Time course of reverse remodeling of the left ventricle during support with a left ventricular assist device.

BACKGROUND: Support with a left ventricular assist device leads to normalization of left ventricular chamber geometry, regression of myocyte hypertrophy, alterations in left ventricular collagen content, and normalized expression of genes involved with excitation-contraction coupling in patients with heart failure. The objective of this study was to investigate the time course of these processes. METHODS: Passive left ventricular pressure-volume relationships were obtained from explanted hearts of 19 patients with heart failure undergoing transplantation without left ventricular assist device support, 25 patients with heart failure supported before transplantation (duration of support ranging between 8 and 155 days), and 5 normal human hearts not suitable for transplantation. Left ventricular size was indexed by the volume at which left ventricular pressure reached 30 mm Hg. Left ventricular tissue samples were probed for sarcoplasmic endoreticular calcium adenosine triphosphatase 2a expression and processed for analysis of myocyte diameter and relative myocardial collagen content. RESULTS: The volume at which left ventricular pressure reached 30 mm Hg was not significantly different between hearts without and with assist device support for less than 40 days. However, the volume at which left ventricular pressure reached 30 mm Hg in patients with assist devices supported for more than 40 days was significantly smaller than that of the hearts without assist devices but was larger than that of normal hearts. A similar pattern was observed for myocyte diameter. Sarcoplasmic endoreticular calcium adenosine triphosphatase 2a expression increased to normal levels by about 20 days of support with an assist device. Relative collagen content was significantly increased in hearts supported for more than 40 days. CONCLUSION: Maximum structural reverse remodeling by left ventricular assist devices is complete by about 40 days. Molecular reverse remodeling of sarcoplasmic endoreticular calcium adenosine triphosphatase 2a expression is quicker, being complete by about 20 days.

Chronic unloading by left ventricular assist device reverses contractile dysfunction and alters gene expression in end-stage heart failure.

BACKGROUND: Left ventricular (LV) assist devices (LVADs) can improve contractile strength and normalize characteristics of the Ca(2+) transient in myocytes isolated from failing human hearts. The purpose of the present study was to determine whether LVAD support also improves contractile strength at different frequencies of contraction (the force-frequency relationship [FFR]) of intact myocardium and alters the expression of genes encoding for proteins involved in Ca(2+) handling. METHODS AND RESULTS: The isometric FFRs of LV trabeculae isolated from 15 patients with end-stage heart failure were compared with those of 7 LVAD-supported patients and demonstrated improved contractile force at 1-Hz stimulation, with reversal of a negative FFR after LVAD implantation. In 20 failing hearts, Northern blot analysis for sarcoplasmic endoreticular Ca(2+)-ATPase subtype 2a (SERCA2a), the ryanodine receptor, and the sarcolemmal Na(+)-Ca(2+) exchanger was performed on LV tissue obtained before and after LVAD implantation. These paired data demonstrated an upregulation of all 3 genes after LVAD support. In tissue obtained from subsets of these patients, Western blot analysis was performed, and oxalate-supported Ca(2+) uptake by isolated sarcoplasmic reticular membranes was determined. Despite higher mRNA for all genes after LVAD support, only SERCA2a protein was increased. Functional significance of increased SERCA2a was confirmed by augmented Ca(2+) uptake by sarcoplasmic reticular membranes isolated from LVAD-supported hearts. CONCLUSIONS: LVAD support can improve contractile strength of intact myocardium and reverse the negative FFR associated with end-stage heart failure. The expression of genes encoding for proteins involved in Ca(2+) cycling is upregulated (reverse molecular remodeling), but only the protein content of SERCA2a is increased.

A technique of stapled gastrojejunostomy for open gastric bypass results in increased wound complication-rate.

