Gabrielle Gallagher

Regional cardiac dysfunction is associated with specific alterations in inflammatory cytokines and matrix metalloproteinases after acute myocardial infarction in sheep.

Cardiac remodeling following myocardial infarction (MI) is a maladaptive process, fundamental to the progression of ischemic heart failure. The extent of remodeling is influenced by mechanical stress, inflammatory response and activation of matrix metalloproteinases (MMPs). This study examined regional association between these parameters in response to acute MI.Coronary ligation was performed in ten sheep. Sonomicrometer transducers measured segmental length in the infarcted, border and non-infarcted region. Regional tissue samples obtained 3 h post MI from six sheep were analysed using RT-PCR, gelatin zymography and Western blot. Six sham-operated sheep served as controls.Region-specific dilation and reduced contraction was associated with corresponding alterations in matrix molecules.IL-6 and MMP-9 mRNA were increased in the infarcted and border regions compared to controls.MMP-2 and TIMP-1 mRNA increased in non–infarcted myocardium and both correlated positively with segmental shortening. IL-6 mRNA levels, in contrast, were negatively associated with segmental shortening.In summary, inflammatory cytokines and MMPs are altered early after MI in a region-specific manner, and these changes correspond to acute regional myocardial dysfunction. Therapies for LV remodeling from the time of reperfusion may benefit from further understanding this portfolio of acute alterations.

HeartPatch implanted direct cardiac compression: effect on coronary flow and flow patterns in acute heart failure sheep.

A novel HeartPatch direct cardiac compression (DCC) device has been shown to effectively restore circulatory parameters in sheep with acute heart failure (HF). Its effect on the coronary circulation and myocardial perfusion, however, remains uncertain. The effect of DCC assist on coronary artery blood flow (CABF) and its patterns in acute HF sheep were examined in this study. Ten sheep (51 ± 6 kg) were implanted with a heart patch on each of the left ventricular and right ventricular free walls 1 week before study. Stable HF [cardiac output (CO) at 51 ± 8% of baseline] induced by intravenous esmolol resulted in CABF decreasing to 53 ± 16% of baseline (p < 0.001). DCC device activation did not alter CABF (54 ± 15% of baseline, N.S.) but was accompanied by increases in both peak antegrade and retrograde flow velocity (161 ± 75%, p < 0.001 and 413 ± 377%, p < 0.001). A shift in the proportion of flow occurring in diastole (%DF) also was observed: baseline, 81 ± 9%; HF, 82 ± 6%; DCC assist, 121 ± 16% (p < 0.001). Despite significant changes in coronary artery flow pattern resulting from DCC of the failing heart, total antegrade coronary flow was maintained. These findings suggest that myocardial perfusion is not compromised by DCC.

Effect of direct cardiac compression on left ventricular axial dynamics in sheep.

The HeartPatch direct cardiac compression device consists of two separate, nonsurround patches placed on the left and right ventricular free walls. Although the device has been shown to effectively restore circulatory parameters in acute heart failure sheep, the impact of device inflation on left ventricular geometry is yet to be elucidated. This study used sonomicrometer crystal transducers to examine three orthogonal left ventricular dimensions under various cardiac states and assessed the feasibility of determining stroke volume from these dimensions. Seven sheep (weight, 51 ± 5 kg) were implanted with six sonomicrometer crystals, and a heart patch was placed on each of the ventricles. The crystals were positioned to measure anterior-posterior, septal-lateral, and apex-base (long-axis) dimensions. Sheep were studied under both awake and anesthetized conditions. Septal-lateral shortening was increased with direct cardiac compression assist, whereas anterior-posterior and long-axis dimensions were either unchanged (awake) or decreased (anesthetized). Estimation of stroke volume, using the ellipsoid volume model, correlated well with stroke volume measured from an aortic flow probe; however, absolute stroke volumes were lacking in agreement.