Biomedical subjects
Publications and source records attributed to G J Haas.
Asymptomatic left ventricular dysfunction should be treated as an early stage on the continuum that is chronic heart failure. The author presents the clinical trial data on which current management with angiotensin-converting enzyme inhibitors and beta-blockers is based. Issues surrounding screening are also discussed.
BACKGROUND: Administration of angiotensin-converting enzyme (ACE) inhibitors to patients with congestive heart failure has been shown to increase parasympathetic tone as indicated by increases in high-frequency heart rate variability. The mechanism for this effect, including its relation to changes in baroreflex activity, blood pressure variability, and suppression of ACE activity, remains undefined. This study was designed to test the relation of these variables, which may govern changes in autonomic activity, to the previously described increase in parasympathetic tone. METHODS: Seven patients with heart failure received a 3-hour infusion of the ACE inhibitor enalaprilat. Hemodynamic variables and parameters of heart rate and blood pressure variability, baroreflex gain derived from the interaction of heart rate and blood pressure variability, and serum ACE activity were measured during and after the infusion. Measures of heart rate and blood pressure variability were also compared against a historic control group. RESULTS: Serum ACE activity was significantly suppressed throughout and after enalaprilat infusion. Hemodynamic measures did not change other than a small decline in right atrial and pulmonary capillary wedge pressures. Parasympathetic tone showed an initial significant increase with a peak at 2 hours but then declined below baseline 8 hours after initiation of enalaprilat infusion. Sympathetically influenced low-frequency heart rate variability was significantly increased above baseline in the enalaprilat treatment group 8 hours after initiation of the infusion. Baroreflex gain showed a significant trend to an increase with the maximum value coinciding with the peak in parasympathetic tone. There was no change in blood pressure variability in the enalaprilat group and no change in baroreflex gain, heart rate variability, or blood pressure variability in the control group. CONCLUSIONS: Parasympathetic tone and baroreflex gain increased with parenteral administration of an ACE inhibitor but subsequently decreased below baseline values despite continued suppression of serum ACE activity. The dissociation between ACE suppression and autonomic response to ACE inhibition indicates that enzyme systems not reflected by plasma ACE activity or independent from the classic pathways of angiotensin formation contribute to the regulation of the autonomic response to ACE inhibition in patients with heart failure. The absence of significant change in hemodynamic variables or in blood pressure variability indicates that these autonomic changes are not an indirect reflex response to ACE inhibitor-induced vasodilation or hemodynamic baroreceptor stimulation.
Cardiovascular disease is ubiquitous within the elderly population and requires treatment with multiple types of medications. As with any cardiovascular pharmaceutical regimen, the risk versus the benefit of each medication must be strongly considered. This is particularly true where, for various reasons, adverse effects are more often prevalent and pronounced. Over the years, it has been documented that digoxin is a frequently prescribed medication in elderly populations. Although this drug can be beneficial when used in the appropriate setting, recent data would suggest that inappropriate administration of digoxin is common and not without potentially serious consequences. Currently, the use of digoxin can be advocated to control heart failure in atrial fibrillation and when added to ACE inhibitors and diuretics in those patients with symptomatic heart failure related to systolic left ventricular dysfunction. It is likely that the excessive use of digoxin in elderly populations as discussed in this review is perhaps based on the prevalence of diastolic heart failure in the elderly as well as other co-morbid conditions that may mimic heart failure signs and symptoms. Since the elderly appear to be at high risk for digoxin toxicity, the inappropriate use of this medication to treat these conditions could result in significant and unnecessary morbidity. It is proposed that echocardiography should be performed in most elderly patients when congestive heart failure is suspected. This simple diagnostic tool, along with a careful history and medical examination, would hopefully prevent the misinterpretation of confusing clinical findings and would help to identify the patients with normal systolic function or valvular disease such as critical aortic stenosis, where digoxin treatment would not be warranted. If it is necessary to administer digoxin, then the likelihood of significant toxicity can be greatly reduced by using an algorithm to calculate the appropriate dosage, which takes into consideration the patient's gender, bodyweight and creatinine clearance. Although it is probable that the indications for digoxin use to treat congestive heart failure will continue to evolve, at the present time most would recommend using this agent in symptomatic heart failure related to a reduction in left ventricular systolic function or when associated with atrial fibrillation.
