Effects of ischemia, preconditioning, and adenosine deaminase inhibition on interstitial adenosine levels and infarct size

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41750/1/395_2004_Article_BF00796218.pd

Effects of ischemia on epicardial segment shortening

To evaluate the effects of nontransmural ischemia on epicardial contractile function, we implanted sonomicrometers in 15 open-chest, anesthetized (halothane) dogs. One cylindrical crystal (radiating ultrasound 360[deg]) was used as a transmitter for three conventional flat plate crystals arrayed to measure epicardial segment shortening along three different axes that were deviated 0[deg] (parallel), 45[deg] (oblique), and 90[deg] (perpendicular) from surface fiber orientation in the anteriorapical or posterior-basal left ventricle. During baseline conditions, epicardial shortening was maximal parallel with fiber orientation. Shortening decreased in a non-linear manner as deviation from fiber orientation increased, but there were significant differences between the two left ventricular regions suggesting that more substantial lateral strain occurs in the anterior-apical than the posterior-basal area. During coronary inflow restriction, changes in epicardial segment shortening also varied greatly depending on location and alignment. At levels of wall thickening impairment associated with normal subepicardial perfusion, changes in epicardial function were restricted to the segments aligned perpendicular to fiber orientation whereas the parallel and oblique segments displayed moderate dysfunction or none at all. Thus, transmural tethering modifies epicardial segmental motion during coronary inflow restriction, but the severity of the influence depends on the alignment and location of the epicardial measurements.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29525/1/0000612.pd

Increase in experimental infarct size with digoxin in a canine model of myocardial ischemia-reperfusion injury

In the present study, dogs were pretreated with intravenous digoxin, 0.0125 mg/kg/day, for 6 to 7 consecutive days to achieve clinically relevant serum concentrations; untreated animals were used as control subjects. After pretreatment, nine digoxin-pretreated dogs and nine control dogs were anesthetized and subjected to a 60-minute occlusion of the left circumflex coronary artery, followed by 6 hours of reperfusion. Anatomic myocardial infarct size, expressed as a percentage of the areas at risk of infarction and as a percentage of the total left ventricle were: 20.2 +/- 3.3% control vs 35.4 +/- 6.2% digoxin-pretreated (p p < 0.05), respectively (2.04 +/- 0.37 ng/ml serum digoxin). Regional myocardial blood flow in the nonischemic and ischemic zones tended to be lower in digoxin-pretreated than in control animals at baseline testing and were significantly reduced in the anterior subendocardial sites of digoxin-pretreated dogs during ischemia and reperfusion. These data suggest that an exacerbation or enhancement of myocardial ischemial-reperfusion injury may occur in the presence of clinically observable serum digoxin concentrations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27287/1/0000306.pd

Comparison of Marine Spatial Planning Methods in Madagascar Demonstrates Value of Alternative Approaches

The Government of Madagascar plans to increase marine protected area coverage by over one million hectares. To assist this process, we compare four methods for marine spatial planning of Madagascar's west coast. Input data for each method was drawn from the same variables: fishing pressure, exposure to climate change, and biodiversity (habitats, species distributions, biological richness, and biodiversity value). The first method compares visual color classifications of primary variables, the second uses binary combinations of these variables to produce a categorical classification of management actions, the third is a target-based optimization using Marxan, and the fourth is conservation ranking with Zonation. We present results from each method, and compare the latter three approaches for spatial coverage, biodiversity representation, fishing cost and persistence probability. All results included large areas in the north, central, and southern parts of western Madagascar. Achieving 30% representation targets with Marxan required twice the fish catch loss than the categorical method. The categorical classification and Zonation do not consider targets for conservation features. However, when we reduced Marxan targets to 16.3%, matching the representation level of the “strict protection” class of the categorical result, the methods show similar catch losses. The management category portfolio has complete coverage, and presents several management recommendations including strict protection. Zonation produces rapid conservation rankings across large, diverse datasets. Marxan is useful for identifying strict protected areas that meet representation targets, and minimize exposure probabilities for conservation features at low economic cost. We show that methods based on Zonation and a simple combination of variables can produce results comparable to Marxan for species representation and catch losses, demonstrating the value of comparing alternative approaches during initial stages of the planning process. Choosing an appropriate approach ultimately depends on scientific and political factors including representation targets, likelihood of adoption, and persistence goals

Empirical Models of Transitions between Coral Reef States: Effects of Region, Protection, and Environmental Change

There has been substantial recent change in coral reef communities. To date, most analyses have focussed on static patterns or changes in single variables such as coral cover. However, little is known about how community-level changes occur at large spatial scales. Here, we develop Markov models of annual changes in coral and macroalgal cover in the Caribbean and Great Barrier Reef (GBR) regions

