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Biomedical subjects

M A Konstam

Publications and source records attributed to M A Konstam.

At least 19 recordsLinked to original sources
PubMed1992

Effectiveness of preload reserve as a determinant of clinical status in patients with left ventricular systolic dysfunction. The SOLVD Investigators.

The hemodynamic determinants of clinical status in patients with left ventricular (LV) systolic dysfunction have not been established. In the present study, preload reserve--LV distension during exercise--was related to clinical status, and the effect of acute angiotensin-converting enzyme inhibition was examined in 97 patients with ejection fraction less than or equal to 0.35 enrolled in the trial, Studies of Left Ventricular Dysfunction (SOLVD). Sixty-one asymptomatic patients (group I) were compared with 36 patients with symptomatic heart failure (group II). Radionuclide LV volumes were measured at rest and during maximal cycle exercise. Group II patients had higher resting heart rates, end-diastolic and end-systolic volumes, and lower ejection fractions (all p less than 0.005). During exercise, only patients in group I had increased stroke volume (from 35 +/- 8 to 39 +/- 11 ml/m2 [mean +/- SD; p less than 0.0005]) due to an increase in end-diastolic volume (from 119 +/- 29 to 126 +/- 29 ml/m2 [p less than 0.0005]), contributing to a greater increase in LV minute output (p less than 0.0001, group I vs group II). After administration of intravenous enalapril (1.25 mg), LV end-diastolic volume response to exercise was augmented in group II (rest, 140 +/- 42; exercise, 148 +/- 43 ml/m2; p less than 0.0005) and LV output response increased slightly (p less than 0.05). Thus, in patients with asymptomatic systolic dysfunction, recruitment of preload during exercise is responsible for maintaining a stroke volume contribution to the cardiac output response.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1992

Intracardiac echocardiography during simulated aortic and mitral balloon valvuloplasty: in vivo experimental studies.

The feasibility of intracardiac echocardiography with a low-frequency transducer to assess catheter position and detect complications during experimental aortic and mitral balloon valvuloplasty was studied in 10 dogs. Intracardiac echocardiography was performed with a transesophageal echocardiographic probe placed in the right atrium. In all instances high-quality images of cardiac structures were obtained. The guide wire and balloon catheter were clearly seen as they crossed the valves. With inflation the balloon was seen as a hyperechoic structure. Doppler echocardiography documented aortic regurgitation after inflations. Acute pericardial effusion was instantly detected. It is concluded that intracardiac echocardiography is a potentially useful technique for cardiac imaging, assessing wire and balloon catheter position, evaluating valvular regurgitation, and instantly detecting acute pericardial effusion. Further research in humans with low-frequency, catheter-based transducers needs to be performed.

Animals↗
PubMed1992

Effects of the angiotensin converting enzyme inhibitor enalapril on the long-term progression of left ventricular dysfunction in patients with heart failure. SOLVD Investigators.

BACKGROUND: In patients with heart failure, activation of the renin-angiotensin system is common and has been postulated to provide a stimulus for further left ventricular (LV) structural and functional derangement. We tested the hypothesis that chronic administration of the angiotensin converting enzyme (ACE) inhibitor enalapril prevents or reverses LV dilatation and systolic dysfunction among patients with depressed ejection fraction (EF) and symptomatic heart failure. METHODS AND RESULTS: We examined subsets of patients enrolled in the Treatment Trial of Studies of Left Ventricular Dysfunction (SOLVD). Fifty-six patients with mild to moderate heart failure underwent serial radionuclide ventriculograms, and 16 underwent serial left heart catheterizations, before and after randomization to enalapril (2.5-20 mg/day) or placebo. At 1 year, there were significant treatment differences in LV end-diastolic volume (EDV; p less than 0.01), end-systolic volume (ESV; p less than 0.005), and EF (p less than 0.05). These effects resulted from increases in EDV (mean +/- SD, 136 +/- 27 to 151 +/- 38 ml/m2) and ESV (103 +/- 24 to 116 +/- 24 ml/m2) in the placebo group and decreases in EDV (140 +/- 44 to 127 +/- 37 ml/m2) and ESV (106 +/- 42 to 93 +/- 37 ml/m2) in the enalapril group. Mean LVEF increased in enalapril patients from 0.25 +/- 0.07 to 0.29 +/- 0.08 (p less than 0.01). There was a significant treatment difference in LV end-diastolic pressure at 1 year (p less than 0.05), with changes paralleling those of EDV. The time constant of LV relaxation changed only in the placebo group (p less than 0.01 versus enalapril), increasing from 59.2 +/- 8.0 to 67.8 +/- 7.2 msec. Serial radionuclide studies over a period of 33 months showed increases in LV volumes only in the placebo group. Two weeks after withdrawal of enalapril, EDV and ESV increased to baseline levels but not to the higher levels observed with placebo. CONCLUSIONS: In patients with heart failure and reduced LVEF, chronic ACE inhibition with enalapril prevents progressive LV dilatation and systolic dysfunction (increased ESV). These effects probably result from a combination of altered remodeling and sustained reduction in preload and afterload.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Intracardiac echocardiography: current developments.

