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Peripheral blood stem cells (PBSC) were mobilized in 130 patients with autoimmune diseases undergoing autologous hematopoietic stem cell transplantation using cyclophosphamide 2 g/m(2) and either granulocyte colony-stimulating factor (G-CSF) 5 mcg/kg/day (for systemic lupus erythematosus (SLE) and secondary progressive multiple sclerosis, SPMS) or G-CSF 10 mcg/kg/day (for relapsing remitting multiple sclerosis (RRMS), Crohn's disease (CD), systemic sclerosis (SSc), and other immune-mediated disorders). Mobilization-related mortality was 0.8% (one of 130) secondary to infection. Circulating peripheral blood (PB) CD34(+) cells/microl differed significantly by disease. Collected CD34(+) cells/kg/apheresis and overall collection efficiency was significantly better using Spectra apheresis device compared to the Fenwall CS3000 instrument. Patients with SLE and RRMS achieved the lowest and the highest CD34(+) cell yields, respectively. Ex vivo CD34(+) cell selection employing Isolex 300iv2.5 apparatus was significantly more efficient compared to CEPRATE CS device. Circulating PB CD34(+) cells/microl correlated positively with initial CD34(+) cells/kg/apheresis and enriched product CD34(+) cells/kg. Mean WBC and platelet engraftment (ANC>0.5 x 10(9)/l and platelet count >20 x 10(9)/l) occurred on days 9 and 11, respectively. Infused CD34(+) cell/kg dose showed significant direct correlation with faster white blood cell (WBC) and platelet engraftment. When adjusted for CD34(+) cell/kg dose, patients treated with a myeloablative regimen had significantly slower WBC and platelet recovery compared to non-myeloablative regimens.

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One hundred and seventy-seven stem cell apheresis procedures performed on 91 patients using the Fenwal CS 3000 Plus cell separator and 61 procedures performed on 37 patients using the Cobe Spectra cell separator were studied to compare the CD34(+) cell collection efficiencies (CE; the proportion of the total CD34(+) cell content in the blood volumes processed that is harvested) of the two machines. The absolute peripheral blood CD34(+) cell count was comparable for the two groups (P = 0.27). A strong correlation was seen between the blood CD34(+) cell count and the total number of CD34(+) cells collected for the Spectra (r(2) = 0.59; P < 10(-6)) and for the CS 3000 Plus (r(2) = 0.60; P < 10(-6)). No significant correlation emerged between the peripheral blood CD34(+) cell count and the CE of either machine. The total number of CD34(+) cells collected per procedure was comparable (P = 0.51): median 113 x 10(6) for CS 3000 Plus and median 218 x 10(6)for Spectra. CE was significantly higher with the Spectra (median 45.7%, range 9.8-98.6%) than the CS 3000 Plus (median 30.3%, range 1.7-89.3%; P < 0.00001). We conclude that the CD34(+) cell CE of the Spectra is superior to that of the CS 3000 Plus. Therefore, under the usual clinical conditions, Cobe Spectra should be used preferentially for peripheral blood progentor cell collection to maximize the number of hematopoietic stem cells collected.

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One hundred and seventy-seven large-volume leukapheresis procedures performed on 91 patients over a 15 month period were reviewed to see if the pre-apheresis hematocrit (Hct) affected the CD34(+) cell collection efficiency (CE) of the Fenwal CS 3000 Plus cell separator. The Hct was 0.174-0.461 (median 0.317), and the peripheral blood CD34(+) cell count 2-2487 per microl (median 21). The total CD34(+) cell quantity collected was 3.0-2677.2 x 10(6) (median 113.0). Based on the number of CD34(+)cells contained in the blood volume processed (23.3-37303.2 x 10(6); median 318.0), the CE was 1.7-87.5% (median 30.3). No correlation was found between the Hct and CE (r(2) = 0.0034; P = 0.44) or the total CD34(+) cell quantity collected (r2 = 0.0040; P = 0.40). CEs for Hct <0.25 (median CE 36%), Hct 0.25-0.299 (median CE 30%) and Hct 0.30 (median CE 30%) were comparable. As expected, highly significant correlations were seen between the CD34(+) cell quantities collected and quantities processed (r2 = 0.59; P < 10(-6)) as well as the peripheral blood CD34(+) cell counts (r2= 0.60; P < 10(-6)). We conclude that the minimum acceptable Hct or hemoglobin level for leukapheresis should be dictated by clinical circumstances because it does not affect stem cell collection.

