Lawrence Yeatman - Academia.edu (original) (raw)

Papers by Lawrence Yeatman

1-Carbon-11]acetate has been used as a tracer for oxidative metabolism with PET. The aim of this ... more 1-Carbon-11]acetate has been used as a tracer for oxidative metabolism with PET. The aim of this study was to validate, in humans, a previously proposed two-compartment model for [1-11C]acetate for the noninvasive measurement of myocardial ox ygen consumption (MVO2) and myocardial blood flow (MBF) with PET. Methods: Twelve healthy volunteers were studied with [13N]ammonia, [1-11C]acetate and PET. Myocardial oxygen con sumption was invasively determined by the Pick method from arterial and coronary sinus O2 concentrations and from MBF ob tained by [13N]ammonia PET. Results: Directly measured MV02 ranged from 5.2 to 11.1 ml/100 g/min, and MBF ranged from 0.48 to 0.88 ml/g/min. Oxidative flux through the tricarboxylic acid cycle, reflected by the rate constant k2, which correlated linearly with measured MVO2 [k2 = 0.0071 + 0.0074(MVO2); r = 0.74, s.e.e. = 0.015]. With this correlation, MVO2 could be estimated from the model-derived k2 value by MVO2 = 135(k2) -0.96. The slope of this relationship was close to that previously obtained in rats and implies that the tricarboxylic acid cycle intermediate metabolite pool sizes are comparable. The net extraction (K.,)of [1-11C]acetate, measured by PET, from blood into myocardium correlated closely with MBF by Kt = 0.15 + 0.73(MBF) (r = 0.93, s.e.e. = 0.033) and, thus, provided noninvasively obtainable measures of blood flow. Conclusion: The proposed compartment model for [1-11C]acetate fits the measured kinetics well and, with proper calibration, allows estimation of absolute MVO2 rather than only an index of oxidative metabolism. Furthermore, [1-11C]acetate-derived estimates of MBF are feasible.

Fractionated ventricular electrograms recorded during catheter mapping may arise from areas of as... more Fractionated ventricular electrograms recorded during catheter mapping may arise from areas of asynchronous depolarization associated with slow conduction, the substrate for reentrant ventricular tachycardia, but can also be a nonspecific abnormality or even artifact. To determine whether fractionated sinus rhythm electrograms are associated with slow conduction in humans, the results of endocardial catheter mapping and pacing at 133 endocardial sites in 13 patients were analyzed. Eleven patients had sustained monomorphic ventricular tachycardia and two patients had old myocardial infarction without ventricular tachycardia.

Background: Outcomes from this trial's first year data demonstrated significant benefit in heart ... more Background: Outcomes from this trial's first year data demonstrated significant benefit in heart transplant patients treated with pravastatin in cholesterol levels, survival, rejection with hemodynamic compromise, the development of cardiac allograft vasculopathy, and decreased natural killer cell cytotoxicity. Other heart transplant studies have shown similar benefit. We now report the 10-year follow-up of this study.

Annals of Vascular Surgery, 1992

New England Journal of Medicine, 1995

Hypercholesterolemia is common after cardiac transplantation and may contribute to the developmen... more Hypercholesterolemia is common after cardiac transplantation and may contribute to the development of coronary vasculopathy. Pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has been shown to be effective and safe in lowering cholesterol levels after cardiac transplantation. Cell-culture studies using inhibitors of HMG-CoA reductase have suggested an immunosuppressive effect. Early after transplantation, we randomly assigned consecutive patients to receive either pravastatin (47 patients) or no HMG-CoA reductase inhibitor (50 patients). Twelve months after transplantation, the pravastatin group had lower mean (+/- SD) cholesterol levels than the control group (193 +/- 36 vs. 248 +/- 49 mg per deciliter, P < 0.001), less frequent cardiac rejection accompanied by hemodynamic compromise (3 vs. 14 patients, P = 0.005), better survival (94 percent vs. 78 percent, P = 0.025), and a lower incidence of coronary vasculopathy in the transplant as determined by angiography and at autopsy (3 vs. 10 patients, P = 0.049). There was no difference between the two groups in the incidence of mild or moderate episodes of cardiac rejection. In a subgroup of study patients, intracoronary ultrasound measurements at base line and one year after transplantation showed less progression in the pravastatin group in maximal intimal thickness (0.11 +/- 0.09 mm, vs. 0.23 +/- 0.16 mm in the control group; P = 0.002) and in the intimal index (0.05 +/- 0.03 vs. 0.10 +/- 0.10, P = 0.031). In a subgroup of patients, the cytotoxicity of natural killer cells was lower in the pravastatin group than in the control group (9.8 percent vs. 22.2 percent specific lysis, P = 0.014). After cardiac transplantation, pravastatin had beneficial effects on cholesterol levels, the incidence of rejection causing hemodynamic compromise, one-year survival, and the incidence of coronary vasculopathy.