Intracardiac echocardiography refers to the method of imaging cardiac structures from intracardiac locations with the use of ultrasound catheters. Advances in catheter-based interventional cardiologic procedures to treat cardiovascular lesions and the problems encountered during those procedures due to inadequate guidance provided by fluoroscopy have given the impetus to develop other guidance modalities. Experimental explorations with intracardiac ultrasound probes have indicated that detailed visualization of cardiac structures in real-time is possible by intracardiac ultrasound. Recent advances in catheter-based ultrasound technology make it feasible to safely pass small-sized catheters in humans into various intracardiac locations and acquire images of valvular structures and various chambers. Experience with 20 MHz ultrasound catheters indicates that high resolution images of normal and abnormal structures can be obtained if the catheter is manipulated close to the region of interest. The problem of the limited depth of field associated with 20 MHz catheters has led to the fabrication of catheters with lower frequency ultrasound elements. Experimental and clinical experience with 12.5 MHz ultrasound catheters points to the capability and potential of intracardiac echocardiography to not only display normal structures but also aid in the identification of valvular abnormalities, chamber dysfunction and pericardial effusions. In addition, aortic disorders such as acute dissection, coarctation and atherosclerotic disease could be delineated. Similarly, abnormalities involving the pulmonary arteries such as pulmonary embolism, organized thrombi, peripheral pulmonary arterial stenoses, and pulmonary hypertension-induced vascular changes could be recognized. Many modifications in the catheter design are being explored. With further work in the area of catheter technology and ultrasound image processing, intracardiac echocardiography is likely to become a clinical tool.

Animals↗
PubMed1990

Intracardiac, intravascular, two-dimensional, high-frequency ultrasound imaging of pulmonary artery and its branches in humans and animals.

Intravascular ultrasound imaging is a promising new method for assessing vascular morphology. We evaluated the capability of intravascular ultrasound to quantify pulmonary artery (PA) morphology in vitro and explored the feasibility of in vivo PA imaging in animals and humans. In the in vitro study of 15 PA segments, we used a 20-MHz prototype ultrasound catheter. Intravascular ultrasound (y) provided crisp images of PA segments and demonstrated excellent correlations with anatomic measurements (x) in the estimation of luminal area (y = 0.89x + 2.95, r = 0.99, p less than 0.001), luminal diameter (n = 30, y = 0.79x + 0.96, r = 0.92, p less than 0.001), and vessel wall thickness (n = 60, y = 0.65x + 0.33, r = 0.85, p less than 0.001). We subsequently introduced the probe into the PA of 10 dogs and were able to obtain real-time, two-dimensional images of the main PA, its major branches, and farther smaller branches as far as the wedge level. To evaluate the in vivo feasibility of PA imaging in conscious humans, we used a commercially available, 20-MHz intravascular ultrasound (IVUS) catheter in 22 subjects through a femoral or jugular venous sheath at the end of standard diagnostic cardiac catheterization. In 20 subjects, we acquired dynamic, high-resolution, cross-sectional images of the proximal and distal PA. Changes in shape and decreasing luminal area could be clearly recognized as the IVUS catheter reached branching points and as it passed more distally. There were no complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Multicenter trial of oral enoximone in patients with moderate to moderately severe congestive heart failure. Lack of benefit compared with placebo. Enoximone Multicenter Trial Group.

