Lawrence I. Deckelbaum

A Computer-Derived Protocol to Aid in the Diagnosis of Emergency Room Patients with Acute Chest Pain

To determine whether data available to physicians in the emergency room can accurately identify which patients with acute chest pain are having myocardial infarctions, we analyzed 482 patients at one hospital. Using recursive partitioning analysis, we constructed a decision protocol in the format of a simple flow chart to identify infarction on the basis of nine clinical factors. In prospective testing on 468 other patients at a second hospital, the protocol performed as well as the physicians. Moreover, an integration of the protocol with the physicians judgments resulted in a classification system that preserved sensitivity for detecting infarctions, significantly improved the specificity (from 67 per cent to 77 per cent, P less than 0.01) and positive predictive value (from 34 per cent to 42 per cent, P = 0.016) of admission to an intensive-care area. The protocol identified a subgroup of 107 patients among whom only 5 per cent had infarctions and for whom admission to non-intensive-care areas might be appropriate. This decision protocol warrants further wide-scale prospective testing but is not ready for routine clinical use.

Abciximab Suppresses the Rise in Levels of Circulating Inflammatory Markers After Percutaneous Coronary Revascularization

Background—Previous investigators have shown that systemic markers of inflammation may be increased in patients with acute ischemic syndromes or after percutaneous coronary revascularization and that persistent elevation in these markers is predictive of excess risk of subsequent adverse cardiac events. By virtue of its cross-reactivity with the glycoprotein IIb/IIIa, av&bgr;3, and &agr;M&bgr;2 receptors, abciximab may reduce inflammatory processes. Methods and Results—Assays for the inflammatory markers C-reactive protein, interleukin-6, and tumor necrosis factor-&agr; were performed on serum samples obtained from 160 patients in a placebo-controlled, randomized trial of abciximab during angioplasty. Eighty patients each had received a placebo or abciximab bolus plus a 12-hour infusion. Serum samples were drawn at baseline (before revascularization), 24 to 48 hours after study drug administration, and 4 weeks after study drug administration. Between baseline and 24 to 48 hours, the increase in C-reactive protein was 32% less in patients receiving abciximab than placebo (P =0.025); the rise in interleukin-6 levels was 76% less in the abciximab group (P <0.001); and the rise in tumor necrosis factor-&agr; levels was 100% less with abciximab therapy (P =0.112). By 4 weeks, most marker levels had returned to baseline, with no significant differences between placebo and abciximab groups. Conclusions—Systemic markers of inflammation increase in the first 24 to 48 hours after angioplasty, but the magnitude of that rise is diminished by periprocedural abciximab. Some of the long-term clinical benefit derived from this agent may be related to an anti-inflammatory effect.

Laser-induced fluorescence spectroscopy of human colonic mucosa: Detection of adenomatous transformation

To evaluate the potential of laser-induced fluorescence spectroscopy for the detection of premalignant lesions of the gastrointestinal tract, the hypothesis that adenomatous transformation of colonic mucosa results in an alteration of laser-induced fluorescence that enables its differentiation from normal or hyperplastic tissue was tested. A fiberoptic catheter coupled to a helium-cadmium laser (325 nm) and an optical multichannel analyzer were used to obtain fluorescence spectra (350-600 nm) from 35 normal colonic specimens and 35 resected adenomatous polyps. A score based on six wavelengths was derived by stepwise multivariate linear regression analysis of the spectra. The mean score (+/- SEM) was + 0.86 +/- 0.06 for normal mucosa and -0.86 +/- 0.06 for adenomatous polyps (P less than 0.001). Spectra from an additional 34 normal specimens, 16 adenomatous polyps, and 16 hyperplastic polyps were prospectively classified with accuracies of 100%, 100%, and 94%, respectively. The mean score for hyperplastic polyps was significantly different from adenomatous (P less than 0.001) but not from normal tissue. Thus, quantitative analysis of fluorescence spectra enables the detection of adenomatous transformation in colonic mucosa.

Intracoronary Doppler assessment of moderate coronary artery disease: comparison with 201Tl imaging and coronary angiography. FACTS Study Group.

BACKGROUNDnCoronary angiography may not reliably predict whether a stenosis causes exercise-induced ischemia. Intracoronary Doppler ultrasound may enhance diagnostic accuracy by providing a physiological assessment of stenosis severity. The goal of this study was to compare intracoronary Doppler ultrasound with both 201Tl imaging and coronary angiography.nnnMETHODS AND RESULTSnFifty-five patients with 67 stenotic coronary arteries underwent coronary angiography with intracoronary Doppler ultrasound and had exercise 201Tl testing within a 1-week period. Coronary flow reserve was measured, and analyses were performed by independent core laboratories. The mean stenosis was 59+/-12%; 51 of 67 stenoses were intermediate in severity (40% to 70%). A coronary flow reserve < 1.7 predicted the presence of a stress 201Tl defect in 56 of 67 stenoses (agreement=84%; kappa=0.67; 95% CI=0.48 to 0.86). In the patients who achieved 75% of their predicted maximum heart rate, the Doppler and 201Tl imaging data agreed in 46 of 52 stenoses (agreement=88%; kappa=0.77; 95%CI=0.57 to 0.97). Scatter was evident when angiography was compared with coronary flow reserve (r=.43), and the angiogram did not reliably predict the results of the 201Tl stress test (kappa=0.21; agreement=57% to 63%).nnnCONCLUSIONSnDoppler-derived coronary flow reserve accurately predicts the presence of exercise-induced ischemia on stress 201Tl imaging, and coronary angiography does not reliably assess the physiological significance of an intermediate coronary stenosis.

