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J D Bristow

Publications and source records attributed to J D Bristow.

At least 19 recordsLinked to original sources
PubMed1992

Prevalence and etiology of idiopathic dilated cardiomyopathy (summary of a National Heart, Lung, and Blood Institute workshop.

Idiopathic dilated cardiomyopathy (IDC) is the primary indication for cardiac transplantation, with associated costs of approximately $177 million per year. Recognizing the economic implications of IDC, the increasing incidence, and the limited information on pathogenesis and prognosis, the National Heart, Lung, and Blood Institute convened a workshop on the Prevalence and Etiology of Idiopathic Dilated Cardiomyopathy on June 13 to 14, 1991. The difficulties of studying the disease were reviewed, including its relatively low prevalence, its potentially pluricausal nature, and the fact that it is often a diagnosis of exclusion. Still, it presents significant challenges to the cardiovascular scientific community, since the mechanism of myocardial damage and related etiologic and prognostic factors are virtually unknown. The development of more reliable measures of immune-mediated damage and noninvasive measures of impaired cardiac function present new research opportunities in this disorder. Standardized diagnostic criteria for use in observational and interventional trials were developed, and priorities for future research were proposed. Population-based registries and nested case-control studies, where feasible, are appropriate study designs for tracking incidence and prevalence, and for identifying risk factors, respectively. Interventional studies should focus on secondary prevention, through modifying immune-mediated damage in clinically evident dilated cardiomyopathy, and through prevention of sudden death in patients with the disorder. Primary prevention trials must await the identification of modifiable risk factors and of appropriate and effective interventions.

Cardiomyopathy, Dilated↗
PubMed1992

Correlates of aortic distensibility in chronic aortic regurgitation and relation to progression to surgery.

Aortic distensibility decreases with increasing age. Patients with chronic aortic regurgitation eject a large stroke volume into the proximal aorta. A decrease in distensibility of the aorta may impose a higher afterload on the left ventricule and may contribute to deterioration of left ventricular function over time. Accordingly, aortic distensibility was measured in 33 patients aged 13 to 73 years who had chronic isolated aortic regurgitation with minimal or no symptoms. Ascending aortic diameter was measured 4 cm above the aortic valve by two-dimensional echocardiography and pulse pressure was measured simultaneously by sphygmomanometry. Aortic distensibility was calculated as (Change in aortic diameter between systole and diastole/End-diastolic diameter)/Pulse pressure. Left ventricular systolic wall stress and mass were derived from standard M-mode echocardiographic measurements. Left ventricular volumes and ejection fraction were measured by radionuclide ventriculography. Aortic distensibility decreased logarithmically with increasing age (r = -0.62, p less than 0.001) and also correlated inversely with systolic wall stress, left ventricular mass and end-diastolic volume. Patients who eventually underwent aortic valve replacement for symptoms of left ventricular dysfunction had significantly lower aortic distensibility than did those who did not yet require valve replacement: 0.09 +/- 0.08 vs. 0.22 +/- 0.19 x 1/100 (1/mm Hg) (p less than 0.05). Thus, the reduced aortic distensibility that occurs with increasing age may contribute to the gradual left ventricular dilation and dysfunction seen in patients with chronic aortic regurgitation.

Adult↗
PubMed1992

Energy metabolism and contractile function after 15 beats of moderate myocardial ischemia.

Difficulties in studying myocardial metabolism with adequate time resolution have led to contradictory conclusions regarding the mechanisms causing contractile abnormalities during the early stages of ischemia. In acutely instrumented swine, we investigated whether abnormalities in subendocardial ATP, phosphocreatine, or lactate content develop rapidly enough during the first few heart beats after onset of partial myocardial ischemia to contribute to contractile failure. Within the first 15 beats of a 40-50% reduction in left anterior descending coronary artery blood flow, regional myocardial function was significantly reduced but continuing to deteriorate. Rapidly frozen transmural left ventricular biopsies obtained on the 15th heart beat (+/- 1.5 beats) after the onset of ischemia revealed significant decrements in subendocardial phosphocreatine and ATP levels to 77% (p less than 0.05) and 84% (p less than 0.005) of control values, respectively, but minimal change in lactate content. Metabolic effects as assessed by transmural averages took longer to become detectable; thus, there was a tendency to underestimate the importance of subendocardial metabolic effects on myocardial function. When left ventricular preload was assessed during this early time period, left ventricular end-diastolic wall thickness only decreased by 3%, and left ventricular end-diastolic pressure did not change significantly despite a large fall in coronary perfusion pressure. Thus, in an in vivo pig model with techniques optimized to detect subendocardial metabolic changes within the period of very early moderate myocardial ischemia, abnormalities in high energy phosphate compounds occurred rapidly enough to contribute to developing myocardial dysfunction, whereas preload-mediated mechanisms related to vascular distending pressure could not explain the functional deterioration under these conditions.