A multicenter double-blind, randomized, placebo-controlled trial of oral enoximone, a phosphodiesterase inhibitor, was conducted in 102 outpatients (50 receiving enoximone and 52 receiving placebo) with moderate to moderately severe congestive heart failure. All were on a long-term regimen of digoxin and diuretics without vasodilators and converting enzyme inhibitors. Symptom score was obtained, and exercise testing was performed monthly for 4 months. There were no differences between groups in symptoms or exercise duration at the end of 4 months. A subgroup undergoing analysis of oxygen consumption with measurement of anaerobic threshold during exercise showed an increase (p less than 0.05) in anaerobic threshold at 1 month with enoximone. (2.7 +/- 0.8 ml O2/kg/min) compared with placebo (-0.8 +/- 1.2 ml O2/kg/min). This improvement was not sustained at 4 months (0.5 +/- 1.7 ml O2/kg/min with enoximone and 0.2 +/- 1.5 ml O2/kg/min with placebo). The dropout rate was significantly higher (p less than 0.02) with enoximone (46%) than with placebo (25%). Adverse effects other than death were slightly, but not significantly, higher with enoximone (32%) than with placebo (22%). During therapy, five deaths occurred in the enoximone group, and none occurred in the placebo group (p less than 0.05). Two deaths were sudden, two were from progressive congestive heart failure, and one was from acute myocardial infarction. With intention-to-treat analysis and inclusion of patients who were removed from therapy because of lack of study drug effect, 10 deaths occurred in the enoximone group, and three occurred in the placebo group (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1990

Effect of acute angiotensin converting enzyme inhibition on left ventricular filling in patients with congestive heart failure. Relation to right ventricular volumes.

To examine the manner in which changes in diastolic performance can contribute to the effect of vasodilation in patients with left ventricular (LV) systolic dysfunction, we examined the effect of acute inhibition of angiotensin converting enzyme with intravenous enalaprilat on early LV diastolic filling. We studied 43 patients with congestive heart failure and depressed LV systolic function (mean ejection fraction +/- SD, 0.24 +/- 0.06), performing radionuclide ventriculography before and after administration of 1.25 mg intravenous enalaprilat. We measured the effect of enalaprilat on the maximum rate of early LV diastolic filling normalized in four different ways and related these changes to both LV and right ventricular (RV) volumes. Enalaprilat induced a small but statistically significant reduction in LV end-systolic volume and increase in LV ejection fraction. For the entire patient group, there was no significant change in LV peak filling rate after enalaprilat administration. For individual patients, however, the effect of enalaprilat on peak filling rate was related to resting RV end-diastolic and end-systolic volumes. In patients with enlarged RV end-diastolic volumes (greater than or equal to 120 ml/m2), mean peak filling rate increased from 1.38 +/- 0.6 to 1.71 +/- 0.6 end-diastolic volumes (EDV)/sec and from 244 +/- 131 to 297 +/- 162 ml/sec/m2 after enalaprilat administration, whereas no change in mean peak filling rate was observed in patients with nondilated RVs. These observations were present regardless of the method of normalizing peak filling rate. Thus, the response of LV peak filling rate to enalaprilat is influenced by the presence of RV dilatation.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Left ventricular inotropic effect of atrial pacing after coronary artery bypass grafting.