Coronary laser angioplasty.

With the widespread growth of percutaneous transluminal coronary angioplasty (PTC A), the realization of limitations of balloon angioplasty stimulated the development of alternative revascularization approaches such as laser angioplasty. PTCA is best suited for the treatment of discrete atherosclerotic stenoses, with lower success rates and more difficult application in patients with diffuse atherosclerotic disease or total occlusions [1–3]. Moreover, despite an initially high primary success rate, coronary angioplasty is still plagued by a restenosis rate as high as 57% [4].

Graded global ischemia and reperfusion. Cardiac function and lactate metabolism.

The effect of global ischemia of different degrees of severity and reperfusion was studied in the isolated working rat heart. Four degrees of ischemia were induced by reducing the control total coronary flow of 8 ml/min to 0, 0.04, 0.4, or 0.8 ml/min for 30 minutes, after which the coronary flow was returned to the control level. After severe ischemia (0 and 0.04 ml/min ischemic coronary flow groups), recovery of contractility was to less than 30% of the control, pre-ischemic value of ventricular developed pressure and dP/dt, and irreversible cardiac contracture and an increised pacing threshold occurred. After moderate ischemia (0.4 and 0.8 ml/min ischemic coronary flow groups), contractile function recovered com- pletely, ischemic contracture was rapidly reversible and the pacing threshold did not increase. The moderately ischemic groups were able to function at a stable, low level of contractility for the 30 minute ischemic period, whereas the severely ischemic groups had no contractile activity. The amount of calculated tissue lactate accumulation correlated with the occurrence of irreversible ischemic injury; the severely ischemic groups which failed to recover with reperfusion accumulated 3-5 times as much lactate as the moderately ischemic groups which recovered completely. The results suggest that relatively small differences in the severity of the ischemic condition can markedly affect the degree of tissue injury.

Biochemical basis for the difference between normal and atherosclerotic arterial fluorescence.

The observation that laser-induced fluorescence (LIF) spectra of atherosclerotic and normal artery are different has been proposed as the basis for guiding a smart laser angioplasty system. The purpose of this study was to investigate the causes of this difference in LIF. Helium-cadmium laser-induced (325 nm) fluorescence was recorded from pure samples of known constituents of normal and atherosclerotic artery including collagen, elastin, calcium, cholesterol, and glycosaminoglycans. Similarities between the LIF spectra of atherosclerotic plaque and collagen and normal aorta and elastin were noted. LIF spectroscopy was then performed on specimens of atherosclerotic aortic plaque (n = 9) and normal aorta (n = 13) and on their extracted lipid, collagen, and elastin. Lipid extraction did not significantly alter atherosclerotic plaque or normal aortic LIF, suggesting a minor contribution of lipid to arterial LIF. The LIF spectra of normal aorta wall was similar to the spectra of the extracted elastin, whereas the LIF spectra of atherosclerotic aortic plaque was similar to the spectra of the extracted collagen. These observations are consistent with the reported relative collagen-to-elastin content ratio of 0.5 for normal arterial wall and 7.3 for atherosclerotic plaque. A classification algorithm was developed to discriminate normal and atherosclerotic aortic spectra based on an elastin and collagen spectral decomposition. A discriminant score was formed by the difference of elastin and collagen (E-C) coefficients and used to classify 182 aortic fluorescence spectra. The mean E-C value was +0.83 +/- 0.04 for normal and -0.48 +/- 0.07 for atherosclerotic aorta (p less than 0.001). Classification accuracy was 92%.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of intracoronary saline infusion on dissection during excimer laser coronary angioplasty: A randomized trial

