Patrick G. Mullen

Effect of triiodothyronine on postischemic myocardial function in the isolated heart

Thyroid dysfunction has been shown to have a significant impact on hemodynamic status and cardiac function. The purpose of this study was to determine the influence of triiodothyronine (T3) on cardiac functional recovery after ischemia in a dose-dependent manner. Postischemic functional recovery was assessed in isolated rabbit hearts mounted in a modified Langendorff preparation. Left ventricular systolic, diastolic, and peak developed pressures were measured before and after ischemia, and calculated as a percentage of preischemic function. Two cohorts of hearts were studied: the first was exposed to warm ischemia until a myocardial contracture of 4 mmHg was produced; the second cohort was exposed to warm ischemia until a contracture of 15 mm Hg was observed. In each cohort, T3 was added to the perfusion solution after ischemia in a physiologic concentration (2.5 x 10(-9) g/mL; 1 x T3), as well as ten times (2.5 x 10(-8) g/mL; 10 x T3) and a hundred times (2.5 x 10(-7) g/mL; 100 x T3) the physiologic concentration. One group, given the carrier only but without T3, served as the control. Rabbit hearts exposed to a short period of ischemia (4-mmHg diastolic contracture) showed increased recovery with 1 x T3 and 10 x T3. 100 x T3 did not bring about improved left ventricular recovery versus that in the control group. Rabbit hearts in the 15 mm Hg-diastolic contracture cohort showed increased recovery with 10 x T3 but not with 1 x T3. 100 x T3 led to decreased recovery in this cohort versus that in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential Activation Of Alveolar, Pulmonary Arterial, And Systemic Arterial Neutrophils Demonstrates The Existence Of Distinct Neutrophil Subpopulations In Experimental Sepsis

Neutrophils (PMNs) are considered key cellular mediators of sepsis induced acute lung injury. PMN activation is manifest by increased β2 integrin expression and enhanced superoxide radial (O-2) generation. What is unclear is at which anatomical sites PMNs are activated and at which sites they release O-2 and mediate lung injury. In this study we compare alveolar (ALV), systemic arterial (SA), and pulmonary arterial (PA) PMNs CD18 receptor expression, measured by fluorescent immunophenotyping and, O-2 generation, measured by reduction of ferricytochrome C, in septic swine. Swine were anesthetized and ventilated, and given a 1-h infusion of live Pseudomonas aeruginosa. PA, SA, and ALV PMNs were isolated at 0 and 5 h. ALV PMNs O-2 was reduced compared to SA blood PMNs O-2 at 5 h, (AIV 5 h 23.6 ± 3 vs. SA 0 h 34.3 ± 5, p < .05). SA PMNs O-2 generation was also significantly reduced compared to PA PMNs at 5 h (PA 5 h 21 ± 2.5 vs. SA 5 h 16.9 ± 2.6, p < .05). Alv PMNs expressed significantly greater CD18 receptor levels than SA blood PMNs at 5 h (AIV PMNs 5 h, 76 ± 6 vs. SA PMNs 5 h 51 ± 3, p < .05), however, PA PMNs CD18 receptor levels were not significantly different from SA PMNs levels at 5 h. These data corroborate a dissociation between two PMN functions in sepsis. O-2 generation was reduced across the lung and following migration. However, alveolar PMNs had significantly upregulated CD18 expression compared to PMNs in PA and SA. These data suggest distinct PMN populations exist in sepsis, and distribution seeems to depend on PMN CD18 expression. Thus, functional assessment of circulating cells may not reflect the true ability of PMNs to mediate host tissue injury (versus time, 0 h; versus mixed venous, p < .05).