BACKGROUND: Gastric bypass may be facilitated by a stapled gastrojejunostomy. This study compared two different techniques for performing this critical anastomosis in open surgery. METHODS: 67 consecutive patients were retrospectively studied for weight loss, hospital length of stay, anastomotic stricture, wound complication, and incisional hernia. 49 patients had a two layer hand-sutured gastrojejunostomy over a 34 Fr bougie via a laparotomy (sutured). 18 patients had a stapled gastrojejunostomy using the technique of Wittgrove and Clark via a laparotomy (stapled). All patients received prophylactic intravenous antibiotics preoperatively. RESULTS: Initial BMI, % of excess weight lost at 6 weeks and 6 months, and hospital length of stay were not statistically different between the groups. However, the rate of wound complication and incisional hernia rate were significantly higher in the stapled group when compared to the sutured group (p< 0.01). CONCLUSIONS: Based on these data we suggest that the technique of Wittgrove and Clark for performing the gastrojejunostomy should not be used in open gastric bypass as it results in increased rates of wound complication and incisional hernia.

Vascular clips have no significant effect on the cellular proliferation, intimal changes, or peak systolic velocity at anastomoses in rabbit vein grafts.

OBJECTIVE: This study compares vascular closure staples (VCSs) with conventional sutures in the rabbit carotid vein graft model to determine whether anastomotic technique affects cellular proliferation, blood velocity, or intimal changes when measured over a period of 3 months postoperatively. METHODS: Twenty-six New Zealand White rabbits weighing 3.0-3.2 kg underwent interposition of jugular vein grafts in left carotid arteries. Half of the animals had anastomoses performed with small VCSs (n = 13) and half had anastomoses performed with 8-O interrupted polypropylene suture. Animals were allowed to survive for 1 week (n = 4, VCS; n = 4, suture), 2 weeks (n = 4, VCS; n = 4, suture), and 3 months (n = 5, VCS; n = 5, suture). The peak systolic velocity (PSV) at the distal anastomosis was measured after completion of the graft and again at sacrifice in the 3-month survival groups. At sacrifice, sections were taken from the middle and distal end of the vein graft and the distal carotid artery. Vascular cell proliferation was measured using 5-bromo-2'-deoxyuridine labeling and intimal changes were measured using digitized microscopic images. RESULTS: All 26 grafts were open at the time of sacrifice. PSV at the distal clipped anastomosis was 40.52 cm/s (t = 0) and 34.3 cm/s (t = 3 months, P = 0.31). PSV at the distal sutured anastomosis was 38.30 cm/s (t = 0) and 39.23 cm/s (t = 3 months, P = 0.82). There was no difference between the two techniques at either t = 0 or t = 3 months (P = 0.51 and P = 0.31, respectively). Endothelial cell proliferation and smooth muscle cell proliferation at the anastomosis was highest during the 2 weeks after the procedure, then returned to baseline levels by 3 months. But there was no significant difference between the clipped and sutured groups with respect to vascular cell proliferation postoperatively. The intimal thickness changed significantly in the vein graft at the anastomosis for both the clipped and sutured groups (P = 0.0007 and P = 0.002). But there was no difference when the intimal changes for each technique were compared (P = 0.94). CONCLUSION: No differences were observed when peak systolic velocity, vascular cell proliferation, and intimal changes were compared between sutured and stapled anastomoses in rabbit vein interposition grafts over a period of 3 months after surgery.

Surgical management of the patient with an implanted cardiac device: implications of electromagnetic interference.

OBJECTIVE: To identify the sources of electromagnetic interference (EMI) that may alter the performance of implanted cardiac devices and develop strategies to minimize their effects on patient hemodynamic status. SUMMARY BACKGROUND DATA: Since the development of the sensing demand pacemaker, EMI in the clinical setting has concerned physicians treating patients with such devices. Implanted cardiovertor defibrillators (ICDs) and ventricular assist devices (VADs) can also be affected by EMI. METHODS: All known sources of interference to pacemakers, ICDs, and VADs were evaluated and preventative strategies were devised. RESULTS: All devices should be thoroughly evaluated before and after surgery to make sure that its function has not been permanently damaged or changed. If electrocautery is to be used, pacemakers should be placed in a triggered or asynchronous mode; ICDs should have arrhythmia detection suspended before surgery. If defibrillation is to be used, the current flow between the paddles should be kept as far away from and perpendicular to the lead system as possible. Both pacemakers and ICDs should be properly shielded if magnetic resonance imaging, positron emission tomography, or radiation therapy is to be used. The effect of EMI on VADs depends on the model. Magnetic resonance imaging adversely affects all VADs except the Abiomed VAD, and therefore its use should be avoided in this population of patients. CONCLUSIONS: The patient with an implanted cardiac device can safely undergo surgery as long as certain precautions are taken.

