Microwave ablation for atrial fibrillation: dose-response curves in the cardioplegia-arrested and beating heart.

BACKGROUND: Microwave ablation has been used to replace the traditional incisions used in the surgical treatment of atrial fibrillation. However, dose-response curves have not been established in surgically relevant models. The purpose of this study was to develop dose-response curves for the Flex 10 (Guidant, Inc) microwave device in both the acute cardioplegia-arrested heart and on the beating heart. METHODS: Twelve domestic pigs (40 to 45 kg) were subjected to microwave ablation in either the arrested (n = 6) or beating heart (n = 6). The cardioplegia-arrested heart was maintained at 10 degrees to 15 degrees C while six atrial endocardial and seven right ventricular epicardial lesions were created in each animal. On the beating heart, six right atrial and seven ventricular epicardial lesions were created. Ablations were performed for 15, 30, 45, 60, 90, 120, and 150 seconds (65 W, 2.45 GHz). The tissue was stained with 2,3,5-triphenyl-tetrazolium chloride, and sectioned at 5-mm intervals. Lesion depth and width were determined from digital micrographs. RESULTS: Mean atrial wall thickness was 2.8 mm (range, 1 to 8 mm). In the arrested heart, 94% of atrial lesions were transmural at 45 seconds and 100% were transmural at 90 seconds. In the beating heart, only 20% of atrial lesions were transmural despite prolonged ablation times (90 seconds). Ventricular lesion width and depth increased with duration of application, and were similar on the arrested and beating hearts. CONCLUSIONS: Microwave ablation produces linear dose-response curves. Transmural lesions can be reliably produced on the arrested heart, but not consistently on the beating heart.

Hyperkalemic cardioplegia-induced myocyte swelling and contractile dysfunction: prevention by diazoxide.

BACKGROUND: Hyperkalemic cardioplegia (9 degrees C) results in significant myocyte swelling and reduced contractility, representing a possible mechanism of myocardial stunning. Adenosine triphosphate-sensitive potassium channel (KATP) openers have been shown to ameliorate stunning. This study evaluated the hypothesis that a KATP opener would prevent hyperkalemic cardioplegia-induced myocyte swelling and reduced contractility. METHODS: Isolated rabbit myocytes were perfused with 37 degrees C Tyrode's solution for 20 minutes, followed by test solution (9 degrees C or 37 degrees C) including control Tyrode's, Tyrode's + 100 micromol/L diazoxide (KATP opener), St. Thomas's solution; or 9 degrees C St. Thomas's + 100 micromol/L diazoxide or St. Thomas's + 100 micromol/L diazoxide + 20 micromol/L HMR1098 or 50 micromol/L 5-hydroxydeconoate (KATP blockers) for 20 minutes (n = 8 per group). Myocytes were then reexposed to 37 degrees C Tyrode's solution for 20 minutes. Volume and contractility were measured by videomicroscopy and video-based edge detection, respectively. RESULTS: St. Thomas's solution (9 degrees C) caused significant myocyte swelling and associated reduced contractility (p < 0.05). The addition of diazoxide abolished myocyte swelling (p < 0.0001), and eliminated the associated reduced contractility (p < 0.05). Findings were unchanged by the addition of HMR 1098 and 5-hydroxydeconoate. CONCLUSIONS: Diazoxide prevented myocyte swelling and reduced contractility secondary to hyperkalemic cardioplegia, and this was unchanged by the addition of either KATP channel blocker. Prevention of myocyte swelling was associated with improved contractility, consistent with the hypothesis that myocyte swelling may be a mechanism of myocardial stunning. Diazoxide may play a role in myocyte volume homeostasis by means of a mechanism separate from opening the KATP channel.

Progress towards a more physiologic approach to donor heart preservation: the advantages of hyperpolarized arrest.