Adenosine Triphosphate↗
PubMed1992

Effects of stopping long-term vasodilator therapy in patients with chronic aortic insufficiency.

We studied the effects of stopping long-term vasodilator therapy in 17 patients with chronic stable aortic insufficiency. These patients received hydralazine for 37 +/- 15 months (mean +/- SD) and, as a result, had experienced a significant decrease in left ventricular volumes. All patients were followed clinically and ten of the patients underwent serial radionuclide evaluation at baseline, while receiving drug, and at 20 +/- 7 months after stopping drug therapy. No patient showed evidence of acute clinical deterioration when drug therapy was stopped. The rate of progression to valve replacement due to onset of symptoms or left ventricular dysfunction was not significantly different from that previously reported in a population with similar characteristics. Left ventricular size, however, returned to levels similar to baseline after drug therapy was stopped. We conclude that long-term vasodilator therapy may be discontinued in patients with chronic stable aortic insufficiency without causing clinical deterioration or significant alteration in rate of progression to valve replacement.

Adult↗
PubMed1991

Effects of long-term vasodilator therapy on electrocardiographic abnormalities in chronic aortic regurgitation.

Electrocardiographic abnormalities develop in patients with chronic aortic regurgitation (AR). Although vasodilator drugs may reduce left ventricular (LV) volume overload, the effects of such therapy on electrocardiographic abnormalities have not been previously evaluated. Accordingly, electrocardiograms were analyzed before and after double-blind, randomized administration of either hydralazine or placebo in 54 patients with chronic AR. These patients were without limiting symptoms and had preserved ejection fraction on entry in the study. The magnitude of ST-segment depression and Romhilt-Estes point score for LV hypertrophy were assessed. Baseline ST depression and LV hypertrophy scores in the placebo and hydralazine groups were not significantly different. At follow-up, after a mean of 19 +/- 6 months, there was a significant reduction in ST depression in patients taking hydralazine (n = 28) compared with patients given placebo (n = 26): -0.023 +/- 0.044 vs 0.029 +/- 0.055 mV, respectively (p = 0.0001); and in the LV hypertrophy score (-1.1 +/- 2.2 vs 0.9 +/- 2.3 points, respectively; p = 0.002). Hydralazine-treated patients also had significant decreases in LV end-diastolic and end-systolic volume indexes, and a significant increase in ejection fraction. These results suggest that such vasodilator therapy may be beneficial in patients with chronic AR.

Adult↗
PubMed1991

Cardiac metabolism during exercise in healthy volunteers measured by 31P magnetic resonance spectroscopy.

A technique was devised for individuals to exercise prone in a magnet during magnetic resonance spectroscopy of the heart and phosphorus-31 magnetic resonance spectra of the heart were obtained by the phase modulated rotating frame imaging technique in six healthy volunteers during steady state dynamic quadriceps exercise. During prone exercise heart rate, blood pressure, and total body oxygen consumption were measured at increasing loads and the results were compared with those during Bruce protocol treadmill exercise. During prone exercise with a 5 kg load the heart rate was similar and the systolic and diastolic blood pressures were higher than those during stage 1 of the Bruce protocol. The rate-pressure products were similar but the total body oxygen consumption was lower during prone exercise. There was no difference in the ratio of phosphocreatine to adenosine triphosphate during rest and exercise.Thus during exercise that produced a local cardiac stress equal to or greater than that during stage 1 of the Bruce protocol treadmill exercise, the energy requirements of the normal human myocardium were adequately supplied by oxidative phosphorylation.

Blood Pressure↗
PubMed1991

Active downregulation of myocardial energy requirements during prolonged moderate ischemia in swine.

We studied the effects of rapid atrial pacing during the final 10 minutes of a 70-minute, 31% reduction in coronary blood flow in anesthetized swine to understand the significance of apparent metabolic improvements during the initial 60 minutes of segmental ischemia. Within 5-10 minutes of ischemia, subendocardial phosphocreatine (PCr) and ATP were depleted to 47% and 63% of control, respectively; lactate accumulated within the subendocardium to 300% of control; and net arteriovenous lactate production occurred. Despite continued ischemia and no significant changes in the external determinants of myocardial oxygen consumption, by 60 minutes subendocardial PCr and lactate contents returned to near control levels and there was net arteriovenous lactate consumption. Ischemic left ventricular wall thickening and ATP levels remained depressed throughout the experiment. Atrial pacing during the final 10 minutes of ischemia again resulted in depletion of PCr and lactate production. Since the myocardium was capable of hydrolyzing PCr in response to atrial pacing at 60 minutes of ischemia, we conclude it was capable of hydrolyzing PCr during the period of constant ischemia when instead it was accumulating PCr. We propose the ischemic myocardium downregulates regional energy requirements below blood flow-limited rates of energy production during ischemia. This appears to be an active adaptation to ischemia and not a result of passive damage or cellular injury.