New England Journal of Medicine, 1976

Purified Fab fragments of ovine digoxin-specific antibodies reversed severe digoxin intoxication ... more Purified Fab fragments of ovine digoxin-specific antibodies reversed severe digoxin intoxication in a patient who had taken 22.5 mg of the drug with suicidal intent. Atrioventricular block with extreme bradycardia was temporarily managed by pacing, but progressive, intractable hyperkalemia (serum potassium of 8.7 meq per liter) with increasing pacing threshold and progressive intraventricular conduction delay was controlled only after infusion of 1100 mg of Fab. Sinus rhythm returned 10 minutes after completion of Fab infusion. Within five hours, the serum potassium concentration fell to 4.0 meq per liter. Free digoxin concentrations in serum fell sharply to undetectable levels, whereas total serum digoxin concentration concomitantly increased 12-fold. Renal excretion of digoxin bound to Fab was documented. Reversal of toxicity was not accompanied by hemodynamic instability, and antibodies to sheep Fab fragments were not detected in the patient's serum after treatment. Thus, purified digoxin-specific Fab fragments are capable of rapid reversal of advanced digoxin toxicity.

The Journal of Trauma: Injury, Infection, and Critical Care, 1987

All victims of blunt injury to the chest or precordium admitted to a Level I trauma center in a 1... more All victims of blunt injury to the chest or precordium admitted to a Level I trauma center in a 1-year period were evaluated prospectively with two-dimensional echocardiography on the day of admission, serial determinations of creatine kinase (CK) and MB isoenzyme radioimmunoassay (CK-MB) over the first 24 hours, continuous electrocardiographic monitoring over at least the first day, and serial 12-lead electrocardiography (ECG) over the first 3 days. The patients were divided into four groups based upon the results of echocardiography. Group A (n = 35) had normal ECHO and ECG; Group B (n = 16), normal ECHO and abnormal ECG; group C (n = 14), ECHO showing abnormal wall motion and/or pericardial fluid; group D (n = 8), ECHO showing a nontraumatic valvular or wall motion abnormality. Nineteen patients required an operation under general anesthesia. Group C patients had significantly higher CK, CK-MB, numbers of associated injuries, and Injury Severity Scores; seven required invasive hemodynamic monitoring. No cardiac morbidity of general anesthesia was seen. We conclude that echocardiography is an important tool for diagnosis and triage which may be used to stratify a homogeneous patient population into groups with acute, chronic, and no cardiac disease. Cardiac injury occurs in a setting of multisystem trauma. Patients with normal echocardiogram and ECG on admission do not require intensive care monitoring.

Journal of the American College of Cardiology, 1989

Journal of the American College of Cardiology, 1988

Analysis uflucal endurardkl ekctrugrarm rewarded during reentrant vrnlrlculsr txbvcardia dm nut u... more Analysis uflucal endurardkl ekctrugrarm rewarded during reentrant vrnlrlculsr txbvcardia dm nut ururib dhxt iolurmaii aa to the p&ipatiun uf :b+ r&ding site in the tachycardk circuit. To detemtim il programmed eke.

Journal of the American College of Cardiology, 1987

Thirty patients with stable exertional angina undergoing percutaneous transluminal coronary angio... more Thirty patients with stable exertional angina undergoing percutaneous transluminal coronary angioplasty of an isolated obstructive lesion of the proximal left anterior descending artery were prospectively evaluated to investigate the relation between angina induced by balloon inflation and the quantity and severity of myocardial ischemia as determined by electrocardiographic (ECG) monitoring and by echocardiographic assessment of regional and global lett ventricular wall motion. Anginal pain interviews, continuous two-dimensional echocardiographic recordings and 12 lead ECG recordings at to second intervals were obtained for the first two inflation sequences.

