Nonsurround, nonuniform, biventricular-capable direct cardiac compression provides Frank-Starling recruitment independent of left ventricular septal damage.

OBJECTIVES: Right ventricular (RV) function is compromised in 25% of left ventricular (LV) assist device recipients despite effective LV support. The risk of such dysfunction has been enhanced by an ischemic or undamaged interventricular septum; however, we found septal infarction to be paradoxically protective. We, therefore, evaluated the potential of nonsurround, nonuniform, biventricular-capable direct cardiac compression (DCC) (using the HeartPatch DCC) to overcome RV dysfunction in hearts with a normal or infarcted interventricular septum. METHODS: Ethanol ablation was used to create an interventricular septal infarction in 6 sheep, and 6 others served as the control sheep. The load-independent and in-series RV response to DCC was assessed using sonomicrometer heart dimension sensors. Triphenyltetrazolium perfusion delineated the septal damage. RESULTS: LV DCC caused a greater increase of the RV preload recruitable stroke work in the control sheep than in the study sheep (190.6 ± 23.5 and 135.0 ± 40.8 erg*10^3, respectively, P < .001). In contrast, RV end-systolic elastance increased more in the septal-ablated sheep with RV DCC (17.29 ± 3.40 vs 9.88 ± 2.01 mm Hg/mL in the control sheep, P < .001). Abnormal RV diastolic function before device insertion in the septal-ablated sheep was normalized with both passive DCC placement and after activation (RV diastolic relaxation constant 23.5 ± 2.3 and 20.0 ± 2.1 ms, respectively, P < .001). Both biventricular and RV DCC actuation increased the RV systolic pressure more in the septal-ablated sheep than in the control sheep (37.9 ± 6.3 and 47.7 ± 4.6 mm Hg vs 29.7% ± 4.8% and 40.3% ± 8.3%, respectively, P < .001). In contrast, the RV end-systolic diameter decreased more during LV DCC (70.1% ± 15.9% vs 90.5% ± 5.0%, P < .001). CONCLUSIONS: The HeartPatch DCC support of LV and RV function results from improvement of the systolic septal-lateral fractional change that is not influenced by septal infarction. The latter attenuated LV to RV device energy delivery during LV patch actuation but enhanced RV energy delivery during RV patch actuation. This DCC technique can provide effective support in high-risk RV failure situations arising from left ventricular assist device use.

Chronic septal infarction confers right ventricular protection during mechanical left ventricular unloading.

OBJECTIVE: Right ventricular failure manifests in 25% of left ventricular assist device recipients because of ventricular coupling mechanism disruption. Septal ischemia accentuates this process, but the effect of septal infarction has not been elucidated. Right ventricular response to incremental left ventricular unloading was studied in sheep with septal infarction. METHODS: Septal infarction was induced in 6 sheep using ethanol delivery into the main septal perforating artery. Six shams avoided ethanol. Load-independent and in-series right ventricular response to incremental (0%-100%) left ventricular unloading was measured 4 weeks later. Dimensions of whole heart, wall thickness, and chamber volumes were obtained using sonomicrometers. Selective perfusion with triphenyltetrazolium quantified septal damage. RESULTS: Right ventricular preload-recruitable-stroke-work, contractility, and ejection fraction were lower at 75% and 100% left ventricular unloading in sham compared with infarcted animals (75%: 26.3 +/- 3.4, 0.70 +/- 0.15, and 23.9 +/- 4.6 vs 37 +/- 2.6 erg *10;3, 0.99 +/- 0.18 mm Hg/mL, and 35.5% +/- 3.4%, all P < . 01, 100%: 24.8 +/- 4.5, 0.67 +/- 0.14, and 23.8 +/- 5.8 vs 36.0 +/- 4.6 erg *10;3, 0.90 +/- 0.09 mm Hg/mL, and 32.7% +/- 11.0%, all P < . 01). Central venous pressure was higher at 75% and 100% unloading in sham compared with infarcted animals (75%: 8.6 +/- 1.0 vs 4.5 +/- 1.0, 100%: 12.4 +/- 0.8 vs 3.4 +/- 1.0 mm Hg, all P < . 01). Right ventricular cardiac output was less in shams with 100% unloading (1.2 +/- 0.2 L/min vs 2.1 +/- 0.3 L/min, P < . 01). End-diastolic and end-systolic right ventricular short-axis dimension at 75% and 100% unloading was greater in sham compared with infarcted animals (75%: 34.4 +/- 5.5 mm and 29.1 +/- 5.5 mm vs 25.6 +/- 4.7 mm and 20.5 +/- 4.0 mm; 100%: 37.6 +/- 6.6 mm and 29.9 +/- 5.9 mm vs 25.5 +/- 3.9 mm and 21.1 +/- 3.8 mm, all P < .01). Prolonged diastolic relaxation (Tau) in infarcted animals was normalized with 75% and 100% unloading. CONCLUSION: High-level (>or=75%) left ventricular unloading causes right ventricular dilatation and compromised function. Chronic septal damage, however, confers protection by preserving right ventricular dimensions.