BACKGROUND: The growth of the US cardiac transplant waiting list has outpaced the increase in donors, resulting in a widening gap between the number of waiting recipients and available donors. These trends have generated concern that longer waiting times may result in more patients deteriorating to urgent status and that transplanting only patients who are in an advanced state of decompensation will reduce posttransplant survival. Furthermore, the shortage of donors may result in extending the guidelines for donor acceptability to a degree that increases graft failure and posttransplant mortality. We measured these secular trends in the Cardiac Transplant Research Database to provide current data on time-dependent changes in US cardiac transplant practice and survival. METHODS AND RESULTS: At the time of this analysis, the Cardiac Transplant Research Database included all 2749 patients transplanted from January 1, 1990, to June 30, 1994, in the 25 participating transplant centers. During this 4.5-year period, the median waiting time for recipients who received a transplant increased from 2.7 to 3.5 months (P < .0001), and the proportion of recipients whose status was urgent at transplantation increased from 41% to 60% (P < .0001). Donor ischemic time increased from 150 to 166 minutes (P < .0001), and the proportion of donors requiring pressor support increased from 68% to 85% (P < .0001). Despite these changes in practice, the 1-year survival rate remained constant at 84% during this 4.5-year interval. There was no significant difference in 1-year survival rate between urgent status patients (83%) and nonurgent status patients (85%) (P = .08). CONCLUSIONS: The widening gap between the number of waiting recipients and the number of donors has resulted in a continuing trend toward transplanting urgent status recipients and to a liberalization of donor acceptance criteria. Despite these changes, posttransplant survival has remained constant.
Growth of Listeria monocytogenes was inhibited in culture media and in certain foods by four hop extracts (I-IV) containing varying concentrations of alpha-and beta-acids. Extracts (II and III) containing the highest concentrations of beta-acids were inhibitory at 0.01 mg/l in trypticase soy broth. In food, these hop extracts showed varying magnitudes of inhibition. In coleslaw, hop extract III at 1 mg/g enhanced the rate of inactivation of L. monocytogenes Scott A. Hop extract II was inhibitory at 0.1 and 1 mg/ml in skim and 2% milk, and was inhibitory at 1 mg/ml in whole milk. Hop extract II was listericidal in cottage cheese at 0.1 to 3 g/kg. No inhibition of L. monocytogenes by hop extract III was observed in Camembert cheese. Overall, the antimicrobial activity of hop extracts in food appeared to increase with acidity and lower fat content. Our results indicate that hop extracts could be used to control L. monocytogenes in minimally processed food with low fat content.
Positive inotropic intervention with dobutamine in patients with congestive heart failure is accompanied by complementary vascular changes, as measured by the aortic input impedance spectrum, that promote the efficient transfer of augmented myocardial contractile power. It is unknown whether this is a nonspecific response to increased ventricular contractility or is a function of the properties of the positive inotropic agent employed. Therefore, the influence of two different positive inotropic interventions, dobutamine and dopamine, on ventricular-vascular coupling was examined in 15 patients with congestive heart failure. Significant reductions in characteristic aortic impedance, wave reflection, and low-frequency impedance moduli were noted with dobutamine and were not seen with dopamine. Consequently, a significantly (P = 0.0008) greater increase in pulsatile, rather than steady-state, power output was noted with dopamine that was reflective of a significantly diminished efficiency of power transfer. Therefore, optimal transfer of increased ventricular contractile power in patients with congestive heart failure requires increases in large vessel compliance and complementary changes in ventriculoarterial coupling.
