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Biomedical subjects

Hal A Skopicki

Publications and source records attributed to Hal A Skopicki.

4 recordsLinked to original sources
PubMed2005

Risk of worsening renal function with nesiritide in patients with acutely decompensated heart failure.

BACKGROUND: Renal function is an important prognostic factor for patients with acutely decompensated heart failure (ADHF). We investigated the renal effects of nesiritide as treatment for ADHF. METHODS AND RESULTS: Randomized clinical trials comparing nesiritide with either placebo or active control for ADHF were identified by electronic and manual searches and thorough review of US Food and Drug Administration files available via the website. Worsening renal function was defined as an increase in serum creatinine >0.5 mg/dL. Relative risk across all studies was determined by meta-analysis with Mantel-Haenszel fixed-effects models (RR(MH)). Risk of dialysis and medical intervention for worsening renal function were compared between therapies. Frequency of worsening renal function was determined from 5 randomized studies that included 1269 patients. Use of Food and Drug Administration-approved doses of nesiritide (< or =0.03 microg x kg(-1) x min(-1)) significantly increased the risk of worsening renal function compared with non-inotrope-based control (RR(MH), 1.52; 95% CI, 1.16 to 2.00; P=0.003) or any control therapy, including non-inotrope- and inotrope-based therapies (RR(MH), 1.54; 95% CI, 1.19 to 1.98; P=0.001). Even low-dose nesiritide (< or =0.015 microg x kg(-1) x min(-1)) significantly increased risk (P=0.012 and P=0.006 compared with non-inotrope- and inotrope-based controls, respectively), as did nesiritide administered at any dose up to 0.06 microg x kg(-1) x min(-1) (P=0.002 and P=0.001, respectively). There was no difference in the need for dialysis between therapies. CONCLUSIONS: Nesiritide significantly increases the risk of worsening renal function in patients with ADHF. Whether worsening renal function reflects hemodynamic effect or renal injury is unknown, but the prognostic importance of worsening renal function suggests the need for further investigation in appropriately powered clinical trials.

Creatine↗
PubMed2005

Macrophage migration inhibitory factor within the alveolar spaces induces changes in the heart during late experimental sepsis.

Respiratory dysfunction during sepsis is common. However, although lung function can often be adequately supported, death frequently results from cardiovascular collapse. Despite intense investigation, the mechanism underlying the myocardial dysfunction of sepsis remains unclear. Macrophage migration inhibitory factor (MIF), an important cytokine released in sepsis and the acute respiratory distress syndrome, is a known cardiac depressant. We hypothesized that MIF released from the lung results in myocardial dysfunction during sepsis. In murine models of polymicrobial sepsis, we demonstrate a significant increase in the lungs of total and lavagable MIF between 20 and 30 h post induction of sepsis. At 30 h post sepsis, the lungs released MIF into the pulmonary circulation, increasing the plasma concentration by up to 51% in a single pass. Exogenous MIF, instilled into the lungs, increased alveolar keratinocyte-derived chemokine (KC), Macrophage inflammatory protein-2 (MIP2), and tumor necrosis factor alpha (TNFalpha) at 3 h, and plasma KC and MIP2 at 6 h postinstillation. This was associated with an increase in p38 mitogen-activated protein kinase and c-Jun N-terminal kinase phosphorylation. Because changes in mitogen-activated protein kinase activation can lead to myocardial depression, these data suggest that MIF released from the lungs may be responsible, at least in part, for the cardiac dysfunction seen in the late stages of sepsis.

Animals↗
PubMed2002

Viability of hypokinetic segments: influence of tethering from adjacent segments: influence of tethering from adjacent segments.

Hypokinetic myocardium is presumed to be reversibly dysfunctional. However, hypokinetic segments do not necessarily improve after revascularization since their outcome can be influenced by tethering effects of adjacent myocardium. To assess whether hypokinetic segments improve following revascularization, 24 patients underwent resting and dobutamine stress echocardiography (DSE), with a total of 420 (20 per patient) myocardial segments studied pre- and postrevascularization. One hundred fifty-five hypokinetic segments were identified prerevascularization. Postrevascularization, only 57% of these segments improved in wall motion, while 43% showed no improvement or worsening of wall motion. Low dose (5-10 microg/kg/min) DSE identified correctly 57 (65%) of 88 segments that improved, and falsely predicted improvement in 26 (39%) of 67 segments that ultimately did not improve postrevascularization. Of the hypokinetic segments that did not improve, 90% were adjacent to at least one severely hypokinetic or akinetic segment as compared with 73% of the segments that improved following revascularization (P = 0.009). Sixty-five percent of all true positive DSE responses were adjacent to at least one akinetic or severely hypokinetic segment, while 87% of all false negative DSE responses were adjacent to at least one akinetic or severely hypokinetic segment (P = 0.03). In conclusion, myocardial segments found to be hypokinetic do not necessarily improve after revascularization. This may be related to tethering influences of adjacent segments, which have a contrasting level of function.

Coronary Disease↗