Time-dependent response of both ventricles after septal ablation: implications for biventricular support after left ventricular assist device placement.

OBJECTIVES: An ovine model of septal ablation was studied to elucidate the mechanisms involved in right ventricular failure when commencing left ventricular mechanical assistance. The disruption of ventricular interdependence after acute and chronic septal injury was examined. METHODS: Twelve sheep underwent percutaneous transluminal septal myocardial ablation using 0.6 mL ethanol. Twelve other sheep underwent a sham procedure. Left ventricular and right ventricular pressure and volume (conductance) response 15 minutes and 4 weeks postinjury were measured. Ultrasonic crystals measured chamber dimensions and wall movement. Areas at risk and infarct zones were quantified. RESULTS: Compared with sham, ablation chronically reduced systolic interventricular septal thickening (18.4% +/- 5.8% vs 7.3% +/- 3.1%; P < .001) and acutely increased right ventricular ejection fraction (37.6% +/- 8.5% vs 69.9% +/- 7.2%; P < .001), preload recruitable stroke work (42.0 +/- 4.4 erg x 10(3) vs 48.7 +/- 2.0 erg x 10(3), P < .001), end-systolic elastance (1.03 +/- 0.19 mm Hg mL(-1) vs 1.31 +/- 0.18 mm Hg mL(-1); P < .001), and Tau (24.9 +/- 3.8 ms vs 29.6 +/- 8.2 ms; P < .001). In contrast, for left ventricular ejection fraction (55.5% +/- 5.9% vs 38.9% +/- 7.7%; P < .001), preload recruitable stroke work (85.9 +/- 10.6 mm Hg vs 66.5 +/- 9.6 mm Hg; P < .001) and elastance (2.13 +/- 0.51 mm Hg mL(-1) vs 1.81 +/- 0.44 mm Hg mL(-1); P < .001) were reduced, but Tau increased (22.0 +/- 3.5 ms vs 28.9 +/- 5.8 ms; P < .001) and remained elevated at 4 weeks compared with sham. The area at risk was the same between groups, and injury was limited to the septum (17.2% +/- 2.7% vs 2.9% +/- 5.8%; P < .001). CONCLUSIONS: Acute and chronic hemodynamic responses are distinctly different after septal injury; the acute response demonstrates a paradoxical motion. Resolution of this motion at 4 weeks is suggestive of reduced septal compliance and buttressing. Ventricular interactions after placement of a left ventricular assist device will vary depending on the injury duration.

Effect of 6-dimethylaminopurine on electrically activated in vitro matured porcine oocytes.

The effect of the protein kinase inhibitor, 6-dimethylaminopurine (6-DMAP), on the maturation promoting factor (MPF) activity, pronuclear formation, and parthenogenetic development of electrically activated in vitro matured (IVM) porcine oocytes was investigated. Oocytes were activated by exposure to two DC pulses, each of 1.5 kV/cm field strength and 60 microsec duration, applied 1 sec apart. In the first experiment, subsequent incubation with 2 or 5 mM 6-DMAP for 3 hr increased the incidence of blastocyst formation compared with no treatment, whereas incubation with 2 or 5 mM 6-DMAP for 5 hr did not. In the proceeding experiments, oocytes exposed to 6-DMAP were incubated with 2 mM of the reagent for 3 hr. Assaying histone H1 kinase activity in the second experiment revealed that the levels of active MPF in electrically activated oocytes treated with 6-DMAP were depleted more rapidly and remained depleted for longer compared with electrical activation alone. The kinetics of MPF activity following 6-DMAP treatment were similar to that found in inseminated oocytes in the third experiment. The effect of 6-DMAP was correlated with an increased incidence of parthenogenetic blastocyst formation. A fourth experiment was undertaken to examine the diploidizing effect of 6-DMAP. Electrically activated oocytes treated with 6-DMAP and cytochalasin B, either alone or in combination, displayed a higher incidence of second polar body retention compared with those that were untreated or treated with cycloheximide alone. After 6 days of culture in vitro, parthenotes exposed to 6-DMAP, either alone or in combination with cytochalasin B, formed blastocysts at a greater rate compared with those exposed to cytochalasin B alone, cycloheximide alone or no treatment. The combined 6-DMAP and cytochalasin B treatment induced the highest rate of blastocyst formation (47%), but the numbers of trophectoderm and total cells in these blastocysts were lower compared with those obtained following exposure to 6-DMAP alone. These results suggest that the increased developmental potential of 6-DMAP-treated parthenotes may be attributable to the MPF-inactivating effect of 6-DMAP, rather than the diploidizing effect of 6-DMAP.