Development of an off bypass mitral valve repair.

BACKGROUND: The Bow Tie Repair (BTR), a single edge-to-edge suture opposing the anterior and posterior leaflets of the mitral valve (MV), has led to satisfactory reduction of mitral regurgitation (MR) with few re-operations and excellent hemodynamic results. The simplicity of the repair lends itself to minimally invasive approaches. A MV grasper has been developed that will coapt both leaflets and fasten the structures with a graduated spiral screw. METHODS: Eleven explanted adult human MVs were mounted in a mock circulatory loop created for simulating a variety of hemodynamic conditions. The MV grasper was used to place a screw in each valve, which was then continuously run for 300,000 to 1,000,000 cycles with a fixed transvalvular pressure gradient. At the completion of these studies, the valves were stressed to a maximal transvalvular gradient for ten minutes. In seven cases, MR was induced and subsequently repaired using the MV screw. In vivo, the MV screw was tested in nine male canines. Through a subcostal incision, the MV grasper entered the left ventricle, approximated the mitral leaflets and deployed the MV screw under direct visualization via an atriotomy. Follow-up transthoracic echocardiograms were done at postoperative week 1, 6, and 12 to identify screw migration, MV regurgitation/stenosis or clot formation. Dogs were sacrificed up to postoperative week 12 to allow gross and histologic assessment. RESULTS: In vitro, no MV screw detached from the valve leaflets or migrated during the durability testing period of 6.8 million cycles, including periods of stress load testing up to 350 mm Hg. The percent regurgitant flow used to assess MR statistically decreased with the placement of the screw from 72 +/- 7% to 34 +/- 17%; p = 0.0025. In vivo, seven dogs whose valves were examined within the first 48 hours revealed leaflet coaptation with an intact MV screw and no evidence of MR. Two dogs, followed for a prolonged period, had serial postoperative echocardiograms demonstrating consistent coaptation, no screw migration, no clot, and no regurgitation or stenosis. In the animal sacrificed at 12 weeks, the MV screw was integrated into the tissue of both leaflets. CONCLUSIONS: The MV screw has provided durable leaflet coaptation and has reduced regurgitation in human MVs. Initial data on the MV screw's biocompatibility and interactions with living valve tissue is promising. Our early success supports further efforts towards the maturation of this prototype into off bypass mitral valve repair technology.

Evidence for unconscious memory processing during elective cardiac surgery.

BACKGROUND: Many anesthetic drugs have been shown to disrupt conscious recall (explicit memory) in volunteers. However, unconscious processing (implicit memory) of intraoperative auditory material may occur during general anesthesia and may provide an opportunity for intraoperative therapeutic intervention. In this study, we examined patients undergoing elective cardiac surgery for evidence of intraoperative implicit and explicit memory. METHODS AND RESULTS: Twenty-five subjects provided written informed consent and underwent general anesthesia and cardiopulmonary bypass for cardiac surgery. During the operation, patients were randomized to receive 1 of 2 different audiotapes of associated word pairs. Postoperatively, a blinded observer conducted a standardized interview to determine the extent of intraoperative implicit and explicit memory. With the use of free association, significant intraoperative implicit memory was found. In contrast, no patient had spontaneous or directed recall of intraoperative events, and we did not find evidence of intraoperative explicit memory with a recognition task. CONCLUSIONS: Patients undergoing general anesthesia for cardiac surgery were reliably able to reinforce associations between word pairs solely on the basis of their intraoperative presentation. This provides further evidence that patients are capable of processing intraoperative auditory information.

