Validation and application of single breath cardiac output determinations in man

Cardiac outputs by single breath (Qsb) and Fick (Qf) procedures were compared in five healthy males during supine rest and exercise with Qf ranging from 6-19 L X min-1. The prolonged exhalation (SB) was not controlled. The Qsb calculations incorporated an equation of the CO2 dissociation curve and a "moving spline" sequential curve-fitting technique to calculate the instantaneous R from points on the original expirogram. The resulting linear regression equation for all 38 comparisons obtained (r = +0.76, p less than 0.001, mean difference +/- S.D. = 2.93 +/- 2.72 L X min-1) indicated a 24% underestimation of Qf. A substantial portion of the variability during exercise (n = 28) was due to a difference in alveolar ventilation between the time of the mixed expired (E) gas collection and the SB maneuver. When Qsb was corrected (Qsb) by a linear regression based on the difference between Re and Rsb during exercise and by adding 2.44 L X min-1 at rest (the mean difference), the relationship was greatly improved (Qsb = 0.14 + 0.99 Qf, r = +0.93, mean difference +/- S.D. = 0 +/- 1.47 L X min-1). A subsequent study during upright rest and exercise to 80% of VO2max in 6 subjects indicated a close linear relationship between Q'sb and VO2 for all 95 values obtained (r = +0.94), with slope and intercept close to published studies utilizing invasive cardiac output measurements. Considerations of measured blood gases in relation to estimated values suggested that underestimates of Qf arose, at least in part, from arterial desaturation during the SB maneuver. Detailed computational procedures are provided for implementing this improved Qsb procedure.     

Regulation of MAC-1 (CD11b/CD18) expression on circulating granulocytes in endurance runners

PURPOSE: We tested the hypothesis that degranulation of granulocytes and upregulation of the granulocyte integrin MA-1 (CD11b/CD18) are related to exercise duration and/or intensity. We also investigated whether or not the expression of MAC-1 would be influenced by body temperature or dehydration. Moreover, we tested the hypothesis that changes in leukocyte counts and changes in MAC1 expression with endurance exercise are independently regulated. METHODS: In eight amateur runners, MAC-1 (CD11b/CD18) surface expression on granulocytes was determined by fluorescent antibody cell sorting, before and after an incremental maximal treadmill test, a moderate 3-h run, and a competitive marathon race. RESULTS: Expression CD11b on granulocytes was increased by 10+/-9.6% (P < 0.05) after the maximal treadmill test and by 84+/-76% (P < 0.01) after the marathon run. There was no change in CD11b expression after the moderate 3-h run. CD18 expression was not significantly changed after any of the exercise protocols. CONCLUSION: Expression of CD11b on granulocytes is increased with intense endurance exercise, either incremental maximal treadmill testing or competitive marathon running, but not in moderate endurance training. Thus, exhaustive exercise may be one mechanism for the upregulation of integrin adhesive receptors on granulocytes. This phenomenon could be in part responsible for increased adhesion of granulocytes to endothelial cells and could facilitate tissue infiltration after endurance exercise.     

Hemin enhances the in vitro growth of primitive erythroid progenitor cells

Since exogenous hemin has been shown to exert a variety of stimulatory effects on erythroid cells, including the augmentation of hemoglobin synthesis, we determined its effect on early stages of erythroid development by employing clonal cells assays. The addition of hemin at a concentration of 2 X 10(-4) M to cultures of normal murine marrow substantially increased the observed number of primitive BFU-E, which was in contrast to its lack of an effect on more mature erythroid colony-forming cells. This cell-specific enhancement of primitive BFU-E resulted in marrow frequencies equivalent to or exceeding those reported in the presence of "burst-promoting activity." In the presence of hemin, the number of BFU-E was also observed to be linearly related to the number of cells plated at very low plating densities, and the cell titration curve was observed to extrapolate to the origin. The evidence suggests that hemin may be a primary growth regulator of early developmental stages of erythroid progenitor cells.     