The effect of atrial pacing on left ventricular (LV) performance was studied in 19 patients, 24 hours after coronary artery bypass grafting (CABG). LV volumes were calculated from simultaneous radionuclide-thermodilution measurements at rest (heart rate 82 +/- 12 beats/min), 10 minutes after the start of atrial pacing (100 beats/min), and with atrial pacing plus volume loading to return preload toward baseline. Atrial pacing reduced preload as reflected by LV end-diastolic volume index (69 +/- 14 vs 60 +/- 14 ml/m2, mean +/- standard deviation) (p less than 0.0001), but returned to baseline with volume loading. Afterload, as reflected by arterial end-systolic pressure, did not change with atrial pacing (63 +/- 9 at baseline vs 64 +/- 8 mm Hg with pacing, difference not significant). Afterload increased with volume loading (68 +/- 10 mm Hg, p less than 0.025 vs baseline and pacing). LV stroke volume decreased with atrial pacing due to reduced preload, but returned to baseline with volume loading. Cardiac index increased with atrial pacing and increased further with volume loading. Compared with baseline, LV end-systolic volume index was reduced during atrial pacing both before and after volume loading, despite unchanged or augmented afterload. The combination of atrial pacing and volume loading resulted in augmentation of LV stroke work, despite no increase in preload compared with baseline. Thus, after CABG, increased (paced) heart rate augments inotropic state, as indicated by reduced LV end-systolic volume under conditions of unchanged or increased afterload, and elevated LV stroke work without an increase in preload or a decrease in afterload.

Aged↗
PubMed1989

Dipyridamole thallium-201 imaging pre- and post-coronary angioplasty for assessment of regional myocardial ischemia in humans.

To examine the effect of coronary angioplasty on myocardial perfusion and to examine anatomic correlates of dipyridamole-thallium images, we performed dipyridamole thallium scanning before and after 24 angioplasty procedures in 23 patients with clinical ischemia. Dipyridamole thallium tomography was performed 1 to 4 (mean +/- S.D. 1.5 +/- 0.9) days before and 1 to 25 (6.3 +/- 6.9) days after angioplasty. Coronary angioplasty was anatomically successful (less than 50% residual stenosis) in 23 of 24 patients. Before angioplasty, 3 of 24 scans were interpreted as normal, with no change in these patients following angioplasty. Prior to angioplasty, 19 scans showed redistribution. After successful coronary angioplasty in 18 of 19, 17 showed improvement in dipyridamole thallium scanning; one did not show improvement and later required repeat coronary dilatation. In one patient with failed angioplasty, images before and after angioplasty were unchanged. Nine scans showed "fixed" defects before angioplasty, with improvement in three of nine following angioplasty. Quantitative analysis of the dipyridamole thallium scans revealed significant improvement in uptake in the myocardial regions supplied by the successfully dilated artery (involved regions), but not in the remote (uninvolved) regions. We conclude that myocardial perfusion, as judged by dipyridamole thallium scanning, almost always improves following anatomically successful coronary angioplasty. "Fixed" defects may improve following angioplasty and presumably represent ischemia with incomplete redistribution, rather than infarction.

Adult↗
PubMed1989

Effects of atrial cardioplegia on the ischemic right ventricle after acute coronary artery occlusion and reperfusion.

Right atrial cardioplegia has been advocated as a simple method of delivering retrograde cardioplegia. Passive distention of the right heart inherent with right atrial cardioplegia has been shown to impair right ventricular function in a canine model of global ischemia. This study was designed to compare right ventricular performance after right atrial cardioplegia administered intermittently (n = 5) and continuously (n = 5) with coronary sinus retrograde cardioplegia (n = 5) and aortic root cardioplegia (n = 8) in a canine model of acute right ventricular ischemia and reperfusion. Right ventricular performance was assessed using the load-independent relationship of end-systolic pressure versus dimension (myocardial fiber length). Right ventricular performance was well preserved after reperfusion in those dogs protected with intermittent right atrial cardioplegia (95% of control). Results with continuous right atrial cardioplegia (66% of control) and coronary sinus retrograde cardioplegia (40% of control) demonstrated diminished postreperfusion right ventricular performance. Right ventricular performance in the group protected with aortic root cardioplegia was significantly impaired after reperfusion when compared with all retrograde groups (34% of control, p less than 0.05). In this model, postreperfusion right ventricular performance was preserved in the right atrial cardioplegia groups despite passive ventricular distention. All methods of retrograde cardioplegia resulted in superior preservation of right ventricular performance when compared with standard aortic root cardioplegia.

Animals↗
PubMed1989

Thrombus imaging in a primate model with antibodies specific for an external membrane protein of activated platelets.