BACKGROUND: The University of Wisconsin (UW) solution is the gold standard for heart preservation but has limitations in terms of both duration and adequacy of protection. Our laboratory has been interested in a more physiologic approach to heart preservation by maintaining the heart at its resting membrane potential (hyperpolarized arrest) with the K(ATP) channel agonist pinacidil. This study compared our extracellular solution (WashU) with the UW intracellular depolarizing solution and quantified the protective effect of pinacidil in both solutions. METHODS: Thirty-two rabbit hearts received 1 of 4 solutions in a crystalloid-perfused Langendorff apparatus: (1) UW, (2) WashU containing 0.5 mmol/liter pinacidil, (3) UW with 0.5 mmol/liter pinacidil, or (4) WashU without pinacidil. Thirty minutes of perfusion was followed by data acquisition consisting of left ventricular pressure-volume curves generated by inflating an intraventricular balloon. All hearts were placed in cold storage for 8 hours, followed by 1 hour of reperfusion before data acquisition. RESULTS: Post-ischemic developed pressure (DP) was better preserved by WashU (76.8% +/- 3.8%) than by UW (48.3% +/- 2.5%). Diastolic compliance was better preserved by WashU (239.9% +/- 77.2%) compared with UW (711.1% +/- 193.1%). Removing pinacidil from our solution resulted in decreased DP (46.6% +/- 3.2%) and diastolic compliance (688.8% +/- 158.2%) Adding pinacidil to UW had a limited effect on DP and compliance. CONCLUSIONS: Our results support the superiority of the WashU hyperpolarizing solution for heart preservation over UW. Pinacidil was beneficial in maintaining cardiac function and compliance. This benefit was not observed when pinacidil was placed into the UW depolarizing solution.

Dose response curves for microwave ablation in the cardioplegia-arrested porcine heart.

INTRODUCTION: Microwave ablation has been used clinically for the surgical treatment of atrial fibrillation, particularly during valve procedures. However, dose- response curves have not been established for this surgical environment. The purpose of this study was to examine dosimetry curves for the Flex 4 and Flex 10 microwave devices in an acute cardioplegia-arrested porcine model. METHODS: Twelve domestic pigs (40-45 kg) were acutely subjected to Flex 4 (n = 6) and Flex 10 (n = 6) ablations. On a cardioplegically arrested heart maintained at 10-15(o)C, six endocardial atrial and seven epicardial ventricular lesions were created in each animal. Ablations were performed for 15 s, 30 s, 45 s, 60 s, 90 s, 120 s, and 150 s (65 W, 2.45 GHz). The tissue was stained with 2,3,5-triphenyl-tetrazolium chloride and lesions were sectioned at 5 mm intervals. Lesion depth and width were determined from digital photomicrographs of each lesion (resolution +/- .03 mm). RESULTS: Average atrial thickness was 2.88 +/- .4 mm (range 1.0 to 8.0 mm). 94% of ablated atrial sections created by the FLEX 4 (n = 16) and the FLEX 10 (n = 16) were transmural at 45 seconds. 100% of atrial sections were transmural at 90 seconds with the FLEX 10 (n = 14) and at 60 seconds with the Flex 4 device (n = 15). Lesion width and depth increased with duration of application. CONCLUSION: Both devices were capable of producing transmural lesions on the cardioplegically arrested heart at 65 W. These curves will allow surgeons to ensure transmural ablation by tailoring energy delivery to the specific atrial geometry.

Successful performance of Cox-Maze procedure on beating heart using bipolar radiofrequency ablation: a feasibility study in animals.