Prevention and treatment of thromboembolic and ischemic complications associated with endovascular procedures: Part II--Clinical aspects and recommendations

We reviewed the incidence, risk factors, and clinical features of thromboembolic and ischemic events associated with diagnostic cerebral angiography, endovascular treatment of aneurysms using coils or balloons, angioplasty and stent placement to treat extracranial carotid artery stenosis, and embolization of arteriovenous malformations using glue or other embolic agents. We performed a cumulative analysis to determine the frequency and characteristics of these events and a subset analysis (whenever possible) to determine the benefits of various strategies for complication avoidance. Of the 1,547 patients who underwent Guglielmi detachable coil treatment, thromboembolic events were observed for 127 (8.2%), consisting of asymptomatic events for 12 patients, transient ischemic attacks for 29, and strokes for 86. The outcomes for the 86 patients with strokes were categorized as full recovery for 15, good recovery for 27, partial recovery for 19, no recovery for 11, death for 12, and undetermined outcome for 2. Of the 834 patients who underwent carotid angioplasty and stent placement, thromboembolic events were observed for 73 (8.8%), consisting of transient ischemic attacks for 26 patients and strokes for 47. The outcomes for the patients with strokes were categorized as full recovery for 20, good recovery for 15, partial recovery for 6, no recovery for 2, and death for 4. High rates of thromboembolic events were also observed with balloon occlusion of aneurysms (11%) or parent arteries (19%) and carotid angioplasty alone (5.9%). Arteriovenous malformation embolization was associated with an ischemic event/procedure rate of 9.4%. High rates of thromboembolic and ischemic complications, with subsequent morbidity and death, are associated with most endovascular procedures. Further research and the formulation of standard preventive guidelines may help to reduce these risks and improve the overall success of these procedures.     

Ischemia-reperfusion injury in renal transplantation is independent of the immunologic background

BACKGROUND: Adhesion molecule expression is important to early transplant failure. However, whether or not adhesion molecule-facilitated inflammation is antigen-dependent is unknown. We tested this hypothesis. METHODS: Rat renal grafts were four-hours cold-preserved in University of Wisconsin (UW) solution, transplanted to syngeneic or allogeneic recipients, and harvested after 2, 6, 12, 24, and 48 hours and after 1 week. The first allogeneic group receive no immunosuppression; two additional groups received either low (1.5 mg/kg) or standard (5 mg/kg) cyclosporine A (CsA). Renal function and morphology were determined; frozen sections were immunostained for P-selectin, L-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), platelet endothelial cell adhesion molecule-1 (PECAM-1), leukocyte function associated molecule-1 (LFA-1), very late antigen-4 (VLA-4), as well as for neutrophils and monocytes. RESULTS: Selectins increased rapidly at 2 hours and quickly decreased by 12 hours. While P-selectin was expressed on vasculature, L-selectin was found on inflammatory cells. Neutrophil influx and that of LFA-1-positive cells occurred early, peaked between 12 and 24 hours, and paralleled the maximal impairment in renal function. ICAM-1 and PECAM-1 showed similar kinetics and a diffuse distribution. VCAM-1 increased more slowly after 12 hours, peaked at 24 hours, and was localized predominantly on the endothelium of elastic vessels. Between 24 hours and 1 week, all grafts progressively developed dense VLA-4-positive monocytic infiltrates adjacent to vessels expressing VCAM-1. Functional, morphological, and immunohistochemical parameters did not differ between isografts and allografts at one week. However, by day 10, allografts showed severe vascular and cellular rejection, while injury in isografts resolved. Immunosuppression with CsA did not reverse the inflammation induced by ischemia-reperfusion injury. CONCLUSIONS: The early inflammation after ischemia-reperfusion injury is largely independent of the immunologic background. We suggest that initial injury prevention should receive the highest priority.