BACKGROUND: Previous reports indicate that heart transplant recipients lack a normal nocturnal decline in blood pressure. This prospective study was designed to determine the evolution of circadian blood pressure patterns after heart transplantation. METHODS: Twenty-four-hour ambulatory blood pressure and heart rate was measured in eight heart transplant recipients early (47 +/- 35 days) and late (740 +/- 10 days) after transplantation. RESULTS: Early transplant recordings and the normal control group recordings showed similar daytime systolic blood pressure but had different nighttime systolic blood pressure (138 +/- 15 mm Hg versus 112 +/- 9 mm Hg, p = 0.0002). The percent nocturnal change in systolic blood pressure showed a nocturnal increase in blood pressure in the early recordings versus a decrease in the healthy subjects (+4 +/- 2.7 versus -13 +/- 5.4, p < 0.0001). The late recordings showed a significant decrease in the nighttime systolic blood pressure (138 +/- 15 mm Hg versus 119 +/- 7 mm Hg, p = 0.011). The percent nocturnal change in systolic blood pressure was also significantly different between the early and late recordings (+4 +/- 2.7 versus -9 +/- 9, p = 0.0082) indicating a return of a nocturnal decline in systolic blood pressure. Similar patterns in diastolic blood pressure were observed. No significant change in the percent nocturnal change in heart rate occurred (-10 +/- 4.1 versus -7 +/- 5.5). CONCLUSIONS: Prospective follow-up of this heart transplant population showed that diurnal blood pressure variation is restored in some patients; diurnal variation is not related to corticosteroids, cyclosporine, or heart rate.
This study uses echocardiography to characterize the pattern of left ventricular hypertrophy in a new hypertensive heart failure-prone rat strain designated SHHF/Mcc-cp (SHHF). M-mode echocardiograms of the left ventricle in nine 10- to 12-month old SHHF rats and nine age-matched spontaneously hypertensive rats (SHR) were compared. Wistar-Kyoto and Sprague-Dawley strains served as the normotensive control group. SHHF rats had significantly greater left ventricular mass than did rats in the normotensive control group. Although left ventricular mass was not different between SHHF and SHR, significant differences were seen in the pattern of left ventricular remodeling as determined by relative wall thickness. These differences in left ventricular remodeling may explain the earlier development of heart failure in SHHF. The different patterns of left ventricular hypertrophy in SHHF and SHR suggests that heart failure in SHHF is not mediated by hypertension alone.
Early ventricular filling and therefore passive left atrial emptying may be impaired in patients with cardiac transplantation. As a result, left atrial function may be an important factor in maintaining stroke volume in recipients of orthotopic cardiac transplants. Left atrial volumes maximal (mitral valve opening), minimal (mitral valve closure), and onset of atrial systole (P wave on electrocardiogram) were determined by echocardiography using the biplane area-length method in 12 patients after cardiac transplantation and 12 control subjects. Maximal and minimal left atrial volumes and left atrial volumes at onset of atrial systole were larger in patients who had cardiac transplantation than in control subjects (89.8 vs 41.8 cm3, 48 vs 15.2 cm3, and 70.4 vs 27.0 cm3, respectively; p < 0.01). In patients undergoing cardiac transplantation, good correlations were found between left atrial maximal volume and left ventricular mass (r = 0.56) and between left atrial maximal volume and mean pulmonary capillary wedge pressure (r = 0.81). Left atrial passive emptying volume (maximal minus volume at P wave), was not statistically different between the two groups (19.3 in patients receiving transplants vs 14.7 cm3 in control subjects), but left atrial stroke volume (beginning atrial systole to minimal) was larger in patients receiving transplants than in control subjects (22.4 vs 11.8 cm3, respectively; p < 0.001). Thus left atrial contraction contributed 42% to the left ventricular stroke volume in patients who had cardiac transplantation but only 17% in control subjects (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
As the AT1 receptor is the primary angiotensin II receptor in the myocardium and vasculature, we assessed the acute myocardial and vascular response to the AT1 angiotensin II antagonist losartan in the spontaneously hypertensive rat (SHR) to determine the contribution of angiotensin II in this genetic form of hypertension. In a preliminary dose response study, which evaluated losartan at 1.0, 3.0, and 10 mg/kg, 10 mg/kg uniformly lowered blood pressure. In a second group of experiments, 10 mg/kg also completely attenuated the pressor effects of angiotensin II administration. In nine adult SHR, intravenous losartan, 10 mg/kg, was given, with hemodynamics measured immediately and at steady-state intervals to delineate the hemodynamic response to angiotensin II antagonism. Losartan significantly lowered systolic, diastolic, and mean blood pressures, yet heart rate was unchanged. Cardiac function, as assessed by cardiac output and blood flow acceleration, demonstrated only transient increases which were not sustained during steady-state blood pressure reduction. Significant increases of peak blood flow and pulse pressure were sustained throughout the blood pressure response. At immediate and steady-state determinations, system vascular resistance and characteristic aortic impedance were significantly reduced with losartan (both P < .01). In addition, concomitant reduction of the wave reflectance index also occurred, achieving significance at steady state (P < .05). These changes demonstrate that the AT1 angiotensin II receptor contributes to both central and peripheral vasoconstriction in the spontaneously hypertensive rat. Absence of sustained increase of cardiac output and blood flow acceleration are consistent with inhibition of the previously reported positive inotropic effect of angiotensin II.