BACKGROUND: The Cox-Maze procedure is the gold standard for the surgical treatment of atrial fibrillation with proven long-term efficacy. However, its application has been limited by its complexity and significant morbidity. The purpose of this study was to test the feasibility and safety of performing the Cox-Maze procedure using bipolar radiofrequency ablation on the beating heart without cardiopulmonary bypass. METHODS: After median sternotomy, 6 Hanford mini-pigs underwent a modified Cox-Maze procedure using bipolar radiofrequency energy. The animals survived for 30 days. Atrial function, coronary artery, pulmonary vein anatomy, and valve function were assessed by magnetic resonance imaging. At reoperation, pacing documented electrical isolation of the pulmonary veins. Induction of atrial fibrillation was attempted by burst pacing with cholinergic stimulation. Histologic assessment was performed after sacrifice. RESULTS: There were no perioperative mortalities or neurologic events. At 30 days, atrial fibrillation was unable to be induced, and pulmonary vein isolation was confirmed by pacing. Magnetic resonance imaging assessment revealed no coronary artery or pulmonary vein stenoses. Although atrial ejection fraction decreased slightly from 0.344 +/- 0.0114 to 0.300 +/- 0.055 (p = 0.18), atrial contractility was preserved in every animal. Histologic assessment showed all lesions to be transmural, and there were no significant stenoses of the coronary vessels or injuries to the valves. CONCLUSIONS: Virtually all of the lesions of the Cox-Maze procedure can be performed without cardiopulmonary bypass using bipolar radiofrequency energy. There were no late stenoses of the pulmonary veins. Clinical trials of this new technology on the beating heart are warranted.

A prospective, single-center clinical trial of a modified Cox maze procedure with bipolar radiofrequency ablation.

OBJECTIVE: The Cox maze III procedure has excellent long-term efficacy in curing atrial fibrillation. It has not been widely practiced because it is technically challenging and requires prolonged cardiopulmonary bypass. The aim of this study was to examine a simplified Cox maze III procedure that uses bipolar radiofrequency energy as an ablative source. METHODS: Beginning January 2002, a total of 40 consecutive patients underwent a modified Cox maze III procedure with bipolar radiofrequency energy. Nineteen had a lone maze procedure and 21 had a maze procedure plus a concomitant operation. One month after the operation, the first 8 patients were investigated with high-resolution magnetic resonance imaging. Patients were followed up monthly with clinical examination and electrocardiography. RESULTS: There was no operative deaths. The crossclamp times were 47 +/- 26 minutes for the modified lone Cox maze III procedure and 92 +/- 37 minutes for the Cox maze III procedure plus concomitant procedures. These were significantly shorter than our previous times for the traditional Cox maze III procedure (93 +/- 34 minutes and 122 +/- 37 minutes, respectively, P <.05). Follow-up magnetic resonance imaging showed no evidence of pulmonary vein stenosis, and atrial contractility was preserved in all patients. There were no late strokes. At 6-month follow-up, 91% of patients (21/23) were in sinus rhythm. CONCLUSIONS: Bipolar radiofrequency ablation can be used to replace the surgical incisions of the Cox maze procedure. This energy source did not result in pulmonary vein stenosis. The modification of the Cox maze III procedure to use bipolar radiofrequency ablation simplified and shortened this procedure without sacrificing short-term efficacy.

Repair of ischemic mitral regurgitation does not increase mortality or improve long-term survival in patients undergoing coronary artery revascularization: a propensity analysis.

BACKGROUND: The purpose of this study was to compare operative mortality and midterm outcome of patients with ischemic mitral regurgitation (MR) undergoing either coronary artery bypass grafting (CABG) alone or CABG with mitral valve (MV) repair. METHODS: From 1996 to 2001, 51 consecutive patients underwent CABG with MV repair for ischemic MR. All patients in this group were matched to similar patients with ischemic MR undergoing CABG alone during the same 6-year period using propensity analysis (considering 24 covariates, including severity of MR and New York Heart Association [NYHA] class). RESULTS: Propensity score matching yielded 51 closely matched control patients. Preoperative MR severity was 3+ or 4+ in 94% of CABG with MV repair and 96% of CABG-alone patients, and 86% of patients in each group were NYHA class III or IV. Operative mortality was 3.9% +/- 2.8% in both groups. Survival was also similar between CABG with MV repair and CABG alone at 1 year (84% +/- 5% versus 82% +/- 5%) and 3 years (70% +/- 7% versus 71% +/- 7% (p = 0.43). Among survivors, NYHA class improved at follow-up (50 +/- 20 months) from 3.4 +/- 0.7 to 1.7 +/- 1.0 for CABG with MV repair (p < 0.001) and from 3.4 +/- 0.7 to 1.8 +/- 1.0 for CABG alone (p < 0.001). CONCLUSIONS: Operative mortality, midterm survival, and late functional class were similar between two well-matched groups of patients undergoing CABG for ischemic MR, differing only in the addition of MV repair. Whereas MV repair can be added safely to CABG in this group of high-risk patients without increasing mortality, its impact on late survival and functional class may be limited.