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This article describes clinical situations in which stunning occurs and updates previous reviews on the topic. Stunning following angioplasty, angina and exercise-induced ischemia, infarction, and after cardiac surgery are described. In addition, newer concepts regarding stunning, including neurogenic stunned myocardium, are discussed. Left atrial stunning following cardioversion is a recently recognized phenomenon with important clinical implications, but differs from the original concept of post-ischemic stunning.

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Ischemic preconditioning is among the most consistent and powerful modes of reducing myocardial infarct size. Although several clinical studies have suggested that the human heart can be preconditioned, controversy exists in both the experimental and clinical literature as to whether the senescent heart can be preconditioned. The authors recently reported that older patients (> or = 60 years of age) in the Thrombolysis in Myocardial Infarction-4 study appeared to benefit from a history of angina prior to acute myocardial infarction. This observation may lead to a clinical counterpart to successful preconditioning in the older heart.

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BACKGROUND: The timing of onset of angina before myocardial infarction in relation to outcome is unknown. METHODS AND RESULTS: We prospectively determined the importance of the time of onset of preinfarction angina in relation to 30-day outcomes in the TIMI-9B study from standardized forms. Of the 3002 patients entered into the study, 425 reported angina before their myocardial infarction. Patients with angina onset within 24 hours of infarction had a lower 30-day cardiac event rate (mortality, recurrent myocardial infarction, heart failure, or shock) at 4% than those with onset of angina >24 hours (17%; P=.030). A history of any angina alone was not associated with reduced event rate. Peak creatine kinase levels tended to be lower in the group with angina within 24 hours. These benefits were not due to higher rates of use of antianginal medicines or aspirin and were not a consequence of differences in baseline characteristics or disease states (hypertension, hypercholesterolemia) among subgroups. CONCLUSIONS: These temporal observations are consistent with the concept of preconditioning by preinfarction angina but do not rule out other mechanisms.

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There has been debate regarding the issue of whether ischemic preconditioning is effective in the aging and diseased heart. Therefore, we retrospectively analyzed the effect of preinfarction angina in patients less than versus greater than 60 years of age in the TIMI 4 study. Preinfarction angina was defined as an episode of typical angina pectoris that occurs prior to the time of index chest pain associated with the myocardial infarction itself. Patients who were 60 years and older had a higher rate of death and the combined endpoints of death, heart failure/shock, and/or reinfarction compared with younger patients. However, patients 60 years or older who had preinfarction angina had lower rates of the combined endpoints of death, heart failure/shock, and/or reinfarction (11%) compared with patients without angina (23%; P = 0.04). They also had lower creatine kinase (CK) values. Therefore, preinfarction angina was protective in patients 60 years or older in the TIMI 4 study.

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Extraction atherectomy utilizes suction aspiration as an attempt to limit distal emboli during atherectomy. We sought to test the hypothesis that extraction atherectomy produces less distal embolization than balloon angioplasty when treating saphenous vein grafts. Among 163 consecutive, nonrandomized patients, 103 patients underwent transluminal extraction catheter (TEC) atherectomy with or without adjunctive balloon angioplasty, and 60 patients had conventional balloon angioplasty. Both groups showed comparably high procedural success rates (TEC 90.3%, angioplasty 83.3%, P = NS). TEC cases had a significantly lower incidence of angiographic distal embolization, compared with angioplasty (3.9% vs. 16.7%, P = 0.005). In cases with angiographic evidence of thrombus in the grafts, TEC maintained a significantly lower incidence of distal embolization than angioplasty (5.6% vs. 31.8%, P = 0.004). There were no statistical differences between the two groups regarding the incidence of other procedure-related complications, including death, myocardial infarction, or emergency coronary artery bypass grafting. TEC atherectomy appears to have a significantly lower incidence of distal embolization than balloon angioplasty when treating saphenous vein grafts, particularly in the presence of angiographically apparent thrombus.

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The use of bivariable selection (BVS) for selecting variables to be used in multivariable analysis is inappropriate despite its common usage in medical sciences. In BVS, if the statistical p value of a risk factor in bivariable analysis is greater than an arbitrary value (often p = 0.05), then this factor will not be allowed to compete for inclusion in multivariable analysis. This type of variable selection is inappropriate because the BVS method wrongly rejects potentially important variables when the relationship between an outcome and a risk factor is confounded by any confounder and when this confounder is not properly controlled. This article uses both hypothetical and actual data to show how a nonsignificant risk factor in bivariable analysis may actually be a significant risk factor in multivariable analysis if confounding is properly controlled. Furthermore, problems resulting from the automated forward and stepwise modeling with or without the presence of confounding are also addressed. To avoid these improper procedures and deficiencies, alternatives in performing multivariable analysis, including advantages and disadvantages of the BVS method and automated stepwise modeling, are reviewed and discussed.