Journal of the American College of Cardiology, 1985

Positron emission tomography allows noninvasive assessment of myocardial blood flow and metabolis... more Positron emission tomography allows noninvasive assessment of myocardial blood flow and metabolism, and may aid in defining the extent and severity of an ischemic injury. This hypothesis was tested by studying, in chronically instrumented dogs, regional blood flow and metabolism during and after a 3 hour balloon occlusion of the left anterior descending coronary artery. The metabolic findings after ischemia were compared with the recovery of regional function over a 4 week period. N-13 ammonia was used as a blood flow tracer, and C-11 palmitic acid and F-18 deoxyglucose as tracers of fatty acid and glucose metabolism, respectively. Regional myocardial function was monitored with ultrasonic crystals implanted subendocardially. Regional function improved most between 24 hours and 1 week after reperfusion, but was still attenuated at 4 weeks. The slow functional recovery was paralleled by sustained metabolic abnormalities, reflected by segmentally delayed clearance of C-11 activity from myocardium and increased uptake of F-18 deoxyglucose. Absence of blood flow and C-11 palmitic acid uptake at 24 hours of reperfusion correlated with extensive necrosis as evidenced by histologic examination. Conversely, uptake of C-11 palmitic acid with delayed C-11 clearance and increased F-18 deoxyglucose accumulation identified reversibly injured tissue that subsequently recovered functionally and revealed little necrosis. Thus, recovery of metabolism after 3 hours of ischemia is slow in canine myocardium and paralleled by slow recovery of function. Metabolic indexes by positron tomography early after reperfusion can identify necrotic and reversibly injured tissue. Positron tomography may therefore aid in defining the extent and prognosis of an ischemic injury in patients undergoing reperfusion during evolving myocardial infarction.

Journal of the American College of Cardiology, 1991

Allhough revascularization of hypoperfured bul metatmlically active human myoclardium improves se... more Allhough revascularization of hypoperfured bul metatmlically active human myoclardium improves segmentaal function, the temporal relations among restoration of blood Row, normalization of Iissue meiabttlism and recovery of segmental function have not been determined. To examine the effects of coronary angiqdasty on 13 asynergic vascular territories in 12 patients, poritron emission tomography and two.dimensianal echocardiography were performed before and within 12 h of revnxalarirstion. Ten patients underneol l&e echwardiagrapby (67 f 19 da)s) and eight underwent a late positron emission tomographic study 168 d 19 days). The cxtcnt and severity of abnormsliliesofwatl motion, perfusion and glucose metabolism were expressed as wall motion scores, perfusion defecr wires and perfusion-metabolism ridsmatch scores. decreased from 159 + 175 to 6S r 117 early after sngioplas~ (p < 0.01) and to 26 t 29 at Iale follow-up (p < 0.601 vs. l&ore angioplasty; p = NS vs. early ahr angioplasty). However, absolute rates of glucose utilization remained elevated early after revBSeuIariration, normalizing only at late follow-up. The average wall motion scare did not improve significantly early after angioplasty (from III t 76 to 81 t 72). but a btghly sign&-ant improvement was observed at late follmwp (43 * 44, p < 0.005).

The Journal of Heart and Lung Transplantation, 2005

The American Journal of Medicine, 1981

In this report we show that coronary arterial and esophageal spasm are sometimes clinically indis... more In this report we show that coronary arterial and esophageal spasm are sometimes clinically indistinguishable. Pain patterns can be identical, nitroglycerin can bring relief, interval electrocardiograms and exercise electrocardiograms generally disclose no abnormalities, coronary arteriograms may be within normal limits or nearly so, and, importantly, an ergonovine provocative test can provoke esophageal spasm accompanied by pain mistaken for Prinzmetal's angina. Accordingly, chest pain in response to the administration of ergonovine is not evidence of coronary arterial spasm without simultaneous arteriographic proof together with changes in the monitoring electrocardiogram. Conversely, gastroenterologists should not expose patients to the risk of ergonovine without prior assurance that the coronary arterial response is normal. Our observations illustrate these points and identify a patient with symptomatic esophageal spasm previously diagnosed as Prinzmetal's angina.