Adaptation, Physiological↗
PubMed1990

Regeneration of myocardial phosphocreatine in pigs despite continued moderate ischemia.

The effects of 1 hour of mild and moderate reductions in coronary blood flow on myocardial high-energy phosphate levels were evaluated. Thirty anesthetized pigs were instrumented with left anterior descending arterial and venous catheters, crystals for instantaneous wall thickness, and a fluid-filled occluder. Measurement of myocardial blood flow was performed with microspheres, and a series of myocardial biopsies also was performed. In 10 pigs, overall coronary blood flow was lowered by 22%, with a fall in subendocardial-to-subepicardial flow ratio from 1.11 to 0.54 and in wall thickening from 33% to 15%. Subendocardial flow fell 48%. Coronary blood flow and thickening were constant during 1 hour of ischemia. Phosphocreatine (mumol/g wet wt) in the subendocardial third of the ischemic zone fell from 7.6 to 3.8 at 5 minutes of ischemia (p less than 0.005 versus control) and returned to normal (7.9) at 60 minutes (p = NS), despite ongoing ischemia. Subendocardial ATP (mumol/g wet wt) fell slowly from 4.3 and leveled off at 2.1 at 60 minutes of ischemia (p less than 0.001 versus control). Similar regeneration of phosphocreatine was found in seven additional pigs, with a 43% transmural reduction in coronary blood flow and a 66% reduction in subendocardial flow. No significant changes in ATP and phosphocreatine were noted in two different control groups (n = 13 pigs). The regeneration of phosphocreatine despite ongoing ischemia and low ATP levels was not related to changes in myocardial oxygen demand or consumption, or in regional function during the period of ischemia. This may reflect 1) a successful downregulation of the energy needs of the ischemic myocardium to maintain cell viability, or 2) a metabolic abnormality in the ability of the cells to produce ATP primarily or by use of phosphocreatine.

Adenosine Triphosphate↗
PubMed1989

Chronic aortic insufficiency: factors associated with progression to aortic valve replacement.

STUDY OBJECTIVE: To determine whether the initial measurement of clinical variables in patients with chronic stable aortic insufficiency is helpful in identifying patients at risk for earlier progression to aortic valve replacement. DESIGN: Prospective analysis of a cohort of patients for a median follow-up time of 44 months (range, 8 to 57). SETTING: Referral-based cardiology clinics at two university hospitals and their affiliated Veterans Administration medical centers. PATIENTS: Cohort of 50 asymptomatic or minimally symptomatic patients with chronic aortic insufficiency and left ventricular enlargement. Patients had preserved left ventricular ejection fraction at rest and no evidence of coronary artery disease or significant noncardiac illness. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Baseline evaluation included a history and physical examination, chest roentgenogram. M-mode echocardiogram, treadmill test, and radionuclide angiogram done at rest and during supine bicycle exercise. Ten patients progressed to surgery because of the onset of limiting symptoms or objective evidence of left ventricular dysfunction, or both; the overall rate was 4% +/- 3% per year. The Breslow and Mantel-Cox statistics were used to compute survival (surgery-free) dichotomized by prognostic variables. The progression to surgery was earlier in patients with left ventricular end-diastolic volume indices of 150 cc/m2 or more, end-systolic volume indices of 60 cc/m2 or more, a left ventricular ejection fraction at maximal exercise of less than 0.50, or an end-systolic wall stress of 86 dynes/cm2 or more. CONCLUSIONS: Patients at higher and lower risk for early progression to aortic valve replacement can be identified through the measurement of left ventricular size and function. This information can be used to decide the frequency and intensity of follow-up evaluation in these patients.

Actuarial Analysis↗
PubMed1989

Measurement of transmural distribution of phosphorus metabolites in the pig heart by 31P magnetic resonance spectroscopy.