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Whether higher operator case volume is associated with improved percutaneous transluminal coronary angioplasty (PTCA) clinical and cost outcomes is the subject of this study. Hospital volume-related improvement in clinical outcomes has been shown for coronary artery bypass grafting (CABG) and PTCA. Physician case volume-related differences in clinical outcomes have not been clearly demonstrated, and differences in hospital costs have not been examined. For clinical and cost outcomes, risk-adjusted analysis of differences in PTCA outcomes has not been reported. In addition, controversy exists about the appropriate annual case volume considered adequate to maintain skills and achieve optimal clinical outcomes in performing PTCA procedures. We studied 2,350 PTCAs performed between March 1, 1991, and February 28, 1994. Physicians were divided into 2 volume groups: high (>50 cases/year) and low (<50 cases/year). The rate of emergency CABG after PTCA was 2.1% for high- and 3.9% for low-volume operators (p = 0.009). Hospital morbidity associated with PTCA was lower in high-than in low-volume operators (6.46% vs 10.73%, p <0.001). The risk-adjusted ratios for emergency CABG and morbidity were 2.05 (p = 0.005) and 1.79 (p <0.001), respectively. The length of stay averaged 4.07 +/- 4.54 days for high- and 4.49 +/- 4.33 days for low-volume operators (p = 0.003). Hospital costs averaged $7,977 +/-$7,269 for high- and $8,278 +/- $6,289 for low-volume operators (p = 0.065). The risk adjusted ratio was 1.091 (p = 0.004) for length of stay and 1.050 (p = 0.029) for cost. Thus, PTCA performed by high-volume operators is significantly less likely to require emergency CABG and is also significantly associated with lower hospital morbidity, shorter hospital length of stay, and lower hospital costs.

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Ischemic preconditioning is one of the most powerful means to reduce myocardial ischemic cell death in the experimental laboratory. Data are now emerging suggesting that ischemic preconditioning also can occur in the human heart. Studies performed on human myocardial biopsies, angioplasty studies, clinical studies assessing acute tolerance to angina, and some studies evaluating the effect of angina prior to myocardial infarction, lend support to the concept that the human heart can be preconditioned. The ultimate objective is to develop preconditioning-mimetic agents that can be administered prophylactically prior to the time of cardiopulmonary bypass surgery or administered to hearts that have been harvested for transplant in order to better preserve the ischemically jeopardized myocyte.

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BACKGROUND: Ischemic preconditioning has been shown to reduce myocardial infarct size in experimental models, but its role in patients remains unclear. Angina before myocardial infarction reflects brief episodes of ischemia and may be a marker of preconditioning. As part of the Thrombolysis in Myocardial Infarction (TIMI) 4 study, we performed an analysis on the effect of a history of previous angina on in-hospital outcomes for patients with acute myocardial infarction. METHODS AND RESULTS: Patients eligible for thrombolytic therapy were enrolled into the study. Data were collected from case report forms regarding previous history of angina, in-hospital outcome and 6-week follow-up. Two hundred eighteen patients had a history of previous angina at any time before acute myocardial infarction, and 198 patients did not have previous angina. Patients with any previous history of angina were less likely than with those without angina to experience in-hospital death (3% versus 8%) (P = .03), severe congestive heart failure (CHF) or shock (1% versus 7%, P = .006), or the combined end point of in-hospital death, severe CHF, or shock (4% versus 12%, P = .004). Moreover, patients with any history of angina were more likely to have a smaller creatine kinase (CK)-determined infarct size (119 versus 154 CK integrated units; P = .01) and were less likely to have Q waves on their ECG (57% versus 69%; P = .01). In the subset of patients who experienced angina within the 48 hours before infarction (compared with those who did not), there was a trend toward less likely in-hospital death (3% versus 6%; P = .09), a lower incidence of severe CHF or shock (1% versus 6% P = .008), a lower combined end point of death, CHF, or shock (3% versus 10%; P = .006), smaller infarct size assessed by CK (115 versus 151 CK units; P = .03), and a trend toward fewer Q-wave infarcts. However, patients with a history of previous angina did have a trend toward more recurrent ischemic pain. Of importance is that the beneficial in-hospital effects of previous angina were not dependent on angiographically visible coronary collaterals. CONCLUSIONS: Previous angina confers a beneficial effect on in-hospital outcome after acute myocardial infarction. The reasons for this benefit are uncertain, but one potential mechanism for this observation may be ischemic preconditioning.