Does functional mitral regurgitation improve with isolated aortic valve replacement?

BACKGROUND: The surgical treatment of mitral valve regurgitation (MR) at the time of aortic valve replacement (AVR) remains controversial. The purpose of this study was to evaluate the change in severity of MR following isolated AVR, and to determine survival benefit. METHODS: Between 1991 and 2001, 250 patients underwent isolated AVR; 196 patients had concomitant functional MR. Follow-up transthoracic echocardiography (TTE) was available on 107 patients, with a median of 818 +/- 752 days. Aortic valve was stenotic in 77 and regurgitant in 30 patients. RESULTS: Mean age was 67 +/- 15 years and 57 (53%) were male. Preoperative MR was trivial (1+) in 27 (25%), mild (2+) in 44 (41%), moderate (3+) in 29 (27%), and severe (4+) in 7 (7%). At follow-up TTE, MR improved by 1 or 2 grades in 48 patients (45%). Of patients with preoperative 2+ MR, 19 (43%) improved, 16 (36%) remained unchanged, and 9 (21%) worsened. Although some patients with preoperative 3+ MR exhibited improvement, 11 (38%) remained with moderate-to-severe MR. Of those with a preoperative MR of 4+, 3 (71%) improved, and 4 remained with 3-4+ MR. For patients with preoperative 1 to 2+ MR, survival at 3 years was 98% compared to 78% for those with 3 to 4+ MR (p = 0.038). CONCLUSION: Functional MR does not always improve after isolated AVR. Survival is lower for patients with preoperative 3 to 4+ MR. Moderate-to-severe MR should be repaired at the time of aortic valve surgery.

Optimizing motion scaling and magnification in robotic surgery.

BACKGROUND: Motion scaling is one possible advantage of robotic surgery. The aim of this study was to determine which scaling optimized precision and speed at different magnifications. METHODS: Three levels of motion scaling were tested at each of 3 camera magnifications. Surgically nave subjects (n = 12) were randomized as to the order of magnification level testing (3.5x, 6.5x, 9.5x) and motion scalings (10:1, 5:1, 1:1). The subjects were asked to pierce a needle through 6 printed microtargets; then accuracy and drill completion time were scored. RESULTS: At 3.5x magnification, no differences between groups were observed. At 6.5x magnification, the 5:1 scaling was superior to the 1:1 scaling in total errors, and the 10:1 scaling was significantly slower. At 9.5x magnification, 10:1 scaling resulted in fewer errors than 1:1 with no difference in time. Overall, the 10:1 and 5:1 scalings resulted in fewer errors. The 5:1 scaling resulted in less drill completion time than the 10:1 scaling. The 9.5x magnification resulted in the fewest errors. CONCLUSIONS: Motion scaling reduces the number of errors at higher magnifications, but can increase the task completion time. It is necessary to optimize both the motion scaling and magnification components of robotic systems to balance precision and speed.

Donor heart preservation with pinacidil: the role of the mitochondrial K ATP channel.