The American Journal of Cardiology, 2006

Late morbidity and death as a result of progressive coronary vascular obliteration remains a majo... more Late morbidity and death as a result of progressive coronary vascular obliteration remains a major unsolved problem after orthotopic heart transplantation. Various percutaneous catheter intervention (PCI) methods have been used to treat transplant coronary artery disease (CAD), but few reports have assessed the longitudinal results of these procedures. Of 1,440 cardiac transplant patients at University of California, Los Angeles, Medical Center, treated between 1984 and 2004, 65 patients who had undergone orthotopic heart transplantation underwent PCI on a total of 156 coronary artery lesions because of transplant CAD between July 1993 and August 2004. The procedural success rate was 93%. Angiographic follow-up was available for 42 patients and 101 lesions 9.5 ؎ 5.8 months after PCI. The global restenosis rate was 36%. Multivariate analysis was used to assess 49 clinical, angiographic, and immunologic variables per lesion. The use of a cutting balloon increased the risk of restenosis (odds ratio 11.5, p <0.01) and the use of stents decreased the risk of restenosis (odds ratio 0.34, p <0.05) compared with other PCI methods. The restenosis rate with drugeluting stents was 19%, lower than that with bare metal stents (31%). Of the 65 patients, 20 (31%) died within 1.9 ؎ 1.8 years after PCI. The actuarial survival rate was 56% at 5 years after the first PCI. In conclusion, although the restenosis rate after PCI was higher than that in nontransplant patients with CAD, the immediate and long-term results were acceptable in this high-risk population. Despite the intense inflammation associated with transplant CAD, drug-eluting stents appeared to reduce the occurrence of restenosis. Compared with historical controls, PCI may also improve the actuarial survival rate of patients undergoing orthotopic heart transplantation.

The American Journal of Cardiology, 1981

The hospital and long-term course of 67 patients with nontransmural myocardial infarction was com... more The hospital and long-term course of 67 patients with nontransmural myocardial infarction was compared with that of 66 patients with transmural anterior and 63 patients with transmural inferior infarction matched for age, sex, previous infarction and prior congestive heart failure. During their hospital stay, patients with nontransmural infarction had significantly less congestive heart failure and fewer intraventricular conduction defects than did patients with transmural anterior infarction; fewer atrial tachyarrhythmias and less sinus bradycardia and atrioventricular block than did patients with transmural inferior infarction; and an incidence of hypotension, pericarditis and ventricular irritability similar to that of patients in the other two groups. Patients with nontransmural infarction had a significantly lower coronary care unit mortality rate (9 percent) than that of patients with transmural anterior or transmural inferior infarction (20 and 19 percent, respectively). By 3 months, the mortality rate had risen to 14 percent in patients with nontransmural infarction, but was significantly higher (29 and 27 percent, respectively) in patients with transmural anterior or transmural inferior infarction. Angina was common in all three groups, occurring in more than 50 percent of patients during a mean follow-up period of 26.6 months after hospital discharge.

The American Journal of Cardiology, 1992

V entricular tachycardia (VT) late after myocardial infarction is generally attributed to reentry... more V entricular tachycardia (VT) late after myocardial infarction is generally attributed to reentry due to slowed conduction and heterogeneous refractoriness in surviving myocytes bordering and traversing the infarcted area.' Thrombolytic trials and angiographic studies indicate that a patent infarct-related artery (IRA) is associated with lower sudden death mortality and that this benefit may be independent of measurable preservation of global left ventricular function.2-s Similarly, the presence of coronary collateral circulation to nonreperfused IRAs is associated with a reduction in infarct size, and a decrease in early ventricular arrhythmias>-* Predictors of VT development after myocardial infarction including inducible arrhythmias at programmed electrical stimulation,9-1 l development of a left ventricular aneurysm and late potentials detected by signal-averaged electrocardi-ography12J3 are also favorably influenced by IRA perfusion. To determine if absence of residual IRA flow distinguishes post-myocardial infarction patients with VT, we reviewed coronary angiograms of 14 patients with recurrent VT late after myocardial infarction and 14 matched control patients.

The American Journal of Cardiology, 1985

The American Journal of Cardiology, 1984