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BACKGROUND: Identification of whether episodes of ambulatory ischemia are caused by increases in myocardial oxygen demand or to episodic coronary vasoconstriction in patients with stable coronary disease may be important to guide selection of optimal anti-ischemic therapy and to gain insight into mechanisms responsible for adverse cardiac events. METHODS AND RESULTS: Mean minute heart rate activity during ambulatory ECG (AECG) monitoring was determined for 50 patients treated with propranolol, diltiazem, nifedipine, or placebo in a randomized, double-blind, crossover trial. Periods of heart rate increases of various magnitudes and durations and starting at various baseline heart rates on each therapy were identified throughout each 48-hour AECG recording, and the proportion of these periods associated with an ischemic episode was determined. The circadian variation of ischemic episodes categorized by the presence or absence of an increase in heart rate was analyzed. Eighty-one percent of ischemic episodes were preceded by an increase in heart rate > or = 5 beats per minute. The likelihood of developing ischemia associated with a heart rate increase was proportional to the magnitude and duration of the heart rate increase and the baseline heart rate before the increases in heart rate: likelihood ranged from 4% when the heart rate increased 5-9 beats per minute and lasted < 10 minutes to 60% when the heart rate increased > or = 20 beats per minute and lasted > or = 40 minutes. The likelihoods of developing ischemia based on changes in the heart rate variables were similar for each of the therapies. Propranolol therapy significantly reduced the magnitude and duration of heart rate increase and the baseline heart rate compared with therapy with placebo, diltiazem, or nifedipine (P < .001). Ischemic episodes associated with a heart rate increase displayed a daytime peak, whereas ischemia occurring without a heart rate increase occurred evenly throughout the day. Propranolol reduced the proportion of heart rate-related ischemic episodes and increased the proportion of non-heart rate-related episodes compared with placebo (P < .02), and nifedipine exerted the opposite effect (P = .005). Multivariate analysis indicated that the probability of developing ischemia was strongly associated with heart rate variables and was unaffected by time of day. CONCLUSIONS: Most episodes of ambulatory ischemia are associated with a preceding period of increased heart rate. The likelihood of developing ischemia is predicted by heart rate variables and unaffected by time of day. Anti-ischemic efficacy is generally a result of the medication's efficacy in reducing heart rate variables. A minority of ischemic episodes are not associated with preceding periods of increased heart rate, may be caused by episodic coronary vasoconstriction, and are more effectively reduced by nifedipine than propranolol.

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OBJECTIVES: We sought to define the extent to which the therapeutic efficacy of three single-drug regimens on ambulatory ischemia paralleled efficacy on other clinical manifestations of ischemia, specifically exercise test performance and anginal symptoms. BACKGROUND: Some studies have shown that the presence and severity of ambulatory ischemia are predictive of anginal symptoms and exercise test performance, whereas other studies have not. Less is known about effects of antianginal treatment and whether response to therapy for one clinical manifestation reflects therapeutic responses for other clinical manifestations. METHODS: We studied 50 patients in the Angina and Silent Ischemia Study who had documented coronary disease, an exercise test positive for ischemia, the presence of ambulatory and asymptomatic ischemia on ambulatory electrocardiographic (ECG) Holter monitoring and stable anginal symptoms. Patients received maximally tolerated doses of sustained release propranolol (mean 293 mg/day), sustained release diltiazem (mean 350 mg/day), nifedipine (mean 79 mg/day) and placebo, each for 2-week periods in a double-blind, crossover fashion. Patients' responses to treatment were assessed by 48-h ambulatory ECG monitoring, exercise test (standard Bruce protocol) and diaries of angina. Levels of efficacy for each agent and for each clinical measure were compared using Spearman correlation analysis. RESULTS: With placebo there was no correlation among the frequency of ischemic episodes by ambulatory ECG monitoring, exercise time to 1.0-mm ST segment depression or frequency of anginal episodes. Furthermore, for a given patient the efficacy of each active medication in reducing ambulatory ischemia was not correlated with response in anginal symptoms or exercise test performance (r = -0.21 to 0.24, p = NS). Within each of these clinical measures, efficacy of one drug was more strongly correlated with efficacy of another drug (r = 0.64 to 0.81 for ambulatory ischemia, 0.48 to 0.56 for exercise test performance and 0.16 to 0.54 for anginal symptoms). CONCLUSIONS: Different measures of ischemia, specifically ambulatory ischemia assessed by ambulatory ECG monitoring, exercise performance on exercise test and anginal symptoms, are independent. Efficacy for each clinical end point must be assessed separately when considering response to drug treatment.