Mechanical unloading with a miniature in-line axial flow pump as an alternative to cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) causes a well described systemic inflammatory response. To avoid these potential detrimental effects, coronary artery bypass grafting (CABG) has been attempted off CPB on the beating heart. With the use of a left ventricular (LV) assist device during CABG, the heart can be made flaccid with beta-blockade, and the systemic circulation can continue to be supported. The hemodynamic and hematologic consequences of left heart bypass with a miniature axial flow pump were studied in a sheep CABG model. The pump weighs 45 g and was connected to standard venous and arterial cannulas. Left sided inflow and brachiocephalic outflow were employed. A pump speed of 14,000 rpm resulted in a flow of 5.63 +/- 0.18 L/min and provided 75% of the LV output during a 2 hr pump run. This resulted in complete capture of the aortic pressure tracing (mean 56.3 mmHg) with a 15.5 mmHg augmentation in the esmolol depressed ventricle. Reductions in LV end diastolic pressure and LV end systolic pressure resulted in a 66% reduction in LV external work under baseline conditions and an 83% reduction in the beta-blocked ventricle. Myocardial oxygen demand was reduced 16% after axial flow unloading in the esmolol depressed condition. Right ventricular pressures, pulmonary artery flow, LV filling, and oxygenation were adequate in the esmolol depressed animal and remained unchanged throughout the experiment. No changes in hematocrit, total bilirubin, lactate dehydrogenase, or plasma free hemoglobin were detected after 2 hr of assist. Axial flow left heart bypass results in acceptable hemodynamics with no hemolysis and may provide an alternative to CPB during CABG.

Selective anticoagulation with active site blocked factor IXa in synthetic patch vascular repair results in decreased blood loss and operative time.

Heparin has been the mainstay of anti thrombic therapy in arterial repair procedures. With increasing use of synthetic patch angioplasty (polytetrafluoroethylene [PTFE] or Dacron, Medical Products, Flagstaff, AZ) to improve long-term patency and limit aneurysmal dilation, however, the use of heparin has been associated with excessive needle hole bleeding, resulting in time delay in the operating room to achieve hemostasis, as well as clinically significant blood loss. Because of the multiple sites of action of heparin in the coagulation cascade, both intravascular (desired effect) and extravascular (untoward side effect) hemostasis are impaired. The authors therefore tested the hypothesis that selective inhibition of intravascular coagulation, without significant impairment of extravascular hemostasis, would prevent clotting intraluminally while preserving hemostasis at the suture line of the patch graft. The unique position of factor IX/IXa in the coagulation cascade renders its inhibition an ideal target in this setting. The authors prepared active site blocked factor IXa (IXai) using dansyl-Glu-Gly-Arg chloromethylketone, and tested this hypothesis in a New Zealand rabbit aortotomy model with PTFE patch closure using either heparin (25 i.u./kg; n = 16) or IXai (300 micrograms/kg; n = 21). The infrarenal aorta was identified and isolated, the anti coagulant infused, aortic cross clamp placed, and aortotomy repaired with a 2 x 6 mm PTFE patch. After cross-clamp removal, blood loss was measured and time to hemostasis was recorded. Compared with heparin, IXai resulted in significantly reduce blood loss (6.97 +/- 4.4 g vs 2.72 +/- 2.51 g, respectively, p < 0.008), and time to hemostasis (2.94 +/- 0.77 min vs 2.0 +/- 0.63 min, respectively, p < 0.003). To assess long-term patency and thrombosis, 12 rabbits (given heparin; n = 6 and IXai; n = 6) were observed for up to 2 months post-operatively. No differences were observed between rabbits treated with heparin or IXai; 100% of the grafts were patent with no differences in degree of intimal hyperplasia by histologic analysis. Together, these data suggest that use of IXai in PTFE vascular repair will safely allow realization of the benefits of long-term patency and decreased aneurysmal dilatation, while eliminating the intraoperative morbidity of needle hole bleeding.