The activated platelet is a potential target for the localization of thrombi in vivo since, after stimulation and secretion of granule contents, activated platelets are concentrated at sites of blood clot formation. In this study, we used antibodies specific for a membrane protein of activated platelets to detect experimental thrombi in an animal model. PADGEM (platelet activation-dependent granule-external membrane protein), a platelet alpha-granule membrane protein, is translocated to the plasma membrane during platelet activation and granule secretion. Since PADGEM is internal in unstimulated platelets, polyclonal anti-PADGEM and monoclonal KC4 antibodies do not bind to circulating resting platelets but do interact with activated platelets. Dacron graft material incubated with radiolabeled KC4 or anti-PADGEM antibodies in the presence of thrombin-activated platelet-rich plasma bound most of the antibody. Imaging experiments with 123I-labeled anti-PADGEM in baboons with an external arterial-venous Dacron shunt revealed rapid uptake in the thrombus induced by the Dacron graft; control experiments with 123I-labeled nonimmune IgG exhibited minimal uptake. Deep venous thrombi, formed by using percutaneous balloon catheters to stop blood flow in the femoral vein of baboons, were visualized with 123I-labeled anti-PADGEM. Thrombi were discernible against blood pool background activity without subtraction techniques within 1 hr. No target enhancement was seen with 123I-labeled nonimmune IgG. 123I-labeled anti-PADGEM cleared the blood pool with an initial half-disappearance time of 6 min and did not interfere with hemostasis. These results indicate that radioimmunoscintigraphy with anti-PADGEM antibodies can visualize thrombi in baboon models and is a promising technique for clinical thrombus detection in humans.

Animals↗
PubMed1989

Protective effects of retrograde compared with antegrade cardioplegia on right ventricular systolic and diastolic function during coronary bypass surgery.

The effect of retrograde cardioplegia delivered through the right atrium on right ventricular performance has not been critically examined in humans. We randomized 20 patients with right coronary artery lesions to receive cold blood cardioplegia solution either retrograde through the right atrium (group 1, n = 10) or antegradely (group 2, n = 10). The patients were similar in age, sex, severity of coronary artery disease, cross-clamp time, and completeness of revascularization. Before operation, right ventricular function was assessed by radionuclide ventriculography, and 18-24 hours after operation, right ventricular volumes and performance were assessed at a constant-paced heart rate by simultaneous hemodynamic-radionuclide measurements, before and after a fluid challenge. Intraoperative right ventricular temperatures were not different between the groups. Right ventricular volumes and ejection fractions were not different at baseline. After operation, at similar heart rates and loading conditions, there was a trend for the antegrade group to increase right ventricular end-systolic volume (p less than 0.1) whereas the retrograde group had no change in this parameter from the preoperative state. Postoperative ventricular function curves (p = NS, retrograde versus antegrade) suggest equivalent systolic performance in both groups. Right ventricular diastolic performance showed no significant differences between the two groups, suggesting no detriment to compliance due to right ventricular distension during operation. This suggests that retrograde cardioplegia adequately protects the right ventricular myocardium during bypass surgery and may be used as an alternative procedure in situations where ventricular cooling is inadequate with antegrade delivery due to severe coronary artery disease or aortic valvular disease.

Aged↗
PubMed1989

Kinetics of pulmonary platelet deposition and clearance during thrombin-induced microembolism in rabbits.

Using 111In-labeled autologous platelets, we studied the kinetics of pulmonary platelet deposition and clearance in relation to hemodynamic and structural events during thrombin-induced pulmonary microembolism in rabbits. Autologous platelets were radiolabeled and returned to animals prior to infusion of thrombin (100 units/kg over 15 min) (n = 20) or saline (n = 6). All animals were pretreated with tranexamic acid, an inhibitor of fibrinolysis. Thrombin-treated animals manifested progressive increases in mean pulmonary platelet activity, reaching a maximum of 38% above baseline (p less than .0001), whereas no change was observed in saline-treated controls. Animals that died during, or immediately following, thrombin infusion manifested significantly greater increases in pulmonary platelet uptake (mean 1.55 +/- 0.47 times baseline), compared to surviving animals (1.14 +/- 0.16; p less than .05 survivors vs. nonsurvivors). In surviving animals, following cessation of thrombin, pulmonary platelet activity cleared gradually, with a half-time of approximately 12 min. Thrombin reduced circulating platelet counts (p less than .001), increased mean pulmonary artery pressure (13 +/- 3 mm Hg to 18 +/- 6 mm Hg; p less than .0001), and reduced mean systemic arterial pressure (55 +/- 10 mm Hg to 44 +/- 7 mm Hg; p less than .001). The time courses of these events approximated that of thrombin-induced pulmonary platelet uptake. Furthermore, the increase in pulmonary artery pressure occurred predominantly in the group of animals in which the increase in pulmonary radiolabeled platelet activity exceeded the median value of 20%. Postmortem histology showed extensive pulmonary thrombus extending from small arterial to capillary levels in animals that died during, or immediately following, thrombin infusion, but not in surviving animals. Our findings suggest that platelet aggregation plays an important role in the pathogenesis of hemodynamic change following thrombin-induced pulmonary embolization.