Changing Patterns of Microhabitat Utilization by the Threespot Damselfish, Stegastes planifrons, on Caribbean Reefs

Background: The threespot damselfish, Stegastes planifrons (Cuvier), is important in mediating interactions among corals, algae, and herbivores on Caribbean coral reefs. The preferred microhabitat of S. planifrons is thickets of the branching staghorn coral Acropora cervicornis. Within the past few decades, mass mortality of A. cervicornis from white-band disease and other factors has rendered this coral a minor ecological component throughout most of its range. Methodology/Principal Findings: Survey data from Jamaica (heavily fished), Florida and the Bahamas (moderately fished), the Cayman Islands (lightly to moderately fished), and Belize (lightly fished) indicate that distributional patterns of S. planifrons are positively correlated with live coral cover and topographic complexity. Our results suggest that speciesspecific microhabitat preferences and the availability of topographically complex microhabitats are more important than the abundance of predatory fish as proximal controls on S. planifrons distribution and abundance. Conclusions/Significance: The loss of the primary microhabitat of S. planifrons—A. cervicornis—has forced a shift in the distribution and recruitment of these damselfish onto remaining high-structured corals, especially the Montastraea annulari

Capacity shortfalls hinder the performance of marine protected areas globally

Marine protected areas (MPAs) are increasingly being used globally to conserve marine resources. However, whether many MPAs are being effectively and equitably managed, and how MPA management influences substantive outcomes remain unknown. We developed a global database of management and fish population data (433 and 218 MPAs, respectively) to assess: MPA management processes; the effects of MPAs on fish populations; and relationships between management processes and ecological effects. Here we report that many MPAs failed to meet thresholds for effective and equitable management processes, with widespread shortfalls in staff and financial resources. Although 71% of MPAs positively influenced fish populations, these conservation impacts were highly variable. Staff and budget capacity were the strongest predictors of conservation impact: MPAs with adequate staff capacity had ecological effects 2.9 times greater than MPAs with inadequate capacity. Thus, continued global expansion of MPAs without adequate investment in human and financial capacity is likely to lead to sub-optimal conservation outcomes

Phase I trial of chemoradiation with capecitabine and vorinostat in pancreatic cancer.

225 Background: Histone deacetylase inhibitors (HDACi) and fluoropyrimidines are synergistic and are radiation (R) sensitizers. The combination of the fluoropyrimidine capecitabine ( C) and the HDACi vorinostat (V) with R was evaluated in the treatment (tx) of non-metastatic pancreatic cancer (NMPC). Methods: Patients (Pts) with NMPC were treated with C + V + R. C dose was 1000 mg q12 Monday (M) - Friday (F) on the days of R. R was given via 3D conformal therapy to a total dose of 3000 cGy in 10 fractions over 2 weeks (wk). V dose was given daily M-F x 4 wk. V doses evaluated were: 100, 200, 300, and 400 mg. Resectability assessment occurred within 6 wk after completion of tx. Diffusion weighted- MRIs (DW-MRIs) were obtained pre tx and one wk after tx initiation to assess tumor cellularity. Peripheral blood mononuclear cells (PBMCs) were collected pre tx, during tx, and after completion to assess whole cell HDAC activity. Unresectable pts could opt for continuation of C and V (CCV) at systemic doses (C 1000 mg q12 x 14 days and V 300 mg QD x 14 days of every 21 day cycle) or come off study. Results: 18 pts were enrolled and evaluable. Disease statuses pre-tx were: resectable (n=1), borderline resectable (n=9), and unresectable (n=8). One DLT occurred at dose levels 1, 3, and 4, 2 GI toxicities and one thrombocytopenia. Most common adverse events were lymphopenia, GI toxicity, and fatigue. On MRI, the apparent diffusion coefficient (ADC) increased in most, but not all, tumors after one wk of tx but did not correlate to change in tumor size at completion. PBMC histone acetylation increased in some pts. Eight pts (Pre-tx status: 1 resectable and 7 borderline resectable) underwent exploration with 4 undergoing tumor resection. No unresectable pt converted to resectable. Four of ten potential pts opted for CCV after being deemed unresectable, 2 with stable disease for 6 cycles. Conclusions: C + V + R is feasible with no unexpected toxicity. HDAC inhibition and ADC decrease on DWI-MRI was seen. Accrual to the final cohort (V 400 mg) is ongoing. This study was approved and funded by the National Comprehensive Cancer Network (NCCN) from general research support provided by Merck & Co., Inc. Study was also supported by the Vanderbilt-Ingram Center Support Grant P30CA68485. Clinical trial information: NCT00983268