This study was performed to examine cognitive function in patients with end-stage heart failure, to identify possible cardiovascular factors associated with cognitive function, and to evaluate changes in cognitive function in a subgroup of patients who received heart transplantation. An extensive battery of neuropsychological tests were given to 62 patients with end-stage cardiac failure as part of their evaluation for cardiac transplantation. Most patients were consecutive referrals, not selected because of cognitive complaints. A small subgroup of transplanted (n = 7) and non-transplanted (n = 4) patients received a repeat neuropsychological examination. At initial examination, approximately 50% of the patients met criteria for impairment in reference to normal control values. Higher stroke volume index and cardiac index and lower right atrial pressure were correlated with better cognitive function. In the subgroup of patients re-examined, the transplanted patients demonstrated significantly improved cognitive function, whereas the non-transplanted subjects were unchanged. These data indicate that in patients with end-stage heart failure there is a high prevalence of impaired cognitive function which is related to measures of cardiovascular efficiency. Preliminary evidence suggests that these impairments may be partially ameliorated by cardiac transplantation.
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OBJECTIVES: The objective of this investigation was to evaluate the changes in parasympathetic tone associated with long-term angiotensin-converting enzyme inhibitor therapy in patients with congestive heart failure. BACKGROUND: Angiotensin-converting enzyme inhibitors provide hemodynamic and symptomatic benefit and are associated with improved survival in patients with congestive heart failure. Angiotensin II, whose production is ultimately inhibited by these agents, exerts significant regulatory influence on a variety of target organs including the central and peripheral nervous systems. Accordingly, it would be anticipated that angiotensin-converting enzyme inhibitors would significantly alter the autonomic imbalance characteristic of patients with congestive heart failure and that this influence over neural mechanisms of cardiovascular control may significantly contribute to the hemodynamic benefit and improved survival associated with angiotensin-converting enzyme inhibitor therapy. METHODS: In the current investigation, changes in autonomic tone associated with long-term administration of an angiotensin-converting enzyme inhibitor were measured using spectral analysis of heart rate variability in 13 patients with congestive heart failure who were enrolled in a double-blind randomized placebo-controlled trial of the angiotensin-converting enzyme inhibitor zofenopril. Both placebo and treatment groups were balanced at baseline study in terms of functional class, ventricular performance and autonomic tone. RESULTS: After 12 weeks of therapy with placebo, there was no change in total heart rate variability, parasympathetically governed high frequency heart rate variability or sympathetically influenced low frequency heart rate variability. In contrast, therapy with zofenopril was associated with a 50% increase in total heart rate variability (p = 0.09) and a significant (p = 0.03) twofold increase in high frequency heart rate variability, indicating a significant augmentation of parasympathetic tone. CONCLUSIONS: These results demonstrate that long-term treatment of patients having congestive heart failure with an angiotensin-converting enzyme inhibitor is associated with a restoration of autonomic balance, which derives in part from a sustained augmentation of parasympathetic tone. Such augmentation of vagal tone is known to be protective against malignant ventricular arrhythmias in patients with ischemic heart disease and therefore may have similar benefit in the setting of ventricular failure, thus contributing to the improved survival associated with angiotensin-converting enzyme inhibitor therapy in patients with congestive heart failure.