Animals↗
PubMed1988

Efficacy of retrograde coronary sinus cardioplegia in patients undergoing myocardial revascularization: a prospective randomized trial.

The efficacy of retrograde coronary sinus cardioplegia (RCSC) administered through the right atrium compared with aortic root cardioplegia (ARC) has not been examined critically in patients undergoing coronary artery bypass grafting (CABG). Twenty patients having elective CABG were randomized prospectively to receive cold blood ARC (Group I, 10 patients) or cold blood RCSC (Group II, 10 patients). Patient demographics were similar in both groups. Ventricular function was assessed preoperatively by radionuclide ventriculography and postoperatively by simultaneous hemodynamic and radionuclide ventriculographic studies with volume loading. There was no change in ejection fraction (EF) (preoperative versus postoperative value) in Group I (50 +/- 6% versus 53 +/- 6%) but in group II, at similar peak systolic pressure and similar left ventricular end-diastolic volume index (LVEDVI), LVEF improved significantly (49 +/- 6% versus 60 +/- 12%, p less than 0.05). Postoperative ventricular function (stroke work index versus EDVI) for the left ventricle and right ventricle were similar in both groups. Evaluation of postoperative LV systolic function (end-systolic blood pressure versus end-systolic volume index) and diastolic function (pulmonary capillary wedge pressure versus EDVI) were also similar in both groups. Retrograde coronary sinus cardioplegia is as effective as ARC for intraoperative myocardial protection, and provides excellent postoperative function in patients undergoing elective CABG.

Blood↗
PubMed1988

Magnetic resonance imaging with gadolinium-DTPA for detecting cardiac transplant rejection in rats.

To date, no noninvasive tool has gained widespread acceptance as an adequate substitute for endomyocardial biopsy for the diagnosis and grading of cardiac transplant rejection. We examined the potential role of magnetic resonance imaging with gadolinium (Gd)-diethylenetriamine penta-acetic acid (DTPA) image enhancement for the diagnosis of cardiac graft rejection. We studied 15 rats with heterotopic cardiac transplants, nine of which received no immunosuppression, and six of which received cyclosporine, azathioprine, and methylprednisolone. The animals underwent magnetic resonance imaging, which was immediately followed by sacrifice (2-12 days after transplant). Myocardial image enhancement was assessed on T1-weighted images performed before and after administration of Gd-DTPA, 0.5 mmol/kg. Histological specimens were graded I, II, or III to indicate increasing severity of rejection. In the absence of rejection, Gd-DTPA induced mild homogeneous myocardial enhancement. Ten of 11 cases with Grade II or III rejection manifested one or more areas of intense myocardial enhancement. The extent and distribution of intense myocardial enhancement corresponded to the severity and distribution of histological rejection. Quantitative myocardial enhancement, expressed as the ratio of maximal signal intensity after Gd-DTPA to signal intensity before Gd-DTPA administration, separated Grade I animals (1.61 +/- 0.27; mean +/- SD) from Grades II (2.89 +/- 0.58) and III (3.10 +/- 0.77; p less than 0.01) animals. In conclusion, cardiac transplant rejection is characterized by intense T1-weighted image enhancement after administration of Gd-DTPA. Magnetic resonance imaging with Gd-DTPA thus has potential application in the clinical diagnosis of cardiac transplant rejection.

Animals↗