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Episodes of transient myocardial ischemia during ambulatory activities are common in patients with stable coronary artery disease and who are often asymptomatic. Selection of therapy for episodes of asymptomatic ischemia is limited by a lack of direct comparative studies. To determine the most effective monotherapy for patients with stable angina and a high frequency of asymptomatic ischemic episodes, propranolol-LA (mean daily dose, 293 mg), diltiazem-SR (mean daily dose, 350 mg), nifedipine (mean daily dose, 79 mg) were each compared with placebo, each for 2 weeks, in a randomized, double-blinded, crossover trial. Entry criteria were a positive exercise treadmill test during placebo therapy characterized by 1.0 mm or more ST segment depression and angina pectoris, and six or more episodes of transient ST segment depression of 1.0 mm or more on a 48-hour ambulatory electrocardiogram. One hundred ninety-four patients were screened, 63 were eligible and received randomized therapy, of which 56 patients completed at least two of the four treatment periods and were included in an intent-to-treat analysis. Fifty patients completed all four treatment phases and were included in the protocol-completed analysis. Anti-ischemia efficacy was assessed by 48-hour ambulatory electrocardiographic monitoring, exercise treadmill tests, and anginal diaries. Ninety-four percent of all episodes of ambulatory ischemia were asymptomatic. Compared with placebo, only propranolol was associated with a marked reduction in all manifestations of asymptomatic ischemia during ambulatory electrocardiographic monitoring (2.3 versus 1.0 episodes/24 hr; mean duration of ischemia per 24 hours, 43.6 versus 5.7 minutes; both p less than 0.0001). Diltiazem's reduction of the frequency of episodes compared with placebo (2.3 versus 1.9 episodes/24 hr) was associated with a trend (p = 0.08) in the protocol-completed analysis and with a significant reduction in the intent-to-treat analysis (p = 0.03). Nifedipine had no significant effect on any measured variable of ambulatory ischemia. The dosages of medication used may have been excessive for some patients, and a more beneficial effect may have been evident at a lower dose. In contrast to the marked effects of the active agents on ambulatory asymptomatic ischemia, the effects on exercise performance and angina pectoris were slight. The active agents modestly improved treadmill exercise duration time until 1 mm ST segment depression (3%), and only propranolol and diltiazem had significant effects. Only diltiazem significantly prolonged the total exercise time. Anginal frequency was significantly decreased by both propranolol and diltiazem.(ABSTRACT TRUNCATED AT 400 WORDS)

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To determine the effect of metoprolol on silent ischemia and platelet aggregability, 10 patients with coronary artery disease were studied with a randomized, double-blind, placebo-controlled, crossover trial. Patients were treated with metoprolol (200 mg b.i.d.) or placebo for 1 week and then received the alternate therapy. Two days before the end of each treatment period, platelet aggregability was studied for 24 hours, and a 48-hour ambulatory electrocardiogram was obtained. Compared with placebo, metoprolol significantly decreased the total number (from 26 to 4, p less than 0.1) and duration (from 735 to 84 minutes, p less than 0.01) of silent ischemic episodes. This decrease was accompanied by a decrease in the mean blood pressure (from 127/81 to 118/71 mm Hg, p less than 0.01) and the mean heart rate (from 70 to 54 beats/min, p less than 0.01). The incidence of silent ischemic episodes in the morning was significantly higher in untreated patients than in treated patients. The few episodes observed during metoprolol treatment occurred at the same time as the peak incidence observed during placebo treatment. During placebo treatment, platelet aggregability increased from 6:00 to 9:00 AM as reflected by a decrease in the threshold concentrations of ADP and epinephrine required to induce biphasic platelet aggregation (from 4.8 +/- 0.8 to 2.6 +/- 0.4 microM, p less than 0.02; and from 7.3 +/- 2.3 to 1.8 +/- 0.9 microM, respectively, p less than 0.02). Metoprolol did not alter the basal level nor blunt the morning increase of platelet aggregability.(ABSTRACT TRUNCATED AT 250 WORDS)