OBJECTIVESnWe sought to evaluate whether intracoronary saline infusion during excimer laser coronary angioplasty decreases the incidence of significant laser-induced coronary artery dissections.nnnBACKGROUNDnDespite procedural success rates > 90%, coronary artery dissections occur in 17% to 27% of excimer laser coronary angioplasty procedures. Excimer laser irradiation of blood results in vapor bubble formation and acoustomechanical trauma to the vessel wall. Saline infusion into a coronary artery may minimize blood irradiation and consequent arterial wall damage.nnnMETHODSnIn this prospective, randomized, controlled study, consecutive patients undergoing excimer laser coronary angioplasty were randomly assigned to conventional laser irradiation in a blood medium or to laser irradiation with blood displacement by intracoronary saline infusion. In the patients randomized to intracoronary saline infusion, prewarmed normal saline was injected through the coronary artery guide catheter at a rate of 1 to 2 ml/s using a power injector. The incidence and severity of dissection after excimer laser ablation were evaluated in a core laboratory by angiographers with no knowledge of treatment assignment. The severity of coronary artery dissection was rated on an ordinal scale of 1 to 5. Dissections of grade 2 or higher were considered significant.nnnRESULTSnThe mean (+/- SE) dissection grade after laser angioplasty in patients treated with intracoronary saline infusion was 0.43 +/- 0.13 compared with 0.91 +/- 0.26 in patients undergoing laser angioplasty in a blood medium. The incidence of significant dissection was 7% in saline-treated patients compared with 24% in conventionally treated patients (p < 0.05). No significant complications were associated with saline infusion.nnnCONCLUSIONSnIntracoronary saline infusion should be incorporated into all excimer laser coronary angioplasty procedures.

Hyperinsulinemia Inhibits Myocardial Protein Degradation in Patients With Cardiovascular Disease and Insulin Resistance

BACKGROUNDnInsulin resistance, hyperinsulinemia, and myocardial hypertrophy frequently coexist in patients. Whether hyperinsulinemia directly affects myocardial protein metabolism in humans has not been examined, however. To test the hypothesis that hyperinsulinemia is anabolic for human heart protein, we examined the effects of insulin infusion on myocardial protein synthesis, degradation, and net balance in patients with ischemic heart disease.nnnMETHODS AND RESULTSnEleven men (aged 57 +/- 3 years) with coronary artery disease who had fasted for 12 to 16 hours received a constant infusion of insulin (50 mU.m-2.min-1) while plasma concentrations of glucose and amino acids were kept constant. Rates of myocardial protein synthesis, degradation, and net balance were estimated from steady state extraction and isotopic dilution of L-[ring-2,6-3H]phenylalanine across the heart basally and 90 minutes into infusion. Subjects had elevated fasting plasma insulin concentrations (173 +/- 21 pmol/L) and used little exogenous glucose during insulin infusion, suggesting resistance to the effects of insulin on whole-body carbohydrate metabolism. Basally, myocardial protein degradation, as estimated by phenylalanine release (133 +/- 28 nmol/min), exceeded protein synthesis, estimated by phenylalanine uptake (31 +/- 15 nmol/min), resulting in net negative phenylalanine balance (-102 +/- 17 nmol/min). Insulin infusion reduced myocardial protein degradation by 80% but did not affect protein synthesis, returning net phenylalanine balance to neutral.nnnCONCLUSIONSnAcute hyperinsulinemia markedly suppresses myocardial protein degradation in patients with cardiovascular disease who are resistant to its effects on whole-body glucose metabolism. This antiproteolytic action represents a potential mechanism by which hyperinsulinemia could contribute to the development of myocardial hypertrophy in patients with cardiovascular disease.

Preservation of left ventricular ejection fraction during percutaneous transluminal coronary angioplasty by distal transcatheter coronary perfusion of oxygenated fluosol DA 20

The cardioprotective efficacy of coronary perfusion during angioplasty was evaluated. Forty-two patients underwent transcatheter infusion of oxygenated Fluosol DA, 20% emulsion (FDA-20), a perfluorocarbon oxygen transport fluid, into the distal coronary artery during balloon inflations. Left ventricular function was continuously monitored by two-dimensional echocardiography, and left ventricular ejection fraction was quantitatively analyzed from the video record by an area-length method with a validated computer algorithm. Each patient had multiple nonperfused and perfused balloon inflations lasting more than 45 seconds. Nineteen of the 42 patients also received control solutions of oxygenated Ringers lactate and nonoxygenated FDA-20. The ejection fraction of nonperfused sequences fell from a baseline value of 57 +/- 15% to 36 +/- 14% at 45 seconds of inflation time (p less than 0.0005). Falls of similar magnitude were seen in the lactated Ringers and nonoxygenated FDA-20 perfused balloon inflations. The ejection fraction fall was associated with a 54% rise in end-systolic volume (p less than 0.0005) and a 4% rise in end-diastolic volume (p = ns) compared to baseline. Inflations perfused with oxygenated FDA-20 showed a 45-second, left ventricular ejection fraction of 53 +/- 13% (p = ns compared to baseline), which was significantly greater (p less than 0.0001) than the 45-second ejection fraction of the nonperfused, or control solution perfused sequences. Results indicate that the profound fall in ejection fraction occurring during percutaneous transluminal coronary angioplasty can be ameliorated by distal coronary perfusion with an oxygenated perfluorocarbon emulsion.