We used the phase modulated rotating frame imaging technique to measure transmural distribution of phosphorus metabolites in 10 anaesthetised ventilated pigs using a double surface coil placed on the surface of the left ventricle. Anaesthesia was maintained in five animals with halothane, barbiturate and nitrous oxide and in five others with intravenous chloralose. 31Phosphorus spectra were acquired, gated to expiration and systole. From phantom experiments the resolution of the experiment was shown to be approximately 2 mm. The anatomical limits of the myocardium were identified by the appearance of 2,3-diphosphoglycerate peaks from red blood cells. The limits of the epicardium were confirmed by obtaining images after placing a phantom containing fluorophosphate on the surface of the heart. The endocardium was identified by inserting a small balloon catheter through the centre of the coil into the left ventricular cavity, filling it with 0.5 ml of fluorophosphate and pulling it gently against the endocardium. No transmural differences in phosphocreatine to ATP ratio were identified in the normal heart. The animals anaesthetised with chloralose showed a significantly higher phosphocreatine to ATP ratio compared to those anaesthetised with halothane and barbiturate. The chloralose animals tended to have a higher blood pressure and a lower heart rate when compared to the other animals. No transmural differences, however, were identified in either group. When regional ischaemia was produced using a snare to occlude the left coronary artery, phosphocreatine fell and the signal from the inorganic phosphate + 2,3-diphosphoglycerate region increased. The inner wall tended to become more acid compared to the outer wall during ischaemia. These experiments show that the phase modulated rotating frame imaging technique can be used to study the effects of changes in workload, ischaemia, or pharmacological intervention on transmural distribution of metabolites in the heart and thus help elucidate factors responsible for subendocardial vulnerability to stress.

2,3-Diphosphoglycerate↗
PubMed1989

Stable-label intravenous glucose tolerance test minimal model.

The minimal model approach to estimating insulin sensitivity (Sl) and glucose effectiveness in promoting its own disposition at basal insulin (SG) is a powerful tool that has been underutilized given its potential applications. In part, this has been due to its inability to separate insulin and glucose effects on peripheral uptake from their effects on hepatic glucose inflow. Prior enhancements, with radiotracer labeling of the dosage, permit this separation but are unsuitable for use in pregnancy and childhood. In this study, we labeled the intravenous glucose tolerance test (IVGTT) dosage with [6,6-2H2]glucose, [2-2H]glucose, or both stable isotopically labeled glucose tracers and modeled glucose kinetics in six postabsorptive, nonobese adults. As previously found with the radiotracer model, the tracer-estimated S*l derived from the stable-label IVGTT was greater than Sl in each case except one, and the tracer-estimated SG* was less than SG in each instance. More importantly, however, the stable-label IVGTT estimated each parameter with an average precision of +/- 5% (range 3-9%) compared to average precisions of +/- 74% (range 7-309%) for SG and +/- 22% (range 3-72%) for Sl. In addition, because of the different metabolic fates of the two deuterated tracers, there were minor differences in basal insulin-derived measures of glucose effectiveness, but these differences were negligible for parameters describing insulin-stimulated processes. In conclusion, the stable-label IVGTT is a simple, highly precise means of assessing insulin sensitivity and glucose effectiveness at basal insulin that can be used to measure these parameters in individuals of all ages, including children and pregnant women.

Adult↗
PubMed1988

Left ventricular response to submaximal and maximal exercise in asymptomatic aortic regurgitation.

In patients with chronic aortic regurgitation the quantitative changes in loading conditions and left ventricular performance from rest to submaximal exercise have not been related to the magnitude of change observed from rest to maximal exercise. Changes in end-diastolic volume index, as a measure of preload, and measures of contractile performance (ejection fraction and the systolic blood pressure/end-systolic volume index ratio) were assessed at rest, submaximal and maximal supine bicycle exercise using radionuclide angiography in 74 patients with chronic moderate to severe aortic regurgitation. With exercise, end-diastolic volume index decreased in a stepwise manner from 166 +/- 47 to 152 +/- 41 to 143 +/- 41 ml/m2 at rest, submaximal and maximal exercise, respectively. For the entire group, these changes were not associated with a significant change in ejection fraction but were associated with stepwise increases in systolic blood pressure to end-systolic volume index ratio. However, when patients were divided into 3 subgroups based on an increase (group I), minimal change (group II) or a decrease (group III) in ejection fraction from rest to maximal exercise, stepwise increases in systolic blood pressure to end-systolic volume index were again observed in groups I and II but not in group III. These changes were significantly greater in group I than in group II at submaximal and maximal exercise levels. Differences in ejection fraction response and end-diastolic and end-systolic volumes with exercise in the 3 groups were evident at the submaximal exercise level.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Valve Insufficiency↗
PubMed1988

Increased vascular resistance due to a reduction in red cell deformability in the isolated hind limb of swine.