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The slope of the left ventricular end-systolic pressure-volume relationship is thought to be a load-independent index of contractile state. However, clinical application requires a practical technique to simultaneously measure pressure and volume in man. We used a left ventricular conductance catheter to derive the left ventricular end-systolic pressure-volume relationship over a range of arterial pressures during nitroprusside infusion and washout in 14 patients, and to characterize the effect of dobutamine, a positive inotropic drug. End-systole was defined as the maximum pressure-to-volume ratio. Dobutamine (5 micrograms/kg/min) increased the slope of the end-systolic pressure-volume relationship in 11 of 14 patients, the mean slope increasing by 43% from 1.4 +/- 0.1 to 2.1 +/- 0.2 mm Hg/% end-diastolic volume (p less than 0.01). In 12 of 14 patients there was a leftward and upward shift of the end-systolic pressure-volume relationship with dobutamine. T quantitate this shift, we derived left ventricular pressure at control end-systolic volume before and after dobutamine. Dobutamine increased the mean end-systolic pressure at control end-systolic volume in 12 of 14 patients, the average increased by 37% from 134 +/- 10 to 189 +/- 23 mm Hg (p less than 0.01). We conclude that the conductance catheter can be used in man to detect a drug-induced change in left ventricular contractile state. This technique may be useful in the evaluation of drugs with positive inotropic actions, and in assessing the response of individual patients to positive inotropic agents.

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Although silent myocardial ischemia (SI) occurs frequently in patients with angina and is of prognostic significance, little is known of its occurrence in other subgroups. We assessed the incidence of SI in offspring of Framingham Heart Study (FHS) patients following unrecognized myocardial infarction (UMI) and in controls without MI but who were matched for age, sex, hypertension, diabetes, smoking, and total cholesterol at entry into the FHS. Of the 20 UMI patients, six had died and one with left bundle branch block was excluded. The remaining 13 UMI patients and 26 control patients underwent 24-hour ambulatory electrocardiographic monitoring (AECG) for SI. Two patients (one from each group) with angina were excluded from the AECG analysis. Only two (15.4%) of the UMI patients and two (7.7%) of the control patients had any AECG evidence of SI. These preliminary results suggest that routine monitoring for SI is not indicated in asymptomatic long-term survivors of UMI or in asymptomatic patients without prior MI but with otherwise similar risk profiles.

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The presence of a varicocele in adult men has been correlated with infertility. This study documents the effect of an experimentally induced unilateral varicocele in 21-day-old juvenile prepubertal and 51-day-old adult rats (n = 10 per group) on subsequent adult testicular function. Varicoceles were induced by partial occlusion of the spermatic vein. There were ten sham-operated and five nonoperated control rats in each age group. The rats were sacrificed 1 month after surgery. Intrascrotal temperatures were elevated in both groups with varicoceles. Histologically, the ipsilateral testes of rats in both age groups demonstrated a decrease in the numbers of functioning seminiferous tubules and germ cells, but the decrease was significantly greater in the juveniles than in the adult rats. No changes were seen in the contralateral testes. Significant titers of cytotoxic sperm antibodies were present in all animals with varicoceles, which is in contrast to controls. The juveniles had significantly lower antibody titers (mean log2 +/- SEM; 3.2 +/- 0.09 vs. 8.5 +/- 1.1, P less than 0.001) than the adults. The induction of a unilateral varicocele damaged spermatogenesis and testicular function to a greater extent in juveniles than in adult rats. This damage may be immune complex-mediated.

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The possible role of group specific component (Gc) (vitamin D-binding protein) in the clearance of cellular actin entering the circulation was examined with 125I-labeled Gc and actin injected into a rabbit model. Although filamentous F-actin is depolymerized primarily by plasma gelsolin, greater than or equal to 90% 125I-actin injected in either monomeric G- or F-form became complexed eventually with Gc (1:1 molar ratio). Clearance of Gc complexes was much faster (greater than 90% within 5 h) than that of native Gc (t1/2 = 17.2 h). Nephrectomy did not significantly alter the clearance of either Gc or actin. Since Gc complexes are dramatically increased in situations of tissue necrosis such as in fulminant hepatic failure, the current results suggest a crucial role for Gc in sequestration and clearance of released cellular actin.

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