BACKGROUND: Pinacidil solutions have been shown to have significant cardioprotective effects. Pinacidil activates both sarcolemmal and mitochondrial potassium-adenosine triphosphate (K(ATP)) channels. This study was undertaken to compare pinacidil solution with University of Wisconsin (UW) solution and to determine if the protective effect of pinacidil involved mitochondrial or sarcolemmal K(ATP) channels. METHODS: Thirty-two rabbit hearts received one of four preservation solutions in a Langendorff apparatus: (1) UW; (2) a solution containing 0.5 mmol/L pinacidil; (3) pinacidil with Hoechst-Marion-Roussel 1098 (HMR-1098), a sarcolemmal channel blocker; and (4) pinacidil with 5-hydroxydecanote, a mitochondrial channel blocker. Left ventricular pressure-volume curves were generated by an intraventricular balloon. All hearts were placed in cold storage for 8 hours, followed by 60 minutes of reperfusion. RESULTS: Postischemic developed pressure was better preserved by pinacidil than by UW. This cardioprotective effect was eliminated by 5-hydroxydecanote and diminished by HMR-1098. Diastolic compliance was better preserved by pinacidil when compared with UW. This protection was abolished by the addition of 5-hydroxydecanote and moderately decreased by HMR-1098. CONCLUSIONS: Our results support the superiority of pinacidil over UW after 8 hours of storage. The cardioprotective role of pinacidil is mediated primarily by the mitochondrial K(ATP) channel.

Physiological consequences of bipolar radiofrequency energy on the atria and pulmonary veins: a chronic animal study.

BACKGROUND: Alternative energy sources have been proposed for the transvenous and surgical treatment of atrial fibrillation. This study examined the physiologic consequences of a novel energy source, bipolar radiofrequency energy, in a chronic animal model in order to determine its ability to produce transmural lesions on the beating heart. METHODS: Five dogs underwent baseline pacing from the following target areas: right and left atrial appendage, superior and inferior vena cavae, and right and left pulmonary veins. A cuff of atrial myocardium, proximal to the target tissue was clamped and ablated between the arms of the bipolar radiofrequency energy device. Tissue conductance was used as a transmural indicator. After ablation, the pacing protocol was repeated. Baseline and postablation pulmonary vein flows were measured. Animals were survived for 30 days, and permanent electrical isolation was evaluated by pacing, epicardial mapping, and histology. RESULTS: Mean ablation time was 5.0 +/- 1.8 seconds and mean peak tissue temperature was 46.7 degrees C +/- 2.8 degrees C. All lesions (30/30) acutely and permanently isolated atrial tissue. There was no change in pulmonary vein flow. Mapping studies with pacing of atrial tissue on both sides of the lesion confirmed isolation. Histology demonstrated that all lesions were linear, continuous, and transmural with no thrombus formation or stenosis. CONCLUSIONS: Bipolar radiofrequency energy rapidly produced permanent transmural linear lesions on the beating heart. Measurement of tissue conductance reliably predicted transmural lesions. This new technology may enable the development of a less invasive, surgical approach to atrial fibrillation.

Immunomodulatory effects of dehydroepiandrosterone in proestrus female mice after trauma-hemorrhage.

Studies indicate that administration of the adrenal steroid dehydroepiandrosterone (DHEA) after trauma-hemorrhage in male mice improved cellular immune functions and reduced mortality rates from subsequent sepsis. There is evidence, however, that DHEA is converted to estrogens in males and that estrogens are immunoprotective after trauma-hemorrhage (TH). In contrast, DHEA in females can be converted to testosterone that has deleterious effects on immune functions. The aim of our study, therefore, was to determine whether administration of DHEA in proestrus females after TH would deteriorate immune responses. Proestrus female C3H/HeN mice (age 7-8 wk) were subjected to laparotomy (i.e., soft tissue trauma induced) and hemorrhagic shock (35 +/- 5 mmHg for 90 min) or sham operation. The mice then received DHEA (100 micro/25 g body wt) or vehicle subcutaneously followed by fluid resuscitation (4x the shed blood volume). Plasma IL-6, splenocyte proliferation, splenocyte IL-2, IL-3, IFN-gamma, IL-10 release, and splenic Mphi IL-1beta, IL-6, IL-10, and IL-12 release were determined 24 h after TH. Plasma IL-6 levels were significantly increased in vehicle-treated females, and DHEA administration markedly attenuated this response. In vehicle-treated females, splenocyte proliferation, IL-2, IL-3, and IFN-gamma release, and splenic Mphi IL-1 beta, IL-6, and IL-12 release were maintained or slightly enhanced after TH. In DHEA-treated females, however, these immune functional parameters were either unaltered compared with vehicle-treated animals or even further enhanced, but surprisingly were not depressed. Moreover, DHEA reduced splenocyte and splenic M phi anti-inflammatory cytokine (i.e., IL-10) production after TH compared with vehicle-treated females. Because DHEA further enhances the immune responsiveness in proestrus females after TH, this hormone might be a useful adjunct even in females for further enhancing immune responses and decreasing the mortality rate after trauma and severe blood loss.