This study investigated whether red cells with reduced deformability impeded flow through the microcirculation. Red cells were made less deformable in their normal biconcave disc shape by incubation with 2% formaldehyde (fRBCs). The blood supply to the right hind limb was isolated in 26 swine and the femoral artery was instrumented with two fine catheters, a flow probe, and an inflatable occluder. Flow was measured over a range of different perfusion pressures during adenosine-induced vasodilation under control conditions (C) and during an infusion of fRBCs at 1 ml/kg per minute (not to exceed 20 ml) into the femoral artery. At the same perfusion pressure (P), flow was significantly reduced 5 min after the fRBC infusion: Flow at P = 20 mm Hg, C = 41 ml/min vs fRBC = 10 ml/min; at P = 40, C = 160 ml/min vs fRBC = 79 ml/min; and at P = 60, C = 278 ml/min vs fRBC = 147 ml/min, with P less than 0.02 for all comparisons. Flow was still significantly reduced 15 min after the fRBCs, but by 30 min, it had returned to the control value. Chromium-51-labeling of red cells revealed that about one-third of fRBCs was trapped in the microcirculation compared to less than 3% of normal cells. This reduction in flow with fRBC infusion was not altered by alpha blockade, indicating that adrenergically mediated spasm was not responsible for the reduced flow. Aspirin 35 mg/kg iv completely prevented the reduction in flow despite an absence of change in the percentage of fRBCs trapped. Thus, red cells with reduced deformability infused into the circulation caused a significant, but transient, reduction in flow. The reduction in flow was not primarily related to entrapment of the abnormal RBCs, but may be mediated through platelet aggregation or release of potent vasoconstrictor substances from platelets or endothelial cells.

Adenosine↗
PubMed1988

Effect of coronary sinus occlusion on coronary flow, resistance, and zero flow pressure during maximum vasodilatation in swine.

The effects of coronary sinus occlusion on the relation between coronary artery pressure and flow during maximum vasodilatation were studied in seven swine. The left anterior descending (LAD) coronary artery was instrumented with two catheters, a hydraulic occluder, and a flowprobe. Mean flow was measured at a series of pressures produced by partial LAD occlusion during maximum vasodilatation induced by an intracoronary infusion of adenosine. Observations were made under control conditions and during occlusion of the coronary sinus produced by inflating the balloon on the catheter positioned in the coronary sinus. Systemic haemodynamic variables did not change significantly after the coronary sinus was occluded. The mean right atrial pressure was 4 mmHg. At any given LAD perfusion pressure mean flow during coronary sinus occlusion was always less than during the control state: at LAD pressure 30 mmHg, control flow was 53 ml.min-1 vs occluded flow 24 ml.min-1; at LAD pressure 40 mmHg, control flow 79 ml.min-1 vs occluded flow 49 ml.min-1; and at LAD pressure 50 mmHg, control flow 105 ml.min-1 vs occluded flow 74 ml.min-1; p less than 0.001 for all comparisons. The mean (SD) LAD pressure at which flow stopped (Pzf) when the coronary sinus was unobstructed was 10(2) mmHg. The Pzf during occlusion of the coronary sinus was significantly higher at 20(4) mmHg (p less than 0.001). The slopes of the mean pressure-flow relations were not significantly different during the control state (2.62(0.65) ml.min-1 per mmHg) vs the occluded state (2.47(0.63) ml.min-1 per mmHg), indicating no change in vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Long-term vasodilator therapy of chronic aortic insufficiency. A randomized double-blinded, placebo-controlled clinical trial.

Although vasodilator drugs acutely reduce regurgitation and improve cardiac performance in aortic insufficiency, their long-term effects on left ventricular size and function are uncertain. Consequently, we performed a double-blinded, placebo-controlled trial using hydralazine in 80 minimally symptomatic patients who had clinically stable, moderate-to-severe aortic insufficiency. Patients randomized to hydralazine displayed a progressive reduction in left ventricular end-diastolic volume index (LVEDVI) measured by radionuclide angiography, the predetermined end point of the study. At 24 months, mean LVEDVI had been reduced by 30 +/- 38 ml/m2, an 18% reduction from baseline. In contrast, LVEDVI changed minimally in patients randomized to placebo, and the intergroup differences over time were statistically significant (p less than 0.03). The hydralazine group also experienced reductions in left ventricular end-systolic volume index and increases in ejection fraction that were significantly different (both p less than 0.01) from changes in placebo-treated patients. These findings show that long-term treatment with hydralazine reduces the volume overload in aortic insufficiency and suggest that such therapy may have a beneficial effect on the natural history of the disease.

Administration, Oral↗