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A significant component of restenosis after coronary angioplasty is due to medial proliferation. Targeted ablation of the proliferating cells by ionizing radiation may prevent restenosis. We delivered high-dose intracoronary gamma-irradiation in porcine coronary arteries and assessed vasomotor function acutely and at 32 days, with pathological analysis at 32 days. Changes in luminal area were assessed by intravascular ultrasound. Irradiated segments acutely displayed vasoconstriction to acetylcholine, with loss of smooth muscle response to nitroglycerin. Restudy revealed restoration of normal vasodilatory response to acetylcholine but persistent loss of response to nitroglycerin. Histopathology at 32 days revealed minor neointima formation without luminal compromise and diffuse fibrosis of the smooth muscle layer. The surrounding myocardium was normal. Focal medial fibrosis without significant endothelial or myocardial damage can be achieved via this technique; intracoronary irradiation, therefore, may be an effective way of impairing the restenosis process.

To examine the possible involvement of cytokines in reperfusion injury, we have studied production of IL-1 by human vascular cells, including smooth muscle and mononuclear phagocytes. Exposure of cells to hypoxia (pO2 approximately 14 torr) followed by reoxygenation led to significant release of IL-1 only from the mononuclear phagocytes. Elaboration of IL-1 was dependent on the oxygen tension and duration of hypoxia (optimal at lower pO2s, approximately 14-20 torr, and after 9 h), as well as the time in reoxygenation (maximal IL-1 release at 6-9 h). Although a period of hypoxia was necessary for subsequent IL-1 production during reoxygenation of either peripheral blood monocytes or cultured monocyte-derived macrophages, no IL-1 release occurred during the hypoxic exposure. IL-1 released during reoxygenation was newly synthesized, and its production was triggered by the generation of oxygen free radicals, as it could be blocked by the addition of either allopurinol or free radical scavengers to cultures and could be stimulated in part by low concentrations of hydrogen peroxide or xanthine/xanthine oxidase. The potential pathophysiological effects of IL-1-containing supernatants from reoxygenated macrophages was shown by their induction of endothelial tissue factor and enhancement of endothelial adhesiveness for neutrophils, both of which could be blocked by anti-IL-1 antibody. The relevance of IL-1 to hypoxia/reoxygenation in vivo was suggested by the presence of circulating nanogram amounts of this cytokine in the plasma of mice during the reoxygenation period following a hypoxia.

Background and Methods: Physicians have long believed that the erythrocyte sedimentation rate is low in patients with congestive heart failure, but this concept is based on a misinterpretation of the results in a single report published in 1936. To reevaluate this concept in the modern era, we measured the sedimentation rate in 242 patients who were referred for treatment of chronic heart failure., Results: The sedimentation rate was low (less than 5 mm per hour) in only 24 patients (10 percent) but was increased (above 25 mm per hour) in 50 percent. Patients with low or normal sedimentation rates (less than or equal to 25 mm per hour) had more severe hemodynamic abnormalities than patients with elevated rates: lower cardiac index (mean +/- SEM, 1.7 +/- 0.1 vs. 2.0 +/- 0.1 liters per minute per square meter of body-surface area) and higher mean right atrial pressure (mean +/- SEM, 12 +/- 1 vs. 9 +/- 1 mm Hg) (both P less than 0.0001). New York Heart Association functional class IV symptoms were present in 66 percent of the patients with a low or normal sedimentation rate, as compared with 42 percent of those with elevated rates (P less than 0.0001). After one to three months of therapy, patients whose sedimentation rates decreased showed little hemodynamic or clinical response to treatment, whereas both cardiac performance and functional status improved in patients whose rates increased (P less than 0.02 for the comparison between groups). The sedimentation rate was correlated with the plasma fibrinogen level (r = 0.64, P = 0.0025), and changes in the sedimentation rate during treatment were correlated inversely with changes in mean right atrial pressure (r = -0.57, P = 0.0002). During long-term follow-up, patients with low or normal sedimentation rates had a worse one-year survival than patients with elevated rates (41 vs. 66 percent, P = 0.01)., Conclusions: These data indicate that the erythrocyte sedimentation rate is correlated with the severity of illness in patients with chronic heart failure. Because of its lack of discriminatory power, however, the test is of limited value in the clinical management of this disorder.

An electrode-based lactate analyzer was recently developed to facilitate "stat" laboratory measurement of lactate in whole blood. The results obtained with this technique were compared with those of our continuous-flow enzymatic method for 172 analyses of samples from 25 pigs; 88 analyses of samples from 12 normal human volunteers before, during, and after exercise; and 91 analyses of samples from 80 critically ill patients. This comparison revealed strongly significant linear correlations: r = 0.992 for the porcine analyses and r = 0.994 for the combined human analyses. In analytical-recovery studies with pooled porcine plasma with an initial lactate concentration of 3.85 mmol/L, 94.3% of added lactate (1, 5, and 10 mmol/L) was accounted for in the electrode technique, 96% in the reference technique. We conclude that the electrode-based lactate analyzer is rapid, precise, and accurate for measurement of lactate in whole-blood samples.

The measurement of arterial blood lactate concentration for the purpose of estimating the severity and prognosis of acute perfusion failure is suspect because of theoretical errors due to systemic "lactate washout" immediately following restoration of perfusion. If arterial lactate concentrations continue to increase following resuscitation, the assumption that increasing lactate concentrations indicate progression of anaerobiosis due to perfusion failure would be invalidated. Lactate washout was therefore investigated in a porcine model of cardiac arrest due to electromechanical dissociation. Cardiopulmonary resuscitation was initiated and maintained for intervals of 30 minutes or until spontaneous circulation was restored. In 25 trials on 14 successfully resuscitated animals, the arterial blood lactate concentration decreased within four minutes after resuscitation from cardiac arrest. In 24 animals in whom resuscitation efforts failed, arterial lactate concentrations increased throughout the observation period. Lactate washout occurred during an interval of only 2.6 +/- 0.3 minutes (mean +/- SEM). These results indicate that lactate measurements are not invalidated because of a washout phenomenon under the extreme conditions of cardiac arrest.