Robotic cardiac surgery: overview.

Most endoscopic procedures are excisional, not reconstructive or microsurgical, mostly because conventional endoscopic instrumentation lacks dexterity due to long, nonarticulated instruments, a fixed pivot point and counterintuitive movement of the instrument tip, and lack of depth perception. Endoscopic approaches to cardiac surgery have not been successful; however, the development of robotic surgical systems has overcome many limitations of endoscopy. Computer-assisted surgery has created a computerized digital interface between the surgeon's hands and surgical instrument tips and enhances surgical ability, thereby enabling endoscopic microsurgery. Recently, robotic systems have allowed cardiac surgeons to perform minimally invasive endoscopic coronary artery bypass grafting (CABG) and valve procedures. This article summarizes the use of robotics in cardiac surgery and discusses its potential in our specialty.

Female sex hormones regulate macrophage function after trauma-hemorrhage and prevent increased death rate from subsequent sepsis.

OBJECTIVE: To determine whether reduction of circulating female sex hormones by ovariectomy causes suppression of macrophage (Mphi) function after trauma-hemorrhage and increases susceptibility to subsequent sepsis. SUMMARY BACKGROUND DATA: Studies indicate that immune functions are markedly depressed in males but not in proestrus females after trauma-hemorrhage. Although male sex steroids are immunosuppressive, it remains unknown whether female sex hormones are immunoprotective after trauma-hemorrhage. METHODS: Circulating female sex hormones were reduced by ovariectomy of 8-week-old female CBA/J mice. Two weeks afterward, ovariectomy and proestrus sham-ovariectomy mice were subjected to laparotomy (i.e., soft tissue trauma) and hemorrhagic shock (35 +/- 5 mm Hg for 90 minutes, then resuscitated) or sham operation. Two hours afterward, splenic and peritoneal Mphi and Kupffer cells were isolated and cytokine production was assessed. In a second series of experiments, animals were subjected to sepsis by cecal ligation and puncture at 24 hours after trauma-hemorrhage or sham operation, and survival was assessed. RESULTS: Release of interleukin-1 and interleukin-6 by splenic and peritoneal Mphi from proestrus mice was maintained after trauma-hemorrhage, whereas release of interleukin-1 and interleukin-6 by Mphi from ovariectomized mice was depressed by approximately 50%. In contrast, trauma-hemorrhage resulted in a fourfold increase of Kupffer cell release of tumor necrosis factor-alpha in ovariectomized females and a fivefold increase in plasma concentrations of tumor necrosis factor-alpha. Release of tumor necrosis factor-alpha and plasma concentrations were unchanged in proestrus mice under such conditions. When proestrus and ovariectomized animals were subjected to sepsis by cecal ligation and puncture at 24 hours after trauma-hemorrhage or sham operation, ovariectomized mice had a significantly higher death rate than proestrus mice. CONCLUSIONS: These findings suggest that female sex hormones play a critical role in maintaining immune responses after trauma-hemorrhage by suppressing the elaboration of tumor necrosis factor-alpha and prevent the increased lethality from subsequent sepsis. Thus, female sex hormones may be a useful adjunct in preventing trauma-induced immunodepression and increased susceptibility to subsequent sepsis.