral valve orifice area in mitral stenosis.

Atrial fibrillation with a rapid ventricular response in patients with mitral stenosis (MS) is often accompanied by pulmonary congestion and reduced cardiac output owing to a diminished diastolic filling period and the loss of the end-diastolic left ventricular (LV) pressure increment. To test the hypothesis that loss of atrial contraction (atrial kick) also results in a decrease in effective mitral valve orifice area, 6 patients with pure, isolated MS were studied in sinus rhythm during atrial pacing and simultaneous atrioventricular pacing. Atrial pacing at 140 beats/min caused no significant change from baseline in cardiac output or mitral valve area, but there was a decrease in LV end-diastolic volume and ejection fraction as well as an increase in left atrial pressure and mean diastolic gradient. Simultaneous atrioventricular pacing (to eliminate atrial kick) induced a decrease in cardiac output (4.4 +/- 0.9 vs 5.2 +/- 0.8 liters/min at 110 beats/min, 4.2 +/- 0.9 vs 5.1 +/- 0.9 liters/min at 140 beats/min; p less than 0.05) and LV end-diastolic volume (77 +/- 27 vs 93 +/- 29 ml at 110 beats/min, 54 +/- 17 vs 65 +/- 19 ml at 140 beats/min; p less than 0.05), an increase in left atrial pressure (28 +/- 3 vs 20 +/- 5 mm Hg at 110 beats/min, 30 +/- 4 vs 25 +/- 5 mm Hg at 140 beats/min; p less than 0.05), and a decrease in mitral valve area (1.2 +/- 0.4 vs 1.4 +/- 0.5 cm2 at 110 beats/min, 1.2 +/- 0.4 vs 1.4 +/- 0.4 cm2 at 140 beats/min; p less than 0.05). Thus, loss of atrial kick may cause pulmonary congestion and reduced cardiac output in patients with MS, partly because of a decrease in effective mitral valve area.

Adult↗
PubMed1985

Analysis of factors affecting the variability of Fick versus indicator dilution measurements of cardiac output.

This study was performed to assess the relation between Fick and indicator dilution measurements of cardiac output (CO) in a large number of subjects and to evaluate this relation in patients with a low CO, a high CO, and left-sided cardiac regurgitation. In 808 patients (428 men, 380 women, mean age 50 +/- 11), CO was measured by Fick and either thermodilution (right atrium to pulmonary artery)(n = 252) or indocyanine green dye ("dye")(pulmonary artery to systemic artery)(n = 556) within 10 minutes of each other. There was excellent agreement between Fick and both thermodilution and dye. The difference between Fick and indicator dilution measurements was 9 +/- 9%; it was 10% or less in 67% and 20% or less in 91% of patients. The disparity between Fick and indicator dilution measurements was increased in patients with a low CO (less than 2 liters/min/m2)(n = 152) (difference 14 +/- 11%, p less than 0.001) and those with aortic or mitral regurgitation (n = 83) (difference 13 +/- 11%, p less than 0.001). In these groups, the disparity between Fick and thermodilution measurements was not exaggerated, but the disparity between Fick and dye measurements was greater. Thus, although there is excellent agreement between Fick and both thermodilution and dye measurements of CO, thermodilution is preferable to dye in patients with a low CO and those with aortic or mitral regurgitation.

Adolescent↗
PubMed1985

Measurements of left-to-right intracardiac shunting in adults: oximetric versus indicator dilution techniques.

Of the various techniques that are available to assess the presence and magnitude of intracardiac shunting, oximetry and indicator dilution are used most frequently. This study was performed to compare these methods in adult patients with pure left-to-right intracardiac shunting. In 27 patients [12 men, 15 women, aged 32 +/- 12 (mean +/- SD) years], shunt magnitude was assessed in close temporal proximity by both techniques. The oximetric percentage left-to-right shunt averaged 55 +/- 16%, whereas the indocyanine green dye percentage shunt was significantly less (36 +/- 14%, p less than 0.001). The oximetric percentage shunt exceeded the indocyanine green dye percentage shunt in 26 and did so by greater than 20% in 23 patients. Thus, there is a substantial difference in shunt magnitude between the oximetric and the indicator dilution techniques. In infants, indicator dilution yields results that are larger than those obtained with the oximetric method. Conversely, in adults, the indicator dilution technique gives results that are consistently smaller than those obtained with oximetry. As a result, the decision regarding therapy of an intracardiac shunt should be made with this in mind.

Adolescent↗
PubMed1984

Assessment of the inotropic and vasodilator effects of amrinone versus isoproterenol.

The hemodynamic effects of graded-dose infusions of amrinone (maximal dose 30 micrograms/kg/min) (10 patients) and isoproterenol (maximum dose 4 micrograms/min) (11 patients) were assessed in patients with a range of left ventricular (LV) function. LV ejection fraction ranged from 0.13 to 0.77 (mean +/- standard deviation 0.47 +/- 0.23) among the patients who received amrinone and from 0.24 to 0.77 (mean 0.52 +/- 0.18) among those who received isoproterenol. Peak-dose amrinone produced a reduction in LV filling pressure (from 15 +/- 10 to 10 +/- 7 mm Hg, p less than 0.001), but no significant change in heart rate, cardiac output, mean aortic pressure, total systemic vascular resistance (TSVR) or LV dP/dt max. In contrast, peak-dose isoproterenol produced a similar reduction in LV filling pressure (from 17 +/- 12 to 13 +/- 13 mm Hg, p less than 0.05), but also caused increases in heart rate, cardiac output and LV dP/dt max and decreases in mean aortic pressure and TSVR (p less than 0.001). The absolute change in cardiac output and stroke volume correlated closely with the change in TSVR in response to amrinone (r = -0.90, p less than 0.001 and r = -0.84, p = 0.002, respectively), but not in response to isoproterenol. Although isoproterenol produced a marked increase in cardiac output and LV dP/dt max (not explained by heart rate changes alone) in all patients, amrinone produced an increase in cardiac output only in those with markedly elevated LV filling pressures (who had a reduction in TSVR), and an increase in LV dP/dt in a minority.

Aminopyridines↗